WorldWideScience

Sample records for activate kcl cotransport

  1. The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.

    Science.gov (United States)

    Rees, David C; Thein, Swee Lay; Osei, Anna; Drasar, Emma; Tewari, Sanjay; Hannemann, Anke; Gibson, John S

    2015-05-01

    HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.

  2. Sites of regulated phosphorylation that control K-Cl cotransporter activity.

    Science.gov (United States)

    Rinehart, Jesse; Maksimova, Yelena D; Tanis, Jessica E; Stone, Kathryn L; Hodson, Caleb A; Zhang, Junhui; Risinger, Mary; Pan, Weijun; Wu, Dianqing; Colangelo, Christopher M; Forbush, Biff; Joiner, Clinton H; Gulcicek, Erol E; Gallagher, Patrick G; Lifton, Richard P

    2009-08-07

    Modulation of intracellular chloride concentration ([Cl(-)](i)) plays a fundamental role in cell volume regulation and neuronal response to GABA. Cl(-) exit via K-Cl cotransporters (KCCs) is a major determinant of [Cl(-)](I); however, mechanisms governing KCC activities are poorly understood. We identified two sites in KCC3 that are rapidly dephosphorylated in hypotonic conditions in cultured cells and human red blood cells in parallel with increased transport activity. Alanine substitutions at these sites result in constitutively active cotransport. These sites are highly phosphorylated in plasma membrane KCC3 in isotonic conditions, suggesting that dephosphorylation increases KCC3's intrinsic transport activity. Reduction of WNK1 expression via RNA interference reduces phosphorylation at these sites. Homologous sites are phosphorylated in all human KCCs. KCC2 is partially phosphorylated in neonatal mouse brain and dephosphorylated in parallel with KCC2 activation. These findings provide insight into regulation of [Cl(-)](i) and have implications for control of cell volume and neuronal function.

  3. ROS activate KCl cotransport in nonadherent Ehrlich ascites cells but K+ and Cl- channels in adherent Ehrlich Lettré and NIH3T3 cells

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Klausen, Thomas Kjær; Bergdahl, Andreas;

    2009-01-01

    the electrochemical driving force for K(+). On the other hand, the H2O2-induced cell shrinkage was impaired in the presence of the KCl cotransport inhibitor DIOA, following substitution of NO3(-) for Cl(-), and when the driving force for KCl cotransport was omitted. It is suggested that H2O2 activates electro neutral...

  4. BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2.

    Science.gov (United States)

    Aguado, Fernando; Carmona, Maria A; Pozas, Esther; Aguiló, Agustín; Martínez-Guijarro, Francisco J; Alcantara, Soledad; Borrell, Victor; Yuste, Rafael; Ibañez, Carlos F; Soriano, Eduardo

    2003-04-01

    Spontaneous neural activity is a basic property of the developing brain, which regulates key developmental processes, including migration, neural differentiation and formation and refinement of connections. The mechanisms regulating spontaneous activity are not known. By using transgenic embryos that overexpress BDNF under the control of the nestin promoter, we show here that BDNF controls the emergence and robustness of spontaneous activity in embryonic hippocampal slices. Further, BDNF dramatically increases spontaneous co-active network activity, which is believed to synchronize gene expression and synaptogenesis in vast numbers of neurons. In fact, BDNF raises the spontaneous activity of E18 hippocampal neurons to levels that are typical of postnatal slices. We also show that BDNF overexpression increases the number of synapses at much earlier stages (E18) than those reported previously. Most of these synapses were GABAergic, and GABAergic interneurons showed hypertrophy and a 3-fold increase in GAD expression. Interestingly, whereas BDNF does not alter the expression of GABA and glutamate ionotropic receptors, it does raise the expression of the recently cloned K(+)/Cl(-) KCC2 co-transporter, which is responsible for the conversion of GABA responses from depolarizing to inhibitory, through the control of the Cl(-) potential. Together, results indicate that both the presynaptic and postsynaptic machineries of GABAergic circuits may be essential targets of BDNF actions to control spontaneous activity. The data indicate that BDNF is a potent regulator of spontaneous activity and co-active networks, which is a new level of regulation of neurotrophins. Given that BDNF itself is regulated by neuronal activity, we suggest that BDNF acts as a homeostatic factor controlling the emergence, complexity and networking properties of spontaneous networks.

  5. Memantine treatment reduces the expression of the K(+)/Cl(-) cotransporter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABA(A) receptor activation in mice.

    Science.gov (United States)

    Molinaro, Gemma; Battaglia, Giuseppe; Riozzi, Barbara; Di Menna, Luisa; Rampello, Liborio; Bruno, Valeria; Nicoletti, Ferdinando

    2009-04-10

    A 7-day treatment with memantine (25 mg/kg, i.p.), a drug that is currently prescribed for the treatment of Alzheimer's disease, increased the levels of brain-derived neurotrophic factor (BDNF) and reduced the expression of the neuron-specific K(+)/Cl(-) co-transporter, KCC2, in the hippocampus and cerebral cortex of mice. Knowing that KCC2 maintains low intracellular Cl(-) concentrations, which drive Cl(-) influx in response to GABA(A) receptor activation, we monitored the behavioural response to the GABA(A) receptor enhancer, diazepam, in mice pre-treated for 7 days with saline or 25 mg/kg of memantine. Memantine treatment substantially attenuated motor impairment induced by an acute challenge with diazepam (6 mg/kg, i.p.), as assessed by the rotarod test and the horizontal wire test. We suggest that a prolonged treatment with memantine induces changes in the activity of GABA(A) receptors that might contribute to the therapeutic and/or toxic effects of the drug.

  6. With no lysine L-WNK1 isoforms are negative regulators of the K+-Cl- cotransporters.

    Science.gov (United States)

    Mercado, Adriana; de Los Heros, Paola; Melo, Zesergio; Chávez-Canales, María; Murillo-de-Ozores, Adrián R; Moreno, Erika; Bazúa-Valenti, Silvana; Vázquez, Norma; Hadchouel, Juliette; Gamba, Gerardo

    2016-07-01

    The K(+)-Cl(-) cotransporters (KCC1-KCC4) encompass a branch of the SLC12 family of electroneutral cation-coupled chloride cotransporters that translocate ions out of the cell to regulate various factors, including cell volume and intracellular chloride concentration, among others. L-WNK1 is an ubiquitously expressed kinase that is activated in response to osmotic stress and intracellular chloride depletion, and it is implicated in two distinct hereditary syndromes: the renal disease pseudohypoaldosteronism type II (PHAII) and the neurological disease hereditary sensory neuropathy 2 (HSN2). The effect of L-WNK1 on KCC activity is unknown. Using Xenopus laevis oocytes and HEK-293 cells, we show that the activation of KCCs by cell swelling was prevented by L-WNK1 coexpression. In contrast, the activity of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 was remarkably increased with L-WNK1 coexpression. The negative effect of L-WNK1 on the KCCs is kinase dependent. Elimination of the STE20 proline-alanine rich kinase (SPAK)/oxidative stress-responsive kinase (OSR1) binding site or the HQ motif required for the WNK-WNK interaction prevented the effect of L-WNK1 on KCCs, suggesting a required interaction between L-WNK1 molecules and SPAK. Together, our data support that NKCC1 and KCCs are coordinately regulated by L-WNK1 isoforms.

  7. Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold

    OpenAIRE

    Boettger, Thomas; Rust, Marco B.; Maier, Hannes; Seidenbecher, Thomas; Schweizer, Michaela; Damien J. Keating; Faulhaber, Jörg; Ehmke, Heimo; Pfeffer, Carsten; Scheel, Olaf; Lemcke, Beate; Horst, Jürgen; Leuwer, Rudolf; Pape, Hans-Christian; Völkl, Harald

    2003-01-01

    K-Cl co-transporters are encoded by four homologous genes and may have roles in transepithelial transport and in the regulation of cell volume and cytoplasmic chloride. KCC3, an isoform mutated in the human Anderman syndrome, is expressed in brain, epithelia and other tissues. To investigate the physiological functions of KCC3, we disrupted its gene in mice. This severely impaired cell volume regulation as assessed in renal tubules and neurons, and moderately raised intraneuronal Cl– concentr...

  8. Molecular characterization of a putative K-Cl cotransporter in rat brain. A neuronal-specific isoform.

    Science.gov (United States)

    Payne, J A; Stevenson, T J; Donaldson, L F

    1996-07-05

    Using a combination of data base searching, polymerase chain reaction, and library screening, we have identified a putative K-Cl cotransporter isoform (KCC2) in rat brain that is specifically localized in neurons. A cDNA of 5566 bases was obtained from overlapping clones and encoded a protein of 1116 amino acids with a deduced molecular mass of 123.6 kDa. Over its full length, the amino acid sequence of KCC2 is 67% identical to the widely distributed K-Cl cotransporter isoform (KCC1) identified in rat brain and rabbit kidney (Gillen, C., Brill, S., Payne, J.A., and Forbush, B., III(1996) J. Biol. Chem. 271, 16237-16244) but only approximately25% identical to other members of the cation-chloride cotransporter gene family, including "loop" diuretic-sensitive Na-K-Cl cotransport and thiazide-sensitive Na-Cl cotransport. Based on analysis of the primary structure as well as homology with other cation-chloride cotransporters, we predict 12 transmembrane segments bounded by N- and C-terminal cytoplasmic regions. Four sites for N-linked glycosylation are predicted on an extracellular intermembrane loop between putative transmembrane segments 5 and 6. Northern blot analysis using a KCC2-specific cDNA probe revealed a very highly expressed approximately5.6-kilobase transcript only in brain. Reverse transcriptase-polymerase chain reaction revealed that KCC1 was present in rat primary astrocytes and rat C6 glioma cells but that KCC2 was completely absent from these cells, suggesting KCC2 was not of glial cell origin. In situ hybridization studies demonstrated that the KCC2 transcript was expressed at high levels in neurons throughout the central nervous system, including CA1-CA4 pyramidal neurons of the hippocampus, granular cells and Purkinje neurons of the cerebellum, and many groups of neurons throughout the brainstem.

  9. Role of the neuronal K-Cl co-transporter KCC2 in inhibitory and excitatory neurotransmission

    Directory of Open Access Journals (Sweden)

    Ingrid eChamma

    2012-02-01

    Full Text Available The K-Cl co-transporter KCC2 plays multiple roles in the physiology of central neurons and alterations of its function and/or expression are associated with several neurological conditions. By regulating intraneuronal chloride homeostasis, KCC2 strongly influences the efficacy and polarity of the chloride-permeable -aminobutyric acid (GABA type A and glycine receptor (GlyR mediated synaptic transmission. This appears particularly critical for the development of neuronal circuits as well as for the dynamic control of GABA and glycine signaling in mature networks. The activity of the transporter is also associated with transmembrane water fluxes which compensate solute fluxes associated with synaptic activity. Finally, KCC2 interaction with the actin cytoskeleton appears critical both for dendritic spine morphogenesis and the maintenance of glutamatergic synapses. In light of the pivotal role of KCC2 in the maturation and function of central synapses, it is of particular importance to understand the cellular and molecular mechanisms underlying its regulation. These include development- and activity-dependent modifications both at the transcriptional and post-translational levels. We emphasize the importance of post-translational mechanisms such as phosphorylation and dephosphorylation, oligomerization, cell surface stability, clustering and membrane diffusion for the rapid and dynamic regulation of KCC2 function.

  10. Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene.

    Science.gov (United States)

    Woo, Nam-Sik; Lu, Jianming; England, Roger; McClellan, Robert; Dufour, Samuel; Mount, David B; Deutch, Ariel Y; Lovinger, David M; Delpire, Eric

    2002-01-01

    Four genes encode electroneutral, Na+-independent, K-Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl- to low concentrations and shift the reversal potential for Cl- conductances such as GABA(A) or glycine receptor channels, thus participating in the postnatal development of inhibitory mechanisms in the brain. Indeed, expression of the cotransporter is low at birth and increases postnatally, at a time when the intracellular Cl- concentration in neurons decreases and gamma-aminobutyric acid switches its effect from excitatory to inhibitory. To assert the significance of KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal-specific K-Cl cotransporter. We demonstrate that animals deficient in KCC2 exhibit frequent generalized seizures and die shortly after birth. We also show upregulation of Fos, the product of the immediate early gene c-fos, and the significant loss of parvalbumin-positive interneurons, both indicative of brain injury. The regions most affected are the hippocampus and temporal and entorhinal cortices. Extracellular field potential measurements in the CA1 hippocampus exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABA(A) receptor, further increased hyperexcitability in homozygous hippocampal sections. Pharmacological treatment of pups showed that diazepam relieved the seizures while phenytoin prevented them between postnatal ages P4-P12. Finally, we demonstrate that adult heterozygote animals show increased susceptibility for epileptic seizure and increased resistance to the anticonvulsant effect of propofol. Taken together, these results indicate that KCC2 plays an important role in controlling CNS excitability during both postnatal development and adult life.

  11. Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.

    Science.gov (United States)

    Boettger, Thomas; Hübner, Christian A; Maier, Hannes; Rust, Marco B; Beck, Franz X; Jentsch, Thomas J

    2002-04-25

    Hearing depends on a high K(+) concentration bathing the apical membranes of sensory hair cells. K(+) that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+) recycling() by siphoning K(+) ions after their exit from outer hair cells into supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to some human genetic syndromes(), deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl(-) recycling across the basolateral membrane of acid-secreting alpha-intercalated cells of the distal nephron.

  12. Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold.

    Science.gov (United States)

    Boettger, Thomas; Rust, Marco B; Maier, Hannes; Seidenbecher, Thomas; Schweizer, Michaela; Keating, Damien J; Faulhaber, Jörg; Ehmke, Heimo; Pfeffer, Carsten; Scheel, Olaf; Lemcke, Beate; Horst, Jürgen; Leuwer, Rudolf; Pape, Hans-Christian; Völkl, Harald; Hübner, Christian A; Jentsch, Thomas J

    2003-10-15

    K-Cl co-transporters are encoded by four homologous genes and may have roles in transepithelial transport and in the regulation of cell volume and cytoplasmic chloride. KCC3, an isoform mutated in the human Anderman syndrome, is expressed in brain, epithelia and other tissues. To investigate the physiological functions of KCC3, we disrupted its gene in mice. This severely impaired cell volume regulation as assessed in renal tubules and neurons, and moderately raised intraneuronal Cl(-) concentration. Kcc3(-/-) mice showed severe motor abnormalities correlating with a progressive neurodegeneration in the peripheral and CNS. Although no spontaneous seizures were observed, Kcc3(-/-) mice displayed reduced seizure threshold and spike-wave complexes on electrocorticograms. These resembled EEG abnormalities in patients with Anderman syndrome. Kcc3(-/-) mice also displayed arterial hypertension and a slowly progressive deafness. KCC3 was expressed in many, but not all cells of the inner ear K(+) recycling pathway. These cells slowly degenerated, as did sensory hair cells. The present mouse model has revealed important cellular and systemic functions of KCC3 and is highly relevant for Anderman syndrome.

  13. The KCl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in the rat hippocampus.

    Science.gov (United States)

    Gulyás, A I; Sík, A; Payne, J A; Kaila, K; Freund, T F

    2001-06-01

    Immunocytochemical visualization of the neuron-specific K+/Cl- cotransporter, KCC2, at the cellular and subcellular level revealed an area- and layer-specific diffuse labelling, and a discrete staining outlining the somata and dendrites of some interneurons in all areas of the rat hippocampus. KCC2 was highly expressed in parvalbumin-containing interneurons, as well as in subsets of calbindin, calretinin and metabotropic glutamate receptor 1a-immunoreactive interneurons. During the first 2 postnatal weeks, an increase of KCC2 staining was observed in the molecular layer of the dentate gyrus, correlating temporally with the arrival of entorhinal cortical inputs. Subcellular localization demonstrated KCC2 in the plasma membranes. Immunoreactivity in principal cells was responsible for the diffuse staining found in the neuropil. In these cells, KCC2 was detected primarily in dendritic spine heads, at the origin of spines and, at a much lower level on the somata and dendritic shafts. KCC2 expression was considerably higher in the somata and dendrites of interneurons, most notably of parvalbumin-containing cells, as well as in the thorny excrescences of CA3 pyramidal cells and in the spines of spiny hilar and stratum lucidum interneurons. The data indicate that KCC2 is highly expressed in the vicinity of excitatory inputs in the hippocampus, perhaps in close association with extrasynaptic GABAA receptors. A high level of excitation is known to lead to a simultaneous net influx of Na+ and Cl-, as evidenced by dendritic swelling. KCC2 located in the same microenvironment may provide a Cl- extrusion mechanism to deal with both ion and water homeostasis in addition to its role in setting the driving force of Cl- currents involved in fast postsynaptic inhibition.

  14. K-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spines

    KAUST Repository

    Puskarjov, Martin

    2017-03-16

    Background: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABA A)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). Methods: In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABA A)-mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. Results: The authors found a robust effect of the developmental up-regulation of KCC2-mediated Cl - transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. Conclusions: The KCC2-dependent developmental increase in the efficacy of GABA A -mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.

  15. Differential expression of Na+-K+-Cl- cotransporter 1 and K+-Cl- cotransporter 2 in the somata and dendrites of adult rat neocortical neurons[1]%NKCC1和KCC2在成年大鼠大脑皮质神经元的胞体和树突的不同表达

    Institute of Scientific and Technical Information of China (English)

    王德广

    2008-01-01

    γ-氨基丁酸(GABA)是成年哺乳动物脑内主要的抑制性神经递质,但电生理的研究表明,GABA在成熟皮质神经元的树突部位可以产生兴奋性作用,但该现象的形态学基础,目前尚不清楚.GABA产生兴奋性作用的关键主要依赖于神经元胞内的氰离子浓度,其中Na+-K-Cl-共转运体1(NKCC1)促进细胞内Cl-堆积,而K+-Cl-共转运体2(KCC2)则外排胞内的Cl-,降低胞内的Cl-浓度.本研究应用免疫荧光组织化学双重标记结合荧光强度分析,检测NKCC1和KCC2在成年大鼠脑皮质和培养的大鼠脑皮质神经元树突和胞体的表达和分布情况.结果显示:成年大鼠皮质神经元的胞浆和细胞膜均有NKCC1的表达,而KCC2主要表达在神经元胞体和树突膜上,其中NKCC1在神经元树突上的表达水平比胞体高.而KCC2的表达水平在树突和胞体膜上没有明显差异.皮质神经元经培养20 d后,NKCC1和KCC2在树突和胞体的表达模式与在体的分布相类似.本研究结果提示,NKCC1在大鼠皮质神经元树突的表达较多,可能是GABA兴奋神经元树突的原因.%γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the adult brain. However, electrophysiological findings indicate that GABA exerts excitation in dendrites of mature eorlieal neurons. Little is known about morphological basis of GABA-medi-ated excitation in dendrites of mature cortical neurons. The effect of activated GABAA receptors is mainly determined by intraceUular chloride ion, whose active influx is mainly mediated by Na+-K +-Cl- cotransporter isoform 1 (NKCC1) and exclusion is mainly executed by K+-Cl- cotransporter isoform 2 ( KCC2 ). In the present study, by using immunofluorescent double staining and fluorescent density analysis, the expression and distribution of NKCCI- and KCC2-immunoreactivities in the dendrite and soma of adult rat neocortical neurons were detected in vivo and in vitro. The present results showed that both

  16. Absence of Na +/sugar cotransport activity in Barrett's metaplasia

    Institute of Scientific and Technical Information of China (English)

    Lisa J Murray; Owen Tully; David S Rudolph; Marysue Whitby; Mary C Valenzano; Giancarlo Mercogliano; James J Thornton; James M Mullin

    2008-01-01

    AIM:To evaluate the presence of Na+-dependent,active,sugar transport in Barrett's epithelia as an intestinal biomarker,based on the well-documented,morphological intestinal phenotype of Barrett's esophagus (BE).METHODS:We examined uptake of the nonmeta-bolizable glucose analogue,alpha-methyl-D-glucoside (AMG),a substrate for the entire sodium glucose cotransporter (SGLT) family of transport proteins.During upper endoscopy,patients with BE or with uncomplicated gastroesophageal reflux disease (GERD)allowed for duodenal,gastric fundic,and esophageal mucosal biopsies to be taken.Biopsies were incubated in bicarbonate-buffered saline (KRB) containing 0.1 mmol/L 14C-AMG for 60 min at 20℃.Characterized by abundant SGLT,duodenum served as a positive control while gastric fundus and normal esophagus,known to lack SGLT,sewed as negative controls.RESULTS:Duodenal biopsies accumulated 249.84± 35.49 (SEM) picomoles AMG/μg DNA (n = 12),gastric fundus biopsies 36.20 ± 6.62 (n = 12),normal esophagus 12.10 ± 0.59 (n = 3) and Barrett's metaplasia 29.79 ± 5.77 (n = 8).There was a statistical difference (P<0.01) between biopsies from duodenum and each other biopsy site but there was no statistically significant difference between normal esophagus and BE biopsies.0.5 mmol/L phlorizin (PZ) inhibited AMG uptake into duodenal mucosa by over 89%,but had no significant effect on AMG uptake into gastric fundus,normal esophagus,or Barrett's tissue.In the absence of Na+ (all Na+ salts replaced by Li+ salts),AMG uptake in duodenum was decreased by over 90%,while uptake into gastric,esophageal or Barrett's tissue was statistically unaffected.CONCLUSION:Despite the intestinal enterocyte phenotype of BE,Na+-dependent,sugar transport activity is not present in bhese cells.

  17. Prolactin increases hepatic Na+/taurocholate co-transport activity and messenger RNA post partum.

    Science.gov (United States)

    Ganguly, T C; Liu, Y; Hyde, J F; Hagenbuch, B; Meier, P J; Vore, M

    1994-01-01

    We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity. Images Figure 2 PMID:7945260

  18. Activation analysis of indium, KCl, and melamine by using a laser-induced neutron source

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sungman; Lee, Kitae [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cha, Hyungki [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2014-04-15

    A laser-induced repetitively operated fast neutron source with a neutron yield of 4 x 10{sup 5} n/pulse and a pulse repetition rate of 5 Hz, which was developed using a deuterated polystyrene film target and a 24-TW femtosecond laser, was applied for laser activation analyses of indium, KCl, and melamine samples. The nuclear reactions of the measured gamma spectra for the activated samples were identified as (n, γ), (n, n'), and (n, 2n) reactions. These indicate possible usage of the neutron source for practical activation analyses of various materials.

  19. Human NKCC2 cation–Cl– co-transporter complements lack of Vhc1 transporter in yeast vacuolar membranes.

    Science.gov (United States)

    Petrezselyova, Silvia; Dominguez, Angel; Herynkova, Pavla; Macias, Juan F; Sychrova, Hana

    2013-10-01

    Cation–chloride co-transporters serve to transport Cl– and alkali metal cations. Whereas a large family of these exists in higher eukaryotes, yeasts only possess one cation–chloride co-transporter, Vhc1, localized to the vacuolar membrane. In this study, the human cation–chloride co-transporter NKCC2 complemented the phenotype of VHC1 deletion in Saccharomyces cerevisiae and its activity controlled the growth of salt-sensitive yeast cells in the presence of high KCl, NaCl and LiCl. A S. cerevisiae mutant lacking plasma-membrane alkali–metal cation exporters Nha1 and Ena1-5 and the vacuolar cation–chloride co-transporter Vhc1 is highly sensitive to increased concentrations of alkali–metal cations, and it proved to be a suitable model for characterizing the substrate specificity and transport activity of human wild-type and mutated cation–chloride co-transporters.

  20. Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl cotransporters via local and systemic mechanisms.

    Science.gov (United States)

    Blankenstein, K I; Borschewski, A; Labes, R; Paliege, A; Boldt, C; McCormick, J A; Ellison, D H; Bader, M; Bachmann, S; Mutig, K

    2017-03-01

    Calcineurin dephosphorylates nuclear factor of activated T cells transcription factors, thereby facilitating T cell-mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation but may cause side effects, including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA). An involvement of major hormones like angiotensin II or arginine vasopressin (AVP) has been proposed. To resolve this issue, the effects of CsA treatment in normal Wistar rats, AVP-deficient Brattleboro rats, and cultured renal epithelial cells endogenously expressing either NKCC2 or NCC were studied. Acute administration of CsA to Wistar rats rapidly augmented phosphorylation levels of NKCC2, NCC, and their activating kinases suggesting intraepithelial activating effects. Chronic CsA administration caused salt retention and hypertension, along with stimulation of renin and suppression of renal cyclooxygenase 2, pointing to a contribution of endocrine and paracrine mechanisms at long term. In Brattleboro rats, CsA induced activation of NCC, but not NKCC2, and parallel effects were obtained in cultured cells in the absence of AVP. Stimulation of cultured thick ascending limb cells with AVP agonist restored their responsiveness to CsA. Our results suggest that the direct epithelial action of calcineurin inhibition is sufficient for the activation of NCC, whereas its effect on NKCC2 is more complex and requires concomitant stimulation by AVP. Copyright © 2017 the American Physiological Society.

  1. Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter.

    Science.gov (United States)

    Becker, Holger M; Deitmer, Joachim W

    2007-05-04

    Several acid/base-coupled membrane transporters, such as the electrogenic sodium-bicarbonate cotransporter (NBCe1), have been shown to bind to different carbonic anhydrase isoforms to create a "transport metabolon." We have expressed NBCe1 derived from human kidney in oocytes of Xenopus leavis and determined its transport activity by recording the membrane current in voltage clamp, and the cytosolic H(+) and Na(+) concentrations using ion-selective microelectrodes. When carbonic anhydrase isoform II (CAII) had been injected into oocytes, the membrane current and the rate of cytosolic Na(+) rise, indicative for NBCe1 activity, increased significantly with the amount of injected CAII (2-200 ng). The CAII inhibitor ethoxyzolamide reversed the effects of CAII on the NBCe1 activity. Co-expressing wild-type CAII or NH(2)-terminal mutant CAII together with NBCe1 provided similar results, whereas co-expressing the catalytically inactive CAII mutant V143Y had no effect on NBCe1 activity. Mass spectrometric analysis and the rate of cytosolic H(+) change following addition of CO(2)/HCO(3)(-) confirmed the catalytic activity of injected and expressed CAII in oocytes. Our results show that the transport capacity of NBCe1 is enhanced by the catalytic activity of CAII, in line with the notion that CAII forms a transport metabolon with NBCe1.

  2. Na+-K+-2Cl- cotransporter type 2 trafficking and activity: the role of interacting proteins.

    Science.gov (United States)

    Carmosino, Monica; Procino, Giuseppe; Svelto, Maria

    2012-04-01

    The central role of Na+-K+-2Cl- cotransporter type 2 (NKCC2) in vectorial transepithelial salt reabsorption in thick ascending limb cells from Henle's loop in the kidney is evidenced by the effects of loop diuretics, the pharmacological inhibitors of NKCC2, that are amongst the most powerful antihypertensive drugs available to date. Moreover, genetic mutations of the NKCC2 encoding gene resulting in impaired apical targeting and function of NKCC2 transporter give rise to a pathological phenotype known as type I Bartter syndrome, characterised by a severe volume depletion, hypokalaemia and metabolic alkalosis with high prenatal mortality. On the contrary, excessive NKCC2 activity has been linked with inherited hypertension in humans and in rodent models. Interestingly, in animal models of hypertension, NKCC2 upregulation is achieved by post-translational mechanisms underlining the need to analyse the molecular mechanisms involved in the regulation of NKCC2 trafficking and activity to gain insights in the pathogenesis of hypertension. Copyright © 2012 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France.

  3. Electrochemical measurements of diffusion coefficients and activity coefficients for MnCl2 in molten eutectic LiCl-KCl

    Science.gov (United States)

    Horvath, D.; Rappleye, D.; Bagri, P.; Simpson, M. F.

    2017-09-01

    An electrochemical study of manganese chloride in molten salt mixtures of eutectic LiCl-KCl was carried out using a variety of electrochemical methods in a high temperature cell including cyclic voltammetry (CV), chronopotentiometry (CP), chronoamperometry (CA), and open circuit potentiometry. Single step reduction from Mn2+ to Mn(0) was observed on both W and Mo working electrodes. Using a combination of these methods, measurements were made of activity coefficient and diffusion coefficient for MnCl2 in LiCl-KCl as a function of concentration (3.54 × 10-4 to 3.60 × 10-3 mol fraction of MnCl2) at 773K. From OCP measurements, values for activity coefficient varied from 0.014 to 0.0071. Diffusion coefficients varied with concentration and differed based on measurement method (CV, CA, or CP). Based on cyclic Mn(II) ranged from 1.1 to 2.8 × 10-5 cm2/s depending on concentration.

  4. Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and decreases edema formation in permanent middle cerebral artery occlusion.

    Science.gov (United States)

    O'Donnell, Martha E; Lam, Tina I; Tran, Lien Q; Foroutan, Shahin; Anderson, Steven E

    2006-10-01

    Estrogen has been shown to protect against stroke-induced brain damage, yet the mechanism is unknown. During the early hours of stroke, cerebral edema forms as increased transport of Na and Cl from blood into brain occurs across an intact blood-brain barrier (BBB). We showed previously that a luminal BBB Na-K-Cl cotransporter is stimulated by hypoxia and arginine vasopressin (AVP), factors present during cerebral ischemia, and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema in rats subjected to permanent middle cerebral artery occlusion (MCAO). The present study was conducted to determine whether estrogen protects in stroke at least in part by reducing activity of the BBB cotransporter, thereby decreasing edema formation. Ovariectomized rats were subjected to 210 mins of permanent MCAO after 7-day or 30-min pretreatment with 17beta-estradiol and then brain swelling and 2,3,5-triphenyltetrazolium chloride staining were assessed as measures of brain edema and lesion volume, respectively. Diffusion-weighed imaging was used to monitor permanent MCAO-induced decreases in apparent diffusion coefficient (ADC) values, an index of changes in brain water distribution and mobility. Na-K-Cl cotransporter activity of cerebral microvascular endothelial cells (CMECs) was assessed as bumetanide-sensitive K influx and cotransporter abundance by Western blot analysis after estradiol treatment. Estradiol significantly decreased brain swelling and lesion volume and attenuated the decrease in ADC values during permanent MCAO. Estradiol also abolished CMEC cotransporter stimulation by chemical hypoxia or AVP and decreased cotransporter abundance. These findings support the hypothesis that estrogen attenuates stimulation of BBB Na-K-Cl cotransporter activity, reducing edema formation during stroke.

  5. Na+,2Cl-,K+ cotransport system as a marker of antihypertensive activity of new torasemide derivatives.

    Science.gov (United States)

    Masereel, B; Ferrari, P; Ferrandi, M; Pirotte, B; Schynts, M; Parenti, P; Delarge, J

    1992-09-04

    A series of compounds related to torasemide, a loop diuretic, were synthesized and examined for their diuretic potency and inhibitory activity on the erythrocyte and renal medullary thick ascending limb vesicle Na+,2Cl-,K+ cotransport in Milan hypertensive (MHS) and normotensive (MNS) rat strains, where previous studies had demonstrated an alteration of the cotransport system genetically related to hypertension. From the results of the screening, structure-activity relationships were drawn and two compounds, JDL 961 and C 2921 were selected. Their IC50 on renal vesicle cotransport were similar in the two strains (JDL 961: MHS = 1.8 microM; MNS = 1.2 microM; C 2921: MHS = 4 microM; MNS = 3.8 microM), and were 4-8 times lower than those of torasemide (MHS = 13 microM; MNS = 31 microM, P less than 0.01) and 50-60 times lower than those of bumetanide (MHS = 145 microM; MNS = 206 microM, P less than 0.05) taken as reference compounds. Their ability to reduce the development rate of hypertension was tested both in MHS and in Okamoto spontaneously hypertensive rats (SHR) strain, in which cotransport alterations are opposite to those of MHS. Both torasemide derivatives (7.5 mg.kg-1 os per day) prevented development of hypertension in the two strains. The time course of this hypotensive activity was faster and the percentage of blood pressure fall greater in MHS (20-25%) than in SHR rats (12-15%), even though the absolute value of blood pressure fall was similar in MHS (JDL 961 = -17 mm Hg; C 2921 = -30 mm Hg) and SHR (JDL 961 = -25 mm Hg; C 2921 = -20 mm Hg). A superimposable effect of bumetanide was observed in the two strains, but at 8 times higher daily dose (60 mg.kg-1). These results suggest that new loop diuretics can be selected for their antihypertensive activity on the basis of their in vitro potency in inhibiting the Na+,2Cl-,K+.

  6. Activity-dependent regulation of the K/Cl transporter KCC2 membrane diffusion, clustering, and function in hippocampal neurons.

    Science.gov (United States)

    Chamma, Ingrid; Heubl, Martin; Chevy, Quentin; Renner, Marianne; Moutkine, Imane; Eugène, Emmanuel; Poncer, Jean Christophe; Lévi, Sabine

    2013-09-25

    The neuronal K/Cl transporter KCC2 exports chloride ions and thereby influences the efficacy and polarity of GABA signaling in the brain. KCC2 is also critical for dendritic spine morphogenesis and the maintenance of glutamatergic transmission in cortical neurons. Because KCC2 plays a pivotal role in the function of central synapses, it is of particular importance to understand the cellular and molecular mechanisms underlying its regulation. Here, we studied the impact of membrane diffusion and clustering on KCC2 function. KCC2 forms clusters in the vicinity of both excitatory and inhibitory synapses. Using quantum-dot-based single-particle tracking on rat primary hippocampal neurons, we show that KCC2 is slowed down and confined at excitatory and inhibitory synapses compared with extrasynaptic regions. However, KCC2 escapes inhibitory synapses faster than excitatory synapses, reflecting stronger molecular constraints at the latter. Interfering with KCC2-actin interactions or inhibiting F-actin polymerization releases diffusion constraints on KCC2 at excitatory but not inhibitory synapses. Thus, F-actin constrains KCC2 diffusion at excitatory synapses, whereas KCC2 is confined at inhibitory synapses by a distinct mechanism. Finally, increased neuronal activity rapidly increases the diffusion coefficient and decreases the dwell time of KCC2 at excitatory synapses. This effect involves NMDAR activation, Ca(2+) influx, KCC2 S940 dephosphorylation and calpain protease cleavage of KCC2 and is accompanied by reduced KCC2 clustering and ion transport function. Thus, activity-dependent regulation of KCC2 lateral diffusion and clustering allows for a rapid regulation of chloride homeostasis in neurons.

  7. PSD-95 interacts with NBCn1 and enhances channel-like activity without affecting Na/HCO(3) cotransport.

    Science.gov (United States)

    Lee, Soojung; Yang, Han Soo; Kim, Eunjin; Ju, Eun Ji; Kwon, Min Hyung; Dudley, R Kyle; Smith, Yoland; Yun, C Chris; Choi, Inyeong

    2012-01-01

    The sodium/bicarbonate transporter NBCn1 plays an essential role in intracellular pH regulation and transepithelial HCO(3)(-) movement in the body. NBCn1 also has sodium channel-like activity uncoupled to Na/HCO(3) cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD-95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD-95 interaction. In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C-terminal 131 amino acids of NBCn1 pulled down PSD-95 from rat brain lysates, whereas GST/NBCn1-ΔETSL (deletion of the last four amino acids) and GST/NBCn2 (NCBE) lacking the same ETSL did not. NBCn1 and PSD-95 were coimmunoprecipitated in HEK 293 cells, and their interaction did not affect the efficacy of PSD-95 to bind to the NMDA receptor NR2A. PSD-95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD-95 increased an ionic conductance produced by NBCn1 channel-like activity. This increase was abolished by NBCn1-ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Our data suggest that PSD-95 interacts with NBCn1 and increases its channel-like activity while negligibly affecting Na/HCO(3) cotransport. The possibility that the channel-like activity occurs via an intermolecular cavity of multimeric NBCn1 proteins is discussed. Copyright © 2012 S. Karger AG, Basel.

  8. PSD-95 Interacts with NBCn1 and Enhances Channel-like Activity without Affecting Na/HCO3 Cotransport

    Science.gov (United States)

    Lee, Soojung; Yang, Han Soo; Kim, Eunjin; Ju, Eun Ji; Kwon, Min Hyung; Dudley, R. Kyle; Smith, Yoland; Yun, C. Chris; Choi, Inyeong

    2013-01-01

    Background/Aims The sodium/bicarbonate transporter NBCn1 plays an essential role in intracellular pH regulation and transepithelial HCO3− movement in the body. NBCn1 also has sodium channel-like activity uncoupled to Na/HCO3 cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD-95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD-95 interaction. Methods: Results In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C-terminal 131 amino acids of NBCn1 pulled down PSD-95 from rat brain lysates, whereas GST/NBCn1-ΔETSL (deletion of the last four amino acids) and GST/NBCn2 (NCBE) lacking the same ETSL did not. NBCn1 and PSD-95 were coimmunoprecipitated in HEK 293 cells, and their interaction did not affect the efficacy of PSD-95 to bind to the NMDA receptor NR2A. PSD-95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD-95 increased an ionic conductance produced by NBCn1 channel-like activity. This increase was abolished by NBCn1-ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Conclusion Our data suggest that PSD-95 interacts with NBCn1 and increases its channel-like activity while negligibly affecting Na/HCO3 cotransport. The possibility that the channel-like activity occurs via an intermolecular cavity of multimeric NBCn1 proteins is discussed. PMID:23183381

  9. New Data on Activity Coefficients of Potassium, Nitrate, and Chloride Ions in Aqueous Solutions of KNO3 and KCl by Ion Selective Electrodes

    OpenAIRE

    Debasmita Dash; Shekhar Kumar; C. Mallika; U. Kamachi Mudali

    2012-01-01

    Ion selective electrodes (ISEs) are used to measure the single-ion activity coefficients in aqueous solutions of KNO3 and KCl at 298.15 K against a double-junction reference electrode. The EMF responses of ISEs up to 0.01 m are plotted to obtain the slope and intercept values. The obtained slopes and intercepts are used in Nernst equation for higher concentrated solutions for calculation of individual ion activity coefficient. The mean ionic activity coefficients are estimated from single ion...

  10. Inhibition by mercuric chloride of Na-K-2Cl cotransport activity in rectal gland plasma membrane vesicles isolated from Squalus acanthias.

    Science.gov (United States)

    Kinne-Saffran, E; Kinne, R K

    2001-02-09

    The rectal gland of the dogfish shark is a model system for active transepithelial transport of chloride. It has been shown previously that mercuric chloride, one of the toxic environmental pollutants, inhibits chloride secretion in this organ. In order to investigate the mechanism of action of HgCl(2) at a membrane-molecular level, plasma membrane vesicles were isolated from the rectal gland and the effect of mercury on the activity of the Na-K-2Cl cotransporter was investigated in isotope flux studies. During a 30 s exposure HgCl(2) inhibited cotransport activity in a dose-dependent manner with an apparent K(i) of approx. 50 microM. The inhibition was complete after 15 s, partly reversible by dilution of the incubation medium and completely attenuated upon addition of reduced glutathione. The extent of inhibition by mercury depended on the ionic composition of the medium. The sensitivity of the cotransporter was highest when only the high affinity binding sites for sodium and chloride were saturated. Organic mercurials such as p-chloromercuribenzoic acid and p-chloromercuriphenylsulfonic acid at 100 microM did not inhibit the cotransporter, similarly exposure of the vesicles to 10 mM H(2)O(2) or 1 mM dithiothreitol for 30 min at 15 degrees C did not change cotransport activity. Transport activity was, however, reduced by 45.9+/-2.5% after an incubation with 3 mM N-ethylmaleimide for 20 min. Blocking free amino groups by N-hydroxysuccinimide or biotinamidocapronate-N-hydroxysulfosuccinimide had no effect. Investigations on the sidedness of the plasma membrane vesicles, employing the asymmetry of the (Na+K)-ATPase, demonstrated a right-side-out orientation in which the former extracellular face of the membrane is exposed to the incubation medium. In addition, extracellular mercury (5x10(-5) M) inhibited bumetanide-sensitive rubidium uptake into T84 cells by 48.5+/-7.1% after a 2 min incubation period. This inhibition was reversible in a manner similar to that

  11. The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels.

    Science.gov (United States)

    Hawley, Simon A; Ford, Rebecca J; Smith, Brennan K; Gowans, Graeme J; Mancini, Sarah J; Pitt, Ryan D; Day, Emily A; Salt, Ian P; Steinberg, Gregory R; Hardie, D Grahame

    2016-09-01

    Canagliflozin, dapagliflozin, and empagliflozin, all recently approved for treatment of type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose reuptake by sodium/glucose cotransporter (SGLT) 2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMPK, an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin, or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of acetyl-CoA carboxylase (ACC) 1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue, or spleen. Because phosphorylation of ACC by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared with other SGLT2 inhibitors. © 2016 by the American Diabetes Association.

  12. Multiphased (NaCl){sub x}(KCl){sub y-x}(KBr){sub 1-y} single crystals: ac conductivity activation energy versus bulk properties

    Energy Technology Data Exchange (ETDEWEB)

    Katsika-Tsigourakou, Vassiliki, E-mail: vkatsik@phys.uoa.g [Department of Solid State Physics, Faculty of Physics, University of Athens, Panepistimiopolis, 157 84 Zografos (Greece)

    2009-11-01

    The ac electrical measurements have been just reported for alkali halide mixed crystals that were melt grown from NaCl, KCl and KBr starting materials. They showed a nonlinear variation of all the electrical parameters with the bulk composition. In this short paper, we show that these mixed systems, depending on their major constituent, are classified into three categories in each of which, the activation energy for the ac conductivity increases linearly with BOMEGA, where B is the isothermal bulk modulus and OMEGA the mean volume per atom. In addition, the resulting three straight lines are formed to have almost the same slope.

  13. Basolateral Na+/HCO3– cotransport activity is regulated by the dissociable Na+/H+ exchanger regulatory factor

    Science.gov (United States)

    Bernardo, Angelito A.; Kear, Felicidad T.; Santos, Anna V.P.; Ma, Jianfei; Steplock, Debra; Robey, R. Brooks; Weinman, Edward J.

    1999-01-01

    In the renal proximal tubule, the activities of the basolateral Na+/HCO3– cotransporter (NBC) and the apical Na+/H+ exchanger (NHE3) uniformly vary in parallel, suggesting that they are coordinately regulated. PKA-mediated inhibition of NHE3 is mediated by a PDZ motif–containing protein, the Na+/H+ exchanger regulatory factor (NHE-RF). Given the common inhibition of these transporters after protein kinase A (PKA) activation, we sought to determine whether NHE-RF also plays a role in PKA-regulated NBC activity. Renal cortex immunoblot analysis using anti-peptide antibodies directed against rabbit NHE-RF demonstrated the presence of this regulatory factor in both brush-border membranes (BBMs) and basolateral membranes (BLMs). Using a reconstitution assay, we found that limited trypsin digestion of detergent solubilized rabbit renal BLM preparations resulted in NBC activity that was unaffected by PKA activation. Co-reconstitution of these trypsinized preparations with a recombinant protein corresponding to wild-type rabbit NHE-RF restored the inhibitory effect of PKA on NBC activity in a concentration-dependent manner. NBC activity was inhibited 60% by 10–8M NHE-RF; this effect was not observed in the absence of PKA. Reconstitution with heat-denatured NHE-RF also failed to attenuate NBC activity. To establish further a physiologic role for NHE-RF in NBC regulation, the renal epithelial cell line B-SC-1, which lacks detectable endogenous NHE-RF expression, was engineered to express stably an NHE-RF transgene. NHE-RF–expressing B-SC-1 cells (B-SC-RF) exhibited markedly lower basal levels of NBC activity than did wild-type controls. Inhibition of NBC activity in B-SC-RF cells was enhanced after 10 μM of forskolin treatment, consistent with a postulated role for NHE-RF in mediating the inhibition of NBC activity by PKA. These findings not only suggest NHE-RF involvement in PKA-regulated NBC activity, but also provide a unique molecular mechanism whereby

  14. MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2.

    Science.gov (United States)

    Coady, Michael J; El Tarazi, Abdulah; Santer, René; Bissonnette, Pierre; Sasseville, Louis J; Calado, Joaquim; Lussier, Yoann; Dumayne, Christopher; Bichet, Daniel G; Lapointe, Jean-Yves

    2017-01-01

    The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na(+)-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17-SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na(+)/H(+) exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters. Copyright © 2016 by the American Society of Nephrology.

  15. Activation of thiazide-sensitive co-transport by angiotensin II in the cyp1a1-Ren2 hypertensive rat.

    Directory of Open Access Journals (Sweden)

    Ali Ashek

    Full Text Available Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage. Blood pressure and renal parameters were recorded in both conscious and anesthetized (butabarbital sodium; 120 mg/kg IP rats at selected time-points during the development of hypertension. Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter. Renal injury was evident after the first day of transgene induction, being initially limited to the pre-glomerular vasculature. Mircoalbuminuria and tubuloinsterstitial injury developed once hypertension was established. Chronic treatment with either hydrochlorothiazide or an AT1 receptor antagonist normalized sodium reabsorption, significantly blunted hypertension and prevented renal injury. Urinary aldosterone excretion was increased ≈ 20 fold, but chronic mineralocorticoid receptor antagonism with spironolactone neither restored natriuretic capacity nor prevented hypertension. Spironolactone nevertheless ameliorated vascular damage and prevented albuminuria. This study finds activation of sodium-chloride co-transport to be a key mechanism in angiotensin II-dependent hypertension. Furthermore, renal vascular injury in this setting reflects both barotrauma and pressure-independent pathways associated with direct detrimental effects of angiotensin II and aldosterone.

  16. Sodium-glucose cotransport

    Science.gov (United States)

    Poulsen, Søren Brandt; Fenton, Robert A.; Rieg, Timo

    2017-01-01

    Purpose of review Sodium-glucose cotransporters (SGLTs) are important mediators of glucose uptake across apical cell membranes. SGLT1 mediates almost all sodium-dependent glucose uptake in the small intestine, while in the kidney SGLT2, and to a lesser extent SGLT1, account for more than 90% and nearly 3%, respectively, of glucose reabsorption from the glomerular ultrafiltrate. Although the recent availability of SGLT2 inhibitors for the treatment of diabetes mellitus has increased the number of clinical studies, this review has a focus on mechanisms contributing to the cellular regulation of SGLTs. Recent findings Studies have focused on the regulation of SGLT expression under different physiological/pathophysiological conditions, for example diet, age or diabetes mellitus. Several studies provide evidence of SGLT regulation via cyclic adenosine monophosphate/protein kinase A, protein kinase C, glucagon-like peptide 2, insulin, leptin, signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), with-no-K[Lys] kinases/STE20/SPS1-related proline/alanine-rich kinase (Wnk/SPAK) and regulatory solute carrier protein 1 (RS1) pathways. Summary SGLT inhibitors are important drugs for glycemic control in diabetes mellitus. Although the contribution of SGLT1 for absorption of glucose from the intestine as well as SGLT2/SGLT1 for renal glucose reabsorption has been comprehensively defined, this review provides an up-to-date outline for the mechanistic regulation of SGLT1/SGLT2. PMID:26125647

  17. Expressions of ion co-transporter genes in salicylate-induced tinnitus and treatment effects of spirulina.

    Science.gov (United States)

    Hwang, Juen-Haur; Chan, Yin-Ching

    2016-09-02

    Although the activity of tinnitus-related ion co-transporter are known, their mRNA expressions has seldom been reported. We aimed to investigate the mRNA expressions of tinnitus-related ion co-transporter genes, and treatment effects of Spirulina. The mRNA expressions of K(+)-Cl(-) co-transporter (KCC2) and Na-K-2Cl co-transporter 1 (NKCC1) genes in the cochlea and brain of mice were evaluated after tinnitus was induced by intraperitoneal injection of salicylate. The effects of spirulina water extract on these gene expressions were investigated. Compared to the control group, the tinnitus scores increased significantly, however, the salicylate-induced tinnitus could be reduced significantly by spirulina water extract. The tinnitus group had higher of borderline significance mRNA expression of KCC2 gene in the cochlear, significantly higher in the temporal lobes and in the frontal lobes. Meanwhile, compared to the tinnitus group, the spirulina group had significantly lower mRNA expression of KCC2 gene in the cochlear, temporal lobes, frontal lobes and parahippocampus/hippocampus. However, the NKCC1 mRNA expression was not significantly different between three groups in the cochlea and these brain areas. Salicylate-induced tinnitus might be associated with increased mRNA expression of KCC2 gene, but not with mRNA expressions of NKCC1 gene in the cochlear and some tinnitus-related brain areas. Spirulina reduced the expression of KCC2 genes in salicylate-induced tinnitus.

  18. KCl stimulation increases norepinephrine transporter function in PC12 cells.

    Science.gov (United States)

    Mandela, Prashant; Ordway, Gregory A

    2006-09-01

    The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

  19. The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2

    DEFF Research Database (Denmark)

    Lauritzen, Gitte; Stock, Christian-Martin; Lemaire, Justine;

    2012-01-01

    We and others have shown central roles of the Na(+)/H(+) exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (¿NErbB2...

  20. WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4.

    Science.gov (United States)

    Chávez-Canales, María; Zhang, Chong; Soukaseum, Christelle; Moreno, Erika; Pacheco-Alvarez, Diana; Vidal-Petiot, Emmanuelle; Castañeda-Bueno, María; Vázquez, Norma; Rojas-Vega, Lorena; Meermeier, Nicholas P; Rogers, Shaunessy; Jeunemaitre, Xavier; Yang, Chao-Ling; Ellison, David H; Gamba, Gerardo; Hadchouel, Juliette

    2014-11-01

    The with-no-lysine (K) kinases, WNK1 and WNK4, are key regulators of blood pressure. Their mutations lead to familial hyperkalemic hypertension (FHHt), associated with an activation of the Na-Cl cotransporter (NCC). Although it is clear that WNK4 mutants activate NCC via Ste20 proline-alanine-rich kinase, the mechanisms responsible for WNK1-related FHHt and alterations in NCC activity are not as clear. We tested whether WNK1 modulates NCC through WNK4, as predicted by some models, by crossing our recently developed WNK1-FHHt mice (WNK1(+/FHHt)) with WNK4(-/-) mice. Surprisingly, the activated NCC, hypertension, and hyperkalemia of WNK1(+/FHHt) mice remain in the absence of WNK4. We demonstrate that WNK1 powerfully stimulates NCC in a WNK4-independent and Ste20 proline-alanine-rich kinase-dependent manner. Moreover, WNK4 decreases the WNK1 and WNK3-mediated activation of NCC. Finally, the formation of oligomers of WNK kinases through their C-terminal coiled-coil domain is essential for their activity toward NCC. In conclusion, WNK kinases form a network in which WNK4 associates with WNK1 and WNK3 to regulate NCC. © 2014 American Heart Association, Inc.

  1. Paradoxical activation of the sodium chloride cotransporter (NCC) without hypertension in kidney deficient in a regulatory subunit of Na,K-ATPase, FXYD2.

    Science.gov (United States)

    Arystarkhova, Elena; Ralph, Donna L; Liu, Yi Bessie; Bouley, Richard; McDonough, Alicia A; Sweadner, Kathleen J

    2014-12-01

    Na,K-ATPase generates the driving force for sodium reabsorption in the kidney. Na,K-ATPase functional properties are regulated by small proteins belonging to the FXYD family. In kidney FXYD2 is the most abundant: it is an inhibitory subunit expressed in almost every nephron segment. Its absence should increase sodium pump activity and promote Na(+) retention, however, no obvious renal phenotype was detected in mice with global deletion of FXYD2 (Arystarkhova et al. 2013). Here, increased total cortical Na,K-ATPase activity was documented in the Fxyd2(-/-) mouse, without increased α1β1 subunit expression. We tested the hypothesis that adaptations occur in distal convoluted tubule (DCT), a major site of sodium adjustments. Na,K-ATPase immunoreactivity in DCT was unchanged, and there was no DCT hypoplasia. There was a marked activation of thiazide-sensitive sodium chloride cotransporter (NCC; Slc12a3) in DCT, predicted to increase Na(+) reabsorption in this segment. Specifically, NCC total increased 30% and NCC phosphorylated at T53 and S71, associated with activation, increased 4-6 fold. The phosphorylation of the closely related thick ascending limb (TAL) apical NKCC2 (Slc12a1) increased at least twofold. Abundance of the total and cleaved (activated) forms of ENaC α-subunit was not different between genotypes. Nonetheless, no elevation of blood pressure was evident despite the fact that NCC and NKCC2 are in states permissive for Na(+) retention. Activation of NCC and NKCC2 may reflect an intracellular linkage to elevated Na,K-ATPase activity or a compensatory response to Na(+) loss proximal to the TAL and DCT. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  2. Irbesartan, an FDA approved drug for hypertension and diabetic nephropathy, is a potent inhibitor for hepatitis B virus entry by disturbing Na(+)-dependent taurocholate cotransporting polypeptide activity.

    Science.gov (United States)

    Wang, Xue-jun; Hu, Wei; Zhang, Ting-yu; Mao, Ying-ying; Liu, Nan-nan; Wang, Sheng-qi

    2015-08-01

    The liver-specific Na(+)-dependent taurocholate cotransporting polypeptide (NTCP) was recently identified as an entry receptor for hepatitis B virus (HBV) hepatotropic infection. In this study, an NTCP-overexpressing HepG2 cell line named HepG2.N9 susceptible to HBV infection was established using transcription activator-like effector nucleases (TALEN) technology. Using this cell line, irbesartan, the new NTCP-interfering molecule reported recently, was demonstrated here to effectively inhibit HBV infection with an IC50 of 3.3μM for hepatitis B e antigen (HBeAg) expression and exhibited no obvious cytotoxicity up to 1000μM. Irbesartan suppressed HBV uptake weakly but inhibited HBV covalently closed circular DNA (cccDNA) formation efficiently at physiological temperature. These results suggested that irbesartan targeted HBV infection at a post-uptake prior to cccDNA formation step such as the cell membrane fusion. Based on these findings, irbesartan, an FDA approved drug for hypertension and diabetic nephropathy, could be a potential candidate for treatment of HBV infection although further in vivo experiments are required.

  3. Activated PKCδ and PKCϵ Inhibit Epithelial Chloride Secretion Response to cAMP via Inducing Internalization of the Na+-K+-2Cl− Cotransporter NKCC1*

    Science.gov (United States)

    Tang, Jun; Bouyer, Patrice; Mykoniatis, Andreas; Buschmann, Mary; Matlin, Karl S.; Matthews, Jeffrey B.

    2010-01-01

    The basolateral Na+-K+-2Cl− cotransporter (NKCC1) is a key determinant of transepithelial chloride secretion and dysregulation of chloride secretion is a common feature of many diseases including secretory diarrhea. We have previously shown that activation of protein kinase C (PKC) markedly reduces transepithelial chloride secretion in human colonic T84 cells, which correlates with both functional inhibition and loss of the NKCC1 surface expression. In the present study, we defined the specific roles of PKC isoforms in regulating epithelial NKCC1 and chloride secretion utilizing adenoviral vectors that express shRNAs targeting human PKC isoforms (α, δ, ϵ) (shPKCs) or LacZ (shLacZ, non-targeting control). After 72 h of adenoviral transduction, protein levels of the PKC isoforms in shPKCs-T84 cells were decreased by ∼90% compared with the shLacZ-control. Activation of PKCs by phorbol 12-myristate 13-acetate (PMA) caused a redistribution of NKCC1 immunostaining from the basolateral membrane to intracellular vesicles in both shLacZ- and shPKCα-T84 cells, whereas the effect of PMA was not observed in shPKCδ- and shPKCϵ- cells. These results were further confirmed by basolateral surface biotinylation. Furthermore, activation of PKCs by PMA inhibited cAMP-stimulated chloride secretion in the uninfected, shLacZ- and shPKCα-T84 monolayers, but the inhibitory effect was significantly attenuated in shPKCδ- and shPKCϵ-T84 monolayers. In conclusion, the activated novel isoforms PKCδ or PKCϵ, but not the conventional isoform PKCα, inhibits transepithelial chloride secretion through inducing internalization of the basolateral surface NKCC1. Our study reveals that the novel PKC isoform-regulated NKCC1 surface expression plays an important role in the regulation of chloride secretion. PMID:20732874

  4. The effect of NaCl substitution with KCl on proteinase activities of cell-free extract and cell-free supernatant at different pH levels and salt concentrations: Lactobacillus acidophilus and Lactobacillus casei.

    Science.gov (United States)

    Ayyash, M M; Sherkat, F; Shah, N P

    2013-01-01

    The aim of this study was to investigate the effect of substitution of NaCl with KCl at different pH levels and salt concentrations on proteinase activity of cell-free extract and cell-free supernatant of the probiotics Lactobacillus acidophilus and Lactobacillus casei. de Man, Rogosa, and Sharpe broth aliquots were mixed with 2 pure salts (NaCl and KCl) and 2 salt concentrations at 2 concentration levels (5 and 10%), inoculated with Lactobacillus acidophilus or Lactobacillus casei, and incubated aerobically at 37°C for 22 h. The cultures were then centrifuged at 4,000×g for 30 min, and the collected cell pellets were used to prepare cell-wall proteinases and the supernatants used as a source of supernatant (extracellular) proteinases. The proteolytic activity and protein content of both portions were determined. After incubation of both portions with 3 milk caseins (α-, β-, κ-casein), the supernatants were individually subjected to analysis of angiotensin-converting enzyme (ACE)-inhibitory activity and proteolytic activity using the o-phthalaldehyde method. Significant differences were observed in ACE-inhibitory and proteolytic activities between salt substitution treatments of cell-free extract and cell-free supernatant from both probiotic strains at the same salt concentration and pH level.

  5. Kr-KCl exciplex lamp

    Science.gov (United States)

    Klenovskii, M. S.; Riives, R. B.; Kel'Man, V. A.; Zhmenyak, Yu. V.; Shpenik, Yu. O.

    2009-07-01

    A new source of UV radiation (excilamp) based on Kr-KCl vapor-gas mixture excited by a longitudinal high-voltage pulsed-periodic discharge is created. The emission spectrum and time characteristic of the discharge radiation are studied. The B → X transition in the KrCl* excimer molecule (λ = 222 nm) is found to dominate in the radiation spectrum of the source. The dependence of the pulse output power of the lamp on various factors is investigated, and the mechanism of B state formation in the excimer molecule is discussed.

  6. Ionic conductivity in irradiated KCL; Conductiviad ionica de KCL irradiado

    Energy Technology Data Exchange (ETDEWEB)

    Vignolo Rubio, J.

    1979-07-01

    The ionic conductivity of X and gamma irradiated KCL single crystals has been studied between room temperature and 600 degree centigree. the radiation induced damage resulting in a decrease of the conductivity heals by thermal annealing in two steps which are at about 350 and 550 degree centigree respectively. It has been found that the radiation induced colour centres are not involved in the observed decrease of the ionic conductivity. However. It has been observed that the effects of quenching and plastic deformation on the conductivity of the samples are very similar to the effect induced by irradiation. It is suggested that, samples radiation induced dislocation loops might cause the ionic conductivity decrease observed in irradiated samples. (Author)

  7. P2Y2 receptor activation inhibits the expression of the sodium-chloride cotransporter NCC in distal convoluted tubule cells.

    Science.gov (United States)

    Gailly, P; Szutkowska, M; Olinger, E; Debaix, H; Seghers, F; Janas, S; Vallon, V; Devuyst, O

    2014-11-01

    Luminal nucleotide stimulation is known to reduce Na(+) transport in the distal nephron. Previous studies suggest that this mechanism may involve the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which plays an essential role in NaCl reabsorption in the cells lining the distal convoluted tubule (DCT). Here we show that stimulation of mouse DCT (mDCT) cells with ATP or UTP promoted Ca(2+) transients and decreased the expression of NCC at both mRNA and protein levels. Specific siRNA-mediated silencing of P2Y2 receptors almost completely abolished ATP/UTP-induced Ca(2+) transients and significantly reduced ATP/UTP-induced decrease of NCC expression. To test whether local variations in the intracellular Ca(2+) concentration ([Ca(2+)]i) may control NCC transcription, we overexpressed the Ca(2+)-binding protein parvalbumin selectively in the cytosol or in the nucleus of mDCT cells. The decrease in NCC mRNA upon nucleotide stimulation was abolished in cells overexpressing cytosolic PV but not in cells overexpressing either a nuclear-targeted PV or a mutated PV unable to bind Ca(2+). Using a firefly luciferase reporter gene strategy, we observed that the activity of NCC promoter region from -1 to -2,200 bp was not regulated by changes in [Ca(2+)]i. In contrast, high cytosolic calcium level induced instability of NCC mRNA. We conclude that in mDCT cells: (1) P2Y2 receptor is essential for the intracellular Ca(2+) signaling induced by ATP/UTP stimulation; (2) P2Y2-mediated increase of cytoplasmic Ca(2+) concentration down-regulates the expression of NCC; (3) the decrease of NCC expression occurs, at least in part, via destabilization of its mRNA.

  8. Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway.

    NARCIS (Netherlands)

    San-Cristobal, P.; Pacheco-Alvarez, D.; Richardson, C.; Ring, A.M.; Vazquez, N.; Rafiqi, F.H.; Chari, D.; Kahle, K.T.; Leng, Q.; Bobadilla, N.A.; Hebert, S.C.; Alessi, D.R.; Lifton, R.P.; Gamba, G.

    2009-01-01

    Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia). WNK4 has distinct functional states that regulate the balance between renal salt reabsorption and K(+) secretion by modulating the activities of

  9. Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway.

    NARCIS (Netherlands)

    San-Cristobal, P.; Pacheco-Alvarez, D.; Richardson, C.; Ring, A.M.; Vazquez, N.; Rafiqi, F.H.; Chari, D.; Kahle, K.T.; Leng, Q.; Bobadilla, N.A.; Hebert, S.C.; Alessi, D.R.; Lifton, R.P.; Gamba, G.

    2009-01-01

    Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia). WNK4 has distinct functional states that regulate the balance between renal salt reabsorption and K(+) secretion by modulating the activities of re

  10. Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Zeid M Rusan

    Full Text Available Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

  11. Cotransporters as molecular water pumps

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; MacAulay, Nanna

    2002-01-01

    Molecular water pumps are membrane proteins of the cotransport type in which a flux of water is coupled to substrate fluxes by a mechanism within the protein. Free energy can be exchanged between the fluxes. Accordingly, the flux of water may be relatively independent of the external water chemical...

  12. Na+/glucose co-transporter abundance and activity in the small intestine of lambs: enhancement by abomasal infusion of casein.

    Science.gov (United States)

    Mabjeesh, Sameer J; Guy, Dafna; Sklan, David

    2003-05-01

    The purpose of the present study was to determine the effect of abomasal casein infusion on glucose uptake and abundance of the Na+/glucose co-transporter (SGLT1) 1 in the ovine small intestine. Lambs (body weight 35 (sem 1.0) kg) were surgically fitted with abomasal infusion catheters and were fed diets containing equal portions of wheat hay and cracked maize. Lambs were infused with either 500 g water/d or with 500 g water containing 35 g casein/d. The infusion period lasted 10 d, after which lambs were killed, exsanguinated and eviscerated. Brush border membrane vesicles (BBMV) were prepared using mucosa from different small intestinal regions. Intake and total tract digestibility of nutrients were similar between treatments and averaged 1134, 1142 and 486 g/d and 67, 70, and 94 % for DM, organic matter and non-structural carbohydrates respectively. Crude protein (Nx6.25) digestibility was 15 % greater in the casein-infused than control lambs. Glucose uptake to BBMV ranged from 101 to 337 pmol/mg protein per s along the small intestine and was greatest in the mid-section of the small intestine. In the mid-jejunum, glucose uptake was greater (Pinfused with casein and averaged 120 pmol/mg protein per s compared with 68 pmol/mg protein per s in the control group. SGLT1 affinity was similar between treatments and averaged 104 microm in the different segments of the small intestine of lambs. However, lambs infused with casein exhibited similar values along the small intestine and affinity averaged 106 microm, while in the control group a greater affinity (85 microm) was measured in the mid-jejunum. SGLT1 protein abundance was correlated with glucose uptake in the BBMV in the casein-treated lambs, but not in the control group. These results suggest that glucose uptake along the small intestine of lambs is influenced by casein or its derivatives in the small intestine via SGLT1 affinity and activity at the brush border membrane, and that SGLT1 activity may be regulated

  13. Alcohol abuse promotes changes in non-synaptic epileptiform activity with concomitant expression changes in cotransporters and glial cells.

    Directory of Open Access Journals (Sweden)

    Luiz Eduardo Canton Santos

    Full Text Available Non-synaptic mechanisms are being considered the common factor of brain damage in status epilepticus and alcohol intoxication. The present work reports the influence of the chronic use of ethanol on epileptic processes sustained by non-synaptic mechanisms. Adult male Wistar rats administered with ethanol (1, 2 e 3 g/kg/d during 28 days were compared with Control. Non-synaptic epileptiform activities (NEAs were induced by means of the zero-calcium and high-potassium model using hippocampal slices. The observed involvement of the dentate gyrus (DG on the neurodegeneration promoted by ethanol motivated the monitoring of the electrophysiological activity in this region. The DG regions were analyzed for the presence of NKCC1, KCC2, GFAP and CD11b immunoreactivity and cell density. The treated groups showed extracellular potential measured at the granular layer with increased DC shift and population spikes (PS, which was remarkable for the group E1. The latencies to the NEAs onset were more prominent also for the treated groups, being correlated with the neuronal loss. In line with these findings were the predispositions of the treated slices for neuronal edema after NEAs induction, suggesting that restrict inter-cell space counteracts the neuronal loss and subsists the hyper-synchronism. The significant increase of the expressions of NKCC1 and CD11b for the treated groups confirms the existence of conditions favorable to the observed edematous necrosis. The data suggest that the ethanol consumption promotes changes on the non-synaptic mechanisms modulating the NEAs. For the lower ethanol dosage the neurophysiological changes were more effective suggesting to be due to the less intense neurodegenertation.

  14. Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC)

    DEFF Research Database (Denmark)

    Dimke, Henrik Anthony

    2011-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular...... by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC...

  15. Calculation of NaCl, KCl and LiCl Salts Activity Coefficients in Polyethylene Glycol (PEG4000)-Water System Using Modified PHSC Equation of State, Extended Debye-Hückel Model and Pitzer Model

    Science.gov (United States)

    Marjani, Azam

    2016-07-01

    For biomolecules and cell particles purification and separation in biological engineering, besides the chromatography as mostly applied process, aqueous two-phase systems (ATPS) are of the most favorable separation processes that are worth to be investigated in thermodynamic theoretically. In recent years, thermodynamic calculation of ATPS properties has attracted much attention due to their great applications in chemical industries such as separation processes. These phase calculations of ATPS have inherent complexity due to the presence of ions and polymers in aqueous solution. In this work, for target ternary systems of polyethylene glycol (PEG4000)-salt-water, thermodynamic investigation for constituent systems with three salts (NaCl, KCl and LiCl) has been carried out as PEG is the most favorable polymer in ATPS. The modified perturbed hard sphere chain (PHSC) equation of state (EOS), extended Debye-Hückel and Pitzer models were employed for calculation of activity coefficients for the considered systems. Four additional statistical parameters were considered to ensure the consistency of correlations and introduced as objective functions in the particle swarm optimization algorithm. The results showed desirable agreement to the available experimental data, and the order of recommendation of studied models is PHSC EOS > extended Debye-Hückel > Pitzer. The concluding remark is that the all the employed models are reliable in such calculations and can be used for thermodynamic correlation/predictions; however, by using an ion-based parameter calculation method, the PHSC EOS reveals both reliability and universality of applications.

  16. Establishing a definitive stoichiometry for the Na+/monocarboxylate cotransporter SMCT1.

    Science.gov (United States)

    Coady, Michael J; Wallendorff, Bernadette; Bourgeois, Francis; Charron, Francois; Lapointe, Jean-Yves

    2007-10-01

    Several different stoichiometries have been proposed for the Na(+)/monocarboxylate cotransporter SMCT1, including variable Na(+)/substrate stoichiometry. In this work, we have definitively established an invariant 2:1 cotransport stoichiometry for SMCT1. By using two independent means of assay, we first showed that SMCT1 exhibits a 2:1 stoichiometry for Na(+)/lactate cotransport. Radiolabel uptake experiments proved that, unlike lactate, propionic acid diffuses passively through oocyte membranes and, consequently, propionate is a poor candidate for stoichiometric determination by these methods. Although we previously determined SMCT1 stoichiometry by measuring reversal potentials, this technique produced erroneous values, because SMCT1 simultaneously mediates both an inwardly rectifying cotransport current and an outwardly rectifying anionic leak current; the leak current predominates in the range where reversal potentials are observed. We therefore employed a method that compared the effect of halving the external Na(+) concentration to the effect of halving the external substrate concentration on zero-current potentials. Both lactate and propionate were cotransported through SMCT1 using 2:1 stoichiometries. The leak current passing through the protein has a 1 osmolyte/charge stoichiometry. Identification of cotransporter stoichiometry is not always a trivial task and it can lead to a much better understanding of the transport activity mediated by the protein in question.

  17. Water transport by the renal Na(+)-dicarboxylate cotransporter

    DEFF Research Database (Denmark)

    Meinild, A K; Loo, D D; Pajor, A M;

    2000-01-01

    This study investigated the ability of the renal Na(+)-dicarboxylate cotransporter, NaDC-1, to transport water. Rabbit NaDC-1 was expressed in Xenopus laevis oocytes, cotransporter activity was measured as the inward current generated by substrate (citrate or succinate), and water transport...... was monitored by the changes in oocyte volume. In the absence of substrates, oocytes expressing NaDC-1 showed an increase in osmotic water permeability, which was directly correlated with the expression level of NaDC-1. When NaDC-1 was transporting substrates, there was a concomitant increase in oocyte volume....... This solute-coupled influx of water took place in the absence of, and even against, osmotic gradients. There was a strict stoichiometric relationship between Na(+), substrate, and water transport of 3 Na(+), 1 dicarboxylate, and 176 water molecules/transport cycle. These results indicate that the renal Na...

  18. Water transport by the renal Na(+)-dicarboxylate cotransporter

    DEFF Research Database (Denmark)

    Meinild, A K; Loo, D D; Pajor, A M

    2000-01-01

    was monitored by the changes in oocyte volume. In the absence of substrates, oocytes expressing NaDC-1 showed an increase in osmotic water permeability, which was directly correlated with the expression level of NaDC-1. When NaDC-1 was transporting substrates, there was a concomitant increase in oocyte volume....... This solute-coupled influx of water took place in the absence of, and even against, osmotic gradients. There was a strict stoichiometric relationship between Na(+), substrate, and water transport of 3 Na(+), 1 dicarboxylate, and 176 water molecules/transport cycle. These results indicate that the renal Na......This study investigated the ability of the renal Na(+)-dicarboxylate cotransporter, NaDC-1, to transport water. Rabbit NaDC-1 was expressed in Xenopus laevis oocytes, cotransporter activity was measured as the inward current generated by substrate (citrate or succinate), and water transport...

  19. The Na+ glucose co-transporter inhibitor canagliflozin activates AMP-activated protein kinase by inhibiting mitochondrial function and increasing cellular AMP levels

    OpenAIRE

    Hawley, Simon A.; Ford, Rebecca J.; Smith, Brennan K.; Gowans, Graeme J.; Mancini, Sarah; Pitt, Ryan D.; Day, Emily A.; Salt, Ian P.; Steinberg, Gregory R.; Hardie, D. Grahame

    2016-01-01

    Canagliflozin, dapagliflozin and empagliflozin, all recently approved for treatment of Type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose re-uptake by SGLT2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMP-activated protein kinase (AMPK), an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with da...

  20. Increasing Oil Concentration Affects Consumer Perception and Physical Properties of Mayonnaise-type Spreads Containing KCl.

    Science.gov (United States)

    Torrico, Damir Dennis; Prinyawiwatkul, Witoon

    2017-08-01

    Reducing sodium intakes remains a global challenge for the food industry. KCl is a potential salt substitute but imparts bitterness when used at high concentrations. Little is known about how oil concentrations (OC) affect consumers' perception of saltiness and bitterness in emulsion products such as mayonnaise containing KCl. We evaluated consumers' perception and physical properties of mayonnaise-type spreads at various oil and tastant (NaCl or KCl) concentrations. Consumers (N = 306) evaluated saltiness, bitterness, overall taste liking (OTL) and purchase intent (PI). Viscosity, pH, water activity, and consistency/texture were also measured. Oil and tastant (NaCl or KCl) concentrations had significant effects on saltiness, viscosity, and pH. As OC increased, saltiness intensity slightly decreased for spreads. Increasing oil concentration increased viscosity. Generally, spreads containing KCl had higher bitterness and pH than spreads containing NaCl. All spreads containing KCl were penalized for being "too bitter." PI was affected by OTL for all spreads but OC was also a significant factor in the purchase decision of spreads containing NaCl. This study demonstrated that increasing OC affected consumers' taste perception (saltiness and bitterness) and spreads' physical properties including pH and viscosity. © 2017 Institute of Food Technologists®.

  1. Effects of cortisol and salinity acclimation on Na+/K+/2Cl–- cotransporter gene expression and Na+, K+-ATPase activity in the gill of Persian sturgeon, Acipenser persicus, fry

    Directory of Open Access Journals (Sweden)

    Saber Khodabandeh

    2009-10-01

    Full Text Available Na+, K+-ATPase activity and Na+/K+/2Cl–- cotransporter (NKCC gene expression in the gills of Persian sturgeon, Acipenser persicus, fry (2-3 g, 3.30-8.12 cm total body length in freshwater (control group, diluted Caspian Sea water (5 ppt and after treatment with cortisol in freshwater were studied. Na+, K+-ATPase activity was lower in the 5 ppt-acclimated fish (1.07±0.05 _mol Pi/mg protein/h than in the control fish (1.19±0.05 μmol Pi/mg protein/h but this difference was not significant. nKCC gene expression in the 5 ppt-acclimated fish (1.6±0.07 was significantly higher than in the control fish (0.8±0.00. In the cortisol treated fish, Na+, K+-ATPase activity (1.91±0.05 μmol Pi/mg protein/h and NKCC gene expression (3.2±0.1 were significantly higher than in the control group. our results show that Persian sturgeon fry (2-3 g can tolerate 5 ppt salinity by changing their enzymatic content and activity, and that exogenous cortisol application can increase the osmoregulatory capacity of fry before release into brackish water and can reduce their mortality.

  2. Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium–glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents

    Directory of Open Access Journals (Sweden)

    Takahiro Oguma

    2016-12-01

    Full Text Available We investigated whether structurally different sodium–glucose cotransporter (SGLT 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4 inhibitors, could enhance glucagon-like peptide-1 (GLP-1 secretion during oral glucose tolerance tests (OGTTs in rodents. Three different SGLT inhibitors—1-(β-d-Glucopyranosyl-4-chloro-3-[5-(6-fluoro-2-pyridyl-2-thienylmethyl]benzene (GTB, TA-1887, and canagliflozin—were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1 elevation and suppressed glucose excursions in both normal and diabetic rodents. In DPP4-deficient rats, GTB enhanced glucose-induced aGLP-1 elevation without affecting the basal level, whereas metformin, previously reported to enhance GLP-1 secretion, increased both the basal level and glucose-induced elevation. Oral treatment with canagliflozin and TA-1887 also enhanced glucose-induced aGLP-1 elevation when co-administered with either teneligliptin or sitagliptin. These data suggest that structurally different SGLT2 inhibitors enhance plasma aGLP-1 elevation and suppress glucose excursions during OGTT when co-administered with DPP4 inhibitors, regardless of the difference in chemical structure. Combination treatment with DPP4 inhibitors and SGLT2 inhibitors having moderate SGLT1 inhibitory activity may be a promising therapeutic option for improving glycemic control in patients with type 2 diabetes mellitus.

  3. Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC).

    Science.gov (United States)

    Dimke, Henrik

    2011-12-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular explanation for pseudohypoaldosteronism type II (PHAII). Studies suggest that WNK4 regulates NCC via two distinct pathways, depending on its state of activation. Furthermore, an intact STE20-related proline-alanine-rich kinase (SPAK)/oxidative stress response 1 kinase (OSR1) pathway was found to be necessary for a WNK4 PHAII mutation to increase NCC phosphorylation and blood pressure in mice. The mouse protein 25α is a novel regulator of the SPAK/OSR1 kinase family, which greatly increases their activity. The phosphorylation status of NCC and the WNK is regulated by the serum- and glucocorticoid-inducible kinase 1, suggesting novel mechanisms whereby aldosterone modulates NCC activity. Dephosphorylation of NCC by protein phosphatase 4 strongly influences the activity of the cotransporter, confirming an important role for NCC phosphorylation. Finally, γ-adducin increases NCC activity. This stimulatory effect is dependent on the phosphorylation status of the cotransporter. γ-Adducin only binds the dephosphorylated cotransporter, suggesting that phosphorylation of NCC causes the dissociation of γ-adducin. Since γ-adducin is not a kinase, it is tempting to speculate that the protein exerts its function by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC transport activity and ultimately blood pressure.

  4. Activated PKC{delta} and PKC{epsilon} inhibit epithelial chloride secretion response to cAMP via inducing internalization of the Na+-K+-2Cl- cotransporter NKCC1.

    Science.gov (United States)

    Tang, Jun; Bouyer, Patrice; Mykoniatis, Andreas; Buschmann, Mary; Matlin, Karl S; Matthews, Jeffrey B

    2010-10-29

    The basolateral Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) is a key determinant of transepithelial chloride secretion and dysregulation of chloride secretion is a common feature of many diseases including secretory diarrhea. We have previously shown that activation of protein kinase C (PKC) markedly reduces transepithelial chloride secretion in human colonic T84 cells, which correlates with both functional inhibition and loss of the NKCC1 surface expression. In the present study, we defined the specific roles of PKC isoforms in regulating epithelial NKCC1 and chloride secretion utilizing adenoviral vectors that express shRNAs targeting human PKC isoforms (α, δ, ε) (shPKCs) or LacZ (shLacZ, non-targeting control). After 72 h of adenoviral transduction, protein levels of the PKC isoforms in shPKCs-T84 cells were decreased by ∼90% compared with the shLacZ-control. Activation of PKCs by phorbol 12-myristate 13-acetate (PMA) caused a redistribution of NKCC1 immunostaining from the basolateral membrane to intracellular vesicles in both shLacZ- and shPKCα-T84 cells, whereas the effect of PMA was not observed in shPKCδ- and shPKCε- cells. These results were further confirmed by basolateral surface biotinylation. Furthermore, activation of PKCs by PMA inhibited cAMP-stimulated chloride secretion in the uninfected, shLacZ- and shPKCα-T84 monolayers, but the inhibitory effect was significantly attenuated in shPKCδ- and shPKCε-T84 monolayers. In conclusion, the activated novel isoforms PKCδ or PKCε, but not the conventional isoform PKCα, inhibits transepithelial chloride secretion through inducing internalization of the basolateral surface NKCC1. Our study reveals that the novel PKC isoform-regulated NKCC1 surface expression plays an important role in the regulation of chloride secretion.

  5. Mini-review: regulation of the renal NaCl cotransporter by hormones.

    Science.gov (United States)

    Rojas-Vega, Lorena; Gamba, Gerardo

    2016-01-01

    The renal thiazide-sensitive NaCl cotransporter, NCC, is the major pathway for salt reabsorption in the distal convoluted tubule. The activity of this cotransporter is critical for regulation of several physiological variables such as blood pressure, serum potassium, acid base metabolism, and urinary calcium excretion. Therefore, it is not surprising that numerous hormone-signaling pathways regulate NCC activity to maintain homeostasis. In this review, we will provide an overview of the most recent evidence on NCC modulation by aldosterone, angiotensin II, vasopressin, glucocorticoids, insulin, norepinephrine, estradiol, progesterone, prolactin, and parathyroid hormone.

  6. WNK kinases regulate thiazide-sensitive Na-Cl cotransport.

    Science.gov (United States)

    Yang, Chao-Ling; Angell, Jordan; Mitchell, Rose; Ellison, David H

    2003-04-01

    Pseudohypoaldosteronism type II (PHAII) is an autosomal dominant disorder of hyperkalemia and hypertension. Mutations in two members of the WNK kinase family, WNK1 and WNK4, cause the disease. WNK1 mutations are believed to increase WNK1 expression; the effect of WNK4 mutations remains unknown. The clinical phenotype of PHAII is opposite to Gitelman syndrome, a disease caused by dysfunction of the thiazide-sensitive Na-Cl cotransporter. We tested the hypothesis that WNK kinases regulate the mammalian thiazide-sensitive Na-Cl cotransporter (NCC). Mouse WNK4 was cloned and expressed in Xenopus oocytes with or without NCC. Coexpression with WNK4 suppressed NCC activity by more than 85%. This effect did not result from defects in NCC synthesis or processing, but was associated with an 85% reduction in NCC abundance at the plasma membrane. Unlike WNK4, WNK1 did not affect NCC activity directly. WNK1, however, completely prevented WNK4 inhibition of NCC. Some WNK4 mutations that cause PHAII retained NCC-inhibiting activity, but the Q562E WNK4 demonstrated diminished activity, suggesting that some PHAII mutations lead to loss of NCC inhibition. Gain-of-function WNK1 mutations would be expected to inhibit WNK4 activity, thereby activating NCC, contributing to the PHAII phenotype. Together, these results identify WNK kinases as a previously unrecognized sodium regulatory pathway of the distal nephron. This pathway likely contributes to normal and pathological blood pressure homeostasis.

  7. Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium-glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents.

    Science.gov (United States)

    Oguma, Takahiro; Kuriyama, Chiaki; Nakayama, Keiko; Matsushita, Yasuaki; Hikida, Kumiko; Tsuda-Tsukimoto, Minoru; Saito, Akira; Arakawa, Kenji; Ueta, Kiichiro; Minami, Masabumi; Shiotani, Masaharu

    2016-12-01

    We investigated whether structurally different sodium-glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed glucose excursions in both normal and diabetic rodents. In DPP4-deficient rats, GTB enhanced glucose-induced aGLP-1 elevation without affecting the basal level, whereas metformin, previously reported to enhance GLP-1 secretion, increased both the basal level and glucose-induced elevation. Oral treatment with canagliflozin and TA-1887 also enhanced glucose-induced aGLP-1 elevation when co-administered with either teneligliptin or sitagliptin. These data suggest that structurally different SGLT2 inhibitors enhance plasma aGLP-1 elevation and suppress glucose excursions during OGTT when co-administered with DPP4 inhibitors, regardless of the difference in chemical structure. Combination treatment with DPP4 inhibitors and SGLT2 inhibitors having moderate SGLT1 inhibitory activity may be a promising therapeutic option for improving glycemic control in patients with type 2 diabetes mellitus. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  8. Modeling Deactivation of Catalysts for Selective Catalytic Reduction of NOx by KCl Aerosols

    DEFF Research Database (Denmark)

    Olsen, Brian Kjærgaard; Castellino, Francesco; Jensen, Anker Degn

    2017-01-01

    with the catalyst at the surface of the monolith wall, the transport and accumulation of potassium, bound to Brønsted acid sites, throughout the catalyst wall, and the resulting loss in SCR activity. Using an experimentally measured KCl aerosol size distribution as input, the model can replicate the observed...... if the particle size of the incoming aerosol is increased. The model provides, for the first time, a mechanistic framework for understanding and modeling SCR catalyst deactivation by KCl that may be applicable also for deactivation by other salts and at different operating conditions.......A detailed model for the deactivation of a V2O5–WO3/TiO2-based SCR monolith catalyst by potassium poisoning has been developed and validated. The model accounts for deposition of KCl aerosol particles present in the flue gas on the external catalyst surface, the reaction of the deposited particles...

  9. Optically stimulated luminescence in KCl:Cu x-irradiated at room temperature

    CERN Document Server

    Bandyopadhyay, P K; Chakrabarti, K

    1999-01-01

    Optically stimulated luminescence (OSL) has been observed in single crystals of KCl:Cu x-irradiated at room temperature. It is shown that electrons are liberated from anion sites during the OSL process. The OSL predominantly involves emission due to radiative transition (d s) of monovalent copper ions present in the lattice. The OSL emission shows a strong temperature dependence indicating a thermally assisted process. Electron-hole recombination followed by energy transfer to the Cu activator is suggested as a possible OSL mechanism in KCl:Cu. Preliminary results of OSL in KBr:Cu are also presented.

  10. Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes

    Directory of Open Access Journals (Sweden)

    Ravshan Z. Sabirov

    2011-12-01

    Full Text Available Channel-mediated trans-membrane chloride movement is a key process in the active cell volume regulation under osmotic stress in most cells. However, thymocytes were hypothesized to regulate their volume by activating a coupled K-Cl cotransport mechanism. Under the patch-clamp, we found that osmotic swelling activates two types of macroscopic anion conductance with different voltage-dependence and pharmacology. At the single-channel level, we identified two types of events: one corresponded to the maxi-anion channel, and the other one had characteristics of the volume-sensitive outwardly rectifying (VSOR chloride channel of intermediate conductance. A VSOR inhibitor, phloretin, significantly suppressed both macroscopic VSOR-type conductance and single-channel activity of intermediate amplitude. The maxi-anion channel activity was largely suppressed by Gd3+ ions but not by phloretin. Surprisingly, [(dihydroindenyloxy] alkanoic acid (DIOA, a known antagonist of K-Cl cotransporter, was found to significantly suppress the activity of the VSOR-type single-channel events with no effect on the maxi-anion channels at 10 μM. The regulatory volume decrease (RVD phase of cellular response to hypotonicity was mildly suppressed by Gd3+ ions and was completely abolished by phloretin suggesting a major impact of the VSOR chloride channel and modulatory role of the maxi-anion channel. The inhibitory effect of DIOA was also strong, and, most likely, it occurred via blocking the VSOR Cl− channels.

  11. Vasopressin induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter in the distal convoluted tubule

    DEFF Research Database (Denmark)

    Pedersen, Nis Borbye; Hofmeister, Marlene Vind; Rosenbaek, Lena L;

    2010-01-01

    The thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) is important for renal electrolyte balance and its phosphorylation causes an increase in its transport activity and cellular localization. Here, we generated phospho-specific antibodies against two conserved N-terminal phosphorylation sites...

  12. The human Na+-glucose cotransporter is a molecular water pump

    DEFF Research Database (Denmark)

    Meinild, A; Klaerke, D A; Loo, D D

    1998-01-01

    1. The human Na+-glucose cotransporter (hSGLT1) was expressed in Xenopus laevis oocytes. The transport activity, given by the Na+ current, was monitored as a clamp current and the concomitant flux of water followed optically as the change in oocyte volume. 2. When glucose was added to the bathing...

  13. RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter.

    NARCIS (Netherlands)

    Ko, B.; Kamsteeg, E.J.; Cooke, L.L.; Moddes, L.N.; Deen, P.M.T.; Hoover, R.S.

    2010-01-01

    The sodium-chloride cotransporter (NCC) is the principal salt-absorptive pathway in the distal convoluted tubule. Recently, we described a novel pathway of NCC regulation in which phorbol esters (PE) stimulate Ras guanyl-releasing protein 1 (RasGRP1), triggering a cascade ultimately activating ERK1/

  14. RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter.

    NARCIS (Netherlands)

    Ko, B.; Kamsteeg, E.J.; Cooke, L.L.; Moddes, L.N.; Deen, P.M.T.; Hoover, R.S.

    2010-01-01

    The sodium-chloride cotransporter (NCC) is the principal salt-absorptive pathway in the distal convoluted tubule. Recently, we described a novel pathway of NCC regulation in which phorbol esters (PE) stimulate Ras guanyl-releasing protein 1 (RasGRP1), triggering a cascade ultimately activating

  15. Passive water and ion transport by cotransporters

    DEFF Research Database (Denmark)

    Loo, D D; Hirayama, B A; Meinild, A K

    1999-01-01

    1. The rabbit Na+-glucose (SGLT1) and the human Na+-Cl--GABA (GAT1) cotransporters were expressed in Xenopus laevis oocytes, and passive Na+ and water transport were studied using electrical and optical techniques. Passive water permeabilities (Lp) of the cotransporters were determined from...... the changes in oocyte volume in response to osmotic gradients. The specific SGLT1 and GAT1 Lp values were obtained by measuring Lp in the presence and absence of blockers (phlorizin and SKF89976A). In the presence of the blockers, the Lp values of oocytes expressing SGLT1 and GAT1 were indistinguishable from...... the Lp of control oocytes. Passive Na+ transport (Na+ leak) was obtained from the blocker-sensitive Na+ currents in the absence of substrates (glucose and GABA). 2. Passive Na+ and water transport through SGLT1 were blocked by phlorizin with the same sensitivity (inhibitory constant (Ki), 3-5 micro...

  16. Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium–glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents

    OpenAIRE

    Takahiro Oguma; Chiaki Kuriyama; Keiko Nakayama; Yasuaki Matsushita; Kumiko Hikida; Minoru Tsuda-Tsukimoto; Akira Saito; Kenji Arakawa; Kiichiro Ueta; Masabumi Minami; Masaharu Shiotani

    2016-01-01

    We investigated whether structurally different sodium–glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors—1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin—were examined to assess the effect of chemical structure. Oral treatment...

  17. Thermodynamics of the NaCl–KCl system

    Energy Technology Data Exchange (ETDEWEB)

    Sergeev, D., E-mail: sergeevdmn@gmail.com; Kobertz, D.; Müller, M.

    2015-04-20

    Highlights: • The complementary methods of DSC, DTA, DROP and XRD analyses were used. • The heat capacity of solid phase of the NaCl–KCl mixtures was measured. • The heat capacity of liquid phase of the 50NaCl–50KCl mixture was obtained. • The enthalpy of fusion and solid solution formation were determined. • The thermodynamic functions of the 50NaCl–50KCl mixture were calculated. - Abstract: The heat capacity of the solid phase of the NaCl–KCl mixtures was measured by the differential scanning calorimetry. These results and X-ray diffraction data were used for the explanation of the solid solution formation. The heat capacity of the liquid phase of the eutectic 50NaCl–50KCl mixture has been obtained in a closed glass container. The enthalpy increment (H{sup °}{sub T} − H{sup °}{sub 298.15}) and the fusion enthalpy of the 50NaCl–50KCl mixture have been measured by a drop calorimeter. The joint analysis of these values with the heat capacity data allowed the calculation of the enthalpy of the solid solution. As the final result, the thermodynamic functions of the eutectic 50NaCl–50KCl mixture have been obtained.

  18. Evidence for an apical Na-Cl cotransporter involved in ion uptake in a teleost fish

    Science.gov (United States)

    Hiroi, J.; Yasumasu, S.; McCormick, S.D.; Hwang, P.-P.; Kaneko, T.

    2008-01-01

    Cation-chloride cotransporters, such as the Na+/K +/2Cl- cotransporter (NKCC) and Na+/Cl - cotransporter (NCC), are localized to the apical or basolateral plasma membranes of epithelial cells and are involved in active ion absorption or secretion. The objectives of this study were to clone and identify 'freshwater-type' and 'seawater-type' cation-chloride cotransporters of euryhaline Mozambique tilapia (Oreochromis mossambicus) and to determine their intracellular localization patterns within mitochondria-rich cells (MRCs). From tilapia gills, we cloned four full-length cDNAs homologous to human cation-chloride cotransporters and designated them as tilapia NKCC1a, NKCC1b, NKCC2 and NCC. Out of the four candidates, the mRNA encoding NKCC1a was highly expressed in the yolk-sac membrane and gills (sites of the MRC localization) of seawater-acclimatized fish, whereas the mRNA encoding NCC was exclusively expressed in the yolk-sac membrane and gills of freshwater-acclimatized fish. We then generated antibodies specific for tilapia NKCC1a and NCC and conducted whole-mount immunofluorescence staining for NKCC1a and NCC, together with Na+/K+-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR) and Na+/H+ exchanger 3 (NHE3), on the yolk-sac membrane of tilapia embryos acclimatized to freshwater or seawater. The simultaneous quintuple-color immunofluorescence staining allowed us to classify MRCs clearly into four types: types I, II, III and IV. The NKCC1a immunoreactivity was localized to the basolateral membrane of seawater-specific type-IV MRCs, whereas the NCC immunoreactivity was restricted to the apical membrane of freshwater-specific type-II MRCs. Taking account of these data at the level of both mRNA and protein, we deduce that NKCC1a is the seawater-type cotransporter involved in ion secretion by type-IV MRCs and that NCC is the freshwater-type cotransporter involved in ion absorption by type-II MRCs. We propose a novel ion-uptake model by MRCs in

  19. Angiotensin II directly stimulates macula densa Na-2Cl-K cotransport via apical AT(1) receptors.

    Science.gov (United States)

    Kovács, Gergely; Peti-Peterdi, János; Rosivall, László; Bell, P Darwin

    2002-02-01

    ANG II is a modulator of tubuloglomerular feedback (TGF); however, the site of its action remains unknown. Macula densa (MD) cells sense changes in luminal NaCl concentration ([NaCl](L)) via a Na-2Cl-K cotransporter, and these cells do possess ANG II receptors. We tested whether ANG II regulates Na-2Cl-K cotransport in MD cells. MD cell Na(+) concentration ([Na(+)](i)) was measured using sodium-binding benzofuran isophthalate with fluorescence microscopy. Resting [Na(+)](i) in MD cells was 27.7 +/- 1.05 mM (n = 138) and increased (Delta[Na(+)](i)) by 18.5 +/- 1.14 mM (n = 17) at an initial rate (Delta[Na(+)](i)/Deltat) of 5.54 +/- 0.53 x 10(-4) U/s with an increase in [NaCl](L) from 25 to 150 mM. Both Delta[Na(+)](i) and Delta[Na(+)](i)/Deltat were inhibited by 80% with 100 microM luminal furosemide. ANG II (10(-9) or 10(-12) M) added to the lumen increased MD resting [Na(+)](i) and [NaCl](L)-dependent Delta[Na(+)](i) and caused a twofold increase in Delta[Na(+)](i)/Deltat. Bath (10(-9) M) ANG II also stimulated cotransport activity, and there was no additive effect of simultaneous addition of ANG II to bath and lumen. The effects of luminal ANG II were furosemide sensitive and abolished by the AT(1) receptor blocker candesartan. ANG II at 10(-6) M failed to stimulate the cotransporter, whereas increased cotransport activity could be restored by blocking AT(2) receptors with PD-123, 319. Thus ANG II may modulate TGF responses via alterations in MD Na-2Cl-K cotransport activity.

  20. OVER-EXPRESSION OF THE SODIUM CHLORIDE COTRANSPORTER IS NOT SUFFICIENT TO CAUSE FAMILIAL HYPERKALEMIC HYPERTENSION

    OpenAIRE

    McCormick, James A.; Nelson, Joshua H.; Yang, Chao-Ling; Curry, Joshua N.; Ellison, David H.

    2011-01-01

    The sodium chloride co-transporter (NCC) is the primary target of thiazides diuretics, drugs used commonly for long-term hypertension therapy. Thiazides also completely reverse the signs of Familial Hyperkalemic Hypertension (FHHt), suggesting that the primary defect in FHHt is increased NCC activity. To test whether increased NCC abundance alone is sufficient to generate the FHHt phenotype, we generated NCC transgenic mice; surprisingly, these mice did not display an FHHt-like phenotype. Sys...

  1. Study of effect of quenching and deformation on KCl: Gd3+ crystals by using conductivity measurements

    Indian Academy of Sciences (India)

    G Saibabu; A Ramachandra Reddy; D Srikanth

    2004-10-01

    The study of ionic conductivity vs reciprocal temperature of pure KCl and KCl crystal doped with 0.1, 0.3 and 0.5 mole% gadolinium has been carried out in as grown, quenched from elevated temperatures (100, 350 and 500°C) and annealed at various timings i.e. 2–3 h and deformed by different percentages. The plots exhibit three well-known regions, II, III and IV (extrinsic regions). The intrinsic region I was not observed in the plots as the conductivity measurements were taken up to 575°C. From the analysis of these plots, activation energies for the migration of cation vacancy and the association of gadolinium ion with cation vacancy in the lattice of KCl crystals are calculated. These values are compared with previously reported values. Further, an attempt is made to explain the existence of oxidation state of gadolinium ion in + 3 state rather than in + 2 state as reported earlier. The variation in conductivity with effect of concentration of impurity ion, quenching and annealing and deformation with various percentages are explained on the basis of formation of impurity vacancy dipoles, vacancy – vacancy pairs (which appear in the form of precipitation), storage of cation vacancies in the form of defects, introduction of fresh dislocations, etc.

  2. NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity

    NARCIS (Netherlands)

    Tutakhel, O.A.Z.; Moes, A.D.; Valdez Flores, M.A.; Kortenoeven, M.L.A.; Vrie, M. van de; Jelen, S.K.; Fenton, R.A.; Zietse, R.; Hoenderop, J.G.J.; Hoorn, E.J.; Hilbrands, L.B.; Bindels, R.J.M.

    2017-01-01

    Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after

  3. NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity

    NARCIS (Netherlands)

    Tutakhel, O.A.Z. (Omar A. Z.); A.D. Moes (Arthur); Valdez-Flores, M.A. (Marco A.); Kortenoeven, M.L.A. (Marleen L. A.); Vrie, M.V.D. (Mathijs V.D.); Jelen, S. (Sabina); R.A. Fenton (Robert); R. Zietse (Bob); J.G.J. Hoenderop (Joost); E.J. Hoorn (Ewout); L.B. Hilbrands (Luuk); Bindels, R.J.M. (Reneâ J. M.)

    2017-01-01

    textabstractAnimal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles

  4. Entrained Flow Reactor Study of KCl Capture by Solid Additives

    DEFF Research Database (Denmark)

    Wang, Guoliang; Jensen, Peter Arendt; Wu, Hao

    An option for abating deposition and corrosion caused byalkali species during biomass combustion, is the introduction of additivesinto boilers for transforming harmful gaseous alkali compounds (e.g. KCl,KOH) into less corrosive ash species with a higher melting point. Kaolin andcoal fly ash have...

  5. Regulation of renal Na-(K)-Cl cotransporters by vasopressin.

    Science.gov (United States)

    Bachmann, Sebastian; Mutig, Kerim

    2017-08-01

    Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption. Previous work has specified molecular pathways mediating the effects of V2R activation in TAL and DCT, and protein networks involved in intracellular trafficking and phosphoregulation of the two transporters have been identified. This review summarizes recent progress in understanding AVP signalling mechanisms that are responsible for the activation of NKCC2 and NCC. Implications in the pathophysiology of diseases such as nephrogenic diabetes insipidus, diabetes mellitus and salt-sensitive hypertension are discussed in this context.

  6. SU-E-T-476: Improving KCl:Eu2+ Dosimeter Sensitivity: The Role of Oxygen

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Z [Washington University School of Medicine, St. Louis, MO (United States); Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (United States); Mazur, T; Li, H [Washington University School of Medicine, St. Louis, MO (United States); Driewer, J [University of Nebraska Medical Center, Omaha, NE (United States)

    2015-06-15

    Purpose: Recent research has shown that KCl:Eu2+ has great potential for use in megavoltage radiation therapy dosimetry because this material exhibits excellent storage performance and is reusable due to strong radiation hardness. The purpose of this work is to determine if increased signal could be realized in KCl:Eu2+ by incorporating oxygen in the material fabrication process. Methods: The prototype KCl:Eu2+ dosimeters have a physical makeup similar to thermoluminescent dosimeter chips. The photostimulation light source consists of either a He-Ne laser or a UV enhanced Xe arc lamp with wavelength selection provided by a motorized monochromator. X-ray diffraction is used to determine the phase composition of the dosimeters. Photoluminescence (PL) and photostimulated luminescence (PSL) emission spectra are obtained using a Nanolog Spectrofluoremeter. Results: Europium activator is completely incorporated into the KCl parent-matrix without the formation of a noticeable secondary phase. Regardless of synthesis atmosphere, air or pure nitrogen, PSL amplitude shows a maximum at 1.0 mol % Eu. Depending on europium concentration, dosimeters fabricated in air exhibit stronger PSL by a factor of 2 to 4 compared to those made in N2. There is no change in PSL stimulation spectrum while noticeable shifts in both PL and PSL emission spectra are observed for air versus nitrogen. Almost all charge-storage centers are spatially correlated, suggesting oxygen’s stabilization role in the PSL process. KCl:Eu2+ made in oxygen-rich air is capable of measuring a dose-to-water as low as 0.01 cGy from a 6MV photon beam with a signal-to-noise ratio greater than 6. Conclusions: Synthesis in a reduction atmosphere, for example, nitrogen, was thought to be mandatory in order to retain europium activator’s divalent status to be PSL active. Fortunately, divalent europium can be well preserved in an oxygen-rich atmosphere. More importantly, oxygen can enhance PSL by a factor of 2 to 4. HL

  7. Dielectric, piezoelectric, and pyroelectric anisotropy in KCL- modified grain-oriented bismuth vanadate ceramics

    OpenAIRE

    Shantha, K; Varma, KBR

    1999-01-01

    The effect of the additive KCl, on the structural, microstructural, and polar properties of bismuth vanadate (BiV) ceramics is investigated. The scanning electron microscopic (SEM) studies reveal a remarkable modification in the microstructure and the occurrence of high grain-orientation (75%) on KCl addition. The energy dispersive x ray (EDX) analyses indicate the presence of chemically inhomogeneous distribution of KCl, with core-shell-like grain structure. The KCl-modified BiV samples exhi...

  8. Chloride-cotransport blockade desynchronizes neuronal discharge in the "epileptic" hippocampal slice.

    Science.gov (United States)

    Hochman, D W; Schwartzkroin, P A

    2000-01-01

    Antagonism of the chloride-cotransport system in hippocampal slices has been shown to block spontaneous epileptiform (i.e., hypersynchronized) discharges without diminishing excitatory synaptic transmission. Here we test the hypotheses that chloride-cotransport blockade, with furosemide or low-chloride (low-[Cl(-)](o)) medium, desynchronizes the firing activity of neuronal populations and that this desynchronization is mediated through nonsynaptic mechanisms. Spontaneous epileptiform discharges were recorded from the CA1 and CA3 cell body layers of hippocampal slices. Treatment with low-[Cl(-)](o) medium led to cessation of spontaneous synchronized bursting in CA1 >/=5-10 min before its disappearance from CA3. During the time that CA3 continued to burst spontaneously but CA1 was silent, electrical stimulation of the Schaffer collaterals showed that hyperexcited CA1 synaptic responses were maintained. Paired intracellular recordings from CA1 pyramidal cells showed that during low-[Cl(-)](o) treatment, the timing of action potential discharges became desynchronized; desynchronization was identified with phase lags in firing times of action potentials between pairs of neurons as well as a with a broadening and diminution of the CA1 field amplitude. Continued exposure to low-[Cl(-)](o) medium increased the degree of the firing-time phase shifts between pairs of CA1 pyramidal cells until the epileptiform CA1 field potential was abolished completely. Intracellular recordings during 4-aminopyridine (4-AP) treatment showed that prolonged low-[Cl(-)](o) exposure did not diminish the frequency or amplitude of spontaneous postsynaptic potentials. CA3 antidromic responses to Schaffer collateral stimulation were not significantly affected by prolonged low-[Cl(-)](o) exposure. In contrast to CA1, paired intracellular recordings from CA3 pyramidal cells showed that chloride-cotransport blockade did not cause a significant desynchronization of action potential firing times in the

  9. Characterization of Niobium Platings Obtained from NaCl-KCl Melts

    DEFF Research Database (Denmark)

    Gillesberg, Bo; Barner, Jens H. Von; Bjerrum, Niels

    1998-01-01

    oxidation of metallic niobium with NiCl2. The initial valency of niobium was found to 3 when a NaCl-KCl melt was applied as solvent. The deposits were characterised by X-ray analy-sis and Scanning Electron Microscopy (SEM) combined with EDX analysis. From both NaCl-KCl and LiCl-KCl melts dense and coherent...

  10. Determination of the Na(+)/glucose cotransporter (SGLT1) turnover rate using the ion-trap technique.

    Science.gov (United States)

    Longpré, Jean-Philippe; Lapointe, Jean-Yves

    2011-01-05

    The Na(+)/glucose cotransporter (SGLT1) is a membrane protein that couples the transport of two Na(+) ions and one glucose molecule using the so-called alternating access mechanism. According to this principle, each cotransporter molecule can adopt either of two main conformations: one with the binding sites accessible to the extracellular solution and one with the binding sites facing the intracellular solution. The turnover rate (TOR) is the number of complete cycles that each protein performs per second. Determination of the TOR has important consequences for investigation of the cotransport mechanism, as none of the rate constants involved in mediating transport in a given direction (conformational changes and binding and unbinding reactions) can be slower than the TOR measured under the same conditions. In addition, the TOR can be used to estimate the number of cotransporter molecules involved in generating a given ensemble activity. In this study, we obtain an independent estimation of the TOR for human SGLT1 expressed in Xenopus laevis oocytes applying the ion-trap technique. This approach detects the quantity of ions released in or taken up from the restricted space existing between the oocyte plasma membrane and the tip of a large ion-selective electrode. Taking advantage of the fact that hSGLT1 in the absence of Na(+) can cotransport glucose with protons, we used a pH electrode to determine a TOR of 8.00 ± 1.3 s⁻¹ in the presence of 35 mM α-methyl-glucose at -150 mV (pH 5.5). For the same group of oocytes, a TOR of 13.3 ± 2.4 s⁻¹ was estimated under near-V(max) conditions, i.e., in the presence of 90 mM Na(+) and 5 mM α-methyl-glucose. Under these circumstances, the average cotransport current was -1.08 ± 0.61 μA (n = 14), and this activity was generated by an average of 3.6 ± 0.7 × 10¹¹ cotransporter molecules/oocyte. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Determination of the Na+/Glucose Cotransporter (SGLT1) Turnover Rate Using the Ion-Trap Technique

    Science.gov (United States)

    Longpré, Jean-Philippe; Lapointe, Jean-Yves

    2011-01-01

    The Na+/glucose cotransporter (SGLT1) is a membrane protein that couples the transport of two Na+ ions and one glucose molecule using the so-called alternating access mechanism. According to this principle, each cotransporter molecule can adopt either of two main conformations: one with the binding sites accessible to the extracellular solution and one with the binding sites facing the intracellular solution. The turnover rate (TOR) is the number of complete cycles that each protein performs per second. Determination of the TOR has important consequences for investigation of the cotransport mechanism, as none of the rate constants involved in mediating transport in a given direction (conformational changes and binding and unbinding reactions) can be slower than the TOR measured under the same conditions. In addition, the TOR can be used to estimate the number of cotransporter molecules involved in generating a given ensemble activity. In this study, we obtain an independent estimation of the TOR for human SGLT1 expressed in Xenopus laevis oocytes applying the ion-trap technique. This approach detects the quantity of ions released in or taken up from the restricted space existing between the oocyte plasma membrane and the tip of a large ion-selective electrode. Taking advantage of the fact that hSGLT1 in the absence of Na+ can cotransport glucose with protons, we used a pH electrode to determine a TOR of 8.00 ± 1.3 s−1 in the presence of 35 mM α-methyl-glucose at −150 mV (pH 5.5). For the same group of oocytes, a TOR of 13.3 ± 2.4 s−1 was estimated under near-Vmax conditions, i.e., in the presence of 90 mM Na+ and 5 mM α-methyl-glucose. Under these circumstances, the average cotransport current was −1.08 ± 0.61 μA (n = 14), and this activity was generated by an average of 3.6 ± 0.7 × 1011 cotransporter molecules/oocyte. PMID:21190656

  12. Electroreduction of Ho3+ on Nickel Cathode in Molten KCl-HoCl3

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The cyclic voltammetry, open current potential-time curve after potentiostatic electrolysis, the current-time curve at potential step, XRD, EDAX and EPMA were used to study the electrode process of Ho3+ reduction on nickel electrode in molten KCl-HoCl3 and the phases of surface alloy layer. The Ho-Ni alloys were deposited when Ho3+ was reduced on the nickel electrode. The free energies of formation for the intermetallic compounds between Ho and Ni, the diffusion coefficients and diffusion activation energy of Ho atom in the alloy phase were determined.

  13. Thermal Properties of LiCl-KCl Molten Salt for Nuclear Waste Separation

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Kumar [Univ. of Wisconsin, Madison, WI (United States); Allen, Todd [Univ. of Wisconsin, Madison, WI (United States); Anderson, Mark [Univ. of Wisconsin, Madison, WI (United States); Simpson, Mike [Idaho National Lab., (United States)

    2012-11-30

    This project addresses both practical and fundamental scientific issues of direct relevance to operational challenges of the molten LiCl-KCl salt pyrochemical process, while providing avenues for improvements in the process. In order to understand the effects of the continually changing composition of the molten salt bath during the process, the project team will systematically vary the concentrations of rare earth surrogate elements, lanthanum, cerium, praseodymium, and neodymium, which will be added to the molten LiCl-KCl salt. They will also perform a limited number of focused experiments by the dissolution of depleted uranium. All experiments will be performed at 500 deg C. The project consists of the following tasks. Researchers will measure density of the molten salts using an instrument specifically designed for this purpose, and will determine the melting points with a differential scanning calorimeter. Knowledge of these properties is essential for salt mass accounting and taking the necessary steps to prevent melt freezing. The team will use cyclic voltammetry studies to determine redox potentials of the rare earth cations, as well as their diffusion coefficients and activities in the molten LiCl-KCl salt. In addition, the team will perform anodic stripping voltammetry to determine the concentration of the rare earth elements and their solubilities, and to develop the scientific basis for an on-line diagnostic system for in situ monitoring of the cation species concentration (rare earths in this case). Solubility and activity of the cation species are critically important for the prediction of the salt's useful lifetime and disposal.

  14. Cotransport of water by Na¿-K¿-2Cl¿ cotransporters expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Macaulay, Nanna

    2012-01-01

    . The osmotic effects of NaCl were smaller than those of urea and mannitol. This supports the notion of interaction between ions and water in NKCC1 and allows for an estimate of around 600 water molecules transported per turnover of the protein. Osmotic gradients did not induce water transport in NKCC2. We...... increases in external K¿ concentration elicited abrupt inward water fluxes in NKCC1; the K¿ dependence obeyed one-site kinetics with a K0.5 of 7.5 mM. The water fluxes were blocked by bumetanide, had steep temperature dependence and could proceed uphill against an osmotic gradient of 20 mosmol l......¿¹. A comparison between ion and water fluxes indicates that 460 water molecules are cotransported for each turnover of the protein. In contrast, NKCC2 did not support water fluxes.Water transport in NKCC1 induced by increases in the external osmolarity had high activation energy and was blocked by bumetanide...

  15. Oligomeric structure and minimal functional unit of the electrogenic sodium bicarbonate cotransporter NBCe1-A.

    Science.gov (United States)

    Kao, Liyo; Sassani, Pakan; Azimov, Rustam; Pushkin, Alexander; Abuladze, Natalia; Peti-Peterdi, Janos; Liu, Weixin; Newman, Debra; Kurtz, Ira

    2008-09-26

    The electrogenic sodium bicarbonate cotransporter NBCe1-A mediates the basolateral absorption of sodium and bicarbonate in the proximal tubule. In this study the oligomeric state and minimal functional unit of NBCe1-A were investigated. Wild-type (wt) NBCe1-A isolated from mouse kidney or heterologously expressed in HEK293 cells was predominantly in a dimeric state as was shown using fluorescence energy transfer, pulldown, immunoprecipitation, cross-linking experiments, and nondenaturing perfluorooctanoate-PAGE. NBCe1-A monomers were found to be covalently linked by S-S bonds. When each of the 15 native cysteine residues were individually removed on a wt-NBCe1-A backbone, dimerization of the cotransporter was not affected. In experiments involving multiple native cysteine residue removal, both Cys(630) and Cys(642) in extracellular loop 3 were shown to mediate S-S bond formation between NBCe1-A monomers. When native NBCe1-A cysteine residues were individually reintroduced into a cysteineless NBCe1-A mutant backbone, the finding that a Cys(992) construct that lacked S-S bonds functioned normally indicated that stable covalent linkage of NBCe1-A monomers was not a necessary requirement for functional activity of the cotransporter. Studies using concatameric constructs of wt-NBCe1-A, whose activity is resistant to methanesulfonate reagents, and an NBCe1-A(T442C) mutant, whose activity is completely inhibited by methanesulfonate reagents, confirmed that NBCe1-A monomers are functional. Our results demonstrate that wt-NBCe1-A is predominantly a homodimer, dependent on S-S bond formation that is composed of functionally active monomers.

  16. Expression of apical Na(+)-L-glutamine co-transport activity, B(0)-system neutral amino acid co-transporter (B(0)AT1) and angiotensin-converting enzyme 2 along the jejunal crypt-villus axis in young pigs fed a liquid formula

    Science.gov (United States)

    Gut apical amino acid (AA) transport activity is high at birth and during suckling, thus being essential to maintain luminal nutrient-dependent mucosal growth through providing AA as essential metabolic fuel, substrates and nutrient stimuli for cellular growth. Because system-B(0) Na(+)-neutral AA c...

  17. Integrated Data Collection Analysis (IDCA) Program - KClO4/Carbon Mixture

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Sorensen, Daniel N. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Shelley, Timothy J. [Air Force Research Lab. (AFRL), Tyndall AFB, FL (United States); Reyes, Jose A. [Applied Research Associates, Tyndall AFB, FL (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-01-31

    The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of a mixture of KClO4 and activated carbon—KClO4/C mixture. This material was selected because of the challenge of performing SSST testing of a mixture of two solids. The mixture was found to be insensitive to impact, friction, and thermal stimulus, and somewhat sensitive to spark discharge. This effort, funded by the Department of Homeland Security (DHS), ultimately will put the issues of safe handling of these materials in perspective with standard military explosives. The study is adding SSST testing results for a broad suite of different HMEs to the literature. Ultimately the study has the potential to suggest new guidelines and methods and possibly establish the SSST testing accuracies needed to develop safe handling practices for HMEs. Each participating testing laboratory uses identical test materials and preparation methods wherever possible. Note, however, the test procedures differ among the laboratories. The results are compared among the laboratories and then compared to historical data from various sources. The testing performers involved for the KClO4/carbon mixture are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Indian Head Division, Naval Surface Warfare Center, (NSWC IHD), and Air Force Research Laboratory (AFRL/RXQL). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to understand how to compare results when these testing variables cannot be made consistent.

  18. Electrochemical behaviour of dysprosium in the eutectic LiCl-KCl at W and Al electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Castrillejo, Y. [Dpto de Quimica Analitica, Facultad de Ciencias, Universidad de Valladolid, Prado de la Magdalena s/n, 47005 Valladolid (Spain)]. E-mail: ycastril@qa.uva.es; Bermejo, M.R. [Dpto de Quimica Analitica, Facultad de Ciencias, Universidad de Valladolid, Prado de la Magdalena s/n, 47005 Valladolid (Spain); Barrado, A.I. [Dpto de Quimica Analitica, Facultad de Ciencias, Universidad de Valladolid, Prado de la Magdalena s/n, 47005 Valladolid (Spain); Pardo, R. [Dpto de Quimica Analitica, Facultad de Ciencias, Universidad de Valladolid, Prado de la Magdalena s/n, 47005 Valladolid (Spain); Barrado, E. [Dpto de Quimica Analitica, Facultad de Ciencias, Universidad de Valladolid, Prado de la Magdalena s/n, 47005 Valladolid (Spain); Martinez, A.M. [Department of Materials Technology, Sem Saelands vei 6, 7491 Trondheim (Norway)

    2005-03-15

    The electrochemical behaviour of DyCl{sub 3} was studied in the eutectic LiCl-KCl at different temperatures. The cathodic reaction can be written:Dy(III)+3e-bar Dy(0)which can be divided in two very close cathodic steps:Dy(III)+1e-bar Dy(II)andDy(II)+2e-bar Dy(0)Transient electrochemical techniques, such as cyclic voltammetry, chronopotentiometry, and chronoamperometry were used in order to study the reaction mechanism and the transport parameters of electroactive species at a tungsten electrode. The results showed that in the eutectic LiCl-KCl, electrocrystallization of dysprosium seems to be the controlling electrochemical step. Chronoamperometric studies indicated instantaneous nucleation of dysprosium with three dimensional growth of the nuclei whatever the applied overpotential.Mass transport towards the electrode is a simple diffusion process, and the diffusion coefficient of the electroactive species, i.e. Dy(III), has been calculated. The validity of the Arrhenius law was also verified by plotting the variation of the logarithm of the diffusion coefficient versus 1/T.In addition, the electrode reactions of the LiCl-KCl-DyCl{sub 3} solutions at an Al wire were also investigated by cyclic voltammetry and open circuit chronopotentiometry. The redox potential of the Dy(III)/Dy couple at the Al electrode was observed at more positive potentials values than those at the inert electrode. This potential shift was thermodynamically analyzed by a lowering of activity of Dy in the metal phase due to the formation of intermetallic compounds.

  19. Bumetanide, an Inhibitor of NKCC1 (Na-K-2Cl Cotransporter Isoform 1), Enhances Propofol-Induced Loss of Righting Reflex but Not Its Immobilizing Actions in Neonatal Rats

    OpenAIRE

    Koyama, Yukihide; Andoh, Tomio; Kamiya, Yoshinori; Miyazaki, Tomoyuki; Maruyama, Koichi; Kariya, Takayuki; Goto, Takahisa

    2016-01-01

    Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to increased expression of Na+-K+-2Cl- co-transporter isoform 1 (NKCC1), and the transition of GABAergic signaling from excitatory to inhibitory occurs before birth in the rat spinal cord and spreads rostrally according to the developmental changes in cation-chloride co-transporter expression. We previously showed that midazolam activates the hippocampal CA3 area and induces less sedation in neonatal ra...

  20. Electrochemical study of Np in the molten eutectic LiCl-KCl; Etude electrochimique de Np dans l'eutectique fondu LiCl-KCl

    Energy Technology Data Exchange (ETDEWEB)

    Cordoba, G. de; Laplace, A.; Blairat, L

    2003-07-01

    This collaborative work CEA-CIEMAT deals with the electrochemical behaviour of neptunium, and in particular the Np(III)/Np redox system, in the LiCl-KCl molten eutectic and in the temperature range of 450 to 600 deg C. The overall goal of this study is to evaluate the feasibility of its separation from the rest of actinides and fission products. Neptunium solutions were obtained by two ways: - the first one consisted in converting the oxide NpO{sub 2} into its chloride form. Dissolution was performed either with HCl{sub (g)} or by carbo-chlorination (Cl{sub 2(g)}+C{sub (s))} at 5500 C. A mixture of mostly Np(IV) together with the soluble oxychloride NpO{sub 2}{sup +}(V) in the melt was obtained, which complicates the study of the Np(III)/Np(0) reduction reaction. - in order to obtain Np(III) solutions, an Al-Cu-Np alloy was used and oxidation of Np metal to the salt phase was performed. A Np(III) solution was obtained, which has been shown by cyclic voltammetry. The study of the redox system Np(Ill)/Np(0) was performed by different electrochemical techniques such as cyclic voltammetry, square wave voltammetry and chrono-potentiometry. The results for both solutions were compared and found to be similar. Reduction of Np(Ill) ions to metal Np proceeds in a single step with the exchange of three electrons and the electrode reaction shows a quasi-reversible behaviour being controlled by the diffusion of the electro-active species. Apparent standard potential was determined by chrono-potentiometry at zero current technique, from the measurement of the equilibrium potential between a Np electrode, electrodeposited in situ, and a LiCl-KCl-NpCl{sub 3} solution at different temperatures. Also, from those values of potential, standard free energy, enthalpy and entropy of formation of NpCl{sub 3} in LiCl-KCl were determined. A very brief description about the electrochemical behaviour of the redox system Np(IV)/Np(III) was made. Finally, the molten salt bath decontamination

  1. Sodium-glucose co-transporter-2 inhibitors and euglycemic ketoacidosis: Wisdom of hindsight

    OpenAIRE

    Awadhesh Kumar Singh

    2015-01-01

    Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are newly approved class of oral anti-diabetic drugs, in the treatment of type 2 diabetes, which reduces blood glucose through glucouresis via the kidney, independent, and irrespective of available pancreatic beta-cells. Studies conducted across their clinical development program found, a modest reduction in glycated hemoglobin ranging from −0.5 to −0.8%, without any significant hypoglycemia. Moreover, head-to-head studies versus active com...

  2. Na+/HCO3- Cotransport in Normal and Cystic Fibrosis Intestine

    Directory of Open Access Journals (Sweden)

    Seidler U

    2001-07-01

    Full Text Available In a search for the HCO(3(- supply mechanisms to the enterocyte we cloned and sequenced an intestinal subtype of the Na(+HCO(3(- cotransporter isoform I (dNBC1, which turned out to be identical to the pancreatic NBC1 subtype (pNBC1. Within the intestine, we found particularly high NBC1 expression levels in the duodenum and proximal colon. Experiments with stripped rabbit duodenum in Ussing-chambers revealed that Na(+HCO(3(- cotransport (NBC and CO(2 hydration/Na(+/H(+ exchange were equally important duodenal HCO(3(- supply pathways and were both upregulated during cAMP-mediated secretion. In the proximal colon, however, HCO(3(- secretion was low but NBC1 expression even higher than in the duodenum. Ussing-chamber experiments with an NBC-specific inhibitor revealed that NBC, coupled to basolateral Cl(-/HCO(3(- exchange, was an important alternative Cl(- supply pathway to Na(+K(+2Cl(- cotransport (NKCC during cAMP-stimulated colonic Cl(- secretion. To investigate the functional integrity of anion uptake pathways in the absence of cystic fibrosis transmembrane conductance regulator (CFTR, we fluorometrically assessed NBC and NKCC transport rates and cell volume before and during forskolin-stimulation in isolated colonic crypts from normal and CFTR (-/- mice. Although forskolin stimulation decreased cell volume only in normal, not in CFTR (-/- crypts, it activated NBC and NKCC to a similar degree in both normal and CFTR (-/- crypts. We conclude that, depending on the intestinal segment, NBC1 plays an important role in basolateral HCO(3(- or Cl(- uptake. Expression and activation by cAMP is preserved in CFTR (-/- intestine.

  3. [The content of nutrient elements of plant in KCl fertilizer].

    Science.gov (United States)

    Xu, Fang; Rui, Yu-Kui; Lin, Qiang; Zhang, Fu-Suo

    2009-03-01

    Potassium is one of the three most important plant nutrient elements, so many researchers pay attention on its fertilizer efficiency. But fertilizers were all industrial products containing many other nutrient elements in most experiments of fertilizer efficiency. All the other nutrient elements, including necessitous elements and beneficial elements in potassium fertilizer (KCl) were analyzed by method of ICP-MS. The results showed that KCl fertilizer contained many necessitous elements (Mg, Ca, Mn, Fe, Ni, Cu, Zn and Mo), the concentrations of them are 50.51, 1 309.48, 5.44, 500.83 microg x g(-1) and 65.54, 238.85, 212.44, 10.40 ng x g(-1) respectively; beneficial elements (Na, Al, Si, Co and Se) are 25 095.89, 3.83, 3.40 microg x g(-1) and 13.12, 23.25 ng x g(-1) respectively. All the above elements could influence the results of potassium fertilizer efficiency experiments, so pure fertilizer should be used in the future potassium fertilizer efficiency experiments.

  4. Conversion of KCl into KBH4 by Mechano-Chemical Reaction and its Catalytic Decomposition

    Science.gov (United States)

    Bilen, Murat; Gürü, Metin; Çakanyildirim, Çetin

    2017-07-01

    Production of KBH4, in the presence of KCl, B2O3 and MgH2 by means of a mechanical reaction and a dehydrogenation kinetic, constitute the main parts of this study. Operating time and reactant ratio are considered as two parameters for the mechanical reaction to obtain the maximum yield. The production process was carried out in a ball milling reactor, and the product residue was purified with ethylene diamine (EDA) and subsequently characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and x-ray Diffraction (XRD) analyses. Optimum time for mechano-chemical treatment and reactant ratio (MgH2/KCl) were obtained as 1000 min and 1.0, respectively. Synthesized and commercial KBH4 were compared by hydrolysis tests in the presence of Co1-xNix/Al2O3 heterogeneous catalyst. Hydrogen generation rates, activation energy and order of the KBH4 decomposition reaction were obtained as 1578 {mL}_{{{{H}}2 }} \\min^{ - 1} {g}_{{catalyst}}^{ - 1}, 39.2 kJ mol-1 and zero order, respectively.

  5. Electrochemical behaviour of gadolinium ion in molten LiCl-KCl eutectic

    Energy Technology Data Exchange (ETDEWEB)

    Caravaca, C. [CIEMAT/Nuclear Fission Division/Radioactive Wastes Unit, Avda, Complutense, 22, Madrid 28040 (Spain)]. E-mail: c.caravaca@ciemat.es; Cordoba, G. de [CIEMAT/Nuclear Fission Division/Radioactive Wastes Unit, Avda, Complutense, 22, Madrid 28040 (Spain); Tomas, M.J. [CIEMAT/Nuclear Fission Division/Radioactive Wastes Unit, Avda, Complutense, 22, Madrid 28040 (Spain); Rosado, M. [CIEMAT/Nuclear Fission Division/Radioactive Wastes Unit, Avda, Complutense, 22, Madrid 28040 (Spain)

    2007-01-15

    This work presents the electrochemical study of GdCl{sub 3} in the molten LiCl-KCl eutectic in the temperature range 723-823 K. Transient electrochemical techniques such as cyclic voltammetry and chronopotentiometry, on an inert metallic tungsten working electrode, have been used in order to investigate the reduction mechanism and transport parameters. This study shows that Gd{sup 3+} ions are reduced to Gd metal by a single step mechanism with exchange of three electrons. Diffusion coefficient of GdCl{sub 3} ions was determined at various temperatures, at 723 K the value is D = 0.88 10{sup -5} cm{sup 2} s{sup -1}. Apparent standard reduction potential of the redox couple Gd{sup 3+}/Gd has been determined by the open-circuit chronopotentiometry technique at several temperatures. Also the Gibbs free energy of GdCl{sub 3} formation was determined and compared with thermodynamic data for pure compounds in the supercooled state in order to estimate the activity coefficient of Gd{sup 3+} in the molten LiCl-KCl eutectic.

  6. Prediction of Solid-Liquid Equilibrium for KCl in Mixed Water-Ethanol Solutions Using the LIQUAC Model

    Institute of Scientific and Technical Information of China (English)

    LIN Yangzheng; LI Jiding; ZENG Chuyi; CHEN Cuixian

    2005-01-01

    The LIQUAC model is often used to predict vapor-liquid equilibria, osmotic coefficients, and mean ion activity coefficients for electrolyte systems. This paper describes a thermodynamic method to analyze solid-liquid equilibrium for electrolytes in mixed solvents solutions using the LIQUAC model. The KCl solubilities in mixed water-ethanol solutions are predicted with the LIQUAC model and its original interaction parameters. This method is also used to obtain new K+-ethanol interaction parameters in the LIQUAC model from the solubility data. The new interaction parameters accurately predict the vapor-liquid equilibrium data of K+ salts (including KCl, KBr, and KCOOCH3) in mixed water-ethanol solutions. The results illustrate the flexibility of the LIQUAC model which can predict not only vapor-liquid equilibrium but also solid-liquid equilibrium in mixed solvent systems.

  7. Monosodium glutamate, disodium inosinate, disodium guanylate, lysine and taurine improve the sensory quality of fermented cooked sausages with 50% and 75% replacement of NaCl with KCl.

    Science.gov (United States)

    dos Santos, Bibiana Alves; Campagnol, Paulo Cezar Bastianello; Morgano, Marcelo Antônio; Pollonio, Marise Aparecida Rodrigues

    2014-01-01

    Fermented cooked sausages were produced by replacing 50% and 75% of NaCl with KCl and adding monosodium glutamate, disodium inosinate, disodium guanylate, lysine and taurine. The manufacturing process was monitored by pH and water activity measurements. The sodium and potassium contents of the resulting products were measured. The color values (L*, a* and b*), texture profiles and sensory profiles were also examined. Replacing 50% and 75% NaCl with KCl depreciated the sensory quality of the products. The reformulated sausages containing monosodium glutamate combined with lysine, taurine, disodium inosinate and disodium guanylate masked the undesirable sensory attributes associated with the replacement of 50% and 75% NaCl with KCl, allowing the production of fermented cooked sausages with good sensory acceptance and approximately 68% sodium reduction.

  8. Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation.

    Science.gov (United States)

    Rojas-Vega, Lorena; Reyes-Castro, Luis A; Ramírez, Victoria; Bautista-Pérez, Rocío; Rafael, Chloe; Castañeda-Bueno, María; Meade, Patricia; de Los Heros, Paola; Arroyo-Garza, Isidora; Bernard, Valérie; Binart, Nadine; Bobadilla, Norma A; Hadchouel, Juliette; Zambrano, Elena; Gamba, Gerardo

    2015-04-15

    Unique situations in female physiology require volume retention. Accordingly, a dimorphic regulation of the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) has been reported, with a higher activity in females than in males. However, little is known about the hormones and mechanisms involved. Here, we present evidence that estrogens, progesterone, and prolactin stimulate NCC expression and phosphorylation. The sex difference in NCC abundance, however, is species dependent. In rats, NCC phosphorylation is higher in females than in males, while in mice both NCC expression and phosphorylation is higher in females, and this is associated with increased expression and phosphorylation of full-length STE-20 proline-alanine-rich kinase (SPAK). Higher expression/phosphorylation of NCC was corroborated in humans by urinary exosome analysis. Ovariectomy in rats resulted in decreased expression and phosphorylation of the cotransporter and promoted the shift of SPAK isoforms toward the short inhibitory variant SPAK2. Conversely, estradiol or progesterone administration to ovariectomized rats restored NCC phosphorylation levels and shifted SPAK expression and phosphorylation towards the full-length isoform. Estradiol administration to male rats induced a significant increase in NCC phosphorylation. NCC is also modulated by prolactin. Administration of this peptide hormone to male rats induced increased phosphorylation of NCC, an effect that was observed even using the ex vivo kidney perfusion strategy. Our results indicate that estradiol, progesterone, and prolactin, the hormones that are involved in sexual cycle, pregnancy and lactation, upregulate the activity of NCC.

  9. Inhibition of Na(+)-K(+)-2Cl(-) cotransport by mercury.

    Science.gov (United States)

    Jacoby, S C; Gagnon, E; Caron, L; Chang, J; Isenring, P

    1999-10-01

    Mercury alters the function of proteins by reacting with cysteinyl sulfhydryl (SH(-)) groups. The inorganic form (Hg(2+)) is toxic to epithelial tissues and interacts with various transport proteins including the Na(+) pump and Cl(-) channels. In this study, we determined whether the Na(+)-K(+)-Cl(-) cotransporter type 1 (NKCC1), a major ion pathway in secretory tissues, is also affected by mercurial substrates. To characterize the interaction, we measured the effect of Hg(2+) on ion transport by the secretory shark and human cotransporters expressed in HEK-293 cells. Our studies show that Hg(2+) inhibits Na(+)-K(+)-Cl(-) cotransport, with inhibitor constant (K(i)) values of 25 microM for the shark carrier (sNKCC1) and 43 microM for the human carrier. In further studies, we took advantage of species differences in Hg(2+) affinity to identify residues involved in the interaction. An analysis of human-shark chimeras and of an sNKCC1 mutant (Cys-697-->Leu) reveals that transmembrane domain 11 plays an essential role in Hg(2+) binding. We also show that modification of additional SH(-) groups by thiol-reacting compounds brings about inhibition and that the binding sites are not exposed on the extracellular face of the membrane.

  10. Study of thermodynamic properties of Np-Al alloys in molten LiCl-KCl eutectic

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, E.; Soucek, P.; Malmbeck, R.; Glatz, J. P. [Institute for Transuranium Elements, Karlsruhe (Germany); Caravaca, C. [CIEMAT, DE/DFN/URAA, Madrid (Spain)

    2008-08-15

    This work is focused on chemical characterisation and determination of thermodynamic properties of Np-Al alloys. The alloys are formed on a solid Al electrode during Np electrodeposition in molten LiCl-KCl Eutectic. Open circuit potential measurements, after small depositions of Np metal onto the Al electrode were used to determine thermodynamic properties of the Np-Al alloys formed (G, H, S, activity of Np in Al) by an e.m.f. method. Galvanostatic electrolyses were carried out on an Al plates. Stable Np-Al deposit was obtained and identified, by XRD analysis, as a mixture NpAl{sub 3} and NpAl{sub 4} alloys.

  11. High concentrations of KCl release noradrenaline from noradrenergic neurons in the rat anococcygeus muscle

    Directory of Open Access Journals (Sweden)

    C.B.L. Araujo

    2003-01-01

    Full Text Available The aim of the present study was to investigate the effects of high concentrations of KCl in releasing noradrenaline from sympathetic nerves and its actions on postsynaptic alpha-adrenoceptors. We measured the isotonic contractions induced by KCl in the isolated rat anococcygeus muscle under different experimental conditions. The contractile responses induced by KCl were inhibited by alpha-adrenoceptor antagonists in 2.5 mM Ca2+ solution. Prazosin reduced the maximum effect from 100 to 53.9 ± 10.2% (P<0.05 while the pD2 values were not changed. The contractile responses induced by KCl were abolished by prazosin in Ca2+-free solution (P<0.05. Treatment of the rats with reserpine reduced the maximum effect induced by KCl as compared to the contractile responses induced by acetylcholine from 339.5 ± 157.8 to 167.3 ± 65.5% (P<0.05, and increased the pD2 from 1.57 ± 0.01 to 1.65 ± 0.006 (P<0.05, but abolished the inhibitory effect of prazosin (P<0.05. In contrast, L-NAME increased the contractile responses induced by 120 mM KCl by 6.2 ± 2.3% (P<0.05, indicating that KCl could stimulate the neurons that release nitric oxide, an inhibitory component of the contractile response induced by KCl. Our results indicate that high concentrations of KCl induce the release of noradrenaline from noradrenergic neurons, which interacts with alpha1-adrenoceptors in smooth muscle cells, producing a contractile response in 2.5 mM Ca2+ (100% and in Ca2+-free solution, part of which is due to a direct effect of KCl on the rat anococcygeus muscle.

  12. Measurements of the salt-removal of NaCl, KCl and MgCl using a carbon electrode prepared with freezing thawing method in capacitive deionization

    Science.gov (United States)

    Endarko, Sari, Intan Permata; Fatimah, Iim

    2016-04-01

    Carbon electrodes prepared with freezing thawing method for desalination purpose has been synthesized and characterized. The carbon electrodes were prepared with an activated carbon (700 - 1400 m2/g) and polyvinyl alcohol (PVA) as a binder using freezing thawing method with 3 and 4 cycles (1 cycle is 12 hours for freezing and 12 hours for thawing). Electrical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to analyze their electrochemical properties. The main study was to measure the salt-removal of 180 µS/cm NaCl, MgCl and KCl using a capacitive deionization (CDI) unit cell with five pairs of carbon electrodes. The applied potential of 2.0 V and a flow rate of 25 mL/min were used to desalination tests, the result showed that the salt-removal percentage of KCl solution has greater than NaCl and MgCl. The highest value for the salt-removal of NaCl, KCl and MgCl can be achieved for the freezing thawing method with 4 cycles. The salt-removal percentage of KCl was achieved at 64.10% whilst resulted in 54.30 and 54.47 % for NaCl and MgCl, respectively.

  13. Water transport between CNS compartments: contributions of aquaporins and cotransporters

    DEFF Research Database (Denmark)

    MacAulay, N; Zeuthen, T

    2010-01-01

    review we introduce another family of transport proteins as water transporters, namely the cotransporters and the glucose uniport GLUT1. In direct contrast to the aquaporins, these proteins have an inherent ability to transport water against an osmotic gradient. Some of them may also function as water...... or hydrocephalus. The molecular pathways by which water molecules cross the cell membranes of the brain are not well-understood, although the discovery of aquaporin 4 (AQP4) in the brain improved our understanding of some of these transport processes, particularly under pathological conditions. In the present...

  14. Molecular Motions Involved in Na-K-Cl Cotransporter-mediated Ion Transport and Transporter Activation Revealed by Internal Cross-linking between Transmembrane Domains 10 and 11/12*

    Science.gov (United States)

    Monette, Michelle Y.; Somasekharan, Suma; Forbush, Biff

    2014-01-01

    We examined the relationship between transmembrane domain (TM) 10 and TM11/12 in NKCC1, testing homology models based on the structure of AdiC in the same transporter superfamily. We hypothesized that introduced cysteine pairs would be close enough for disulfide formation and would alter transport function: indeed, evidence for cross-link formation with low micromolar concentrations of copper phenanthroline or iodine was found in 3 of 8 initially tested pairs and in 1 of 26 additionally tested pairs. Inhibition of transport was observed with copper phenanthroline and iodine treatment of P676C/A734C and I677C/A734C, consistent with the proximity of these residues and with movement of TM10 during the occlusion step of ion transport. We also found Cu2+ inhibition of the single-cysteine mutant A675C, suggesting that this residue and Met382 of TM3 are involved in a Cu2+-binding site. Surprisingly, cross-linking of P676C/I730C was found to prevent rapid deactivation of the transporter while not affecting the dephosphorylation rate, thus uncoupling the phosphorylation and activation steps. Consistent with this, (a) cross-linking of P676C/I730C was dependent on activation state, and (b) mutants lacking the phosphoregulatory domain could still be activated by cross-linking. These results suggest a model of NKCC activation that involves movement of TM12 relative to TM10, which is likely tied to movement of the large C terminus, a process somehow triggered by phosphorylation of the regulatory domain in the N terminus. PMID:24451383

  15. Extended life-span conferred by cotransporter gene mutations in Drosophila.

    Science.gov (United States)

    Rogina, B; Reenan, R A; Nilsen, S P; Helfand, S L

    2000-12-15

    Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly, Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span.

  16. γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter

    DEFF Research Database (Denmark)

    Dimke, Henrik Anthony; San-Cristobal, Pedro; de Graaf, Mark

    2011-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found...... that γ-adducin interacts with the NCC transporter. γ-Adducin colocalized with NCC to the distal convoluted tubule. (22)Na(+) uptake experiments in the Xenopus laevis oocyte showed that γ-adducin stimulated NCC activity in a dose-dependent manner, an effect that occurred upstream from With No Lysine (WNK......) 4 kinase. The binding site of γ-adducin mapped to the N terminus of NCC and encompassed three previously reported phosphorylation sites. Supporting this site of interaction, competition with the N-terminal domain of NCC abolished the stimulatory effect of γ-adducin on the transporter. γ...

  17. Inflammatory cytokine TNF-α inhibits Na(+)-glutamine cotransport in intestinal epithelial cells.

    Science.gov (United States)

    Talukder, Jamilur R; Boyd, Brittney; Griffin, Ashley; Jaima, Antara; Rajendran, Vazhaikkurichi M

    2013-04-01

    Glutamine (Gln), a preferred fuel source for enterocytes, is critical for intestinal epithelial cell integrity and barrier function. Chronic enteritis inhibits apical Na(+)-Gln cotransport. It is not known whether inflammatory cytokines that are secreted during inflammation inhibit Na(+)-Gln cotransport. Thus, this study aimed to examine whether TNF-α would affect apical Na(+)-Gln cotransport in intestinal epithelial cells. In this study, the presence of Na(+)-Gln cotransport was established by measuring Gln uptake in 10 days postconfluent IEC-6 cells grown on transwell plates. Cation, amino acid specificity, and siRNA transfection studies established that Na(+)-Gln cotransport is mediated via B(0)AT1. Immunoblotting and immunofluorescence studies established the apical membrane localization of B(0)AT1 in IEC-6 cells. Tumour necrosis factor α (TNF-α) inhibited Na(+)-Gln cotransport in a concentration- and time-dependent manner with an inhibitory concentration of 1.53 nmol·L(-1). Quantitative real-time PCR and Western blot analyses indicated that TNF-α did not alter B(0)AT1-specific transcripts or protein expression level. Kinetic studies revealed that TNF-α inhibited Na(+)-Gln cotransport by reducing the affinity of the cotransporters for Gln, and this effect was antagonized by genistein. Thus, we conclude that the TNF-α inhibition of Na(+)-Gln cotransport occurs at the post-translational level, and that the IEC-6 cell line is an excellent system to study the role of cytokines in Na(+)-Gln cotransport.

  18. Optical vibronic spectra of aggregates in Eu sup 2 sup + -doped KCl and KBr crystals

    CERN Document Server

    Pérez, S R; Aceves, R; Rodríguez, R; Barboza, M

    2003-01-01

    The vibronic structure on the optical absorption, emission, and excitation spectra of aggregates in Eu sup 2 sup + -doped KCl and KBr crystals has been obtained. The crystals were annealed at 435 K. During the aggregation process, four groups of narrow bands were found in KCl: Eu sup 2 sup + and two in KBr: Eu sup 2 sup + ,which were considered as the signature of different Eu sup 2 sup + -ion aggregated phases. The vibration frequency for each group is very similar. (Author)

  19. Radiation effects on beta 10.6 of pure and europium doped KCl

    Science.gov (United States)

    Grimes, H. H.; Maisel, J. E.; Hartford, R. H.

    1975-01-01

    Changes in the optical absorption coefficient as a result of X-ray and electron bombardment of pure KCl (monocrystalline and polycrystalline), and divalent europium doped polycrystalline KCl were determined. The optical absorption coefficients were measured by a constant heat flow calorimetric method. Both 300 KV X-irradiation and 2 MeV electron irradiation produced significant increases in beta 10.6, measured at room temperature. The X-irradiation of pure moncrystalline KCl increased beta 10.6 by 0.005/cm for a 113 MR dose. For an equivalent dose, 2 MeV electrons were found less efficient in changing beta 10.6. However, electron irradiation of pure and Eu-doped polycrystalline KCl produced marked increases in adsorption. Beta increased to over 0.25/cm in Eu-doped material for a 30 x 10 to the 14th power electrons/sq cm dose, a factor of 20 increase over unirradiated material. Moreover, bleaching the electron irradiated doped KCl with 649 m light produced and additional factor of 1.5 increase. These findings will be discussed in light of known defect-center properties in KCl.

  20. Influence of partial replacement of NaCl with KCl on profiles of volatile compounds in dry-cured bacon during processing

    Science.gov (United States)

    This study investigated the influence of partial substitution of NaCl with KCl on the formation of volatile compounds in bacons during processing using a purge and trap dynamic headspace GC/MS system. Three substitutions were 0% KCl (I), 40% KCl (II), and 70% KCl (III). The profiles of the volatile ...

  1. Investigation of concentration-dependence of thermodynamic properties of lanthanum, yttrium, scandium and terbium in eutectic LiCl-KCl molten salt

    Science.gov (United States)

    Wang, Yafei; Zhou, Wentao; Zhang, Jinsuo

    2016-09-01

    Thermodynamic properties of rare earth metals in LiCl-KCl molten salt electrolyte are crucial to the development of electrochemical separation for the treatment of used nuclear fuels. In the present study, activity coefficient, apparent potential, and diffusion coefficient of lanthanum, yttrium, scandium, and terbium in the molten salt (58 at% LiCl and 42 at% KCl) were calculated by the method of molecular dynamics simulation up to a concentration around 3 at% at temperatures of 723 K and 773 K. It was found that the activity coefficient and the apparent potential increase with the species concentration while diffusion coefficient shows a trend of increase followed by decrease. The calculated results were validated by available measurement data of dilution cases. This research extends the range of data to a wide component and would provide further insight to the pyroprocessing design and safeguards.

  2. Potassium-chloride cotransporter 3 interacts with Vav2 to synchronize the cell volume decrease response with cell protrusion dynamics.

    Directory of Open Access Journals (Sweden)

    Adèle Salin-Cantegrel

    Full Text Available Loss-of-function of the potassium-chloride cotransporter 3 (KCC3 causes hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC, a severe neurodegenerative disease associated with defective midline crossing of commissural axons in the brain. Conversely, KCC3 over-expression in breast, ovarian and cervical cancer is associated with enhanced tumor cell malignancy and invasiveness. We identified a highly conserved proline-rich sequence within the C-terminus of the cotransporter which when mutated leads to loss of the KCC3-dependent regulatory volume decrease (RVD response in Xenopus Laevis oocytes. Using SH3 domain arrays, we found that this poly-proline motif is a binding site for SH3-domain containing proteins in vitro. This approach identified the guanine nucleotide exchange factor (GEF Vav2 as a candidate partner for KCC3. KCC3/Vav2 physical interaction was confirmed using GST-pull down assays and immuno-based experiments. In cultured cervical cancer cells, KCC3 co-localized with the active form of Vav2 in swelling-induced actin-rich protruding sites and within lamellipodia of spreading and migrating cells. These data provide evidence of a molecular and functional link between the potassium-chloride co-transporters and the Rho GTPase-dependent actin remodeling machinery in RVD, cell spreading and cell protrusion dynamics, thus providing new insights into KCC3's involvement in cancer cell malignancy and in corpus callosum agenesis in HMSN/ACC.

  3. Analgesic effect of intrathecal bumetanide is accompanied by changes in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain

    Institute of Scientific and Technical Information of China (English)

    Yanbing He; Shiyuan Xu; Junjie Huang; Qingjuan Gong

    2014-01-01

    Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.

  4. Structural and functional significance of water permeation through cotransporters

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Gorraitz, Edurne; Her, Ka

    2016-01-01

    and mutated residues lining the sugar transport pathway to cysteine. The mutants were expressed in Xenopus oocytes, and the unitary water and urea permeabilities were determined before and after modifying the cysteine side chain with reversible methanethiosulfonate reagents. The results demonstrate that water......Membrane transporters, in addition to their major role as specific carriers for ions and small molecules, can also behave as water channels. However, neither the location of the water pathway in the protein nor their functional importance is known. Here, we map the pathway for water and urea...... through the intestinal sodium/glucose cotransporter SGLT1. Molecular dynamics simulations using the atomic structure of the bacterial transporter vSGLT suggest that water permeates the same path as Na+ and sugar. On a structural model of SGLT1, based on the homology structure of vSGLT, we identified...

  5. The Electrogenic Na+/HCO3- Cotransporter, NBC

    Directory of Open Access Journals (Sweden)

    Romero MF

    2001-07-01

    Full Text Available Electrogenic Na(+/HCO(3(- (NBC function has been characterized in many mammalian tissues including, kidney, pancreas, and brain. Cloning efforts identified a single cDNA, NBC/NBC1, that possesses all the functional attributes of the electrogenic Na(+/HCO(3(- cotransporter. This NBC clone is related to the anion exchangers and thus forms a bicarbonate transporter superfamily. Presently two N-terminal and one C-terminal isoforms are known. All three isoforms appear to arise from the same gene and seem to have identical function. NBC antibodies have localized NBC isoforms in kidney, pancreas, brain, small intestine, colon, epididymis, eye, heart, liver, salivary glands, stomach, and testis. Functionally, NBC appears HCO(3(- and Na(+ selective. NBC stoichiometry in Xenopus oocytes is 1 Na(+ : 2 HCO(3(-, implicating a possible accessory protein interaction.

  6. Iridoid and aromatic glycosides from Scrophularia ningpoensis Hemsl. and their inhibition of [Ca2+](i) increase induced by KCl.

    Science.gov (United States)

    Chen, Bin; Liu, Yan; Liu, Hong-Wei; Wang, Nai-Li; Yang, Bao-Feng; Yao, Xin-Sheng

    2008-09-01

    Bioassay-guided fractionation of EtOH extract of the roots of Scrophularia ningpoensis Hemsl. resulted in the isolation of three new iridoid glycosides, i.e., 6''-O-caffeoylharpagide (1), 6''-O-feruloylharpagide (2), and 6''-O-beta-glucopyranosylharpagoside (3), and five new aromatic glycosides, i.e., 2-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-arabinopyranosyl-(1-->6)-O-alpha-rhamnopyranosyl-(1-->3)-O-beta-glucopyranoside (4), phenyl O-beta-xylopyranosyl-(1-->6)-O-beta-glucopyranoside (5), 3-methylphenyl O-beta-xylopyranosyl-(1-->6)-O-beta-glucopyranoside (6), 6-O-cinnamoyl beta-fructofuranosyl-(2-->1)-O-alpha-glucopyranosyl-(6-->1)-O-alpha-glucopyranoside (7), and 6-O-feruloyl beta-fructofuranosyl-(2-->1)-O-alpha-glucopyranosyl-(6-->1)-O-alpha-glucopyranoside (8), together with four known compounds, i.e., 6''-O-alpha-D-galactopyranosyl harpagoside (9), 6''-O-(p-coumaroyl) harpagide (10), harpagoside (11), and angoroside C (12). Activity of the isolated compounds on [Ca2+](i) increase induced by KCl was evaluated on rat cardiac myocytes using confocal laser scanning microscopy. Iridoid glycosides 1, 10, and 11, and aromatic glycosides 5 and 6 significantly inhibited the increase of [Ca2+](i) induced by KCl at 100 microM.

  7. Electrodeposition of Mg-Li-Al-La Alloys on Inert Cathode in Molten LiCl-KCl Eutectic Salt

    Science.gov (United States)

    Han, Wei; Chen, Qiong; Sun, Yi; Jiang, Tao; Zhang, Milin

    2011-12-01

    Electrochemical preparation of Mg-Li-Al-La alloys on inert electrodes was investigated in LiCl-KCl melt at 853 K (580 °C). Cyclic voltammograms (CVs) and square wave voltammograms (SWVs) show that the existence of AlCl3 or AlF3 could promote La deposition on an active Al substrate, which is predeposited on inert electrodes. All electrochemical tests show that the reduction of La3+ is a one-step reduction process with three electrons exchanged. The reduction of La(III)→La(0) occurred at -2.04 V, and the underpotential deposition (UPD) of La was detected at -1.55 V ( vs Ag/AgCl). The same phenomena concerning La UPD were observed on two inert cathodes, W and Mo. In addition, Mg-Li-Al-La alloys were obtained by galvanostatic electrolysis on the W cathode from La2O3 in LiCl-KCl-MgCl2-KF melts with aluminum as the anode. X-ray diffraction (XRD) measurements indicated that various phases like the Al2La, Al12Mg17, and βLi phase (LiMg/Li3Mg7) existed in the Mg-Li-Al-La alloys. The distribution of Mg, Al, and La in Mg-Li-Al-La alloys from the analysis of a scan electron micrograph (SEM) and energy dispersive spectrometry (EDS) indicated that the elements Mg, Al, and La distributed homogeneously in the alloys.

  8. Electrochemical formation of holmium-copper alloys on copper cathode in molten KCl-HoCl3

    Institute of Scientific and Technical Information of China (English)

    SU Yu-zhi; YANG Qi-qin; LIU Guan-kun

    2006-01-01

    Cyclic voltammetry, open circuit potential-time curve after potentiostatic electrolysis and potential step chronoamperometry were used to investigate the electrochemical formation processes of holmium-copper alloys on copper cathode in molten HoCl3-KCl. Intermetallic compounds HoCu5, HoCu4, HoCu2 and HoCu are formed in sequence and then the metallic Ho is deposited when Ho3+ is reduced on copper electrode in molten KCl-HoCl3 at 1 066 K. The first charge-transfer reaction is reversible. The structure of holmium-copper alloy film deposited on copper electrode by potentiostatic electrolysis was characterized by X-ray diffraction. The standard free energies of formation for the intermetallic compounds HoCu5, HoCu4, HoCu2 and HoCu are -95.5, -92.6, -73.8 and -44.0 kJ/mol, respectively. The diffusion coefficient and diffusion activation energy of Ho atom in the alloy are estimated to be 10-10-10-11 cm2/s and 75.35 kJ/mol, respectively, from the chronoamperometry data.

  9. The effect of NaCl substitution by KCl on telemea cheese properties

    Directory of Open Access Journals (Sweden)

    Mihai ANGHELOIU

    2016-12-01

    Full Text Available The effect of partial or total substitution of sodium chloride by potassium chloride on the chemical composition, texture profile and sensory properties of Telemea cheese during 28 days of ripening at 4°C was evaluated in the current study. Telemea cheese was ripened in 4 different brine solutions (20%, wt/wt made from different NaCl:KCl ratios as follows: (NaCl (A, KCl (B, 1NaCl:1KCl (C and 1NaCl:2KCl (D. The physicochemical properties of Telemea cheese (dry matter, fat, protein, ash, pH, total nitrogen (TN, water soluble nitrogen (WSN and ripening degree values were determined after 1, 7, 14, 21 and 28 days of ripening. Dry matter, pH and ripening degree values were significantly (p < 0.05 affected during ripening. The results of this study indicated that replacing 66% NaCl with KCl influenced the texture profile and sensorial characteristics of Telemea cheese.

  10. Potentiometric determination of the thermodynamic properties for the ternary system (KCl + KNO{sub 3} + H{sub 2}O) at T = 298.15 K

    Energy Technology Data Exchange (ETDEWEB)

    Ghalami-Choobar, Bahram, E-mail: B-Ghalami@guilan.ac.i [Department of Chemistry, Faculty of Science, University of Guilan, P.O. Box 19141, Rasht (Iran, Islamic Republic of); Moghimi, Majid; Mahmoodi, Nosratollah; Mohammadian, Mohsen [Department of Chemistry, Faculty of Science, University of Guilan, P.O. Box 19141, Rasht (Iran, Islamic Republic of)

    2010-04-15

    In this work, the potentiometric measurements were performed for the ternary (KCl + KNO{sub 3} + H{sub 2}O) systems on the galvanic cell of the type: Ag|AgCl|KCl (m{sub 1}), KNO{sub 3} (m{sub 2}), H{sub 2}O|K-ISE over total ionic strengths from (0.001 to 3.000) mol . kg{sup -1} for different series of salt molal ratios r (r = m{sub 1}/m{sub 2} = 0.20, 1.0, 5.0, 10.0, and 20.0). The electrodes used in this work were prepared in our laboratory and had a reasonably good Nernst response. The activity coefficients data were interpreted by using Pitzer model. The unknown Pitzer mixing interaction parameters have been evaluated for the system under investigation (theta{sub Cl,NO{sub 3}}=0.0186, psi{sub KClNO{sub 3}}=-0.0066). Then, the parameters obtained were used to calculate the values of the mean activity coefficients of KNO{sub 3}, the osmotic coefficients, the solvent activity, the surface tension, and the excess Gibbs free energies for the whole series of the studied mixed electrolyte systems.

  11. Water transport by the Na+/glucose cotransporter under isotonic conditions

    DEFF Research Database (Denmark)

    Zeuthen, T; Meinild, A K; Klaerke, D A;

    1997-01-01

    Solute cotransport in the Na+/glucose cotransporter is directly coupled to significant water fluxes. The water fluxes are energized by the downhill fluxes of the other substrates by a mechanism within the protein itself. In the present paper we investigate the Na+/glucose cotransporter expressed...... in Xenopus oocytes. We present a method which allows short-term exposures to sugar under voltage clamp conditions. We demonstrate that water is cotransported with the solutes despite no osmotic differences between the external and intracellular solutions. There is a fixed ratio of 195:1 between the number...... of water molecules and the number of Na+ ions transported, equivalent to 390 water molecules per glucose molecule. Unstirred layer effects are ruled out on the basis of experiments on native oocytes incubated with the ionophores gramicidin D or nystatin....

  12. Water permeability of Na+-K+-2C1- cotransporters in mammalian epithelial cells

    DEFF Research Database (Denmark)

    Hammann, Steffen; Herrera-Perez, J.J.; Bundgaard, Magnus

    2005-01-01

    Water transport properties of the Na+-K+-2Cl- cotransporter (NKCC) were studied in cultures of pigmented epithelial cells (PE) from the ciliary body of the eye. Here, the membrane that faces upwards contains NKCCs and can be subjected to rapid changes in bathing solution composition and osmolarity...... changes of the cotransporter and interaction with Na+, K+ and Cl-. Similar measurements were performed on immortalized cell cultures from the thick ascending limb of the loop of Henle (TALH). Given similar overall transport rates of bumetanide-sensitive 86Rb+, the NKCCs of this tissue did not contribute...... any bumetanide-sensitive Lp. This suggests that the cotransporters of the two tissues are either different isoforms or the same cotransporter but in two different transport modes....

  13. The Thiazide-Sensitive Co-Transporter Promotes the Development of Sodium Retention in Mice with Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Matthew R P Davies

    2015-09-01

    Full Text Available Background/Aims: Intravascular volume expansion due to sodium retention is involved in the pathogenesis of obesity-related hypertension. Institution of high fat diet (HFD feeding leads to an initial state of positive sodium balance due to enhanced tubular reabsorption of sodium, but which tubular sodium transporters are responsible for this remains undefined. Methods: C57/Bl6 mice were fed control or HFD for 3 weeks. Blood pressures were recorded by tail cuff method. Sodium transporter expression and phosphorylation were determined by Western blotting. In vivo activity of NCC was determined using natriuretic responses to hydrochlorothiazide. Expression of NCC mRNA was determined using qPCR. Results: At 3 weeks HFD mice had significant weight gains compared to control mice, but blood pressures were not yet elevated. There were no changes in expression or phosphorylation of the bumetanide-sensitive cotransporter, NKCC2, or in expression of subunits of the amiloride-sensitive ion channel, ENaC. However, there were significant increases in mRNA and protein expression of the thiazide-sensitive co-transporter, NCC, in kidneys from HFD mice. Consistent with this, HFD mice had increased in vivo activity of NCC. Conclusions: Increased expression of NCC promotes the sodium loading response to institution of HFD feeding before onset of hypertension.

  14. Cotransport of water by the Na+-K+-2Cl(-) cotransporter NKCC1 in mammalian epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Herrera-Perez, José J; Zeuthen, Thomas

    2010-01-01

    ionic and osmotic gradients. The coupling between salt and water transport in NKCC1 represents a novel aspect of cellular water homeostasis where cells can change their volume independently of the direction of an osmotic gradient across the membrane. This has relevance for both epithelial......Water transport by the Na+-K+-2Cl(-) cotransporter (NKCC1) was studied in confluent cultures of pigmented epithelial (PE) cells from the ciliary body of the fetal human eye. Interdependence among water, Na+ and Cl(-) fluxes mediated by NKCC1 was inferred from changes in cell water volume, monitored...... of external Na+ and Cl(-). The water influx could proceed uphill, against a transmembrane osmotic gradient, suggesting that energy contained in the ion fluxes can be transferred to the water flux. The influx of water induced by changes in external [Cl(-)] saturated in a sigmoidal fashion with a Km of 60 mm...

  15. Kinetics of the B1-B2 phase transition in KCl under rapid compression

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chuanlong; Smith, Jesse S.; Sinogeikin, Stanislav V.; Park, Changyong; Kono, Yoshio; Kenney-Benson, Curtis; Rod, Eric; Shen, Guoyin, E-mail: gshen@ciw.edu [HPCAT, Geophysical Laboratory, Carnegie Institution of Washington, Argonne, Illinois 60439 (United States)

    2016-01-28

    Kinetics of the B1-B2 phase transition in KCl has been investigated under various compression rates (0.03–13.5 GPa/s) in a dynamic diamond anvil cell using time-resolved x-ray diffraction and fast imaging. Our experimental data show that the volume fraction across the transition generally gives sigmoidal curves as a function of pressure during rapid compression. Based upon classical nucleation and growth theories (Johnson-Mehl-Avrami-Kolmogorov theories), we propose a model that is applicable for studying kinetics for the compression rates studied. The fit of the experimental volume fraction as a function of pressure provides information on effective activation energy and average activation volume at a given compression rate. The resulting parameters are successfully used for interpreting several experimental observables that are compression-rate dependent, such as the transition time, grain size, and over-pressurization. The effective activation energy (Q{sub eff}) is found to decrease linearly with the logarithm of compression rate. When Q{sub eff} is applied to the Arrhenius equation, this relationship can be used to interpret the experimentally observed linear relationship between the logarithm of the transition time and logarithm of the compression rates. The decrease of Q{sub eff} with increasing compression rate results in the decrease of the nucleation rate, which is qualitatively in agreement with the observed change of the grain size with compression rate. The observed over-pressurization is also well explained by the model when an exponential relationship between the average activation volume and the compression rate is assumed.

  16. Cotransport of H+, lactate, and H2O in porcine retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Kiilgaard, Jens Folke; la Cour, Morten

    2003-01-01

    ) for the H(+) and lactate fluxes. The data suggest that H(2)O is cotransported along with H(+) and lactate ions in MCT1 localized to the retinal membrane. The study emphasizes the importance of this cotransporter in the maintenance of water homeostasis and pH in the subretinal space of a mammalian tissue...... and supports our previous study performed by an invasive technique in an amphibian tissue....

  17. KCl-induced high temperature corrosion of selected commercial alloys. Part I: chromia-formers

    DEFF Research Database (Denmark)

    Kiamehr, Saeed; Dahl, Kristian Vinter; Montgomery, Melanie

    2015-01-01

    Laboratory testing of selected chromia-forming alloys was performed to rank the materials and gain further knowledge on the mechanism of KCl-induced high temperature corrosion. The investigated alloys were stainless steels EN1.4021, EN1.4057, EN1.4521, TP347H (coarse-grained), TP347HFG (fine...... with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray diffractometry (XRD). It was observed that in the salt-free exposure, stainless steels TP347H (coarse-grained) and EN1.4521 failed to form a thin protective oxide layer compared to the oxide formed on the other alloys...... with KCl vapor in static air for the same duration and at the same temperature. This was undertaken to investigate the role of the vapor phase and revealed that KCl vapor at 600 °C can initiate attack....

  18. Integrated Data Collection Analysis (IDCA) Program - KClO4/Aluminum Mixture

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC IHD), Indian Head, MD (United States). Indian Head Division; Sorensen, Daniel N. [Naval Surface Warfare Center (NSWC IHD), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC IHD), Indian Head, MD (United States). Indian Head Division; Whinnery, LeRoy L. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Shelley, Timothy J. [Air Force Research Lab. (AFRL), Tyndall AFB, FL (United States); Reyes, Jose A. [Applied Research Associates (ARA), Tyndall AFB, FL (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2012-01-17

    The Integrated Data Collection Analysis (IDCA) program is conducting a Proficiency Test for Small-Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of a mixture of KClO4 and aluminum—KClO4/Al mixture. This material was selected because of the challenge of performing SSST testing of a mixture of two solids. The mixture was found to be: 1) much less sensitive to impact than RDX, (LLNL being the exception) and PETN, 2) more sensitive to friction than RDX and PETN, and 3) extremely sensitive to spark. The thermal analysis showed little or no exothermic character. One prominent endothermic feature was observed in the temperature range studied and identified as a phase transition of KClO4.

  19. Electrode process of La(Ⅲ) in molten LiCl-KCl

    Institute of Scientific and Technical Information of China (English)

    高繁星; 王长水; 刘利生; 郭建华; 常尚文; 常利; 李瑞雪; 欧阳应根

    2009-01-01

    The electrode process of La(Ⅲ) at Mo electrode in the molten LiCl-KCl for temperatures ranging from 683 K to 773 K was studied by cyclic voltammetry and chronopotentiometry,respectively.The results showed that in the molten LiCl-KCl,reduction of La(Ⅲ) occurred in a step with a global exchange of three electrons.Cyclic voltammetry studies indicated that at a sweep rate lower than 0.2 V/s,the electroreduction of La(Ⅲ) to lanthanum metal was reversible and controlled by diffusion of La(Ⅲ).However,the process b...

  20. ARTICLES: Parametric spectroscopy of the kinetics of luminescence from color centers in KCl and KBr crystals

    Science.gov (United States)

    Antonov, V. A.; Strizhevskiĭ, V. L.; Shukirov, Zh; Yashkir, Yu N.

    1982-12-01

    An investigation was made of the kinetics of infrared luminescence from color centers in KCl and KBr crystals using temporal parametric spectroscopy. It was shown that the infrared luminescence spectrum of color centers excited by YAG laser radiation consists of two bands with significantly different lifetimes. Parametric spectroscopy was used to resolve and identify these bands as transitions of the RF →RK and RN →0 types. Investigations were made of optimal Q switching of a laser resonator using a KCl crystal.

  1. Parametric spectroscopy of the kinetics of luminescence from color centers in KCl and KBr crystals

    Energy Technology Data Exchange (ETDEWEB)

    Antonov, V.A.; Strizhevskii, V.L.; Shukirov, Z.; Yashkir, Y.N.

    1982-12-01

    An investigation was made of the kinetics of infrared luminescence from color centers in KCl and KBr crystals using temporal parametric spectroscopy. It was shown that the infrared luminescence spectrum of color centers excited by YAG laser radiation consists of two bands with significantly different lifetimes. Parametric spectroscopy was used to resolve and identify these bands as transitions of the R/sub F/..-->..R/sub N/ and R/sub N/ ..-->..0 types. Investigations were made of optimal Q switching of a laser resonator using a KCl crystal.

  2. Life at high salt concentrations, intracellular KCl concentrations, and acidic proteomes

    Directory of Open Access Journals (Sweden)

    Aharon eOren

    2013-11-01

    Full Text Available Extremely halophilic microorganisms that accumulate KCl for osmotic balance (the Halobacteriaceae, Salinibacter have a large excess of acidic amino acids in their proteins. This minireview explores the occurrence of acidic proteomes in halophiles of different physiology and phylogenetic affiliation. For fermentative bacteria of the order Halanaerobiales, known to accumulate KCl, an acidic proteome was predicted. However, this is not confirmed by genome analysis. The reported excess of acidic amino acids is due to a high content of Gln and Asn, which yield Glu and Asp upon acid hydrolysis. The closely related Halorhodospira halophila and Halorhodospira halochloris use different strategies to cope with high salt. The first has an acidic proteome and accumulates high KCl concentrations at high salt concentrations; the second does not accumulate KCl and lacks an acidic proteome. Acidic proteomes can be predicted from the genomes of some moderately halophilic aerobes that accumulate organic osmotic solutes (Halomonas elongata, Chromohalobacter salexigens and some marine bacteria. Based on the information on cultured species it is possible to understand the pI profiles predicted from metagenomic data from hypersaline environments.

  3. Release and transformation of chlorine and potassium during pyrolysis of KCl doped biomass

    DEFF Research Database (Denmark)

    Wang, Yang; Wu, Hao; Sárossy, Zsuzsa

    2017-01-01

    The formation of CH3Cl and the transformation of chlorine and potassium during pyrolysis of biomass were investigated. Model biomass compounds (cellulose, xylan, lignin and pectin) and pine wood doped with KCl were pyrolysed in a TGA at different heating rates (10–1000 °C/min), temperatures (300...

  4. Differential expression patterns of chloride transporters, Na+-K+-2Cl--cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of cortical development.

    NARCIS (Netherlands)

    Aronica, E.; Boer, K.; Redeker, S.; Spliet, W.G.; van Rijen, P.C.; Troost, D; Gorter, J.A.

    2007-01-01

    Malformations of cortical development are recognized causes of chronic medically intractable epilepsy. An increasing number of observations suggests an important role for cation-chloride co-transporters (CCTs) in controlling neuronal function. Deregulation of their expression may contribute to the

  5. Sodium-glucose co-transporter-2 inhibitors and euglycemic ketoacidosis: Wisdom of hindsight

    Directory of Open Access Journals (Sweden)

    Awadhesh Kumar Singh

    2015-01-01

    Full Text Available Sodium-glucose co-transporter-2 inhibitors (SGLT-2i are newly approved class of oral anti-diabetic drugs, in the treatment of type 2 diabetes, which reduces blood glucose through glucouresis via the kidney, independent, and irrespective of available pancreatic beta-cells. Studies conducted across their clinical development program found, a modest reduction in glycated hemoglobin ranging from −0.5 to −0.8%, without any significant hypoglycemia. Moreover, head-to-head studies versus active comparators yielded comparable efficacy. Interestingly, weight and blood pressure reduction were additionally observed, which was not only consistent but significantly superior to active comparators, including metformin, sulfonylureas, and dipeptydylpeptide-4 inhibitors. Indeed, these additional properties makes this class a promising oral anti-diabetic drug. Surprisingly, a potentially fatal unwanted side effect of diabetic ketoacidosis has been noted with its widespread use, albeit rarely. Nevertheless, this has created a passé among the clinicians. This review is an attempt to pool those ketosis data emerging with SGLT-2i, and put a perspective on its implicated mechanism.

  6. Protein kinase C induces endocytosis of the sodium taurocholate cotransporting polypeptide.

    Science.gov (United States)

    Stross, Claudia; Helmer, Angelika; Weissenberger, Katrin; Görg, Boris; Keitel, Verena; Häussinger, Dieter; Kubitz, Ralf

    2010-08-01

    Bile salts influence signaling and metabolic pathways. In hepatocytes, the sodium taurocholate cotransporting polypeptide (Ntcp) is a major determinant of intracellular bile salt levels. Short-term downregulation of Ntcp is not well characterized to date. FLAG and enhanced green fluorescent protein (EGFP) tags were cloned to the extra- and intracellular termini of Ntcp. Endocytosis of Ntcp in transfected HepG2 cells was visualized by fluorescence of EGFP, and membrane surface expression of Ntcp was quantified by flow cytometry with fluorochrome-labeled FLAG antibodies. Activation of protein kinase C (PKC) by phorbolester or thymeleatoxin an activator of Ca(2+)-dependent conventional PKCs (cPKCs), induced endocytosis of Ntcp, whereas the Na(+)-K(+)-ATPase remained in the plasma membrane. The PKC inhibitor BIM I and the cPKC-selective inhibitor Gö6976 abolished PMA-induced endocytosis. Because of this internalization, cell surface expression of Ntcp was reduced by 36 +/- 7%, bile salt uptake was decreased by 25%, and taurolithocholate sulfate-induced cell toxicity was prevented. In conclusion, Ca(2+)-dependent PKCs induce vesicular retrieval of Ntcp, thereby reducing bile salt uptake. This mechanism may protect hepatocytes from toxic intracellular bile salt concentrations.

  7. [Canagliflozin (Invokana): kidney SGLT2 cotransporter inhibitor for treating type 2 diabetes].

    Science.gov (United States)

    Scheen, A J

    2014-12-01

    Canagliflozin is an inhibitor of sodium-glucose cotransporters type 2 (SGLT2) that are present in renal tubules. This specific insulin-independent mechanism promotes glucosuria, which results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA(1c)). Furthermore, canagliflozin promotes weight loss and lowers arterial (mainly systolic) blood pressure. Its efficacy is decreased in patients with renal insufficiency and the treatment should be stopped if estimated glomerular filtration rate is below 45 ml/min/1.73 m2. Both the efficacy and safety of canagliflozin have been investigated in 24 to 104-week controlled trials versus placebo or versus an active comparator (glimepiride or sitagliptin). The mean reduction in HbA(1c) averages 0.75% when added to other treatments, as compared to placebo. The 100 mg dose is as active as sitagliptin 100 mg while the 300 mg canagliflozin dose is even more efficacious. Adverse events are mostly mycotic genital infections and more rarely mild urinary tract infections. Caution is required in elderly patients and the risk of volume depletion should be checked (hypotension). Hypoglycaemia may occur only in patients already treated with an insulin-secreting agent or insulin. Canagliflozin is commercialized under the trade name Invokana, at the doses of 100 mg and 300 mg once daily, for the treatment of type 2 diabetes.

  8. Sodium-glucose co-transporter-2 inhibitors and euglycemic ketoacidosis: Wisdom of hindsight

    Science.gov (United States)

    Singh, Awadhesh Kumar

    2015-01-01

    Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are newly approved class of oral anti-diabetic drugs, in the treatment of type 2 diabetes, which reduces blood glucose through glucouresis via the kidney, independent, and irrespective of available pancreatic beta-cells. Studies conducted across their clinical development program found, a modest reduction in glycated hemoglobin ranging from −0.5 to −0.8%, without any significant hypoglycemia. Moreover, head-to-head studies versus active comparators yielded comparable efficacy. Interestingly, weight and blood pressure reduction were additionally observed, which was not only consistent but significantly superior to active comparators, including metformin, sulfonylureas, and dipeptydylpeptide-4 inhibitors. Indeed, these additional properties makes this class a promising oral anti-diabetic drug. Surprisingly, a potentially fatal unwanted side effect of diabetic ketoacidosis has been noted with its widespread use, albeit rarely. Nevertheless, this has created a passé among the clinicians. This review is an attempt to pool those ketosis data emerging with SGLT-2i, and put a perspective on its implicated mechanism. PMID:26693421

  9. Protonation and Solvation Thermodynamics of Some Naphthol Derivatives in KCl Aqueous Solution of Different Ionic Strengths

    Directory of Open Access Journals (Sweden)

    Farid I. El-Dossoki

    2016-01-01

    Full Text Available The acid-base properties of naphthalen-1-ol (L1, naphthalene-1,5-diol (L2, and 4-amino-3-hydroxynaphthalene-1-sulphonic acid (L3 were characterized from pH-metric measurements in pure water and in different concentrations (0–4 mol kg−1 of aqueous KCl solutions at the temperature range of T = (293.15 to 213.15 K at 5 K intervals. The results reveal that naphthalen-1-ol and naphthalene-1,5-diol molecules have two ionisable protons (of the hydroxyl groups while 4-amino-3-hydroxynaphthalene-1-sulphonic acid has three ionisable protons (hydrogen ion of the hydroxyl group, SO3H, and NH3+. Modeling of the data was done by applying Debye-Hückel model. The protonation and the solvation processes of all studied ligands are spontaneous and endothermic processes. Also the solubilities of naphthalen-1-ol, naphthalene-1,5-diol, and 4-amino-3-hydroxynaphthalene-1-sulphonic acid were determined. The data were analyzed using Setschenow equation and the values of Setschenow coefficients (km were determined. From the solubility data, the activity coefficients were obtained. The values of the total solubilities (ST for naphthalen-1-ol and naphthalene-1,5-diol were found equal to the values of their neutral species (S0. On the other hand, the total solubility for 4-amino-3-hydroxynaphthalene-1-sulphonic acid is different from that of its neutral species. The results also indicate solubility decrease in pure water from L1-L2-L3.

  10. Microphysics of KCl and ZnS Clouds on GJ 1214 b

    Science.gov (United States)

    Gao, Peter; Benneke, Björn

    2016-10-01

    Clouds are ubiquitous in the atmospheres of exoplanets. However, as most of these planets have temperatures between 600 and 2000 K, their clouds are likely composed of exotic condensates such as salts, sulfides, silicates, and metals. Treatment of these clouds in current exoplanet atmosphere models do not consider the microphysical processes that govern their formation, evolution, and distribution, such as nucleation and condensation/evaporation, thus creating a gulf between the cloud properties retrieved from observations and the cloud composition predictions from condensation equilibrium models. In this work, we apply a 1D microphysical cloud model to GJ 1214 b and investigate the properties of potassium chloride (KCl) and zinc sulfide (ZnS) clouds as a function of atmospheric metallicity, the intensity of vertical mixing, and the mode of nucleation. Our cloud model has been widely applied to planets in our own Solar System, and as such our work bridges a gap between planetary science and exoplanets. Using model background atmospheres calculated by the SCARLET code, we find that (1) the cloud distribution is not significantly affected by metallicity unless [Fe/H] > 2, (2) higher intensities of vertical mixing leads to more extended cloud decks, more cloud particles at all altitudes, and smaller mean particle radii, (3) the high surface energy of solid ZnS prevents the homogeneous nucleation of pure ZnS cloud particles, such that KCl clouds dominate; solid ZnS can only manifest by nucleating onto pre-existing surfaces (heterogeneous nucleation), such as KCl cloud particles, resulting in mixed clouds, and (4) formation of KCl clouds results in a KCl vapor abundance above the cloud deck ~5 orders of magnitude less than that calculated from equilibrium chemistry. We also examine the transmission spectra that would result from these different cases. Extension of this model to other planets and condensates will shed light on the observed continuum in the "cloudiness

  11. A novel strategy for the treatment of diabetes mellitus - sodium glucose co-transport inhibitors.

    Science.gov (United States)

    Niazi, Asfandyar Khan; Niazi, Saad Hameed

    2010-12-01

    Diabetes is one of the most common chronic diseases, affecting almost 3 million in Canada alone and is characterized by increased blood glucose levels. Treatment varies from lifestyle changes to oral anti-diabetics and/or insulin. Sodium glucose co-transport inhibitors may offer promising treatment for patients suffering from diabetes. The inhibitors act by increasing the loss of glucose in urine by decreasing the reabsorption of glucose from the proximal tubules of nephrons. The aim of this review was to assess the efficacy of sodium glucose co-transport inhibitors in the treatment of diabetes as well as any adverse effects. Databases such as MEDLINE, COCHRANE and EMBASE were systematically searched for literature on the efficacy of sodium glucose co-transport inhibitors in improving the glycemic control of patients with diabetes. Research showed that sodium glucose co-transport inhibitors significantly decreased blood glucose levels by increasing glucosuria. Due to the diuretic effects of these inhibitors, diabetic patients who were suffering from hypertension showed a decrease in blood pressure. The caloric loss associated with these inhibitors resulted in weight loss as well. The most common adverse effect seen in patients on these medications was mycotic infection of the urinary or genital tract. Sodium glucose co-transport inhibitors may be an effective line of treatment for diabetes. Although short-term research has shown these drugs to be safe and well-tolerated, studies should be conducted to assess the long-term effects of these drugs.

  12. Drosophila glia use a conserved cotransporter mechanism to regulate extracellular volume.

    Science.gov (United States)

    Leiserson, William M; Forbush, Biff; Keshishian, Haig

    2011-02-01

    The nervous system is protected by blood barriers that use multiple systems to control extracellular solute composition, osmotic pressure, and fluid volume. In the human nervous system, misregulation of the extracellular volume poses serious health threats. Here, we show that the glial cells that form the Drosophila blood-nerve barrier have a conserved molecular mechanism that regulates extracellular volume: the Serine/Threonine kinase Fray, which we previously showed is an ortholog of mammalian PASK/SPAK; and the Na-K-Cl cotransporter Ncc69, which we show is an ortholog of human NKCC1. In mammals, PASK/SPAK binds to NKCC1 and regulates its activity. In Drosophila, larvae mutant for Ncc69 develop a peripheral neuropathy, where fluid accumulates between glia and axons. The accumulation of fluid has no detectable impact on action potential conduction, suggesting that the role of Ncc69 is to maintain volume or osmotic homeostasis. Drosophila Ncc69 has kinetics similar to human NKCC1, and NKCC1 can rescue Ncc69, suggesting that they function in a conserved physiological mechanism. We show that fray and Ncc69 are coexpressed in nerve glia, interact in a yeast-two-hybrid assay, and have an essentially identical bulging nerve phenotype. We propose that normally functioning nerves generate extracellular solutes that are removed by Ncc69 under the control of Fray. This mechanism may perform a similar role in humans, given that NKCC1 is expressed at the blood-brain barrier.

  13. NaCl-KCl-IrCl3熔盐体系中电沉积Ir层的机理%Electrodeposition of Ir on platinum in NaCl-KCl molten salt

    Institute of Scientific and Technical Information of China (English)

    钱建刚; 赵天

    2012-01-01

    在NaCl-KCl-IrCl3熔盐体系中利用循环伏安法和计时电位法研究Ir的沉积机理并通过恒电位法在Pt基体上制备出Ir层.利用扫描电子、显微镜(SEM)能谱仪(EDS)和X射线衍射仪(XRD)对Ir层的表面形貌和成分进行分析.结果表明:在NaCl-KCl-IrCl3熔盐体系中Ir的电沉积过程为Ir3+获得3个电子一步沉积为Ir,并且Ir(Ⅲ)→Ir(0)的电极反应过程为可逆扩散控制过程;在1063、1113、1143和1183 K下Ir(Ⅲ)离子的扩散系数分别为0.60×10-4、1.23×10-4、2.77×10-4和4.40×10-4 cm2/s,Ir(Ⅲ)在NaCl-KCl-IrCl3熔盐体系中电极反应的活化能Ea=162.61kJ/mol;沉积电位对所获得的Ir层的形貌有较大影响,其中在峰值电位下所获得的Ir层较厚;熔盐温度对电沉积Ir层的形貌也有较大影响,在较低熔盐温度下获得的Ir层较薄,较高熔盐温度获得的Ir层的孔隙较多.%The reduction mechanism of Ir in the NaCl-KCl-IrCl3 molten salt was investigated by cyclic voltammetry and chronopotentiometry,and Ir film was deposited effectively on platinum in potentiostatic mode.The morphology and constitution of Ir film were examined by scanning electron microscopy (SEM),energy dispersivc spectroscopy (EDS) and X-ray diffraction (XRD).It is found that the reduction mechanism of Ir(Ⅲ) is a three-electron step and electro reaction is a reversible diffusion controlled process; the diffusion coefficients of Ir(Ⅲ) at 1083,1113,1143 and 1183 K are 1.56×10-4,2.23×10 4,2.77×10-4 and 4.40×10-4cm2/s,respectively,while the activation energy of the electrode reaction is 102.95 k J/mol.The compacted Ir film reveals that the applied potential greatly affects the deposition of Ir,the thickness of Ir film deposited at the potential of reduction peak is the highest,the temperature of the molten salt also exerts an influence on deposition,the film formed at a lower temperature is thinner,but more micropores would occur on film when the temperature went too high.

  14. Cotransport of bismerthiazol and montmorillonite colloids in saturated porous media.

    Science.gov (United States)

    Shen, Chongyang; Wang, Hong; Lazouskaya, Volha; Du, Yichun; Lu, Weilan; Wu, Junxue; Zhang, Hongyan; Huang, Yuanfang

    2015-01-01

    While bismerthiazol [N,N'-methylene-bis-(2-amino-5-mercapto-1,3,4-thiadiazole)] is one of the most widely used bactericides, the transport of bismerthiazol in subsurface environments is unclear to date. Moreover, natural colloids are ubiquitous in the subsurface environments. The cotransport of bismerthiazol and natural colloids has not been investigated. This study conducted laboratory column experiments to examine the transport of bismerthiazol in saturated sand porous media both in the absence and presence of montmorillonite colloids. Results show that a fraction of bismerthiazol was retained in sand and the retention was higher at pH7 than at pH 4 and 10. The retention did not change with ionic strength. The retention was attributed to the complex of bismerthiazol with metals/metal oxides on sand surfaces through ligand exchange. The transport of bismerthiazol was enhanced with montmorillonite colloids copresent in the solutions and, concurrently, the transport of montmorillonite colloids was facilitated by the bismerthiazol. The transport of montmorillonite colloids was enhanced likely because the bismerthiazol and the colloids competed for the attachment/adsorption sites on collector surfaces and the presence of bismerthiazol changed the Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction energies between colloids and collectors. The transport of bismerthiazol was inhibited if montmorillonite colloids were pre-deposited in sand because bismerthiazol could adsorb onto the colloid surfaces. The adsorbed bismerthiazol could be co-remobilized with the colloids from primary minima by decreasing ionic strength. Whereas colloid-facilitated transport of pesticides has been emphasized, our study implies that transport of colloids could also be facilitated by the presence of pesticides. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Functional assessment of sodium chloride cotransporter NCC mutants in polarized mammalian epithelial cells.

    Science.gov (United States)

    Rosenbaek, Lena L; Rizzo, Federica; MacAulay, Nanna; Staub, Olivier; Fenton, Robert A

    2017-08-01

    The thiazide-sensitive sodium chloride cotransporter NCC is important for maintaining serum sodium (Na(+)) and, indirectly, serum potassium (K(+)) levels. Functional studies on NCC have used cell lines with native NCC expression, transiently transfected nonpolarized cell lines, or Xenopus laevis oocytes. Here, we developed the use of polarized Madin-Darby canine kidney type I (MDCKI) mammalian epithelial cell lines with tetracycline-inducible human NCC expression to study NCC activity and membrane abundance in the same system. In radiotracer assays, induced cells grown on filters had robust thiazide-sensitive and chloride dependent sodium-22 ((22)Na) uptake from the apical side. To minimize cost and maximize throughput, assays were modified to use cells grown on plastic. On plastic, cells had similar thiazide-sensitive (22)Na uptakes that increased following preincubation of cells in chloride-free solutions. NCC was detected in the plasma membrane, and both membrane abundance and phosphorylation of NCC were increased by incubation in chloride-free solutions. Furthermore, in cells exposed for 15 min to low or high extracellular K(+), the levels of phosphorylated NCC increased and decreased, respectively. To demonstrate that the system allows rapid and systematic assessment of mutated NCC, three phosphorylation sites in NCC were mutated, and NCC activity was examined. (22)Na fluxes in phosphorylation-deficient mutants were reduced to baseline levels, whereas phosphorylation-mimicking mutants were constitutively active, even without chloride-free stimulation. In conclusion, this system allows the activity, cellular localization, and abundance of wild-type or mutant NCC to be examined in the same polarized mammalian expression system in a rapid, easy, and low-cost fashion. Copyright © 2017 the American Physiological Society.

  16. SODIUM-POTASSIUM-CHLORIDE COTRANSPORT IN THE REGULATION OF VASCULAR MYOGENIC TONE

    Directory of Open Access Journals (Sweden)

    S. N. Orlov

    2014-01-01

    Full Text Available The article discusses the data on the functioning of Na+,K+,2Cl– cotransport – the carrier providing electroneutral symport of sodium, potassium and chloride, as well as molecular mechanisms of the regulation and physiological significance of this carrier. We analyzed the novel data on involvement of ubiquitous isoform of Na+,K+,2Cl–cotransporter (NKCC1 in regulation of vascular smooth muscle contraction, and role of this carrier in the regulation of cell volume and intracellular chloride concentration.

  17. Conformational Dynamics of hSGLT1 during Na+/Glucose Cotransport

    DEFF Research Database (Denmark)

    Loo, D. D.; Hirayama, B. A.; Karakossian, M. H.

    2006-01-01

    . voltage (Q-V) and fluorescence vs. voltage ( F-V) relations (for medium and slow components) obeyed Boltzmann relations with similar parameters: z (apparent valence of voltage sensor) 1; and V0.5 (midpoint voltage) between -15 and -40 mV. Sugar induced an inward current (Na+/glucose cotransport......This study examines the conformations of the Na+/glucose cotransporter (SGLT1) during sugar transport using charge and fluorescence measurements on the human SGLT1 mutant G507C expressed in Xenopus oocytes. The mutant exhibited similar steady-state and presteady-state kinetics as wild-type SGLT1...

  18. Production and conversion of color centers in OH{sup -}-doped KCl polycrystals colored electrolytically

    Energy Technology Data Exchange (ETDEWEB)

    Wang Fen [Department of Physics, Tianjin University, Tianjin 300072 (China); Gu Hongen, E-mail: jthgu@163.co [Department of Physics, Tianjin University, Tianjin 300072 (China); Qin Fang [Department of Physics, Chengde National Teacher' s College, Chengde 067000 (China); Liu Jia; Chen Weiwei [Department of Physics, Tianjin University, Tianjin 300072 (China)

    2010-02-01

    OH{sup -}-doped KCl polycrystals are colored electrolytically by using a pointed cathode and a flat anode at various temperatures and voltages. Characteristic O{sup -}, OH{sup -}, U, U{sub A} and Cu{sup +} absorption peaks are observed in resolved absorption spectra of uncolored polycrystals. Characteristic V{sub 2}, V{sub 3}, Cu{sup +}, O{sup 2-}-V{sub a}{sup +}, I{sub 2}{sup -}, I{sub 2}, H{sub 2}O{sup -} and F spectral bands are observed at room temperature in Kubelka-Munk functions of colored polycrystals. Current-time curve for electrolytic coloration of an OH{sup -}-doped KCl polycrystal and its relationship with electrolytic coloration process are given. Production and conversion of color centers are explained.

  19. Electronic stopping power of hydrogen in KCl at the stopping maximum and at very low energies

    Science.gov (United States)

    Primetzhofer, D.; Markin, S. N.; Bauer, P.

    2011-10-01

    The electronic energy loss of hydrogen ions in KCl was investigated in a wide energy range. Thin films of KCl were evaporated on an Au/Si substrate. Rutherford Backscattering Spectrometry (RBS) was performed with protons and deuterons at energies from 30 to 400 keV/nucleon. At lower energies experiments were performed by Time-Of-Flight Low energy ion scattering (TOF-LEIS) again with proton and deuteron projectiles. Experimental results are compared to calculated/tabulated values for the electronic energy loss. Whereas at energies beyond the stopping maximum very good agreement is found, at lower ion energies discrepancies between experiment and calculations increase. At very low ion velocities the extrapolated stopping cross section ɛ predicts vanishing electronic energy loss at energies below 100 eV/nucleon.

  20. Effect of NaCl and KCl doping on the growth of sulphamic acid crystals

    Science.gov (United States)

    Thaila, T.; Kumararaman, S.

    2011-11-01

    The nonlinear optical single crystals of doped sulphamic acid (SA) were grown from aqueous solution by doping with NaCl and KCl using slow evaporation method. Powder X-ray diffraction studies confirm that the grown crystals belong to orthorhombic system. The density and melting point measurements of the grown crystals were determined by floatation technique and capillary tube method, respectively. The range of optical transmittance was ascertained by recording the UV-Vis-NIR spectrum. Atomic absorption study reveals the presence of dopants in the doped crystals. The thermal analyses indicated that the doped SA crystals are more stable than pure crystals. The Vicker's microhardness studies revealed that the dopants increased the hardness of the crystals. SHG efficiency studies of the crystals are found to be increased in the presence of NaCl and KCl dopants.

  1. Generation of KCL033 clinical grade human embryonic stem cell line

    OpenAIRE

    2016-01-01

    The KCL033 human embryonic stem cell line was derived from a normal healthy blastocyst donated for research. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment and under current Good Manufacturing Practice (cGMP) standards. Pluripotent state and differentiation potential were confirmed by in vitro assays. The line was also validated for sterility...

  2. Hyperon production in Ar+KCl collisions at 1.76A GeV

    OpenAIRE

    2010-01-01

    We present transverse momentum spectra, rapidity distribution and multiplicity of Lambda-hyperons measured with the HADES spectrometer in the reaction Ar(1.76A GeV)+KCl. The yield of Xi- is calculated from our previously reported Xi-/(Lambda+Sigma0) ratio and compared to other strange particle multiplicities. Employing a strangeness balance equation the multiplicities of the yet unmeasured charged Sigma hyperons can be estimated. Finally a statistical hadronization model is used to fit the yi...

  3. Integrated Data Collection Analysis (IDCA) Program - KClO3/Dodecane Mixture

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Sorenson, Daniel N. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Shelley, Timothy J. [Air Force Research Lab. (AFRL), Tyndall AFB, FL (United States); Whinnery, LeRoy L. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-05-23

    The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small-Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of a mixture of KClO3 and dodecane—KClO3/dodecane mixture. This material was selected because of the challenge of performing SSST testing of a mixture of solid and liquid materials. The mixture was found to: 1) be more sensitive to impact than RDX, and PETN, 2) less sensitive to friction than PETN, and 3) less sensitive to spark than RDX. The thermal analysis showed little or no exothermic features suggesting that the dodecane volatilized at low temperatures. A prominent endothermic feature was observed assigned to melting of KClO3. This effort, funded by the Department of Homeland Security (DHS), ultimately will put the issues of safe handling of these materials in perspective with standard military explosives. The study is adding SSST testing results for a broad suite of different HMEs to the literature. Ultimately the study has the potential to suggest new guidelines and methods and possibly establish the SSST testing accuracies needed to develop safe handling practices for HMEs. Each participating testing laboratory uses identical test materials and preparation methods wherever possible. Note, however, the test procedures differ among the laboratories. The results are compared among the laboratories and then compared to historical data from various sources. The testing performers involved for the KClO3/dodecane mixture are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), and Indian Head Division, Naval Surface Warfare Center, (NSWC IHD). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to understand

  4. On the electrochemical formation of Pu-Al alloys in molten LiCl-KCl

    Science.gov (United States)

    Mendes, E.; Malmbeck, R.; Nourry, C.; Souček, P.; Glatz, J.-P.

    2012-01-01

    Properties of Pu-Al alloys were investigated in connection with development of pyrochemical methods for reprocessing of spent nuclear fuel. Electroseparation techniques in molten LiCl-KCl are being developed in ITU to group-selectively recover actinides from the mixture with fission products. In the process, actinides are electrochemically reduced on solid aluminium cathodes, forming solid actinide-aluminium alloys. This article is focused on electro-chemical characterisation of Pu-Al alloys in molten LiCl-KCl, on electrodeposition of Pu on solid Al electrodes and on determination of chemical composition and structure of the formed alloys. Cyclic voltammetry and chronopotentiometry were used to study Pu-Al alloys in the temperature range 400-550 °C. Pu is reduced to metal in one reduction step Pu 3+/Pu 0 on an inert W electrode. On a reactive Al electrode, the reduction of Pu 3+ to Pu 0 occurs at a more positive potential due to formation of Pu-Al alloys. The open circuit potential technique was used to identify the alloys formed. Stable deposits were obtained by potentiostatic electrolyses of LiCl-KCl-PuCl 3 melts on Al plates. XRD and SEM-EDX analyses were used to characterise the alloys, which were composed mainly of PuAl 4 with some PuAl 3. In addition, the preparation of PuCl 3 containing salt by carbochlorination of PuO 2 is described.

  5. Emission of thermally stimulated luminescence in mixed monocrystals KCl-KBr: Pb{sup 2+}, KCl: Pb{sup 2+} and KBr: Pb{sup 2+} exposed at low doses; Emision de luminiscencia estimulada termicamente en monocristales mixtos KCl-KBr:Pb{sup 2+}, KCl:Pb{sup 2+} y KBr:Pb{sup 2+} expuestos a dosis bajas

    Energy Technology Data Exchange (ETDEWEB)

    Cruz Z, E.; Ramos B, S. [Instituto de Ciencias Nucleares UNAM, A.P. 70-543, 04510 Mexico D.F. (Mexico); Melendrez A, R.; Chernov, V.; Piters, T.M.; Barboza F, M. [Centro de Investigacion en Fisica, Universidad de Sonora, A.P. 5-88 Hermosillo, Sonora (Mexico); Hernandez A, J.; Murrieta S, H. [Instituto de Fisica UNAM, A.P. 20-364, 01000 Mexico D.F. (Mexico)

    2002-07-01

    It is reported the behavior of solid solutions of mixed crystals KCl{sub 1-x} KBr{sub x} doped with divalent lead which were exposed to gamma radiation. The mixtures of KCl-KBr were varied, with x equivalents at 2, 50, 65, and 85 % including the extremes KCl: Pb{sup 2+} and KBr: Pb{sup 2+}. It was maintained a concentration of divalent lead between 20 and 40 ppm in the crystalline lattice. The production of the generated defects by radiation have been correlated with the increase in the brilliance curves depending on the received dose by the mixed doped crystal. It has been used the thermal stimulation (Tl) for obtaining the crystal luminescence depending on the dose until 130 Gy with gammas of cobalt 60. The results shows that this mixed crystalline material of varied composition responds adequately to low doses which indicates that this would be a good detector of ionizing radiation. The results have been correlated with the optical properties of this mixed doped crystal, however it has been found that exists an important loss of luminescence depending on the halogen quantity presents in the mixed crystal. (Author)

  6. Temperature dependence of the photostimulated luminescence in KCl:Eu{sup 2+}

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Zhiyan; Hansel, Rachael; Zhang, Lei; Li, H. Harold, E-mail: hli@radonc.wustl.edu

    2014-05-01

    The goal of this work is to understand the physical mechanism behind the signal stabilization process in KCl:Eu{sup 2+}, a storage phosphor material that has generated renewed interest due to its potential in radiation therapy dosimetry application. The temperature dependency of the photostimulated luminescence (PSL) spectra and intensity vs. time post X-ray irradiation was measured. Commercial BaFBr:Eu{sup 2+} materials were included in this study for comparison. Unlike BaFBr:Eu{sup 2+}, broadening of the F(Cl{sup −}) stimulation band and red-shift of the peak were observed for KCl:Eu{sup 2+} with increasing temperature. For irradiations at temperatures lower than 200 K, PSL intensity of KCl:Eu{sup 2+} showed recuperation behavior in the first 2 h post-irradiation and stayed almost constant with time thereafter. Moreover, spatially-correlated storage centers increased from 24% for irradiation at 50 K to 31% at 195 K and almost 100% at room temperature. The data suggest that certain types of charge storage-centers were mobile and contribute to the fast fading in PSL.

  7. Temperature dependence of the photostimulated luminescence in KCl:Eu2+

    Science.gov (United States)

    Xiao, Zhiyan; Hansel, Rachael; Zhang, Lei; Li, H. Harold

    2014-05-01

    The goal of this work is to understand the physical mechanism behind the signal stabilization process in KCl:Eu2+, a storage phosphor material that has generated renewed interest due to its potential in radiation therapy dosimetry application. The temperature dependency of the photostimulated luminescence (PSL) spectra and intensity vs. time post X-ray irradiation was measured. Commercial BaFBr:Eu2+ materials were included in this study for comparison. Unlike BaFBr:Eu2+, broadening of the F(Cl-) stimulation band and red-shift of the peak were observed for KCl:Eu2+ with increasing temperature. For irradiations at temperatures lower than 200 K, PSL intensity of KCl:Eu2+ showed recuperation behavior in the first 2 h post-irradiation and stayed almost constant with time thereafter. Moreover, spatially-correlated storage centers increased from 24% for irradiation at 50 K to 31% at 195 K and almost 100% at room temperature. The data suggest that certain types of charge storage-centers were mobile and contribute to the fast fading in PSL.

  8. Release of mercury halides from KCl denuders in the presence of ozone

    Directory of Open Access Journals (Sweden)

    S. N. Lyman

    2010-09-01

    Full Text Available KCl-coated denuders have become a standard method for measurement of gaseous oxidized mercury, but their performance has not been exhaustively evaluated, especially in field conditions. In this study, KCl-coated and uncoated quartz denuders loaded with HgCl2 and HgBr2 lost 29–55% of these compounds, apparently as elemental mercury, when exposed to ozone (range of 6–100 ppb tested. This effect was also observed for denuders loaded with gaseous oxidized mercury at a field site in Nevada (3–37% of oxidized mercury lost. In addition, collection efficiency decreased by 12–30% for denuders exposed to 50 ppb ozone during collection of HgCl2. While data presented were obtained from laboratory tests and as such do not exactly simulate field sampling conditions, these results indicate that the KCl denuder oxidized mercury collection method may not be as robust as previously thought. This work highlights needs for further testing of this method, clear identification of gaseous oxidized mercury compounds in the atmosphere, and development of field calibration methods for these compounds.

  9. 用新型KCl/硅酸钠钻井液缓解苏丹页岩钻进过程中的问题%Novel KCl/Silicate Drilling Fluids for Alleviating Problems in Troublesome Shale Formations in Sudan

    Institute of Scientific and Technical Information of China (English)

    郭健康; 鄢捷年; 范维旺; 张洪静; 王群立; 余志海

    2005-01-01

    For several decades, wells drilled in Block 6, Sudan, have experienced serious hole-instability problems related to drilling fluids due to the highly reactive and dispersive shales that exist in the Aradeiba and Abu Gabra formations. These problems included washout hole sections combined with tight holes, as well as serious sloughing. Frequent wiper trips were required and logging of the wells was not usually successful. Previously, several conventional inhibitive water-based drilling fluids such as KCl/polymer, KCl/lime/polymer and KCl/PHPA (partially hydrolyzed polyacrylamide) have been used in this area, but with only marginal improvements in hole stability and drilling performance. Recently, a newly formulated KCl /sodium silicate system, which is characterized by the good rheological properties and filtration control, was developed and used for providing the necessary inhibitive character. The first trial well was drilled with this kind of drilling fluid in Block 6, Sudan, and the following benefits were observed: (1) Excellent integrity exhibited by drilled cuttings for shale formations; (2) Stable borehole kept with lower mud weight; (3) Reduced wiper trips; and (4) In-gauge borehole shown from caliper logs.Later on, five more wells were drilled with the KCl /sodium silicate system in this area. It was found that the KCl/sodium silicate system can fully meet the demands of drilling operations in this area. Case studies are presented in this paper in terms of wiper trips, inhibitive character of cuttings, hole conditions and mud weight.

  10. Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis.

    Science.gov (United States)

    Rosenbaek, Lena L; Kortenoeven, Marleen L A; Aroankins, Takwa S; Fenton, Robert A

    2014-05-09

    The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT). The transport activity of NCC can be regulated by phosphorylation, but knowledge of modulation of NCC trafficking by phosphorylation is limited. In this study, we generated novel tetracycline-inducible Madin-Darby canine kidney type I (MDCKI) cell lines expressing NCC to examine the role of NCC phosphorylation and ubiquitylation on NCC endocytosis. In MDCKI-NCC cells, NCC was highly glycosylated at molecular weights consistent with NCC monomers and dimers. NCC constitutively cycles to the apical plasma membrane of MDCKI-NCC cells, with 20-30% of the membrane pool of NCC internalized within 30 min. The use of dynasore, PitStop2, methyl-β-cyclodextrin, nystatin, and filipin (specific inhibitors of either clathrin-dependent or -independent endocytosis) demonstrated that NCC is internalized via a clathrin-mediated pathway. Reduction of endocytosis resulted in greater levels of NCC in the plasma membrane. Immunogold electron microscopy confirmed the association of NCC with the clathrin-mediated internalization pathway in rat DCT cells. Compared with controls, inducing phosphorylation of NCC via low chloride treatment or mimicking phosphorylation by replacing Thr-53, Thr-58, and Ser-71 residues with Asp resulted in increased membrane abundance and reduced rates of NCC internalization. NCC ubiquitylation was lowest in the conditions with greatest NCC phosphorylation, thus providing a mechanism for the reduced endocytosis. In conclusion, our data support a model where NCC is constitutively cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to both increase NCC activity and decrease NCC endocytosis, together increasing NaCl transport in the DCT.

  11. Phosphorylation Decreases Ubiquitylation of the Thiazide-sensitive Cotransporter NCC and Subsequent Clathrin-mediated Endocytosis*

    Science.gov (United States)

    Rosenbaek, Lena L.; Kortenoeven, Marleen L. A.; Aroankins, Takwa S.; Fenton, Robert A.

    2014-01-01

    The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT). The transport activity of NCC can be regulated by phosphorylation, but knowledge of modulation of NCC trafficking by phosphorylation is limited. In this study, we generated novel tetracycline-inducible Madin-Darby canine kidney type I (MDCKI) cell lines expressing NCC to examine the role of NCC phosphorylation and ubiquitylation on NCC endocytosis. In MDCKI-NCC cells, NCC was highly glycosylated at molecular weights consistent with NCC monomers and dimers. NCC constitutively cycles to the apical plasma membrane of MDCKI-NCC cells, with 20–30% of the membrane pool of NCC internalized within 30 min. The use of dynasore, PitStop2, methyl-β-cyclodextrin, nystatin, and filipin (specific inhibitors of either clathrin-dependent or -independent endocytosis) demonstrated that NCC is internalized via a clathrin-mediated pathway. Reduction of endocytosis resulted in greater levels of NCC in the plasma membrane. Immunogold electron microscopy confirmed the association of NCC with the clathrin-mediated internalization pathway in rat DCT cells. Compared with controls, inducing phosphorylation of NCC via low chloride treatment or mimicking phosphorylation by replacing Thr-53, Thr-58, and Ser-71 residues with Asp resulted in increased membrane abundance and reduced rates of NCC internalization. NCC ubiquitylation was lowest in the conditions with greatest NCC phosphorylation, thus providing a mechanism for the reduced endocytosis. In conclusion, our data support a model where NCC is constitutively cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to both increase NCC activity and decrease NCC endocytosis, together increasing NaCl transport in the DCT. PMID:24668812

  12. Strategies to reduce gaseous KCl and chlorine in deposits during combustion of biomass in fluidised bed boilers

    Energy Technology Data Exchange (ETDEWEB)

    Kassman, Haakan

    2012-11-01

    Combustion of a biomass with an enhanced content of alkali and chlorine (Cl) can result in operational problems including deposit formation and superheater corrosion. The strategies applied to reduce such problems include co-combustion and the use of additives. In this work, measures were investigated in order to decrease the risk of superheater corrosion by reducing gaseous KCl and the content of chlorine in deposits. The strategies applied were sulphation of KCl by sulphur/sulphate containing additives (i.e. elemental sulphur (S) and ammonium sulphate (AS)) and co-combustion with peat. Both sulphation of KCl and capture of potassium (K) in ash components can be of importance when peat is used. The experiments were mainly performed in a 12 MW circulation fluidised bed (CFB) boiler equipped for research purposes but also in a full-scale CFB boiler. The results were evaluated by means of IACM (on-line measurements of gaseous KCl), conventional gas analysis, deposit and corrosion probe measurements and ash analysis. Ammonium sulphate performed significantly better than elemental sulphur. Thus the presence of SO{sub 3} (i.e. AS) is of greater importance than that of SO{sub 2} (i.e. S) for sulphation of gaseous KCl and reduction of chlorine in deposits. Only a minor reduction of gaseous KCl was obtained during co-combustion with peat although chlorine in the deposits was greatly reduced. This reduction was supposedly due to capture of K by reactive components from the peat ash in parallel to sulphation of KCl. These compounds remained unidentified. The effect of volatile combustibles on the sulphation of gaseous KCl was investigated. The poorest sulphation was attained during injection of ammonium sulphate in the upper part of the combustion chamber during the lowest air excess ratio. The explanation for this is that SO{sub 3} was partly consumed by side reactions due to the presence of combustibles. These experimental results were supported by modelling, although the

  13. ¬Immunolocalization of cation-chloride cotransporters in the developing and mature spinal cord of opossums, Monodelphis domestica

    Directory of Open Access Journals (Sweden)

    Ha-Loan ePhan

    2013-05-01

    Full Text Available Spinal inhibition is required to generate coordinated outputs between antagonistic muscles during locomotion. It relies on low neuronal chloride concentration set by two cation-chloride cotransporters, NKCC1 and KCC2 which, respectively, pumps Cl- in or out of neurons. It is generally accepted that NKCC1 is gradually inactivated during development, while KCC2 is upregulated and activated, resulting in low intracellular [Cl-]. Newborn opossums are very immature but perform rhythmic and alternate movements of the forelimbs to crawl on the mother’s belly and attach to a teat. Their hindlimbs are immobile. The alternation of the forelimbs suggests that mechanisms allowing spinal inhibition are present at birth. We studied the anatomical basis of inhibition in the spinal enlargements of postnatal opossums by immunolocalizing NKCC1 and KCC2. In some specimens, motoneurons and sensory afferents were labeled with TRDA prior to immunolabeling. At birth, both NKCC1 and KCC2 are detected in the presumptive grey and white matter of the ventral and the intermediolateral cord of both enlargements, but are sparse in the dorsal horn, where KCC2 is mostly seen on a small bundle of dendrites along primary afferents. KCC2 labeling is bright and has a mesh-like appearance in the grey matter and a radial appearance in the white matter, whereas NKCC1 is pale and diffuse. The subsequent expression of the cotransporters follows general ventrodorsal and mediolateral gradients, with the lumbar segments slightly lagging the cervical segments, until the mature pattern is observed around the 5th week. At all ages studied, KCC2 labeling is strong in the periphery of neurons. NKCC1 labeling decreases and becomes more uniformly distributed in the cells with age. Despite the significant anatomical and motor differences between the forelimbs and the hindlimbs of neonatal opossums, the maturation of KCC2 and NKCC1 is quite similar in both enlargements.

  14. Solubility of NaCl and KCl in aqueous HCl from 20 to 85°C

    Science.gov (United States)

    Potter, Robert W.; Clynne, Michael A.

    1980-01-01

    The solubilities of NaCl and KCl in aqueous HCl solutions were determined from 20 to 85°C at concentrations ranging from 0 to 20 g of HCl/100 g of solution. Equations are given that describe the solubilities over the range of conditions studied. For NaCl and KCl respectively measured solubilities show an average deviation from these equations of ??0.10 and ??0.08 g/100 g of saturated solution.

  15. Alternative splice variant of the thiazide-sensitive NaCl cotransporter

    DEFF Research Database (Denmark)

    Tutakhel, Omar A Z; Jeleń, Sabina; Valdez-Flores, Marco;

    2016-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) is an important pharmacological target in the treatment of hypertension. Human SLC12A3 gene, encoding NCC, gives rise to three isoforms. Only the 3(rd) isoform has been extensively investigated. The aim of the present study was, therefore, to establ...

  16. Isotonic transport by the Na+-glucose cotransporter SGLT1 from humans and rabbit

    DEFF Research Database (Denmark)

    Zeuthen, T; Meinild, A K; Loo, D D;

    2001-01-01

    water transport was divided about equally between cotransport, osmosis across the SGLT1 and osmosis across the native oocyte membrane. 6. Coexpression of AQP1 with the SGLT1 increased the water permeability more than 10-fold and steady state isotonic transport was achieved after less than 2 s of sugar...

  17. Na+/D-glucose cotransporter based bilayer lipid membrane sensor for D-glucose.

    Science.gov (United States)

    Sugao, N; Sugawara, M; Minami, H; Uto, M; Umezawa, Y

    1993-02-15

    A new type of amperometric blosensor for glucose was fabricated using a Na+/D-glucose cotransporter as the signal-transducing sensory element that exploits the D-glucose-triggered Na+ ion current through bilayer lipid membranes (BLMs). The planar BLM was formed by the folding method across a small aperture of a thin Teflon film. The Na+/D-glucose cotransporter, isolated and purified from small intestinal brush border membrane of guinea pigs, was embedded into BLMs through proteoliposomes. The number of the protein molecules thus incorporated in the present sensing membrane was estimated to be ca. 10(7). The sensor response was measured as an ionic current through the BLM arising from cotransported Na+ ion flux under a constant applied potential and was only induced by D-glucose above 10(-9) M, but not by the other monosaccharides except for D-galactose. The effect of applied potentials, Na+ and K+ ion concentrations, and the addition of a competitive inhibitor, phlorizin, were scrutinized to characterize the sensor output. The results were briefly discussed in terms of the potential use of the Na+/D-glucose cotransporter as a sensory element for D-glucose.

  18. Choroid plexus potassium cotransport: modulation by osmotic stress and external potassium.

    Science.gov (United States)

    Keep, R F; Xiang, J

    1995-06-01

    The choroid plexuses are involved in CSF secretion and CSF K homeostasis. This study examines the potential role of K cotransport in these two processes using isolated rat lateral ventricle choroid plexuses. Bumetanide-sensitive 86Rb influx and efflux were measured to assess the response of K cotransport to changes in media osmolality and K concentration. Alterations in osmolality had no effect on K uptake (in the presence or absence of bumetanide). However, the efflux rate constant for K was 0.29 +/- 0.02, 0.44 +/- 0.04, and 0.84 +/- 0.06 min-1 in 240, 300, and 424 mOsm/kg solutions, respectively (p brain shrinkage during hyperosmotic stress if the cotransporter is present on the apical membrane. The rate of bumetanide-sensitive efflux was unaffected by changes in external [K]. However, the rate of K uptake (measured on return to normal [K] media) was reduced gradually by exposure to low [K]. It was 21 +/- 1, 19 +/- 3, 13 +/- 2, and 6 +/- 1 nmol/mg/min after 0, 10, 30, and 60-min exposure to 1 mM K. Sixty minutes of exposure to 1 mM [K] abolished the bumetanide-sensitive K uptake present in plexuses exposed continually to normal media. This modulation of K cotransport by external [K] may be important in CSF K homeostasis by limiting K loss from the CSF if CSF [K] is low.

  19. gamma-Adducin stimulates the thiazide-sensitive NaCl cotransporter

    NARCIS (Netherlands)

    Dimke, H.; San Cristobal, P.; Graaf, M.J. de; Lenders, J.W.M.; Deinum, J.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2011-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found

  20. Type II Na+-Pi cotransporters in osteoblast mineral formation: regulation by inorganic phosphate.

    Science.gov (United States)

    Lundquist, Patrik; Murer, Heini; Biber, Jürg

    2007-01-01

    During calcification of bone, large amounts of phosphate (P(i)) must be transported from the circulation to the osteoid. Likely candidates for osteoblast P(i) transport are the type II sodium-phosphate cotransporters NaPi-IIa and NaPi-IIb that facilitate transcellular P(i) flux in kidney and intestine, respectively. We have therefore determined the 'cotransporters' expression in osteoblast-like cells. We have also studied the 'cotransporters' regulation by P(i) and during mineralization in vitro. Phosphate uptake and cotransporter protein expression was investigated at early, late and mineralizing culture stages of mouse (MC3T3-E1) and rat (UMR-106) osteoblast-like cells. Both NaPi-IIa and NaPi-IIb were expressed by both osteoblast-like cell lines. NaPi-IIa was upregulated in both cell lines one week after confluency. After 7 days in 3mM P(i) NaPi-IIa was strongly upregulated in both cell lines. NaPi-IIb expression was unaffected by both culture stage and P(i) supplementation. The expression of both cotransporters was unaffected by P(i) deprivation. In vitro mineralization at 1.5mM P(i) was preceded by a three-fold increase in osteoblast sodium-dependent P(i) uptake and a corresponding upregulation of both NaPi-IIa and NaPi-IIb. Their expression thus seem regulated by phosphate in a manner consistent with their playing a role in transcellular P(i) flux during mineralization.

  1. [EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES].

    Science.gov (United States)

    Scheen, A J

    2015-09-01

    Empagliflozin is a new inhibitor of sodiumglucose cotransporters type 2 (SGLT2) for the treatment of type 2 diabetes mellitus (T2DM). Its specific action inhibits glucose reabsorption in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA(Ic)), independently of insulin. Furthermore, calorie urinary loss promotes weight reduction and osmotic diuresis lowers arterial blood pressure. The efficacy of empagliflozin increases according to the level of hyperglycaemia but decreases in patients with renal insufficiency. In 24 to 104-week controlled trials versus placebo, empagliflozin reduces HbA(1c) (approximately 0.8%), without hypoglycaemia (except in patients already treated with insulin or sulphonylureas). This improvement in glucose control is rather similar to that observed with active comparators (metformin, glimepiride or sitagliptin), with the advantage for empagliflozin of reducing body weight (approximately 2 kg) and blood pressure (systolic approximately 4 mm Hg and diastolic approximately 2 mm Hg). Empagliflozin has shown a cardiovascular protection in the EMPA-REG OUTCOME trial. Mycotic genital infections occur more frequently, especially in women, while a negligible increase in mild urinary tract infections may be observed. The risk of hypotension and volume depletion is low, although it should be carefully checked in more fragile and at risk patients. Empagliflozin (Jardiance), which is commercialized at the doses of 10 mg and 25 mg once daily, is indicated for the treatment of T2DM and reimbursed in Belgium with conditions as add-on to a background glucose-lowering therapy.

  2. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor.

    Science.gov (United States)

    Scheen, André J

    2014-03-01

    Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors, including empagliflozin, are the first pharmacological class of antidiabetes agents to target the kidney in order to remove excess glucose from the body and, thus, offer new options for T2DM management. SGLT2 inhibitors exert their effects independently of insulin. Following single and multiple oral doses (0.5-800 mg), empagliflozin was rapidly absorbed and reached peak plasma concentrations after approximately 1.33-3.0 h, before showing a biphasic decline. The mean terminal half-life ranged from 5.6 to 13.1 h in single rising-dose studies, and from 10.3 to 18.8 h in multiple-dose studies. Following multiple oral doses, increases in exposure were dose-proportional and trough concentrations remained constant after day 6, indicating a steady state had been reached. Oral clearance at steady state was similar to corresponding single-dose values, suggesting linear pharmacokinetics with respect to time. No clinically relevant alterations in pharmacokinetics were observed in mild to severe hepatic impairment, or in mild to severe renal impairment and end-stage renal disease. Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin. Urinary glucose excretion (UGE) rates were higher with empagliflozin versus placebo and increased with dose, but no relevant impact on 24-h urine volume was observed. Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations.

  3. Deep subthreshold Xi;{-} production in Ar + KCl reactions at 1.76A GeV.

    Science.gov (United States)

    Agakishiev, G; Balanda, A; Bassini, R; Belver, D; Belyaev, A V; Blanco, A; Böhmer, M; Boyard, J L; Braun-Munzinger, P; Cabanelas, P; Castro, E; Chernenko, S; Christ, T; Destefanis, M; Díaz, J; Dohrmann, F; Dybczak, A; Eberl, T; Fabbietti, L; Fateev, O V; Finocchiaro, P; Fonte, P; Friese, J; Fröhlich, I; Galatyuk, T; Garzón, J A; Gernhäuser, R; Gil, A; Gilardi, C; Golubeva, M; González-Díaz, D; Guber, F; Hennino, T; Holzmann, R; Iori, I; Ivashkin, A; Jurkovic, M; Kämpfer, B; Kanaki, K; Karavicheva, T; Kirschner, D; Koenig, I; Koenig, W; Kolb, B W; Kotte, R; Krizek, F; Krücken, R; Kühn, W; Kugler, A; Kurepin, A; Lang, S; Lange, J S; Lapidus, K; Liu, T; Lopes, L; Lorenz, M; Maier, L; Mangiarotti, A; Markert, J; Metag, V; Michalska, B; Michel, J; Mishra, D; Morinière, E; Mousa, J; Müntz, C; Naumann, L; Otwinowski, J; Pachmayer, Y C; Palka, M; Parpottas, Y; Pechenov, V; Pechenova, O; Pietraszko, J; Przygoda, W; Ramstein, B; Reshetin, A; Roy-Stephan, M; Rustamov, A; Sadovsky, A; Sailer, B; Salabura, P; Schmah, A; Sobolev, Yu G; Spataro, S; Spruck, B; Ströbele, H; Stroth, J; Sturm, C; Sudol, M; Tarantola, A; Teilab, K; Tlusty, P; Traxler, M; Trebacz, R; Tsertos, H; Wagner, V; Weber, M; Wisniowski, M; Wojcik, T; Wüstenfeld, J; Yurevich, S; Zanevsky, Y V; Zhou, P; Zumbruch, P

    2009-09-25

    We report first results on a deep subthreshold production of the doubly strange hyperon Xi;{-} in a heavy-ion reaction. At a beam energy of 1.76A GeV the reaction Ar + KCl was studied with the High Acceptance Di-Electron Spectrometer at SIS18/GSI. A high-statistics and high-purity Lambda sample was collected, allowing for the investigation of the decay channel Xi;{-} --> Lambdapi;{-}. The deduced Xi;{-}/(Lambda + Sigma;{0}) production ratio of (5.6 +/- 1.2_{-1.7};{+1.8}) x 10;{-3} is significantly larger than available model predictions.

  4. Charged pion production in C+C and Ar+KCl collisions measured with HADES

    CERN Document Server

    Tlustý, P; Balanda, A; Bellia, G; Belver, D; Belyaev, A; Blanco, A; Boehmer, M; Boyard, J L; Braun-Munzinger, P; Cabanelas, P; Castro, E; Chernenko, S; Christ, T; Destefanis, M; Díaz, J; Dohrmann, F; Dybczak, A; Fabbietti, L; Fateev, O; Finocchiaro, P; Fonte, P; Friese, J; Fröhlich, I; Galatyuk, T; Garzón, J A; Gernhäuser, R; Gil, A; Gilardi, C; Golubeva, M; Gonzalez-Diaz, D; Grosse, E; Guber, F; Heilmann, M; Hennino, T; Holzmann, R; Ierusalimov, A; Iori, I; Ivashkin, A; Jurkovic, M; Kämpfer, B; Kanaki, K; Karavicheva, T; Kirschner, D; König, I; König, W; Kolb, B W; Kotte, R; Kozuch, A; Krasa, A; Krizek, F; Krücken, R; Kühn, W; Kugler, A; Kurepin, A; Lamas-Valverde, J; Lang, S; Lange, J S; Lapidus, K; Liu, T; Lopes, L; Lorenz, M; Maier, L; Mangiarotti, A; Marin, J; Markert, J; Metag, V; Michalska, B; Michel, J; Mishra, D; Moriniere, E; Mousa, J; Müntz, C; Naumann, L; Novotny, R; Otwinowski, J; Pachmayer, Y C; Palka, M; Parpottas, Y; Pechenov, V; Pechenova, O; Cavalcanti, T Perez; Pietraszko, J; Przygoda, W; Ramstein, B; Reshetin, A; Rustamov, A; Sadovskii, A; Salabura, P; Schmah, A; Simon, R; Sobolev, Yu G; Spataro, S; Spruck, B; Ströbele, H; Stroth, J; Sturm, C; Sudol, M; Tarantola, A; Teilab, K; Traxler, M; Trebacz, R; Tsertos, H; Veretenkin, I; Wagner, V; Weber, M; Wisniowski, M; Wüstenfeld, J; Yurevich, S; Zanevsky, Y; Zhou, P; Zumbruch, P

    2009-01-01

    Results of a study of charged pion production in 12C+12C collisions at incident beam energies of 1A GeV and 2A GeV, and 40Ar+natKCl at 1.76AGeV, using the spectrometer HADES at GSI, are presented. We have performed a measurement of the transverse momentum distributions of pi+- mesons covering a fairly large rapidity interval, in case of the C+C collision system for the first time. The yields, transverse mass and angular distributions are compared with a transport model as well as with existing data from other experiments.

  5. An electrochemical study of uranium behaviour in LiCl-KCl-CsCl eutectic melt

    Science.gov (United States)

    Maltsev, D. S.; Volkovich, V. A.; Vasin, B. D.; Vladykin, E. N.

    2015-12-01

    Electrochemical behaviour of uranium was studied in the low melting ternary LiCl-KCl-CsCl eutectic at 573-1073 K employing potentiometry, cyclic voltammetry and chronopotentiometry. Uranium electrode potentials were measured directly and U(III)/U(IV) red-ox potentials were determined from the results of cyclic voltammetry measurements. Formal standard electrode and red-ox potentials of uranium, and thermodynamic properties of uranium chlorides in the studied melt were calculated. Diffusion coefficients of U(III) and U(IV) ions were determined using cyclic voltammetry and chronopotentiometry.

  6. Generation of KCL033 clinical grade human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Liani Devito

    2016-03-01

    Full Text Available The KCL033 human embryonic stem cell line was derived from a normal healthy blastocyst donated for research. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment and under current Good Manufacturing Practice (cGMP standards. Pluripotent state and differentiation potential were confirmed by in vitro assays. The line was also validated for sterility and specific and non-specific human pathogens.

  7. Integrated Data Collection Analysis (IDCA) program--KClO4/Dodecane Mixture

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Sorensen, Daniel N. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Shelley, Timothy J. [Air Force Research Lab. (AFRL), Tyndall AFB, FL (United States); Reyes, Jose A. [Applied Research Associates, Tyndall AFB, FL (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2012-05-11

    The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of a mixture of KClO4 and dodecane—KClO4/dodecane mixture. This material was selected because of the challenge of performing SSST testing of a mixture of solid and liquid materials. The mixture was found to: 1) be less sensitive to impact than RDX, and PETN, 2) less sensitive to friction than RDX and PETN, and 3) less sensitive to spark than RDX and PETN. The thermal analysis showed little or no exothermic features suggesting that the dodecane volatilized at low temperatures. A prominent endothermic feature was observed and assigned to a phase transition of KClO4. This effort, funded by the Department of Homeland Security (DHS), ultimately will put the issues of safe handling of these materials in perspective with standard military explosives. The study is adding SSST testing results for a broad suite of different HMEs to the literature. Ultimately the study has the potential to suggest new guidelines and methods and possibly establish the SSST testing accuracies needed to develop safe handling practices for HMEs. Each participating testing laboratory uses identical test materials and preparation methods wherever possible. Note, however, the test procedures differ among the laboratories. The results are compared among the laboratories and then compared to historical data from various sources. The testing performers involved for the KClO4/dodecane mixture are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Indian Head Division, Naval Surface Warfare Center, (NSWC IHD), and Air Force Research Laboratory (AFRL/RXQL). These tests are conducted as a proficiency study in order to establish some

  8. Dielectron production in Ar + KCl collisions at 1.76A GeV

    OpenAIRE

    2011-01-01

    We present results on dielectron production in Ar+KCl collisions at 1.76A GeV. For the first time $\\omega$ mesons could be reconstructed in a heavy-ion reaction at a bombarding energy which is well below the production threshold in free nucleon-nucleon collisions. The omega multiplicity has been extracted and compared to the yields of other particles, in particular of the phi meson. At intermediate e+e- invariant masses, we find a strong enhancement of the pair yield over a reference spectrum...

  9. Equilibrium distribution of actinides including Cm between molten LiCl-KCl eutectic and liquid cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Koyama, T.; Kinoshita, K.; Inoue, T. [Central Research Inst. of Electric Power Industry, Tokyo (Japan); Ougier, M.; Malmbeck, R.; Glatz, J.P. [Joint Research Centre, Karlsruhe (Germany). Inst. for Transuranium Elements

    2008-07-01

    Equilibrium distribution of actinides both in molten LiCl-KCl eutectic and liquid cadmium were measured from the concentration data obtained in electrorefining tests and reductive extraction tests. Separation factors for U, Np, Am, Cm against Pu were derived in the practical temperature range of 700 K to 783 K. The derived separation factors are consistent with the reported values measured at 773 K and 723 K. The temperature dependence for Cm is different compared to the other actinides (U, Np and Am). This behavior remains unclear and additional experimental measurements of distribution coefficient of Cm are required before ruling on the real behavior. (orig.)

  10. Respon pertumbuhan bibit kakao (Theobroma cacao L.) terhadap pemberian pupuk guano dan KCl

    OpenAIRE

    Rajagukguk, Pispa

    2015-01-01

    Addition of Guano in Cultivation of Cacao Seedling is the one of step to use organic fertilizer that comes from animal feces in the world. For that purpose addition guano aims to increase growth of Cacao in Cultivation of Seedling. This research had been conducted at experimental field of Fakultas Pertanian USU in October 2013 - January 2014 using factorial randomized block design with two factor, i.e. addition dose of Guano (0, 75 , 150 , 225 g/polibag) and dose of KCl (0 , ...

  11. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus : Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications

    NARCIS (Netherlands)

    Heerspink, Hiddo J. L.; Perkins, Bruce A.; Fitchett, David H.; Husain, Mansoor; Cherney, David Z. I.

    2016-01-01

    Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and

  12. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus : Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications

    NARCIS (Netherlands)

    Heerspink, Hiddo J. L.; Perkins, Bruce A.; Fitchett, David H.; Husain, Mansoor; Cherney, David Z. I.

    2016-01-01

    Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and na

  13. Model analysis of effect of canagliflozin (Invokana), a sodium-glucose cotransporter 2 inhibitor, to alter plasma 1,5-anhydroglucitol.

    Science.gov (United States)

    Fortuna, Danielle; McCloskey, Laura J; Stickle, Douglas F

    2016-01-15

    Renal reabsorption of 1,5-anhydroglucitol (AG) is competitively inhibited by elevated glucose and leads to depleted plasma AG in diabetes. Plasma AG recovery in diabetes normally correlates with improved glycemic control. However, use of sodium-glucose co-transporter 2 (SGLT2) inhibitors (e.g., canagliflozin) to treat diabetes by inhibition of renal glucose reabsorption can negate this correlation, via an indirect effect (increase of renal filtrate glucose concentration) to inhibit AG reabsorption by sodium-glucose co-transporter 4 (SGLT4). Conversely, then, AG measurement might be useful as an independent marker for SGLT2 inhibitor activity. Using an AG mass balance model, we analyzed literature data on plasma AG before and after initiation of canagliflozin therapy (CT) to quantitatively characterize the effect of CT on AG reabsorption. According to model calculations, modest decreases (<5%) in fractional reabsorption of AG account for the drastic decrease in [AG] observed during CT. Decreases are predicted to be rapid (t1/2<3days) after CT initiation. CT negates the usual premise of AG measurement (that [AG] should increase with improved glycemic control). However, according to model calculations, a substantial and likely rapid effect of CT on [AG] means that AG measurement might provide an early marker for CT activity. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. General anaesthetics do not impair developmental expression of the KCC2 potassium-chloride cotransporter in neonatal rats during the brain growth spurt

    KAUST Repository

    Lacoh, Claudia Marvine

    2013-03-26

    BackgroundThe developmental transition from depolarizing to hyperpolarizing γ-aminobutyric acid-mediated neurotransmission is primarily mediated by an increase in the amount of the potassium-chloride cotransporter KCC2 during early postnatal life. However, it is not known whether early neuronal activity plays a modulatory role in the expression of total KCC2 mRNA and protein in the immature brain. As general anaesthetics are powerful modulators of neuronal activity, the purpose of this study was to explore how these drugs affect KCC2 expression during the brain growth spurt.MethodsWistar rat pups were exposed to either a single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal days 0, 5, 10, or 15. KCC2 expression was assessed using immunoblotting, immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3 days post-exposure in the medial prefrontal cortex.ResultsThere was a progressive and steep increase in the expression of KCC2 between birth and 2 weeks of age. Exposure to midazolam, propofol, or ketamine up to 6 h at any investigated stages of the brain growth spurt did not influence the expression of this cotransporter protein.ConclusionI.V. general anaesthetics do not seem to influence developmental expression of KCC2 during the brain growth spurt. © 2013 © The Author [2013].

  15. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    OpenAIRE

    Mizerski Grzegorz; Kicinski Pawel; Jaroszynski Andrzej

    2015-01-01

    The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the a...

  16. Study of thermodynamic properties of Np-Al alloys in molten LiCl-KCl eutectic

    Science.gov (United States)

    Souček, P.; Malmbeck, R.; Mendes, E.; Nourry, C.; Sedmidubský, D.; Glatz, J.-P.

    2009-10-01

    Pyrochemical methods are investigated worldwide within the framework of Partitioning and Transmutation concepts for spent nuclear fuel reprocessing. Electroseparation techniques in a molten LiCl-KCl are being developed in ITU to recover all actinides from a mixture with fission products. During the process, actinides are selectively electrochemically reduced on a solid aluminium cathode, forming solid actinide-aluminium alloys. This work is focused on the thermodynamic properties of Np-Al alloys in a temperature range of 400-550 °C and on the characterisation of the structure and chemical composition of deposits obtained by electrodeposition of Np on solid Al electrodes in a LiCl-KCl-NpCl 3 melt. Cyclic voltammetry and open circuit chronopotentiometry have been used to examine the electrochemical behaviour of Np on inert W and reactive Al electrodes. Gibbs energies, enthalpy and entropy of formation and standard electrode potentials of Np-Al alloys were evaluated and compared with ab initio calculations. Galvanostatic electrolyses at 450 °C were carried out to recover Np onto Al plates and the solid surface deposits were characterised by XRD and SEM-EDX analyses. Stable and dense deposits consisting of NpAl 3 and NpAl 4 alloys were identified. In addition, the conversion of NpO 2 to NpCl 3 is described, using chlorination of the oxide in a molten salt media by pure chlorine gas.

  17. Heteroepitaxial strain in alkali halide thin films: KCl on NaCl

    DEFF Research Database (Denmark)

    Baker, J.; Lindgård, Per-Anker

    1999-01-01

    We have pet-formed Monte Carlo simulations of the properties of a NaCl (001) surface covered by full or partial layers of KCl, for coverages up to 5 monolayers (ML). A wide variety of structures of the film is found. For integer ML coverages we find the continuous, so-called floating mode rumple...... structure, as was previously found in the KBr/NaCl system. However, for a coverage of similar to 2.1 ML, we find a discrete structure of periodicity 3:4 of small regularly spaced KCl pyramids. It has the same scattering characteristics as the structure observed by Henzler et al. [Phys. Rev. B 52, 17 060...... (1995)], but it is two-dimensional modulated, rather than the rowlike stacking fault structure proposed by Henzler et al. Also, at a coverage of similar to 0.8 ML there is a stable 3:4 structure. Other structures are found at intermediate coverages, corresponding to regular arrays of dislocation lines...

  18. Determination of the crystal growth mechanism of KCl in ethanol?water system

    Science.gov (United States)

    Liszi, I.; Hasznosné-Nezdei, M.; Lakatos, B. G.; Sapundzhiev, Ts. J.; Popov, R. G.

    1999-03-01

    The mechanism of crystal growth of KCl in ethanol-water system is studied by Nielsen's map-model, and the growth rate is estimated by the induction time (nucleation rate, growth rate) function in a salting-out crystallization system. In the experiments, the induction time and the particle size distribution of the final product were measured, and the solid-liquid interfacial tension was calculated from the induction period data. The map of rate control of crystal-growth for the KCl-ethanol-water salting out system was constructed by taking into consideration that the liquid-vapour interfacial tension varied with the variation of the ethanol concentration, and, as a consequence, the solid-liquid interfacial tension varied as well. As a result, diffusion controlled crystal growth was obtained as a rate-determining step for supersaturation ratios 0.01<0.45. For determining the crystal growth rate, the nucleation rate was estimated from the experimental average particle number and induction period, applying the assumption that all nuclei were born during the induction period. The results, obtained by using linear and non-linear regressions, have appeared to be in good agreement with the data published in the literature.

  19. Generation of (F+2)_AH Centres in Sodium Ion Doped KCl:CO^{2-3}

    Science.gov (United States)

    Diaf, M.; Chihi, I.; Hamaïdia, A.; Akrmi, El.

    1996-01-01

    We demonstrate that (F+2)AH centres of KCl may be obtained from crystals doped with K{2}CO{3} and NaCl, grown by the Czochralski method in open atmosphere. The optical properties of (F+2)AH centres thus produced are exactly the same as those of (F+2)AH centres prepared by the usual technique, which involves superoxide doping and a controlled atmosphere. Nous montrons que les centres (F+2)AH de KCl peuvent être obtenus à partir de cristaux dopés par K{2}CO{3} et NaCl, fabriqués par la méthode de Czochralski à l'air libre. Les propriétés optiques des centres (F+2)AH ainsi produits sont exactement les mêmes que celles des centres (F+2)AH préparés par la technique habituelle, qui comporte le dopage par un superoxyde et l'emploi d'une atmosphère contrôlée.

  20. LiCl-KCl Induced Corrosion of Copper at Low Temperature

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Hoon; Sim, Ji-Hyung; Kim, Yong-Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    Structural materials for PRIDE system are stainless steel and copper mainly. And these are known for maintaining integrity when there is no oxygen and water. But physicochemical behavior of structural materials of PRIDE system when there is some of oxygen and water is lack of research. And when local corrosion is occurred, it can cause crack, so that it will be a big problem of safety and economic efficiency. So evaluation of thermodynamical and mechanical stabilities of structural materials for PRIDE system is necessary to predict lifetime of materials and time to replace the part of the equipment. There is no research of evaluation of long-term structural stability of structural materials for PRIDE system now. The present work investigates how LiCl-KCl molten salts influence the low temperature corrosion of copper. From the corrosion test, we can confirm that LiCl-KCl salt accelerates the corrosion of copper at low temperature. It was observed by surface analysis and gravimetry. The corrosion pattern is general corrosion and corrosion rate is increased as the temperature and time go up.

  1. Experimental observations on electrorefining spent nuclear fuel in molten LiCl-KCl/liquid cadmium system.

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, T. A.; Laug, D. V.; Li, S. X.; Sofu, T.

    1999-07-14

    Argonne National Laboratory (ANL) is currently performing a demonstration program for the Department of Energy (DOE) which processes spent nuclear fuel from the Experimental Breeder Reactor (EBR-II). One of the key steps in this demonstration program is electrorefining of the spent fuel in a molten LiCl-KCl/liquid cadmium system using a pilot scale electrorefiner (Mk-IV ER). This article summarizes experimental observations and engineering aspects for electrorefining spent fuel in the molten LiCl-KCl/liquid cadmium system. It was found that the liquid cadmium pool acted as an intermediate electrode during the electrorefining process in the ER. The cadmium level was gradually decreased due to its high vapor pressure and vaporization rate at the ER operational temperature. The low cadmium level caused the anode assembly momentarily to touch the ER vessel hardware, which generated a periodic current change at the salt/cathode interface and improved uranium recovery efficiency for the process. The primary current distributions calculated by numerical simulations were used in interpreting the experimental results.

  2. Thermally stimulated luminescence of mixed sintered KCl-KBr: EuCl{sub 3} pellets exposed to gamma rays

    Energy Technology Data Exchange (ETDEWEB)

    Cervantes, B.; Bernal, R.; Barboza F, M.; Cruz V, C.; Burruel I, S.E. [Universidad de Sonora, A.P. 5-088, 83190 Hermosillo, Sonora (Mexico); Cruz Z, E. [ICN-UNAM, A.P. 70-543, 04510 Mexico D.F. (Mexico)

    2006-07-01

    Europium-doped pellets of mixed composition type KCI{sub x}Br{sub 1-x}: EuCl{sub 3} were obtained by sintering. Some of these polycrystalline samples were exposed to cobalt-60 gamma rays at 0.56 Gy/min dose rate. The higher TL efficiencies were observed for that phosphors with higher concentration of KCI ions in the composition lattice. The integrated TL as a function of dose were investigated in the 0.25-150 Gy dose range and it showed an increase when increasing dose, and a close linear behavior for the lower doses. Mixed composition samples have a reproducibility of the TL signals better than the end compositions KBr: EuCI{sub 3} and KCl: EuCI{sub 3}. The characteristic fading depends strongly on the relative composition. The kinetics parameters were calculated by the Initial Rise method and showed an important increase of the values of the activation energy with the absorption dose increased. (Author)

  3. Photostimulated luminescence in KBr-KCl mixed matrixes unpurified with Pb{sup 2+}; Luminiscencia fotoestimulada en matrices mixtas KBr-KCl impurificadas con Pb{sup 2+}

    Energy Technology Data Exchange (ETDEWEB)

    Cruz Z, E.; Chernov, V.; Barboza F, M.; Melendrez, R.; Piters, T.M.; Hernandez A, J.; Murrieta S, H. [Instituto de Ciencias Nucleares, UNAM, A.P. 70-543, 04510 Mexico D.F. (Mexico)

    2000-07-01

    Crystals of alkaline halogenides and in solid solutions are good devices as UV radiation or ionizing radiation detectors, also as optical memory. In alkaline halogenides unpurified with ns2 ions, it has been found that with photons of less energy to the gap energy they can be generated defects as the F centers, this makes to suppose that it is possible to create net defects in a KBr-KCl mixed system unpurified with divalent lead under UV radiation. In this work it is presented measurements of optical absorption, photostimulated luminescence and induced thermoluminescence by gamma and UV radiation in this mixed crystalline system at distinct concentrations. We have found that the thermoluminescent signal due to gamma and UV radiation is found between ambient temperature and 400 Centigrade, the brightness curves for both cases are distinct but the forms and positions of the peaks are very similar. It was observed that Tl information, between 150 and 250 Centigrade, generated by UV decays strongly, it compared with the low temperature peaks. The exact position of the emission and excitation spectra are lightly different, between 3.5 and 4.5 eV respectively and it depends of the mixture composition in the crystal and also of the thermal treatments. (Author)

  4. Surface Morphology and Microstructural Characterization of KCl Crystals Grown in Halite-Sylvite Brine Solutions by Electron Backscattered Diffraction Techniques

    Science.gov (United States)

    Podder, Jiban; Basu, Ritwik; Evitts, Richard William; Besant, Robert William

    2015-11-01

    In this paper, a study on the ternary NaCl-KCl-H2O system was carried out by an extractive metallurgy technique from mixed brine solutions of different compositions at room temperature (23°C). The surface morphology and microstructure were examined using a scanning electron microscope (SEM), electron backscattered diffraction (EBSD) and an energy dispersive X-ray (EDX) spectroscopy. The presence of Na{ }+ was found to reduce the stability of the solutions and increase the crystallization induction period, interfacial energy, energy of formation of the nucleus and greatly reduce the nucleation rate of KCl crystal. The surface morphology of KCl crystals is significantly changed due to presence of 5 to 10% (w/w) of NaCl as impurities in the binary solutions and shows the formation of co-crystals of different crystallographic orientation of NaCl on the KCl surface. In addition X-ray diffraction studies performed on KCl crystals grown in halite-sylvite binary solutions reveals that these crystals are cubic in nature and its lattice constant is 6.2952 Å when the NaCl concentration is small.

  5. A reactive distillation process for the treatment of LiCl-KCl eutectic waste salt containing rare earth chlorides

    Science.gov (United States)

    Eun, H. C.; Choi, J. H.; Kim, N. Y.; Lee, T. K.; Han, S. Y.; Lee, K. R.; Park, H. S.; Ahn, D. H.

    2016-11-01

    The pyrochemical process, which recovers useful resources (U/TRU metals) from used nuclear fuel using an electrochemical method, generates LiCl-KCl eutectic waste salt containing radioactive rare earth chlorides (RECl3). It is necessary to develop a simple process for the treatment of LiCl-KCl eutectic waste salt in a hot-cell facility. For this reason, a reactive distillation process using a chemical agent was achieved as a method to separate rare earths from the LiCl-KCl waste salt. Before conducting the reactive distillation, thermodynamic equilibrium behaviors of the reactions between rare earth (Nd, La, Ce, Pr) chlorides and the chemical agent (K2CO3) were predicted using software. The addition of the chemical agent was determined to separate the rare earth chlorides into an oxide form using these equilibrium results. In the reactive distillation test, the rare earth chlorides in LiCl-KCl eutectic salt were decontaminated at a decontamination factor (DF) of more than 5000, and were mainly converted into oxide (Nd2O3, CeO2, La2O3, Pr2O3) or oxychloride (LaOCl, PrOCl) forms. The LiCl-KCl was purified into a form with a very low concentration (<1 ppm) for the rare earth chlorides.

  6. Growth of NaCl on thin epitaxial KCl films on Ag(100) studied by SPA-LEED

    Science.gov (United States)

    Marquardt, Christian; Paulheim, Alexander; Sokolowski, Moritz

    2015-11-01

    We investigated the growth of NaCl on thin (100)-oriented films of KCl by spot profile analysis of low energy electron diffraction (SPA-LEED). The underlying question of this investigation was how the system accommodates to the misfit of - 10% between the NaCl and KCl lattices. The KCl films (3 atomic layers thick) were epitaxially grown on a Ag(100) single crystal. We studied the heteroepitaxial growth of NaCl on KCl at 300 K and at 500 K, respectively. At 300 K, the first NaCl monolayer (ML) grows pseudomorphically on the KCl film. From the second layer onward, the NaCl lattice relaxes. The NaCl multilayers roughen, and a small rotational disorder (± 4°) of the NaCl domains is observed. The roughening results from the formation of multilayer islands of limited lateral size due to the misfit to the pseudomorphic first NaCl layer. At a growth temperature of 500 K, no pseudomorphic NaCl layer forms, instead relaxed multilayer island growth of NaCl is observed from the first layer onward. Similarly to the growth at 300 K, we find NaCl multilayer islands of limited lateral size. For both temperatures, we explain this growth behavior by the misfit that makes the adsorption sites at the island edges of the first relaxed NaCl layer less favorable for larger islands, promoting nucleation of multilayer islands.

  7. Cotransport of H+, lactate, and H2O in porcine retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Kiilgaard, Jens Folke; la Cour, Morten;

    2003-01-01

    and placed in a perfusion chamber in which the solution facing the retinal membrane could be changed rapidly. Two types of experiments were performed: Changes in cell water volume were measured by self-quenching of the fluorescent dye Calcein, and changes in intracellular pH were measured ratiometrically......) for the H(+) and lactate fluxes. The data suggest that H(2)O is cotransported along with H(+) and lactate ions in MCT1 localized to the retinal membrane. The study emphasizes the importance of this cotransporter in the maintenance of water homeostasis and pH in the subretinal space of a mammalian tissue...... and supports our previous study performed by an invasive technique in an amphibian tissue....

  8. Sodium-glucose cotransporter 2 inhibitors with insulin in type 2 diabetes: Clinical perspectives

    OpenAIRE

    Mathew John; Deepa Gopinath; Rejitha Jagesh

    2016-01-01

    The treatment of type 2 diabetes is a challenging problem. Most subjects with type 2 diabetes have progression of beta cell failure necessitating the addition of multiple antidiabetic agents and eventually use of insulin. Intensification of insulin leads to weight gain and increased risk of hypoglycemia. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antihyperglycemic agents which act by blocking the SGLT2 in the proximal tubule of the kidney. They have potential benefits in...

  9. Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy

    OpenAIRE

    Karlócai, MR; Wittner, L; Tóth, K; Maglóczky, Z.; Katarova, Z.; Rásonyi, G; Erőss, L; Czirják, S; Halász, P; G. Szabó; Payne, JA; Kaila, K.; Freund, TF

    2015-01-01

    © 2015 Springer-Verlag Berlin Heidelberg Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interact...

  10. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

    OpenAIRE

    Peters, Anne L.; Buschur, Elizabeth O.; Buse, John B.; Cohan, Pejman; Diner, Jamie C.; Hirsch, Irl B.

    2015-01-01

    OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS Cases identified incidentally are described. RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 d...

  11. Activation of the TASK-2 channel after cell swelling is dependent on tyrosine phosphorylation

    DEFF Research Database (Denmark)

    Kirkegaard, Signe Skyum; Lambert, Ian Henry; Gammeltoft, Steen;

    2010-01-01

    (K,vol) indicating that inhibition of RVD reflects inhibition of TASK-2. We find that in EATC the tyrosine kinase inhibitor genistein inhibits RVD by 90%, and that the tyrosine phosphatase inhibitor monoperoxo(picolinato)-oxo-vanadate(V) [mpV(pic)] shifted the volume set point for inactivation of the channel...... to a lower cell volume. Swelling-activated K(+) efflux was impaired by genistein and the Src kinase family inhibitor 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) and enhanced by the tyrosine phosphatase inhibitor mpV(pic). With the use of the TASK-2 inhibitor clofilium......, it is demonstrated that mpV(pic) increased the volume-sensitive part of the K(+) efflux 1.3 times. To exclude K(+) efflux via a KCl cotransporter, cellular Cl(-) was substituted with NO(3)(-). Also under these conditions K(+) efflux was completely blocked by genistein. Thus tyrosine kinases seem to be involved...

  12. Cotransport of water and solutes in plant membranes: The molecular basis, and physiological functions

    Directory of Open Access Journals (Sweden)

    Lars H. Wegner

    2017-03-01

    Full Text Available Current concepts of plant membrane transport are based on the assumption that water and solutes move across membranes via separate pathways. According to this view, coupling between the fluxes is more or less exclusively constituted via the osmotic force that solutes exert on water transport. This view is questioned here, and experimental evidence for a cotransport of water and solutes is reviewed. The overview starts with ion channels that provide pathways for both ion and water transport, as exemplified for maxi K+ channels from cytoplasmic droplets of Chara corallina. Aquaporins are usually considered to be selective for water (just allowing for slippage of some other small, neutral molecules. Recently, however, a “dual function” aquaporin has been characterized from Arabidopsis thaliana (AtPIP2.1 that translocates water and at the same time conducts cations, preferentially Na+. By analogy with mammalian physiology, other candidates for solute-water flux coupling are cation-chloride cotransporters of the CCC type, and transporters of sugars and amino acids. The last part is dedicated to possible physiological functions that could rely on solute-water cotransport. Among these are the generation of root pressure, refilling of embolized xylem vessels, fast turgor-driven movements of leaves, cell elongation (growth, osmoregulation and adjustment of buoyancy in marine algae. This review will hopefully initiate further research in the field.

  13. [Computation of the K+, Na+ and Cl- fluxes through plasma membrane of animal cell with Na+/K+ pump, NKCC, NC cotransporters, and ionic channels with and without non-Goldman rectification in K+ channels. Norma and apoptosis].

    Science.gov (United States)

    Rubashkin, A A; Iurinskaia, V E; Vereninov, A A

    2010-01-01

    The balance of K+, Na+ and Cl- fluxes through cell membrane with the Na+/K+ pump, ion channels and NKCC and NC cotransporters is considered. It is shown that all unidirectional K+, Na+ and Cl- fluxes through cell membrane, permeability coefficients of ion channels and membrane potential can be computed for balanced ion distribution between cell and the medium if K+, Na+ and Cl- concentration in cell water and three fluxes are known: total Cl- flux, total K+ influx and ouabain-inhibitable "pump" component of the K+ influx. Changes in the mortovalent ion balance in lymphoid cells U937 induced to apoptosis by 1 microM staurosporine are analyzed as an example. It is found that the apoptotic shift in ion and water balance in studied cells is caused by a decrease in the pump activity which is accompanied by a decrease in the integral permeability of Na+ channels without significant increase in K+ and Cl- channel permeabilities. Computation shows that only a small part of the total fluxes of K+, Na+ and Cl- accounts for the fluxes via NKCC and NC cotransporters. Therefore, cotransport fluxes can not be studied using inhibitors.

  14. Luminal fructose inhibits rat intestinal sodium-phosphate cotransporter gene expression and phosphate uptake24

    Science.gov (United States)

    Kirchner, Séverine; Muduli, Anjali; Casirola, Donatella; Prum, Kannitha; Douard, Véronique; Ferraris, Ronaldo P

    2008-01-01

    Background While searching by microarray for sugar-responsive genes, we inadvertently discovered that sodium-phosphate cotransporter 2B (NaPi-2b) mRNA concentrations were much lower in fructose-perfused than in glucose-perfused intestines of neonatal rats. Changes in NaPi-2b mRNA abundance by sugars were accompanied by similar changes in NaPi-2b protein abundance and in rates of inorganic phosphate (Pi) uptake. Objective We tested the hypothesis that luminal fructose regulates NaPi-2b. Design We perfused into the intestine fructose, glucose, and non-metabolizable or poorly transported glucose analogs as well as phlorizin. Results NaPi-2b mRNA concentrations and Pi uptake rates in fructose-perfused intestines were ≈30% of those in glucose and its analogs. NaPi-2b inhibition by fructose is specific because the mRNA abundance and activity of the fructose transporter GLUT5 (glucose transporter 5) increased with fructose perfusion, whereas those of other transporters were independent of the perfusate. Plasma Pi after 4 h of perfusion was independent of the perfusate, probably because normal kidneys can maintain normophosphatemia. Inhibiting glucose-6-phosphatase, another fructose-responsive gene, with tungstate or vanadate nonspecifically inhibited NaPi-2b mRNA expression and Pi uptake in both glucose- or fructose-perfused intestines. The AMP kinase (AMPK)–activator AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) enhanced and the fatty acid synthase–AMPK inhibitor C75 (3-carboxy-4-octyl-2-methylene-butyrolactone trans-4-carboxy-5-octyl-3-methylenebutyrolactone) prevented fructose inhibition of NaPi-2b but had no effect on expression of other transporters. NaPi-2b expression decreased markedly with age and was inhibited by fructose in all age groups. Conclusions Energy levels in enterocytes may play a role in NaPi-2b inhibition by luminal fructose. Consumption of fructose that supplies ≈10% of caloric intake by Americans clearly affects absorption of

  15. Characterization of a novel phosphorylation site in the sodium–chloride cotransporter, NCC

    Science.gov (United States)

    Rosenbaek, L L; Assentoft, M; Pedersen, N B; MacAulay, N; Fenton, R A

    2012-01-01

    The sodium–chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho-specific antibodies targeting pS124-NCC demonstrated a band of 160 kDa in the kidney cortex, but not medulla, which was preabsorbed by a corresponding phosphorylated peptide. Confocal microscopy with kidney tubule segment-specific markers localized pS124-NCC to all distal convoluted tubule cells. Double immunogold electron microscopy demonstrated that pS124-NCC co-localized with total NCC in the apical plasma membrane of distal convoluted tubule cells and intracellular vesicles. Acute treatment of Munich–Wistar rats or vasopressin-deficient Brattleboro rats with the vasopressin type 2 receptor-specific agonist dDAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin–angiotensin–aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1-related proline–alanine-rich kinase and oxidative stress-response kinases (SPAK and OSR1) were not able to phosphorylate NCC at S124. Protein kinase arrays identified multiple kinases that were able to bind to the region surrounding S124. Four of these kinases (IRAK2, CDK6/Cyclin D1, NLK and mTOR/FRAP) showed weak but significant phosphorylation activity at S124. In oocytes, 36Cl uptake studies combined with biochemical analysis showed decreased activity of plasma membrane-associated NCC when replacing S124 with alanine (A) or aspartic acid (D). In novel tetracycline-inducible MDCKII-NCC cell lines, S124A and S124D mutants were able to traffic to the plasma membrane similarly to wildtype NCC. PMID:22966159

  16. Characterization of a novel phosphorylation site in the sodium-chloride cotransporter, NCC.

    Science.gov (United States)

    Rosenbaek, L L; Assentoft, M; Pedersen, N B; MacAulay, N; Fenton, R A

    2012-12-01

    The sodium-chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho-specific antibodies targeting pS124-NCC demonstrated a band of 160 kDa in the kidney cortex, but not medulla, which was preabsorbed by a corresponding phosphorylated peptide. Confocal microscopy with kidney tubule segment-specific markers localized pS124-NCC to all distal convoluted tubule cells. Double immunogold electron microscopy demonstrated that pS124-NCC co-localized with total NCC in the apical plasma membrane of distal convoluted tubule cells and intracellular vesicles. Acute treatment of Munich-Wistar rats or vasopressin-deficient Brattleboro rats with the vasopressin type 2 receptor-specific agonist dDAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin-angiotensin-aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1-related proline-alanine-rich kinase and oxidative stress-response kinases (SPAK and OSR1) were not able to phosphorylate NCC at S124. Protein kinase arrays identified multiple kinases that were able to bind to the region surrounding S124. Four of these kinases (IRAK2, CDK6/Cyclin D1, NLK and mTOR/FRAP) showed weak but significant phosphorylation activity at S124. In oocytes, (36)Cl uptake studies combined with biochemical analysis showed decreased activity of plasma membrane-associated NCC when replacing S124 with alanine (A) or aspartic acid (D). In novel tetracycline-inducible MDCKII-NCC cell lines, S124A and S124D mutants were able to traffic to the plasma membrane similarly to wildtype NCC.

  17. Antioxidants and NOS inhibitors selectively targets manganese-induced cell volume via Na-K-Cl cotransporter-1 in astrocytes.

    Science.gov (United States)

    Alahmari, Khalid A; Prabhakaran, Harini; Prabhakaran, Krishnan; Chandramoorthy, Harish C; Ramugounder, Ramakrishnan

    2015-06-12

    Manganese has shown to be involved in astrocyte swelling. Several factors such as transporters, exchangers and ion channels are attributed to astrocyte swelling as a result in the deregulation of cell volume. Products of oxidation and nitration have been implied to be involved in the pathophysiology of swelling; however, the direct link and mechanism of manganese induced astrocyte swelling has not been fully elucidated. In the current study, we used rat primary astrocyte cultures to investigate the activation of Na-K-Cl cotransporter-1 (NKCC1) a downstream mechanism for free radical induced astrocyte swelling as a result of manganese toxicity. Our results showed manganese, oxidants and NO donors as potent inducer of oxidation and nitration of NKCC1. Our results further confirmed that manganese (50 μM) increased the total protein, phosphorylation and activity of NKCC1 as well as cell volume (p manganese or oxidants and NO induced activation, oxidation/nitration of NKCC1 play an important role in the astrocyte swelling. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine.

    Science.gov (United States)

    Suzuki, Masashi; Van Paesschen, Wim; Stalmans, Ingeborg; Horita, Shoko; Yamada, Hideomi; Bergmans, Bruno A; Legius, Eric; Riant, Florence; De Jonghe, Peter; Li, Yuehong; Sekine, Takashi; Igarashi, Takashi; Fujimoto, Ichiro; Mikoshiba, Katsuhiko; Shimadzu, Mitsunobu; Shiohara, Masaaki; Braverman, Nancy; Al-Gazali, Lihadh; Fujita, Toshiro; Seki, George

    2010-09-07

    Homozygous mutations in SLC4A4, encoding the electrogenic Na(+)-HCO(3)(-) cotransporter NBCe1, have been known to cause proximal renal tubular acidosis (pRTA) and ocular abnormalities. In this study, we report two sisters with pRTA, ocular abnormalities, and hemiplegic migraine. Genetic analysis ruled out pathological mutations in the known genes for familial hemiplegic migraine, but identified a homozygous 65-bp deletion (Delta65bp) in the C terminus of NBCe1, corresponding to the codon change S982NfsX4. Several heterozygous members of this family also presented glaucoma and migraine with or without aura. Despite the normal electrogenic activity in Xenopus oocytes, the Delta65bp mutant showed almost no transport activity due to a predominant cytosolic retention in mammalian cells. Furthermore, coexpression experiments uncovered a dominant negative effect of the mutant through hetero-oligomer formation with wild-type NBCe1. Among other pRTA pedigrees with different NBCe1 mutations, we identified four additional homozygous patients with migraine. The immunohistological and functional analyses of these mutants demonstrate that the near total loss of NBCe1 activity in astrocytes can cause migraine potentially through dysregulation of synaptic pH.

  19. Defective membrane expression of the Na+-HCO3− cotransporter NBCe1 is associated with familial migraine

    Science.gov (United States)

    Suzuki, Masashi; Van Paesschen, Wim; Stalmans, Ingeborg; Horita, Shoko; Yamada, Hideomi; Bergmans, Bruno A.; Legius, Eric; Riant, Florence; De Jonghe, Peter; Li, Yuehong; Sekine, Takashi; Igarashi, Takashi; Fujimoto, Ichiro; Mikoshiba, Katsuhiko; Shimadzu, Mitsunobu; Shiohara, Masaaki; Braverman, Nancy; Al-Gazali, Lihadh; Fujita, Toshiro; Seki, George

    2010-01-01

    Homozygous mutations in SLC4A4, encoding the electrogenic Na+-HCO3− cotransporter NBCe1, have been known to cause proximal renal tubular acidosis (pRTA) and ocular abnormalities. In this study, we report two sisters with pRTA, ocular abnormalities, and hemiplegic migraine. Genetic analysis ruled out pathological mutations in the known genes for familial hemiplegic migraine, but identified a homozygous 65-bp deletion (Δ65bp) in the C terminus of NBCe1, corresponding to the codon change S982NfsX4. Several heterozygous members of this family also presented glaucoma and migraine with or without aura. Despite the normal electrogenic activity in Xenopus oocytes, the Δ65bp mutant showed almost no transport activity due to a predominant cytosolic retention in mammalian cells. Furthermore, coexpression experiments uncovered a dominant negative effect of the mutant through hetero-oligomer formation with wild-type NBCe1. Among other pRTA pedigrees with different NBCe1 mutations, we identified four additional homozygous patients with migraine. The immunohistological and functional analyses of these mutants demonstrate that the near total loss of NBCe1 activity in astrocytes can cause migraine potentially through dysregulation of synaptic pH. PMID:20798035

  20. Interaction between SiO2 and a KF-KCl-K2SiF6 Melt.

    Science.gov (United States)

    Zaykov, Yurii P; Isakov, Andrey V; Zakiryanova, Irina D; Reznitskikh, Olga G; Chemezov, Oleg V; Redkin, Alexander A

    2014-02-13

    The solubility mechanism of silica in a fluoride-chloride melt has been determined in situ using Raman spectroscopy. The spectroscopy data revealed that the silica solubility process involved Si-O bond breakage and Si-F bond formation. The process results in the formation of silicate complexes, fluorine-bearing silicate complexes, and silicon tetrafluoride in the melt. Mass spectrometry of the vapor phase over the KF-KCl-K2SiF6 and KF-KCl-K2SiF6-SiO2 melts and differential scanning calorimetry coupled with thermal gravimetric analysis of these melts were performed to verify the silica solubility mechanism.

  1. Modeling the co-transport of viruses and colloids in unsaturated porous media.

    Science.gov (United States)

    Seetha, N; Mohan Kumar, M S; Majid Hassanizadeh, S

    2015-10-01

    A mathematical model is developed to simulate the co-transport of viruses and colloids in unsaturated porous media under steady-state flow conditions. The virus attachment to the mobile and immobile colloids is described using a linear reversible kinetic model. Colloid transport is assumed to be decoupled from virus transport; that is, we assume that colloids are not affected by the presence of attached viruses on their surface. The governing equations are solved numerically using an alternating three-step operator splitting approach. The model is verified by fitting three sets of experimental data published in the literature: (1) Syngouna and Chrysikopoulos (2013) and (2) Walshe et al. (2010), both on the co-transport of viruses and clay colloids under saturated conditions, and (3) Syngouna and Chrysikopoulos (2015) for the co-transport of viruses and clay colloids under unsaturated conditions. We found a good agreement between observed and fitted breakthrough curves (BTCs) under both saturated and unsaturated conditions. Then, the developed model was used to simulate the co-transport of viruses and colloids in porous media under unsaturated conditions, with the aim of understanding the relative importance of various processes on the co-transport of viruses and colloids in unsaturated porous media. The virus retention in porous media in the presence of colloids is greater during unsaturated conditions as compared to the saturated conditions due to: (1) virus attachment to the air-water interface (AWI), and (2) co-deposition of colloids with attached viruses on its surface to the AWI. A sensitivity analysis of the model to various parameters showed that the virus attachment to AWI is the most sensitive parameter affecting the BTCs of both free viruses and total mobile viruses and has a significant effect on all parts of the BTC. The free and the total mobile viruses BTCs are mainly influenced by parameters describing virus attachment to the AWI, virus interaction

  2. Hyperon production in Ar+KCl collisions at 1.76A GeV

    Energy Technology Data Exchange (ETDEWEB)

    Agakishiev, G.; Belyaev, A.; Chernenko, S.; Fateev, O.; Zanevsky, Y. [Joint Institute of Nuclear Research, Dubna (Russian Federation); Balanda, A.; Dybczak, A.; Michalska, B.; Otwinowski, J.; Przygoda, W.; Salabura, P.; Trebacz, R.; Wisniowski, M.; Wojcik, T. [Jagiellonian University of Cracow, Smoluchowski Institute of Physics, Krakow (Poland); Bannier, B.; Dohrmann, F.; Kaempfer, B.; Kanaki, K.; Kotte, R.; Naumann, L.; Wendisch, C.; Wuestenfeld, J.; Zhou, P. [Institut fuer Strahlenphysik, Forschungszentrum Dresden-Rossendorf, Dresden (Germany); Bassini, R.; Iori, I. [Istituto Nazionale di Fisica Nucleare, Sezione di Milano, Milano (Italy); Belver, D.; Cabanelas, P.; Castro, E.; Garzon, J.A. [Universidad de Santiago de Compostela, Departamento de Fisica de Particulas, Santiago de Compostela (Spain); Blanco, A.; Fonte, P.; Lopes, L.; Mangiarotti, A. [LIP-Laboratorio de Instrumentacao e Fisica Experimental de Particulas, Coimbra (Portugal); Boehmer, M.; Christ, T.; Eberl, T.; Friese, J.; Gernhaeuser, R.; Huck, P.; Jurkovic, M.; Kruecken, R.; Maier, L.; Sailer, B.; Weber, M. [Technische Universitaet Muenchen, Physik Department E12, Muenchen (Germany); Boyard, J.L.; Gumberidze, M.; Hennino, T.; Liu, T.; Moriniere, E.; Ramstein, B.; Roy-Stephan, M. [Universite Paris Sud, Institut de Physique Nucleaire (UMR 8608), CNRS/IN2P3, Orsay Cedex (France); Destefanis, M.; Gilardi, C.; Kirschner, D.; Kuehn, W.; Lange, J.S.; Metag, V.; Mishra, D.; Perez Cavalcanti, T.; Spataro, S.; Spruck, B. [Justus Liebig Universitaet Giessen, II. Physikalisches Institut, Giessen (Germany); Diaz, J.; Gil, A. [Universidad de Valencia-CSIC, Instituto de Fisica Corpuscular, Valencia (Spain); Epple, E.; Fabbietti, L.; Lapidus, K.; Siebenson, J. [Excellence Cluster ' ' Origin and Structure of the Universe' ' , Munich (Germany); Finocchiaro, P. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Catania (Italy)] [and others

    2011-02-15

    We present transverse momentum spectra, rapidity distribution and multiplicity of {lambda} -hyperons measured with the HADES spectrometer in the reaction Ar(1.76AGeV)+KCl. The yield of {xi}{sup -} is calculated from our previously reported {xi}{sup -}/({lambda}+{sigma}{sup 0}) ratio and compared to other strange particle multiplicities. Employing a strangeness balance equation the multiplicities of the yet unmeasured {sigma}{sup {+-}} -hyperons can be estimated. Finally a statistical hadronization model is used to fit the yields of {pi}{sup -}, K{sup +}, K {sup 0} {sub s}, K{sup -}, {phi}, {lambda} and {xi}{sup -}. The resulting chemical freeze-out temperature of T = (76{+-}2) MeV is compared to the measured slope parameters obtained from fits to the transverse mass distributions of the different particles. (orig.)

  3. Hyperon production in Ar+KCl collisions at 1.76A GeV

    CERN Document Server

    Agakishiev, G; Bannier, B; Bassini, R; Belver, D; Belyaev, A; Blanco, A; Böhmer, M; Boyard, J L; Cabanelas, P; Castro, E; Chernenko, S; Christ, T; Destefanis, M; Diaz, J; Dohrmann, F; Dybczak, A; Eberl, T; Epple, E; Fabbietti, L; Fateev, O; Finocchiaro, P; Fonte, P; Friese, J; Froehlich, I; Galatyuk, T; Garzon, J A; Gernhaeuser, R; Gil, A; Gilardi, C; Golubeva, M; Gonzalez-Diaz, D; Guber, F; Gumberidze, M; Heilmann, M; Heinz, T; Hennino, T; Holzmann, R; Huck, P; Iori, I; Ivashkin, A; Jurkovic, M; Kaempfer, B; Kanaki, K; Karavicheva, T; Kirschner, D; Koenig, I; Koenig, W; Kolb, B W; Kotte, R; Krizek, F; Kruecken, R; Kuehn, W; Kugler, A; Kurepin, A; Lang, S; Lange, J S; Lapidus, K; Liu, T; Lopes, L; Lorenz, M; Maier, L; Mangiarotti, A; Markert, J; Metag, V; Michalska, B; Michel, J; Mishra, D; Moriniere, E; Mousa, J; Muentz, C; Naumann, L; Otwinowski, J; Pachmayer, Y C; Palka, M; Parpottas, Y; Pechenov, V; Pechenova, O; Perez-Cavalcanti, T; Pietraszko, J; Przygoda, W; Ramstein, B; Reshetin, A; Roy-Stephan, M; Rustamov, A; Sadovsky, A; Sailer, B; Salabura, P; Schmah, A; Schwab, E; Siebenson, J; Sobolev, Yu G; Spataro, S; Spruck, B; Stroebele, H; Stroth, J; Sturm, C; Tarantola, A; Teilab, K; Tlusty, P; Traxler, M; Trebacz, R; Tsertos, H; Wagner, V; Weber, M; Wendisch, C; Wisniowski, M; Wojcik, T; Wuestenfeld, J; Yurevich, S; Zanevsky, Y; Zhou, P; Zumbruch, P

    2010-01-01

    We present transverse momentum spectra, rapidity distribution and multiplicity of Lambda-hyperons measured with the HADES spectrometer in the reaction Ar(1.76A GeV)+KCl. The yield of Xi- is calculated from our previously reported Xi-/(Lambda+Sigma0) ratio and compared to other strange particle multiplicities. Employing a strangeness balance equation the multiplicities of the yet unmeasured charged Sigma hyperons can be estimated. Finally a statistical hadronization model is used to fit the yields of pi-, K+, K0s, K-, phi, Lambda and Xi-. The resulting chemical freeze-out temperature of T=(76+-2) MeV is compared to the measured slope parameters obtained from fits to the transverse mass distributions of the particles.

  4. Dielectron production in Ar+KCl collisions at 1.76A GeV

    CERN Document Server

    Agakishiev, G; Belver, D; Belyaev, A; Blanco, A; Böhmer, M; Boyard, J L; Cabanelas, P; Castro, E; Chernenko, S; Christ, T; Destefanis, M; Dohrmann, F; Dybczak, A; Eberl, T; Epple, E; Fabbbietti, L; Fateev, O; Finocchiaro, P; Fonte, P; Friese, J; Fröhlich, I; Galatyuk, T; Garzon, J A; Gernhäuser, R; Gilardi, C; Golubeva, M; Gonzalez-Díaz, D; Guber, F; Gumberidze, M; Heinz, T; Hennino, T; Holzmann, R; Huck, P; Iori, I; Ivashkin, A; Jurkovic, M; Kämpfer, B; Kanaki, K; Karavicheva, T; Koenig, I; Koenig, W; Kolb, B W; Kotte, R; Krasa, A; Krizek, F; Krücken, R; Kuc, H; Kühn, W; Kugler, A; Kurepin, A; Lang, S; Lange, J S; Liu, K Lapidus T; Lopes, L; Lorenz, M; Maier, L; Mangiarotti, A; Markert, J; Metag, V; Michalska, B; Michel, J; Moriniere, E; Mousa, J; Müntz, C; Naumann, L; Otwinowski, J; Pachmayer, Y C; Palka, M; Pechenov, V; Pechenova, O; Pietraszko, J; Przygoda, W; Ramstein, B; Reshetin, A; Rustamov, A; Sadovsky, A; Sailer, B; Salabura, P; Schmah, A; Schwab, E; Siebenson, J; Sobolev, Yu G; Spataro, S; Spruck, B; Ströbele, H; Stroth, J; Sturm, C; Tarantola, A; Teilab, K; Tlusty, P; Traxler, M; Trebacz, R; Tsertos, H; Wagner, V; Weber, M; Wendisch, C; Wisniowski, M; Wüstenfeld, J; Yurevich, S; Zanevsky, Y

    2011-01-01

    We present results on dielectron production in Ar+KCl collisions at 1.76A GeV. For the first time $\\omega$ mesons could be reconstructed in a heavy-ion reaction at a bombarding energy which is well below the production threshold in free nucleon-nucleon collisions. The omega multiplicity has been extracted and compared to the yields of other particles, in particular of the phi meson. At intermediate e+e- invariant masses, we find a strong enhancement of the pair yield over a reference spectrum from elementary nucleon-nucleon reactions suggesting the onset of non-trivial effects of the nuclear medium. Transverse-mass spectra and angular distributions have been reconstructed in three invariant mass bins. In the former unexpectedly large slopes are found for high-mass pairs. The latter, in particular the helicity-angle distributions, are largely consistent with expectations for a pair cocktail dominated at intermediate masses by delta Dalitz decays.

  5. Application of aluminum diffusion coatings to mitigate the KCl-induced high-temperature corrosion

    DEFF Research Database (Denmark)

    Kiamehr, Saeed; Lomholt, T. N.; Dahl, Kristian Vinter

    2017-01-01

    Pack cementation was used to produce Fe1−xAl and Fe2Al5 diffusion coatings on ferritic-martensitic steel P91 and a Ni2Al3 diffusion coating on pure nickel. The performance of diffusion coatings against high-temperature corrosion induced by potassium chloride (KCl) was evaluated by exposing......-ray diffractometry (XRD) before and after the exposures. It was found that all the diffusion coatings formed protective oxides under salt-free exposure in air. Under the salt deposit, Fe1−xAl showed local failure while on large parts of the sample a protective layer had formed. Fe2Al5 was attacked over the entire...

  6. Hyperon production in Ar + KCl collisions at 1.76A GeV

    Science.gov (United States)

    Agakishiev, G.; Balanda, A.; Bannier, B.; Bassini, R.; Belver, D.; Belyaev, A.; Blanco, A.; Böhmer, M.; Boyard, J. L.; Cabanelas, P.; Castro, E.; Chernenko, S.; Christ, T.; Destefanis, M.; Dıaz, J.; Dohrmann, F.; Dybczak, A.; Eberl, T.; Epple, E.; Fabbietti, L.; Fateev, O.; Finocchiaro, P.; Fonte, P.; Friese, J.; Fröhlich, I.; Galatyuk, T.; Garzón, J. A.; Gernhäuser, R.; Gil, A.; Gilardi, C.; Golubeva, M.; González-Dıaz, D.; Guber, F.; Gumberidze, M.; Heilmann, M.; Heinz, T.; Hennino, T.; Holzmann, R.; Huck, P.; Iori, I.; Ivashkin, A.; Jurkovic, M.; Kämpfer, B.; Kanaki, K.; Karavicheva, T.; Kirschner, D.; Koenig, I.; Koenig, W.; Kolb, B. W.; Kotte, R.; Krizek, F.; Krücken, R.; Kühn, W.; Kugler, A.; Kurepin, A.; Lang, S.; Lange, J. S.; Lapidus, K.; Liu, T.; Lopes, L.; Lorenz, M.; Maier, L.; Mangiarotti, A.; Markert, J.; Metag, V.; Michalska, B.; Michel, J.; Mishra, D.; Morinière, E.; Mousa, J.; Müntz, C.; Naumann, L.; Otwinowski, J.; Pachmayer, Y. C.; Palka, M.; Parpottas, Y.; Pechenov, V.; Pechenova, O.; Pérez Cavalcanti, T.; Pietraszko, J.; Przygoda, W.; Ramstein, B.; Reshetin, A.; Roy-Stephan, M.; Rustamov, A.; Sadovsky, A.; Sailer, B.; Salabura, P.; Schmah, A.; Schwab, E.; Siebenson, J.; Sobolev, Yu. G.; Spataro, S.; Spruck, B.; Ströbele, H.; Stroth, J.; Sturm, C.; Tarantola, A.; Teilab, K.; Tlusty, P.; Traxler, M.; Trebacz, R.; Tsertos, H.; Wagner, V.; Weber, M.; Wendisch, C.; Wisniowski, M.; Wojcik, T.; Wüstenfeld, J.; Yurevich, S.; Zanevsky, Y.; Zhou, P.; Zumbruch, P.

    2011-02-01

    We present transverse momentum spectra, rapidity distribution and multiplicity of Λ -hyperons measured with the HADES spectrometer in the reaction Ar(1.76AGeV) + KCl . The yield of Ξ^{{-}}_{} is calculated from our previously reported Ξ^{{-}}_{}/( Λ + Σ^{{0}}_{}) ratio and compared to other strange particle multiplicities. Employing a strangeness balance equation the multiplicities of the yet unmeasured Σ^{{±}}_{} -hyperons can be estimated. Finally a statistical hadronization model is used to fit the yields of π-_{} , K+, K 0 s , K-, φ , Λ and Ξ-_{} . The resulting chemical freeze-out temperature of T = (76±2) MeV is compared to the measured slope parameters obtained from fits to the transverse mass distributions of the different particles.

  7. Dielectron production in Ar + KCl collisions at 1.76A GeV

    Science.gov (United States)

    Agakishiev, G.; Balanda, A.; Belver, D.; Belyaev, A.; Blanco, A.; Böhmer, M.; Boyard, J. L.; Cabanelas, P.; Castro, E.; Chernenko, S.; Christ, T.; Destefanis, M.; Dohrmann, F.; Dybczak, A.; Eberl, T.; Epple, E.; Fabbietti, L.; Fateev, O.; Finocchiaro, P.; Fonte, P.; Friese, J.; Fröhlich, I.; Galatyuk, T.; Garzón, J. A.; Gernhäuser, R.; Gilardi, C.; Golubeva, M.; González-Díaz, D.; Guber, F.; Gumberidze, M.; Heinz, T.; Hennino, T.; Holzmann, R.; Huck, P.; Iori, I.; Ivashkin, A.; Jurkovic, M.; Kämpfer, B.; Kanaki, K.; Karavicheva, T.; Koenig, I.; Koenig, W.; Kolb, B. W.; Kotte, R.; Krása, A.; Krizek, F.; Krücken, R.; Kuc, H.; Kühn, W.; Kugler, A.; Kurepin, A.; Lang, S.; Lange, J. S.; Lapidus, K.; Liu, T.; Lopes, L.; Lorenz, M.; Maier, L.; Mangiarotti, A.; Markert, J.; Metag, V.; Michalska, B.; Michel, J.; Morinière, E.; Mousa, J.; Müntz, C.; Naumann, L.; Otwinowski, J.; Pachmayer, Y. C.; Palka, M.; Pechenov, V.; Pechenova, O.; Pietraszko, J.; Przygoda, W.; Ramstein, B.; Reshetin, A.; Rustamov, A.; Sadovsky, A.; Sailer, B.; Salabura, P.; Schmah, A.; Schwab, E.; Siebenson, J.; Sobolev, Yu. G.; Spataro, S.; Spruck, B.; Ströbele, H.; Stroth, J.; Sturm, C.; Tarantola, A.; Teilab, K.; Tlusty, P.; Traxler, M.; Trebacz, R.; Tsertos, H.; Wagner, V.; Weber, M.; Wendisch, C.; Wisniowski, M.; Wüstenfeld, J.; Yurevich, S.; Zanevsky, Y.

    2011-07-01

    We present results on dielectron production in 40Ar+KCl collisions at 1.76A GeV. For the first time ω mesons could be reconstructed in a heavy-ion reaction at a bombarding energy which is well below the production threshold in free nucleon-nucleon collisions. The ω multiplicity has been extracted and compared to the yields of other particles, in particular of the φ meson. At intermediate e+e- invariant masses, we find a strong enhancement of the pair yield over a reference spectrum from elementary nucleon-nucleon reactions, suggesting the onset of nontrivial effects of the nuclear medium. Transverse-mass spectra and angular distributions have been reconstructed in three invariant mass bins. In the former unexpectedly large slopes are found for high-mass pairs. The latter, in particular the helicity-angle distributions, are largely consistent with expectations for a pair cocktail dominated at intermediate masses by Δ Dalitz decays.

  8. Development of high temperature transport technology for LiCl-KCl eutectic salt in pyroprocessing

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Ho; Lee, Hansoo; Kim, In Tae; Kim, Jeong-Guk [Korea Atomic Energy Research Institute, 1045 Daedeok-daaro, Yuseong-gu, Daejeon, 305-353 (Korea, Republic of)

    2013-07-01

    The development of high-temperature transport technologies for molten salt is a prerequisite and a key issue in the industrialization of pyro-reprocessing for advanced fuel cycle scenarios. The solution of a molten salt centrifugal pump was discarded because of the high corrosion power of a high temperature molten salt, so the suction pump solution was selected. An apparatus for salt transport experiments by suction was designed and tested using LiC-KCl eutectic salt. The experimental results of lab-scale molten salt transport by suction showed a 99.5% transport rate (ratio of transported salt to total salt) under a vacuum range of 100 mtorr - 10 torr at 500 Celsius degrees. The suction system has been integrated to the PRIDE (pyroprocessing integrated inactive demonstration) facility that is a demonstrator using non-irradiated materials (natural uranium and surrogate materials). The performance of the suction pump for the transport of molten salts has been confirmed.

  9. High Temperature Corrosion of Inconel 600 in NaCl-KCl Molten Salts

    Directory of Open Access Journals (Sweden)

    G. Salinas-Solano

    2014-01-01

    Full Text Available In this work the corrosion resistance of a high content nickel alloy, Inconel 600, was investigated in mixed NaCl-KCl salts at 700, 800, and 900°C for 100 hours in static air. Investigation was carried out using electrochemical techniques such as polarization curves, rest potential measurements, linear polarization resistance, and electrochemical impedance spectroscopy. Corroded specimens were analyzed by scanning electron microscopy (SEM and energy-dispersive X-ray spectroscopy (EDS. Electrochemical measurements showed an increased degradation rate of Inconel 600 with increasing test temperature. SEM and EDS analysis show that the damage experienced by Inconel 600 is greater than that determined by electrochemical measurements. This damage was identified as internal corrosion due to the reaction of Cl2 with the alloying elements (Cr and Fe; however, at 900°C the internal damage was minor and it was associated with the nickel content in the alloy.

  10. Solubilidade do SrO em NaCl-Kcl fundido a 727ºC

    Directory of Open Access Journals (Sweden)

    Combes Richard Louis

    2000-01-01

    Full Text Available The solubility product value of SrO has been found to be equal to 10-4,2 (molality scale in molten equimolar mixture of NaCl and KCl at 727ºC, using a potentiometric method involving a calcia stabilized zirconia membrane electrode. This value, which is in a logical agreement with other alkaline-earth oxide determined solubilities, is compared to those of 10-5,8, 10-3,0 and 10-3,08 (molality scale found in the litterature 33, 22 and 5 years ago, respectively. Such discrepencies have called the attention of the authors, their possible reasons (methodology, titrating agent are analyzed and a theoretical discussion, for considering the authors' value as more reliable, is given in this paper.

  11. Measurements of pressure for the TiH/sub x//KClO/sub 4/ system

    Energy Technology Data Exchange (ETDEWEB)

    Chong, C.H.H.; Glaub, J.E.

    1978-04-10

    An investigation was conducted to measure the pressure obtained when the pyrotechnic mixture TiH/sub x//KClO/sub 4/ was ignited in a confined variable-volume system. It was possible to derive an expression of the form PV/sup ..gamma../ = k for the pressure-volume relationship obtained. This expression is a polytropic expansion of the ideal gas equation that best fits the data generated. For this particular work, values of ..gamma.. = 0.53 and k = 69.3 were obtained where P is in megapascals and V is in cubic centimeters. In addition, estimates of the reaction rates were calculated based on the times to achieve maximum pressure for a given volume system. An explicit expression relating rate to pressure was derived by a simplified least-squares fit of the data obtained.

  12. Long-term aldosterone administration increases renal Na+-Cl- cotransporter abundance in late distal convoluted tubule

    DEFF Research Database (Denmark)

    Poulsen, Søren Brandt; Christensen, Birgitte M

    2016-01-01

    Renal Na+-Cl- cotransporter (NCC) is expressed in early distal convoluted tubule (DCT) 1 and late DCT (DCT2). NCC activity can be stimulated by aldosterone, and the mechanism is assumed to depend on the enzyme, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids...... that would otherwise occupy aldosterone receptors. Because 11β-HSD2 in rat may only be abundantly expressed in DCT2 cells and not in DCT1 cells, it has been speculated that aldosterone specifically stimulates NCC activity in DCT2 cells. In mice, however, it is debated if 11β-HSD2 is expressed in DCT2 cells....... The present study examined whether aldosterone-administration in mice stimulates NCC abundance and phosphorylation in DCT2 cells but not in DCT1 cells. B6/C57 male mice were administered 100 µg aldosterone (kg body weight)-1 (24 h)-1 for 6 days and euthanized during isoflurane inhalation. Western blotting...

  13. Electrochemical studies and analysis of 1-10 wt% UCl3 concentrations in molten LiCl-KCl eutectic

    Science.gov (United States)

    Hoover, Robert O.; Shaltry, Michael R.; Martin, Sean; Sridharan, Kumar; Phongikaroon, Supathorn

    2014-09-01

    Three electrochemical methods - cyclic voltammetry (CV), chronopotentiometry (CP), and anodic stripping voltammetry (ASV) - were applied to solutions of up to 10 wt% UCl3 in the molten LiCl-KCl eutectic salt at 500 °C to determine electrochemical properties and behaviors and to help provide a scientific basis for the development of an in situ electrochemical probe for determining the concentration of uranium in a used nuclear fuel electrorefiner. Diffusion coefficients of UCl4 and UCl3 were calculated to be (6.72 ± 0.360) × 10-6 cm2/s and (1.04 ± 0.17) × 10-5 cm2/s, respectively. Apparent standard reduction potentials were determined to be (-0.381 ± 0.013) V and (-1.502 ± 0.076) V vs. 5 mol% Ag/AgCl or (-1.448 ± 0.013) V and (-2.568 ± 0.076) V vs. Cl2/Cl- for the U(IV)/U(III) and U(III)/U redox couples, respectively. In comparing this data with supercooled thermodynamic data to determine activity coefficients, the thermodynamic database used was important with resulting activity coefficients ranging from 2.34 × 10-3 to 1.08 × 10-2 for UCl4 and 4.94 × 10-5 to 4.50 × 10-4 for UCl3. Of anodic stripping voltammetry and cyclic voltammetry anodic or cathodic peaks, the CV cathodic peak height divided by square root of scan rate was shown to be the most reliable method of determining UCl3 concentration in the molten salt.

  14. Expression of the sodium potassium chloride cotransporter (NKCC1) and sodium chloride cotransporter (NCC) and their effects on rat lens transparency.

    Science.gov (United States)

    Chee, K N; Vorontsova, I; Lim, J C; Kistler, J; Donaldson, P J

    2010-05-04

    To characterize the expression patterns of the Na+-K+-Cl(-) cotransporter (NKCC) 1 and NKCC2, and the Na+-Cl(-) cotransporter (NCC) in the rat lens and to determine if they play a role in regulating lens volume and transparency. RT-PCR was performed on RNA extracted from fiber cells to identify sodium dependent cotransporters expressed in the rat lens. Western blotting and immunohistochemistry, using NKCC1, NKCC2, and NCC antibodies, were used to verify expression at the protein level and to localize transporter expression. Organ cultured rat lenses were incubated in Artificial Aqueous Humor (AAH) of varying osmolarities or isotonic AAH that contained either the NKCC specific inhibitor bumetanide, or the NCC specific inhibitor thiazide for up to 18 h. Lens transparency was monitored with dark field microscopy, while tissue morphology and antibody labeling patterns were recorded using a confocal microscope. Molecular experiments showed that NKCC1 and NCC were expressed in the lens at both the transcript and protein levels, but NKCC2 was not. Immunohistochemistry showed that both NKCC1 and NCC were expressed in the lens cortex, but NCC expression was also found in the lens core. In the lens cortex the majority of labeling for both transporters was cytoplasmic in nature, while in the lens core, NCC labeling was associated with the membrane. Exposure of lenses to either hypotonic or hypertonic AAH had no noticeable effects on the predominantly cytoplasmic location of either transporter in the lens cortex. Incubation of lenses in isotonic AAH plus the NKCC inhibitor bumetanide for 18 h induced a cortical opacity that was initiated by a shrinkage of peripheral fiber cells and the dilation of the extracellular space between fiber cells in a deeper zone located some approximately 150 microm in from the capsule. In contrast, lenses incubated in isotonic AAH and the NCC inhibitor thiazide maintained both their transparency and their regular fiber cell morphology. We have

  15. Inclusive Dielectron Production in Ar+KCl Collisions at 1.76 AGeV studied with HADES

    CERN Document Server

    Krizek, F; Balanda, A; Bellia, G; Belver, D; Belyaev, A; Blanco, A; Boehmer, M; Boyard, J L; Braun-Munzinger, P; Cabanelas, P; Castro, E; Chernenko, S; Christ, T; Destefanis, M; Díaz, J; Dohrmann, F; Dybczak, A; Fabbietti, L; Fateev, O; Finocchiaro, P; Fonte, P; Friese, J; Fröhlich, I; Galatyuk, T; Garzón, J A; Gernhäuser, R; Gil, A; Gilardi, C; Golubeva, M; Gonzalez-Diaz, D; Grosse, E; Guber, F; Heilmann, M; Hennino, T; Holzmann, R; Ierusalimov, A; Iori, I; Ivashkin, A; Jurkovic, M; Kämpfer, B; Kanaki, K; Karavicheva, T; Kirschner, D; König, I; König, W; Kolb, B W; Kotte, R; Kozuch, A; Krasa, A; Krücken, R; Kühn, W; Kugler, A; Kurepin, A; Lamas-Valverde, J; Lang, S; Lange, J S; Lapidus, K; Liu, T; Lopes, L; Lorenz, M; Maier, L; Mangiarotti, A; Marin, J; Markert, J; Metag, V; Michalska, B; Michel, J; Mishra, D; Moriniere, E; Mousa, J; Müntz, C; Naumann, L; Novotny, R; Otwinowski, J; Pachmayer, Y C; Palka, M; Parpottas, Y; Pechenov, V; Pechenova, O; Cavalcanti, T Perez; Pietraszko, J; Przygoda, W; Ramstein, B; Reshetin, A; Rustamov, A; Sadovskii, A; Salabura, P; Schmah, A; Simon, R; Sobolev, Yu G; Spataro, S; Spruck, B; Ströbele, H; Stroth, J; Sturm, C; Sudol, M; Tarantola, A; Teilab, K; Tlustý, P; Traxler, M; Trebacz, R; Tsertos, H; Veretenkin, I; Wagner, V; Weber, M; Wisniowski, M; Wüstenfeld, J; Yurevich, S; Zanevsky, Y; Zhou, P; Zumbruch, P

    2009-01-01

    Results of the HADES measurement of inclusive dielectron production in Ar+KCl collisions at a kinetic beam energy of 1.76 AGeV are presented. For the first time, high mass resolution spectroscopy was performed. The invariant mass spectrum of dielectrons is compared with predictions of UrQMD and HSD transport codes.

  16. Micro-structural study of the GeS2-In2S3-KCl glassy system by Raman scattering.

    Science.gov (United States)

    Haizheng, Tao; Xiujian, Zhao; Wei, Tong; Shun, Mao

    2006-07-01

    Room temperature Raman spectra of samples on three serials within the GeS(2)-In(2)S(3)-KCl glassy system have been investigated systematically. According to XRD patterns and Raman spectra of several pseudo-binary systems, the Cl atoms, which was added into the GeS(2)-In(2)S(3) glasses through KCl, was considered to be leading to the breaking of In-In bonds among the S(3)In-InS(3) ethane-like units and the forming of InS(4-x)Cl(x), InS(6-x)Cl(x) mixed polyhedra. Considering the effect of K(+) ions upon mixed anion units (InS(4-x)Cl(x) and InS(6-x)Cl(x)) and the corresponding micro-structural model, the Raman spectral evolution of the GeS(2)-In(2)S(3)-KCl glasses can be elucidated successfully. The microstructure of the GeS(2)-In(2)S(3)-KCl glasses was considered to be that the potassium atoms, which exist in the form of chlorine atoms as its nearest neighbor, are homogeneously dispersed in the glassy net formed by the micro-structural units such as InS(4), InS(6), InS(4-x)Cl(x), InS(6-x)Cl(x), GeS(4) polyhedra and S(3)In(Ge)-In(Ge)S(3) ethane-like units.

  17. Uncertainties of Gaseous Oxidized Mercury Measurements Using KCl-Coated Denuders, Cation-Exchange Membranes, and Nylon Membranes: Humidity Influences.

    Science.gov (United States)

    Huang, Jiaoyan; Gustin, Mae Sexauer

    2015-05-19

    Quantifying the concentration of gaseous oxidized mercury (GOM) and identifying the chemical compounds in the atmosphere are important for developing accurate local, regional, and global biogeochemical cycles. The major hypothesis driving this work was that relative humidity affects collection of GOM on KCl-coated denuders and nylon membranes, both currently being applied to measure GOM. Using a laboratory manifold system and ambient air, GOM capture efficiency on 3 different collection surfaces, including KCl-coated denuders, nylon membranes, and cation-exchange membranes, was investigated at relative humidity ranging from 25 to 75%. Recovery of permeated HgBr2 on KCl-coated denuders declined by 4-60% during spikes of relative humidity (25 to 75%). When spikes were turned off GOM recoveries returned to 60 ± 19% of permeated levels. In some cases, KCl-coated denuders were gradually passivated over time after additional humidity was applied. In this study, GOM recovery on nylon membranes decreased with high humidity and ozone concentrations. However, additional humidity enhanced GOM recovery on cation-exchange membranes. In addition, reduction and oxidation of elemental mercury during experiments was observed. The findings in this study can help to explain field observations in previous studies.

  18. The influence of oxide on the electrochemical processes in K2NbF7-NaCl-KCl melts

    DEFF Research Database (Denmark)

    Lantelme, F.; Berghoute, Y.; Barner, Jens H. Von;

    1995-01-01

    Transient electrochemical techniques showed that in NaCl-KCl melts the reduction of K2NbF7 occurs through atwo-step reaction Nb(V) --> Nb(IV) --> Nb. When oxide ions were introduced, cyclic voltammetry indicated that the wavescorresponding to reduction of the complex NbF72- progressively...

  19. Electrochemical extraction of neodymium by co-reduction with aluminum in LiCl-KCl molten salt

    Science.gov (United States)

    Yan, Yong-De; Xu, Yan-Lu; Zhang, Mi-Lin; Xue, Yun; Han, Wei; Huang, Ying; Chen, Qiong; Zhang, Zhi-Jian

    2013-02-01

    The electrochemical behavior of Nd(III) ions in LiCl-KCl and LiCl-KCl-AlCl3 melts on a Mo electrode at 723 K was studied by various electrochemical techniques. The results showed that Nd(III) ions are reduced to Nd(0) through two consecutive steps, and the underpotential deposition of neodymium on pre-deposited Al electrode formed two kinds of Al-Nd intermetallic compounds in LiCl-KCl-AlCl3 solutions. The electrochemical extraction of neodymium was carried out in LiCl-KCl-AlCl3 melts on a Mo electrode at 873 K by potentiostatic and galvanostatic electrolysis. The extraction efficiency was 99.25% after potentiostatic electrolysis for 30 h. Al-Li-Nd bulk alloy was obtained by galvanostatic electrolysis. X-ray diffraction (XRD) suggested that Al2Nd and Al3Nd phases were formed in Al-Li-Nd alloy. The microstructure and micro-zone chemical analysis of Al-Li-Nd alloy were characterized by scanning electron microscopy (SEM) with energy dispersive spectrometry (EDS), respectively.

  20. Densities of L-Glutamic Acid HCl Drug in Aqueous NaCl and KCl Solutions at Different Temperatures

    Science.gov (United States)

    Ryshetti, Suresh; Raghuram, Noothi; Rani, Emmadi Jayanthi; Tangeda, Savitha Jyostna

    2016-04-01

    Densities (ρ ) of (0.01 to 0.07) {mol}{\\cdot } {kg}^{-1} L-Glutamic acid HCl (L-HCl) drug in water, and in aqueous NaCl and KCl (0.5 and 1.0) {mol}{\\cdot } {kg}^{-1} solutions have been reported as a function of temperature at T = (298.15, 303.15, 308.15, and 313.15) K and atmospheric pressure. The accurate density (ρ ) values are used to estimate the various parameters such as the apparent molar volume (V_{2,{\\upphi }}), the partial molar volume (V2^{∞}), the isobaric thermal expansion coefficient (α 2), the partial molar expansion (E2^{∞}), and Hepler's constant (partial 2V2^{∞}/partial T2)P. The Cosphere overlap model is used to understand the solute-solvent interactions in a ternary mixture (L-HCl drug + NaCl or KCl + water). Hepler's constant (partial 2V2^{∞}/partial T2)_P is utilized to interpret the structure-making or -breaking ability of L-HCl drug in aqueous NaCl and KCl solutions, and the results are inferred that L-HCl drug acts as a structure maker, i.e., kosmotrope in aqueous NaCl solutions and performs as a structure breaker, i.e., chaotrope in aqueous KCl solutions.

  1. Elaboration and characterization of a KCl single crystal doped with nanocrystals of a Sb2O3 semiconductor

    Institute of Scientific and Technical Information of China (English)

    L.Bouhdjer; S.Addala; A.Chala; O.Halimi; B.Boudine; M.Sebais

    2013-01-01

    Undoped and doped KCl single crystals have been successfully elaborated via the Czochralski (Cz)method.The effects of dopant Sb2O3 nanocrystals on structural and optical properties were investigated by a number of techniques,including X-ray diffraction (XRD),scanning electron microscopy (SEM),energy dispersive X-ray (EDAX) analysis,UV-visible and photoluminescence (PL) spectrophotometers.An XRD pattern of KCl:Sb2O3 reveals that the Sb2O3 nanocrystals are in the well-crystalline orthorhombic phase.The broadening of diffraction peaks indicated the presence of a Sb2O3 semiconductor in the nanometer size regime.The shift of absorption and PL peaks is observed near 334 nm and 360 nm respectively due to the quantum confinement effect in Sb2O3 nanocrystals.Particle sizes calculated from XRD studies agree fairly well with those estimated from optical studies.An SEM image of the surface KCl:Sb2O3 single crystal shows large quasi-spherical of Sb2O3 crystallites scattered on the surface.The elemental analysis from EDAX demonstrates that the KCl:Sb2O3 single crystal is slightly rich in oxygen and a source of excessive quantities of oxygen is discussed.

  2. KCl -Permeabilized Pancreatic Islets: An Experimental Model to Explore the Messenger Role of ATP in the Mechanism of Insulin Secretion.

    Directory of Open Access Journals (Sweden)

    Javier Pizarro-Delgado

    Full Text Available Our previous work has demonstrated that islet depolarization with KCl opens connexin36 hemichannels in β-cells of mouse pancreatic islets allowing the exchange of small metabolites with the extracellular medium. In this study, the opening of these hemichannels has been further characterized in rat islets and INS-1 cells. Taking advantage of hemicannels'opening, the uptake of extracellular ATP and its effect on insulin release were investigated. 70 mM KCl stimulated light emission by luciferin in dispersed rat islets cells transduced with the fire-fly luciferase gene: it was suppressed by 20 mM glucose and 50 μM mefloquine, a specific connexin36 inhibitor. Extracellular ATP was taken up or released by islets depolarized with 70 mM KCl at 5 mM glucose, depending on the external ATP concentration. 1 mM ATP restored the loss of ATP induced by the depolarization itself. ATP concentrations above 5 mM increased islet ATP content and the ATP/ADP ratio. No ATP uptake occurred in non-depolarized or KCl-depolarized islets simultaneously incubated with 50 μM mefloquine or 20 mM glucose. Extracellular ATP potentiated the secretory response induced by 70 mM KCl at 5 mM glucose in perifused rat islets: 5 mM ATP triggered a second phase of insulin release after the initial peak triggered by KCl-depolarization itself; at 10 mM, it increased both the initial, KCl-dependent, peak and stimulated a greater second phase of secretion than at 5 mM. These stimulatory effects of extracellular ATP were almost completely suppressed by 50 μM mefloquine. The magnitude of the second phase of insulin release due to 5 mM extracellular ATP was decreased by addition of 5 mM ADP (extracellular ATP/ADP ratio = 1. ATP acts independently of KATP channels closure and its intracellular concentration and its ATP/ADP ratio seems to regulate the magnitude of both the first (triggering and second (amplifying phases of glucose-induced insulin secretion.

  3. Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Rosenthal, Norm; Meininger, Gary; Ways, Kirk; Polidori, David; Desai, Mehul; Qiu, Rong; Alba, Maria; Vercruysse, Frank; Balis, Dainius; Shaw, Wayne; Edwards, Robert; Bull, Scott; Di Prospero, Nicholas; Sha, Sue; Rothenberg, Paul; Canovatchel, William; Demarest, Keith

    2015-11-01

    The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin is a novel treatment option for adults with type 2 diabetes mellitus (T2DM). In patients with hyperglycemia, SGLT2 inhibition lowers plasma glucose levels by reducing the renal threshold for glucose (RTG ) and increasing urinary glucose excretion (UGE). Increased UGE is also associated with a mild osmotic diuresis and net caloric loss, which can lead to reductions in body weight and blood pressure (BP). After promising results from preclinical and phase I/II studies, the efficacy and safety of canagliflozin was evaluated in a comprehensive phase III development program in over 10,000 patients with T2DM on various background therapies. Canagliflozin improved glycemic control and provided reductions in body weight and BP versus placebo and active comparators in studies of up to 2 years' duration. Canagliflozin was generally well tolerated, with higher incidences of adverse events (AEs) related to the mechanism of action, including genital mycotic infections and AEs related to osmotic diuresis. Results from the preclinical and clinical studies led canagliflozin to be the first-in-class SGLT2 inhibitor approved in the United States, and support canagliflozin as a safe and effective therapeutic option across a broad range of patients with T2DM. © 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  4. A dileucine motif is involved in plasma membrane expression and endocytosis of rat sodium taurocholate cotransporting polypeptide (Ntcp).

    Science.gov (United States)

    Stross, Claudia; Kluge, Stefanie; Weissenberger, Katrin; Winands, Elisabeth; Häussinger, Dieter; Kubitz, Ralf

    2013-11-15

    The sodium taurocholate cotransporting polypeptide (Ntcp) is the major uptake transporter for bile salts into liver parenchymal cells, and PKC-mediated endocytosis was shown to regulate the number of Ntcp molecules at the plasma membrane. In this study, mechanisms of Ntcp internalization were analyzed by flow cytometry, immunofluorescence, and Western blot analyses in HepG2 cells. PKC activation induced endocytosis of Ntcp from the plasma membrane by ~30%. Endocytosis of Ntcp was clathrin dependent and was followed by lysosomal degradation. A dileucine motif located in the third intracellular loop of Ntcp was essential for endocytosis but also for processing and plasma membrane targeting, suggesting a dual function of this motif for intracellular trafficking of Ntcp. Mutation of two of five potential phosphorylation sites surrounding the dileucine motif (Thr225 and Ser226) inhibited PKC-mediated endocytosis. In conclusion, we could identify a motif, which is critical for Ntcp plasma membrane localization. Endocytic retrieval protects hepatocytes from elevated bile salt concentrations and is of special interest, because NTCP has been identified as a receptor for the hepatitis B and D virus.

  5. Renal Safety of Canagliflozin, a Sodium Glucose Co-transporter 2 Inhibitor, in Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Desai, Mehul; Yavin, Yshai; Balis, Dainius; Sun, Don; Xie, John; Canovatchel, William; Rosenthal, Norm

    2017-01-12

    The incidence of renal-related adverse events (AEs) with canagliflozin in patients with type 2 diabetes mellitus from a pooled population of patients in 7 active- and placebo-controlled trials (N = 5,598) and in a 104-week study versus glimepiride (N = 1,450) was low and similar in canagliflozin and non-canagliflozin groups. In the study versus glimepiride, canagliflozin was associated with an initial acute decrease in estimated glomerular filtration rate (eGFR) that attenuated over time, while eGFR declined progressively over 104 weeks with glimepiride; the incidence of renal-related AEs with canagliflozin was generally stable over time, while the incidence with glimepiride increased over 104 weeks. In the analysis reported in this manuscript based on postmarketing reports from the US Food and Drug Administration Adverse Event Reporting System, a potential signal was identified for acute kidney injury with all approved sodium glucose co-transporter 2 (SGLT2) inhibitors (ie, canagliflozin, dapagliflozin, empagliflozin). The early onset of acute kidney injury events with SGLT2 inhibitors in postmarketing reports likely reflects the acute changes in eGFR due to the known renal haemodynamic effects of SGLT2 inhibition.

  6. Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure.

    Science.gov (United States)

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Shull, Gary E; Siddiqui, Faraz; Zahedi, Kamyar; Amlal, Hassane

    2012-08-14

    The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema.

  7. EPIDURAL ANESTHESIA BUPIVACAINE 0.5%+ KCL 5 MEQ/L VS BUPIVACAINE 0.5%

    Directory of Open Access Journals (Sweden)

    F ALAVI

    2000-03-01

    Full Text Available Background. Although epidural anesthesia is a Successful method for most surgical procedures on lower extremities and lower abdomen. It is not so favorable because of it's slow onset and differential sensory and motor block. In order to solve this problem effects of additive KCl (5 meq/L into Bupivacaine 0.5 percent according to onset, intensity, duration of block and homodynamic changes during epidural anesthesia will be investigated through the present study. Methods. All the ASA I or II patients at medical centers of Isfahan university of medical sciences throughout 1378, candidate for elective Surgical procedures on lower extremities and lower abdomen with no contraindication for epidural anesthesia were Subdivided into Case (35 patients and Control (35 patients groups in a random manner to perform a double blind clinical trial. Epidural anesthesia applied to cases (by Bupivacaine 0.5 percent+ KCl 5meq/L and controls (by Bupivacaine 0.5 percent. Under identical conditions, data indicating basic MAP, basic heart rate and their changes as well as the onset, duration and intensity of motor and sensory block, were obtained and recorded by the anesthesiologist. Quantitative & qualitative variables were examined by T.test and X2 test respectively. Findings. Sensory onset for cases (8.22±1.43Min was faster than controls (11.56±1.45Min (P<0.005. Motor onset for cases (12.77 ± 1.83Min was faster than controls (20.24±1.71Min (P < 0.005. Sensory duration for cases (l86.34±8.37 Min was longer than controls (162.17±7.47Min (P<0.005. Motor duration for cases (106.25±13.50 Min was longer than controls (77.60 ± 9.94Min (P < 0.005.Intensity of sensory block for cases was greater than controls (P < 0.01. Intensity of motor block for cases was greater than controls (P < 0.001. Mean heart rate changes for cases (7.28±9.37 percent and controls (7 ± 8 percent were not different (P < 0.8. Mean decrease in MAP for cases (20.17 ± 2.10n percent was

  8. A quantitative description of the Na-K-2Cl cotransporter and its conformity to experimental data.

    Science.gov (United States)

    Benjamin, B A; Johnson, E A

    1997-09-01

    In epithelia, the Na-K-2Cl cotransporter cooperates with other transport mechanisms to produce transepithelial NaCl transport. The reaction cycle for the Na-K-2Cl cotransporter has been established experimentally, but whether it accounts, quantitatively, for experimental findings has yet to be established. The differential equations that describe the reaction cycle were formulated, and the steady-state solutions were obtained by digital computation. Conformity between this description and the experimental data obtained from the literature was explored by automatic searches for the sets of rate constants that yielded statistical best-fits to the experimental data. Fits were obtained from renal epithelial cell lines, HeLa cells, and duck erythrocytes. Results show that the reaction cycle for the Na-K-2Cl cotransporter conforms well, quantitatively, with the experimental data.

  9. Effect of gravity on Pseudomonas putida and kaolinite cotransport in water saturated porous media

    Science.gov (United States)

    Vasiliadou, Ioanna A.; Chrysikopoulos, Constantinos V.

    2013-04-01

    Bacterial transport in porous media can be affected by several factors, such as cell concentration, water velocity, and attachment onto the solid matrix or suspended in the aqueous phase soil particles (e.g. clays). Gravity, also may significantly influence bacterial transport behavior in the subsurface. The present study aims to determine the gravity effect on transport and cotransport of bacteria species Pseudomonas (P.) putida and kaolinite colloid particles in porous media. Transport experiments were conducted under horizontal-, up- and down-flow conditions in water saturated columns packed with glass beads. These different flow modes represent different gravity effects, namely: no-, negative- and positive-gravity effect. Initial experiments were performed with bacteria and kaolinite alone in order to evaluate the effect of gravity on their individual transport characteristics. No significant gravity effect was observed on the transport of individual bacterial cells. In contrary, each different flow mode was found to differently affect kaolinite transport. Compared to the horizontal-flow mode, the kaolinite mass recovery was decreased during the up-flow mode, and increased during the down-flow mode. Finally, P. putida and kaolinite particles were injected simultaneously into the packed column in order to investigate their cotransport behavior under different flow modes. The experimental data indicated that the kaolinite-P. putida cotransport behavior was similar to that observed for the transport of individual kaolinite particles. It was observed that the P. putida mass recovery decreased during down-flow conditions. This phenomenon may be caused by the attachment of bacteria onto kaolinite particles, which were adsorbed onto the solid matrix.

  10. Substrate specificity of human ABCC4 (MRP4)-mediated cotransport of bile acids and reduced glutathione.

    Science.gov (United States)

    Rius, Maria; Hummel-Eisenbeiss, Johanna; Hofmann, Alan F; Keppler, Dietrich

    2006-04-01

    The multidrug resistance protein ABCC4 (MRP4), a member of the ATP-binding cassette superfamily, mediates ATP-dependent unidirectional efflux of organic anions out of cells. Previous studies showed that human ABCC4 is localized to the sinusoidal membrane of hepatocytes and mediates, among other substrates, the cotransport of reduced glutathione (GSH) with bile acids. In the present study, using inside-out membrane vesicles, we demonstrated that human ABCC4 in the presence of physiological concentrations of GSH has a high affinity for the taurine and glycine conjugates of the common natural bile acids as well as the unconjugated bile acid cholate. Chenodeoxycholyltaurine and chenodeoxycholylglycine were the GSH cosubstrates with the highest affinities for ABCC4, with K(m) values of 3.6 and 5.9 microM, respectively. Ursodeoxycholyltaurine and ursodeoxycholylglycine were cotransported together with GSH by ABCC4 with K(m) values of 7.8 and 12.5 microM, respectively, but no transport of ursodeoxycholate and deoxycholate was observed. The simultaneous transport of labeled GSH and cholyltaurine or cholylglycine was demonstrated in double-labeled cotransport experiments with a bile acid-to-GSH ratio of approximately 1:22. K(m) values of the bile acids for ABCC4 were in a range similar to those reported for the canalicular bile salt export pump ABCB11. Under physiological conditions, the sinusoidal ABCC4 may compete with canalicular ABCB11 for bile acids and thereby play a key role in determining the hepatocyte concentration of bile acids. In cholestatic conditions, ABCC4 may become a key pathway for efflux of bile acids from hepatocytes into blood.

  11. 4D porosity evolution during solid-solid replacement reaction in mineral system (KBr, KCl)

    Science.gov (United States)

    Beaudoin, Nicolas; Hamilton, Andrea; Koehn, Daniel; Shipton, Zoe

    2017-04-01

    An extensive understanding of the controlling mechanisms of phase transformation is key in geosciences to better predicting the evolution of the physical parameters of rocks (porosity, permeability, and rheology) from centimetre-scale (e.g. fingering in siltstones) to kilometer-scale (e.g. Dolostone geobodies), in both the diagenetic and metamorphic domains. This contribution reports the 4D monitoring of a KBr crystal at different time steps during an experimental, fluid-mediated replacement reaction with KCl. Volumes are reconstructed based on density contrast using non-destructive X-ray Computed Tomography (XCT) at a resolution of 3 microns. A sample of KBr was immersed in a static bath of saturated KCl at room temperature and pressure. 5 scans were performed during the reaction at 5, 10, 20, 35 and 55 minutes, until 50% of the original crystal was replaced. As a control experiment, two samples reacted continuously for 15 and 55 minutes, respectively. Each 3D dataset was reconstructed to visualize and quantify the different mineral phases, the porosity distribution and connectivity, along with the reaction front morphology. In the case of successive baths, results show that the front morphology evolves from rough with small fingers to flat and thick during the reaction, suggesting a switch between advection and diffusion controlled reactant distribution through time. This switch is also reflected in the mass evolution and the rate of propagation of the replaced zone, being rapid in the first 20 minutes before reaching steady state. The porosity develops perpendicular to the crystal wall, suggesting a self-organization process governed by advection, before connecting laterally. While the reaction changes from advection controlled to diffusion controlled, the direction of the connected pores becomes parallel to the crystal walls. This phenomenon is not observed when the crystal is reacting discontinuously for 55 minutes. In the latter case, self

  12. DAPAGLIFLOZIN: SELECTIVE SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITOR IN TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    Sudhakar Pemminati

    2011-11-01

    Full Text Available Dapagliflozin is a promising new drug that targets the so far untapped renal glucose reabsorption. By inhibiting sodium-glucose co-transporter-2 (SGLT2 which is mainly localized in the S1 segment of the proximal tubule, Dapagliflozin promotes renal glucose excretion and reduces hyperglycemia in an insulin-independent manner. Dapagliflozin also produces pronounced weight loss which may be an advantage in patients on sulfonylureas and insulin. Dapagliflozin has the potential to be used as monotherapy, as well as in combination with all approved antidiabetic agents.

  13. Sodium-glucose cotransporter-2 inhibition and the insulin: Glucagon ratio: Unexplored dimensions

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available The sodium-glucose cotransporter 2 (SGLT-2 inhibitors are a novel class of glucose-lowering drugs which act by inhibiting the reabsorption of filtered glucose from the kidneys. Their effect on insulin and glucagon levels has recently been studied but is not fully explained. This communication proposes various hypotheses: A direct effect of SGLT-2 inhibition on the alpha cell receptors, a paracrine or intra-islet mediated effect on alpha cell sensitivity to glucose, and a calorie restriction mimetic action, to explain the impact of these drugs on the insulin glucagon ratio.

  14. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect

    Science.gov (United States)

    Kalra, Sanjay; Jain, Arpit; Ved, Jignesh; Unnikrishnan, A. G.

    2016-01-01

    This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a “good person,” who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production. PMID:27730088

  15. Water transport by the Na+/glucose cotransporter under isotonic conditions

    DEFF Research Database (Denmark)

    Zeuthen, T; Meinild, A K; Klaerke, D A

    1997-01-01

    in Xenopus oocytes. We present a method which allows short-term exposures to sugar under voltage clamp conditions. We demonstrate that water is cotransported with the solutes despite no osmotic differences between the external and intracellular solutions. There is a fixed ratio of 195:1 between the number...... of water molecules and the number of Na+ ions transported, equivalent to 390 water molecules per glucose molecule. Unstirred layer effects are ruled out on the basis of experiments on native oocytes incubated with the ionophores gramicidin D or nystatin....

  16. Regulation of the type Mb sodium-dependent phosphate cotransporter expression in the intestine

    Institute of Scientific and Technical Information of China (English)

    Bin WANG; Yulong YIN

    2009-01-01

    Phosphate (Pi) plays important roles in growth, development, bone mineralization, energy metabolism, nucleic acid synthesis, cell signaling, and acid-base regulation. The rate of intestinal absorption of Pi is a major determinant of Pi homeostasis. The type lib sodium- dependent Pi cotransporter (NaPi-Iib) is responsible for intestinal Pi absorption. Many physiological factors regulate the rate of Pi absorption via modulating the expression of NaPi-Iib in the intestine. In this review, we summarize the role of these factors in the regulation of NaPi-Iib expression in the intestine.

  17. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect.

    Science.gov (United States)

    Kalra, Sanjay; Jain, Arpit; Ved, Jignesh; Unnikrishnan, A G

    2016-01-01

    This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

  18. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2 inhibition: Calorie restriction mimicry (CRM and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

  19. Characterization of a novel phosphorylation site in the sodium-chloride cotransporter, NCC

    DEFF Research Database (Denmark)

    Rosenbaek, L L; Assentoft, M; Pedersen, N B

    2012-01-01

    DAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin-angiotensin-aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1......The sodium-chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho...

  20. Sodium-glucose cotransporter 2 inhibitor use: A pharmaco-ergonomic qualification tool

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2017-01-01

    Full Text Available Pharmaco-ergonomics implies tailoring the drug therapy to an individual patient's requirement(s. The development of sodium-glucose cotransporter 2 inhibitor (SGLT2-i agents has impelled multiple clinical considerations, in the management of type-2 diabetes. This paper attempts to summarize the pharmaco-ergonomic considerations for these agents, in the form of an SGLT2-i qualification tool, based on a clinical score. This tool may serve as a simple and inexpensive practical guide, to optimize the risk-benefit considerations for SGLT2-i agents.

  1. Na+,HCO3--cotransport is functionally upregulated during human breast carcinogenesis and required for the inverted pH gradient across the plasma membrane

    DEFF Research Database (Denmark)

    Lee, Soojung; Mele, Marco; Vahl, Pernille

    2015-01-01

    and promoting cancer cell metabolism, proliferation, migration, and invasion. We investigated the effects of breast carcinogenesis on the mechanisms of cellular pH control using multicellular epithelial organoids freshly isolated from human primary breast carcinomas and matched normal breast tissue...... (~0.3 units of magnitude) in steady-state intracellular pH of human primary breast carcinomas compared to normal breast tissue. Na(+)/H(+)-exchange activity and steady-state intracellular pH in the absence of CO2/HCO3 (-) were practically unaffected by breast carcinogenesis. These effects were evident....... Intracellular pH was measured by fluorescence microscopy, while protein expression was investigated by immunofluorescence imaging and immunoblotting. We found that cellular net acid extrusion increased during human breast carcinogenesis due to enhanced Na(+),HCO3 (-)-cotransport, which created an alkaline shift...

  2. Methanol extracts of Hamelia patens containing oxindole alkaloids relax KCl-induced contraction in rat myometrium.

    Science.gov (United States)

    Reyes-Chilpa, Ricardo; Rivera, Jesús; Oropeza, Martha; Mendoza, Pilar; Amekraz, Badia; Jankowski, Christopher; Campos, Maria

    2004-10-01

    Hamelia patens JAQC. (Rubiaceae) is a medicinal bush widely distributed in tropical areas of the American continent. It is used in Mexican Traditional Medicine for the treatment of menstrual disorders, therefore suggesting that its chemical constituents may have some effect on myometrium contractility. Physiological effects might differ due to quantitative variations in the content of alkaloids arising from its wide geographical distribution. To test this hypothesis, the content of oxindole alkaloids in methanol extracts of five different samples collected in Mexico was quantified by GC-MS. Each extract was assayed on contractility of estrogen-primed rat myometrium. Variations in the content of alkaloids were observed among the different samples. All samples relaxed in a concentration-dependent manner the high KCl-induced contraction in rat myometrium. Those which lack rumberine and/or maruquine displayed a higher relaxant effect than samples containing them, suggesting that these alkaloids might counteract the effects of isopteropodine. However, in contrast with verapamil, Hamelia patens metanol extracts are poor relaxants.

  3. On the formation of U Al alloys in the molten LiCl KCl eutectic

    Science.gov (United States)

    Cassayre, L.; Caravaca, C.; Jardin, R.; Malmbeck, R.; Masset, P.; Mendes, E.; Serp, J.; Soucek, P.; Glatz, J.-P.

    2008-08-01

    U-Al alloy formation has been studied in the temperature range of 400-550 °C by electrochemical techniques in the molten LiCl-KCl eutectic. Cyclic voltammetry showed that underpotential reduction of U(III) onto solid Al occurs at a potential about 0.35 V more anodic than pure U deposition. Open circuit potential measurements, recorded after small depositions of U metal onto the Al electrode, did not allow the distinction between potentials associated with UAl x alloys and the Al rest potential, as they were found to be practically identical. As a consequence, a spontaneous chemical reaction between dissolved UCl 3 and Al is thermodynamically possible and was experimentally observed. Galvanostatic electrolyses were carried out both on Al rods and Al plates. Stable and dense U-Al deposits were obtained with high faradic yields, and the possibility to load the whole bulk of a thin Al plate was demonstrated. The analyses (by SEM-EDX and XRD) of the deposits indicated the formation of different intermetallic phases (UAl 2, UAl 3 and UAl 4) depending on the experimental conditions.

  4. On the formation of U-Al alloys in the molten LiCl-KCl eutectic

    Energy Technology Data Exchange (ETDEWEB)

    Cassayre, L. [Laboratoire de Genie Chimique (LGC), Universite Paul Sabatier, UMR CNRS 5503, 31062 Toulouse cedex 9 (France); Caravaca, C. [CIEMAT, DE/DFN/URAA, Avda. Complutense, 22, Madrid 28040 (Spain); Jardin, R. [European Commission, JRC, Institute for Transuranium Elements, P.O. Box 2340, 76125 Karlsruhe (Germany); Malmbeck, R. [European Commission, JRC, Institute for Transuranium Elements, P.O. Box 2340, 76125 Karlsruhe (Germany)], E-mail: rikard.malmbeck@ec.europa.eu; Masset, P.; Mendes, E.; Serp, J.; Soucek, P.; Glatz, J.-P. [European Commission, JRC, Institute for Transuranium Elements, P.O. Box 2340, 76125 Karlsruhe (Germany)

    2008-08-15

    U-Al alloy formation has been studied in the temperature range of 400-550 deg. C by electrochemical techniques in the molten LiCl-KCl eutectic. Cyclic voltammetry showed that underpotential reduction of U(III) onto solid Al occurs at a potential about 0.35 V more anodic than pure U deposition. Open circuit potential measurements, recorded after small depositions of U metal onto the Al electrode, did not allow the distinction between potentials associated with UAl{sub x} alloys and the Al rest potential, as they were found to be practically identical. As a consequence, a spontaneous chemical reaction between dissolved UCl{sub 3} and Al is thermodynamically possible and was experimentally observed. Galvanostatic electrolyses were carried out both on Al rods and Al plates. Stable and dense U-Al deposits were obtained with high faradic yields, and the possibility to load the whole bulk of a thin Al plate was demonstrated. The analyses (by SEM-EDX and XRD) of the deposits indicated the formation of different intermetallic phases (UAl{sub 2}, UAl{sub 3} and UAl{sub 4}) depending on the experimental conditions.

  5. Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Mastroianni, N.; De Fusco, M.; Casari, G. [Univsersita` di Milano (Italy)] [and others

    1996-11-01

    A hereditary defect of the distal tubule accounts for the clinical features of Gitelman syndrome (GS), an autosomal recessive disease characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. Recently, we cloned the cDNA coding for the human Na-Cl thiazide-sensitive cotransporter (TSC; also known as {open_quotes}NCCT{close_quotes} or {open_quotes}SLC12A3{close_quotes}) as a possible candidate for GS, and Simon et al., independently, described rotation in patients with GS. Now, we show 12 additional mutations consistent with a loss of function of the Na-Cl cotransporter in GS. Two missense replacements, R09W and P349L, are common to both studies and could represent ancient mutations. The other mutations include three deletions, two insertions, and six missense mutations. When all mutations from both studies are considered, missense mutations seem to be more frequently localized within the intracellular domains of the molecule, rather than in transmembrane or extracellular domains. One family, previously reported as a GS form with dominant inheritance, has proved to be recessive, with the affected child being a compound heterozygote. A highly informative intragenic tetranucleotide marker, useful for molecular diagnostic studies, has been identified at the acceptor splice site of exon 9. 12 refs., 3 figs., 2 tabs.

  6. Exon loss accounts for differential sorting of Na-K-Cl cotransporters in polarized epithelial cells.

    Science.gov (United States)

    Carmosino, Monica; Giménez, Ignacio; Caplan, Michael; Forbush, Biff

    2008-10-01

    The renal Na-K-Cl cotransporter (NKCC2) is selectively expressed in the apical membranes of cells of the mammalian kidney, where it is the target of the clinically important loop diuretics. In contrast, the "secretory" NKCC1 cotransporter is localized in the basolateral membranes of many epithelia. To identify the sorting signal(s) that direct trafficking of NKCCs, we generated chimeras between the two isoforms and expressed these constructs in polarized renal epithelial cell lines. This analysis revealed an amino acid stretch in NKCC2 containing apical sorting information. The NKCC1 C terminus contains a dileucine motif that constitutes the smallest essential component of its basolateral sorting signal. NKCC1 lacking this motif behaves as an apical protein. Examination of the NKCC gene structure reveals that this dileucine motif is encoded by an additional exon in NKCC1 absent in NKCC2. Phylogenetic analysis of this exon suggests that the evolutionary loss of this exon from the gene encoding the basolateral NKCC1 constitutes a novel mechanism that accounts for the apical sorting of the protein encoded by the NKCC2 gene.

  7. KCl:Eu2+ as a solar UV-C radiation dosimeter.Optically stimulated luminescence and thermoluminescence analyses

    Institute of Scientific and Technical Information of China (English)

    I.Aguirre de Cáarcer; H.L.D'Antoni; M.Barboza-Flores; V.Correcher; F.Jaque

    2009-01-01

    The KCl:Eu2+ system response to UV-C was investigated by analyzing the optically stimulated luminescence (OSL) and thertoo-luminescence (TL) signal produced by ultraviolet light exposure at room temperature.It was found that after UV-C irradiation,OSL was produced on a wide band of visible wavelengths with decay time that varied by several orders of magnitude depending on the Eu2+ aggregation state.In spite of the low intensity of solar UV-C reaching the Earth's surface in Madrid (40° N,700 m a.s.l.),it was possible to measure the UV-C radiation dose at 6:48 solar time by using the TL response of the KCl:Eu2+ system and differentiate it from the ambient beta radiation dose.

  8. Integrated Data Collection Analysis (IDCA) Program — KClO3/Icing Sugar (-100 mesh) Mixture

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (IHD-NSWC), Indian Head, MD (United States). Indian Head Division; Sorenson, Daniel N. [Naval Surface Warfare Center (IHD-NSWC), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (IHD-NSWC), Indian Head, MD (United States). Indian Head Division; Moran, Jesse S. [Naval Surface Warfare Center (IHD-NSWC), Indian Head, MD (United States). Indian Head Division; Shelley, Timothy J. [Air Force Research Lab. (AFRL/RXQF), Tyndall AFB, FL (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Whipple, Richard E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-05-02

    The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small-Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and scanning calorimetry analysis of a mixture of KClO3 sized through a 100-mesh sieve mixed with icing sugar, also sized through a 100-mesh sieve—KClO3/icing sugar (-100) mixture. This material was selected because of the challenge of performing SSST testing of a mixture of two solid materials. The mixture was found to be: 1) more sensitive to impact than RDX, with sensitivity similar to PETN, 2) the same or more sensitive to friction than PETN, and 3) less sensitive to spark than RDX. The analysis showed that the mixture has thermally stability similar to RDX and is perhaps more energetic upon decomposition but variable results indicate sampling issues.

  9. First-Principles Calculation of Principal Hugoniot and K-Shell X-ray Absorption Spectra for Warm Dense KCl

    CERN Document Server

    Zhao, Shijun; Kang, Wei; Li, Zi; Zhang, Ping; He, Xian-Tu

    2015-01-01

    Principal Hugoniot and K-shell X-ray absorption spectra of warm dense KCl are calculated using the first-principles molecular dynamics method. Evolution of electronic structures as well as the influence of the approximate description of ionization on pressure (caused by the underestimation of the energy gap between conduction bands and valence bands) in the first-principles method are illustrated by the calculation. Pressure ionization and thermal smearing are shown as the major factors to prevent the deviation of pressure from global accumulation along the Hugoniot. In addition, cancellation between electronic kinetic pressure and virial pressure further reduces the deviation. The calculation of X-ray absorption spectra shows that the band gap of KCl persists after the pressure ionization of the $3p$ electrons of Cl and K taking place at lower energy, which provides a detailed understanding to the evolution of electronic structures of warm dense matter.

  10. Galvanic reduction of uranium(III) chloride from LiCl-KCl eutectic salt using gadolinium metal

    Science.gov (United States)

    Bagri, Prashant; Zhang, Chao; Simpson, Michael F.

    2017-09-01

    The drawdown of actinides is an important unit operation to enable the recycling of electrorefiner salt and minimization of waste. A new method for the drawdown of actinide chlorides from LiCl-KCl molten salt has been demonstrated here. Using the galvanic interaction between the Gd/Gd(III) and U/U(III) redox reactions, it is shown that UCl3 concentration in eutectic LiCl-KCl can be reduced from 8.06 wt.% (1.39 mol %) to 0.72 wt.% (0.12 mol %) in about an hour via plating U metal onto a steel basket. This is a simple process for returning actinides to the electrorefiner and minimizing their loss to the salt waste stream.

  11. Electrochemical investigation on the redox chemistry of niobium in LiCl-KCl-KF-Na2O melts

    DEFF Research Database (Denmark)

    Gillesberg, Bo; Bjerrum, Niels; Barner, Jens H. Von

    1997-01-01

    The system LiCl-KCl-KF-1 mole percent K2NbF7 (molar ration F-/Nb = 8) has been investigated in-the temperature range 370 to 725 degrees C by cyclic and square wave voltammetry. In the temperature range from 370 to 520 degrees C Nb(V) was reduced to Nb(III) in two reversible steps: Nb(V) --> Nb(IV...

  12. Generation of KCL035 research grade human embryonic stem cell line carrying a mutation in HBB gene

    Directory of Open Access Journals (Sweden)

    Heema Hewitson

    2016-03-01

    Full Text Available The KCL035 human embryonic stem cell line was derived from an embryo donated for research that carried a mutation in the HBB gene, which is linked to the β-thalassemia syndrome. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro assays.

  13. An upper limit on hypertriton production in collisions of Ar(1.76 A GeV) + KCl

    Science.gov (United States)

    Agakishiev, G.; Belver, D.; Blanco, A.; Böhmer, M.; Boyard, J. L.; Cabanelas, P.; Castro, E.; Chernenko, S.; Destefanis, M.; Dohrmann, F.; Dybczak, A.; Epple, E.; Fabbietti, L.; Fateev, O.; Finocchiaro, P.; Fonte, P.; Friese, J.; Fröhlich, I.; Galatyuk, T.; Garzón, J. A.; Gernhäuser, R.; Gilardi, C.; Golubeva, M.; González-Díaz, D.; Guber, F.; Gumberidze, M.; Heinz, T.; Hennino, T.; Holzmann, R.; Iori, I.; Ivashkin, A.; Jurkovic, M.; Kämpfer, B.; Karavicheva, T.; Koenig, I.; Koenig, W.; Kolb, B. W.; Kotte, R.; Krása, A.; Krizek, F.; Krücken, R.; Kuc, H.; Kühn, W.; Kugler, A.; Kurepin, A.; Lang, S.; Lange, J. S.; Lapidus, K.; Liu, T.; Lopes, L.; Lorenz, M.; Maier, L.; Mangiarotti, A.; Markert, J.; Metag, V.; Michalska, B.; Michel, J.; Morinière, E.; Mousa, J.; Müntz, C.; Naumann, L.; Pachmayer, Y. C.; Palka, M.; Pechenov, V.; Pechenova, O.; Pietraszko, J.; Przygoda, W.; Ramstein, B.; Rehnisch, L.; Reshetin, A.; Rustamov, A.; Sadovsky, A.; Salabura, P.; Scheib, T.; Schmah, A.; Schuldes, H.; Schwab, E.; Siebenson, J.; Sobolev, Yu. G.; Spataro, S.; Spruck, B.; Ströbele, H.; Stroth, J.; Sturm, C.; Tarantola, A.; Teilab, K.; Tlusty, P.; Traxler, M.; Trebacz, R.; Tsertos, H.; Wagner, V.; Weber, M.; Wendisch, C.; Wisniowski, M.; Wüstenfeld, J.; Yurevich, S.; Zanevsky, Y.

    2013-11-01

    A high-statistic data sample of Ar(1.76 AGeV)+KCl events recorded with HADES is used to search for a hypertriton signal. An upper production limit per centrality-triggered event of on the 3 level is derived. Comparing this value with the number of successfully reconstructed hyperons allows to determine an upper limit on the ratio , which is confronted with statistical and coalescence-type model calculations.

  14. Intestinal Sodium Glucose Cotransporter 1 Inhibition Enhances Glucagon-Like Peptide-1 Secretion in Normal and Diabetic Rodents.

    Science.gov (United States)

    Oguma, Takahiro; Nakayama, Keiko; Kuriyama, Chiaki; Matsushita, Yasuaki; Yoshida, Kumiko; Hikida, Kumiko; Obokata, Naoyuki; Tsuda-Tsukimoto, Minoru; Saito, Akira; Arakawa, Kenji; Ueta, Kiichiro; Shiotani, Masaharu

    2015-09-01

    The sodium glucose cotransporter (SGLT) 1 plays a major role in glucose absorption and incretin hormone release in the gastrointestinal tract; however, the impact of SGLT1 inhibition on plasma glucagon-like peptide-1 (GLP-1) levels in vivo is controversial. We analyzed the effects of SGLT1 inhibitors on GLP-1 secretion in normoglycemic and hyperglycemic rodents using phloridzin, CGMI [3-(4-cyclopropylphenylmethyl)-1-(β-d-glucopyranosyl)-4-methylindole], and canagliflozin. These compounds are SGLT2 inhibitors with moderate SGLT1 inhibitory activity, and their IC50 values against rat SGLT1 and mouse SGLT1 were 609 and 760 nM for phloridzin, 39.4 and 41.5 nM for CGMI, and 555 and 613 nM for canagliflozin, respectively. Oral administration of these inhibitors markedly enhanced and prolonged the glucose-induced plasma active GLP-1 (aGLP-1) increase in combination treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, in normoglycemic mice and rats. CGMI, the most potent SGLT1 inhibitor among them, enhanced glucose-induced, but not fat-induced, plasma aGLP-1 increase at a lower dose compared with canagliflozin. Both CGMI and canagliflozin delayed intestinal glucose absorption after oral administration in normoglycemic rats. The combined treatment of canagliflozin and a DPP4 inhibitor increased plasma aGLP-1 levels and improved glucose tolerance compared with single treatment in both 8- and 13-week-old Zucker diabetic fatty rats. These results suggest that transient inhibition of intestinal SGLT1 promotes GLP-1 secretion by delaying glucose absorption and that concomitant inhibition of intestinal SGLT1 and DPP4 is a novel therapeutic option for glycemic control in type 2 diabetes mellitus. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Integrated Data Collection Analysis (IDCA) Program — KClO3 (as received)/Icing Sugar

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC IHD), Indian Head, MD (United States). Indian Head Division; Sorenson, Daniel N. [Naval Surface Warfare Center (NSWC IHD), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC IHD), Indian Head, MD (United States). Indian Head Division; Shelley, Timothy J. [Air Force Research Lab. (AFRL/RXQL), Tyndall AFB, FL (United States); Reyes, Jose A. [Applied Research Associates, Inc., Tyndall AFB, FL (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Whipple, Richard E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-05-23

    The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small-Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of a mixture of KClO3 as received from the manufacturer mixed with icing sugar, sized through a 100-mesh sieve—KClO3/icing sugar (AR) mixture. This material was selected because of the challenge of performing SSST testing of a mixture of two solid materials. The mixture was found to: 1) be more sensitive to impact than RDX, similar to PETN, 2) be the same or less sensitive to friction than PETN, and 3) to be less sensitive to spark than RDX. The thermal analysis showed that the mixture has thermally stability similar to RDX and is perhaps more energetic upon decomposition but variable results indicate sampling issues. Compared to the 100-mesh sieved counter part, the KClO3/icing sugar (-100) mixture, the AR mixture was found to be about the same sensitivity towards impact, friction and ESD.

  16. Protective roles of bacterioruberin and intracellular KCl in the resistance of Halobacterium salinarium against DNA-damaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Shahmohammadi, H.R.; Asgarani, E.; Terato, Hiroaki; Saito, Takeshi; Ohyama, Yoshihiko; Gekko, Kunihiko; Yamamoto, Osamu; Ide, Hiroshi [Hiroshima Univ. (Japan). Faculty of Science

    1998-12-01

    Halobacterium salinarium, a member of the extremely halophilic archaebacteria, contains a C{sub 50}-carotenoid namely bacterioruberin. We have previously reported the high resistance of this organism against the lethal actions of DNA-damaging agents including ionizing radiation and ultraviolet light (UV). In this study, we have examined whether bacterioruberin and the highly concentrated salts in this bacterium play protective roles against the lethal actions of ionizing radiation, UV, hydrogen peroxide, and mitomycin-C (MMC). The colourless mutant of H. salinarium deficient in bacterioruberin was more sensitive than the red-pigmented wild-type to all tested DNA-damaging agents except MMC. Circular dichroism (CD) spectra of H. salinarium chromosomal DNA at various concentrations of KCl (0-3.5 M) were similar to that of B-DNA, indicating that no conformational changes occurred as a result of high salt concentrations. However, DNA strand-breaks induced by ionizing radiation were significantly reduced by the presence of either bacterioruberin or concentrated KCl, presumably due to scavenging of free radicals. These results suggest that bacterioruberin and intracellular KCl of H. salinarium protect this organism against the lethal effects of oxidative DNA-damaging agents. (author)

  17. Electrochemical Extraction of Nd from NaCl-KCl Melt by Formation of Cu-Nd Alloys

    Science.gov (United States)

    Zhang, Zhong-Lin; Zhou, Lin-Zong; Ji, De-Bin; Yan, Yong-De; Hong, Wei; Liu, Yu-Hui; Wang, Pu; Yin, Tai-Qi; Zheng, Jia-Ning; Xue, Yun; Ye, Yuan-Feng

    2017-10-01

    Electrochemical behavior of Nd was studied in NaCl-KCl melt on W and Cu electrodes via cyclic voltammetry and chronopotentiometry. Generally, the reduction of Nd3+ takes place in two consecutive steps in molten chlorides, such as LiCl-CaCl2, LiCl-BaCl2, CaCl2-NaCl, LiCl-KCl melts. However, the reduction of Nd3+ ions was found to be through a one-step process: Nd3+ + 3e- → Nd. The co-reduction behavior of Nd3+ and Cu2+ ions and the mechanisms of alloy formation were investigated in NaCl-KCl melt on W electrodes at 988 K (715 °C). Four potential plateaus corresponding to four different kinds of Cu-Nd intermetallic compounds were detected. Cu-Nd alloys were prepared on Cu electrodes at 988 K (715 °C) and 1143 K (870 °C). At 988 K (715 °C), Cu5Nd phase was identified by X-ray diffraction. The morphology and micro-zone chemical analysis of the alloys were characterized by scanning electron microscopy equipped with energy-dispersive spectrometry. The alloy film was observed on the Cu electrodes. Moreover, at 1143 K (870 °C), a globate bulk Cu-Nd alloy with Cu5Nd, Cu4Nd, Cu2Nd, CuNd, and Cu phases, as liquid in the melt, was obtained at the bottom of the crucible.

  18. Capture and Solidification of Rare Earth Nuclide (Nd) in LiCl-KCl Eutectic Salt Using a Synthetic Inorganic Composite

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Na-Young; Eun, Hee-Chul; Park, Hwan-Seo; Ahn, Do-Hee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2017-06-15

    In this study, neodymium (Nd) nuclides in LiCl-KCl eutectic salts were captured and solidified using a synthetic inorganic composite (Li{sub 2}O-SiO{sub 2}-Al{sub 2}O{sub 3}-B{sub 2}O{sub 3}), a process that allows the selective capture of Nd and fabrication of a composite with Nd captured from waste, without additional additives or mixing. The Nd nuclides in the LiCl-KCl eutectic salt were mainly captured in the form of LiNdSiO{sub 4}, and it was confirmed that NdSiO{sub 3} can be formed in the composite with captured Nd when the content of Nd in the composite is increased. The capture efficiency was higher than about 98 wt%. It was thought that the salt recovered from the Nd capture test was a renewable form could be reused in the pyroprocessing of used nuclear fuel, because the composite has high chemical durability in a LiCl-KCl eutectic salt at 900 ℃. The composite captured Nd was fabricated into a homogeneous glass form and a stable ceramic form.

  19. Corrosion behavior induced by LiCl-KCl in type 304 and 316 stainless steel and copper at low temperature

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Jee Hyung; Kim, Yong Soo; Cho, Il Je [Dept. of Nuclear Engineering, Hanyang University, Seoul (Korea, Republic of)

    2017-06-15

    The corrosion behavior of stainless steel (304 and 316 type) and copper induced by LiCl-KCl at low temperatures in the presence of sufficient oxygen and moisture was investigated through a series of experiments (at 30°C, 40°C, 60°C, and 80°C for 24 hours, 48 hours, 72 hours, and 96 hours). The specimens not coated on one side with an aqueous solution saturated with LiCl-KCl experienced no corrosion at any temperature, not even when the test duration exceeded 96 hours. Stainless steel exposed to LiCl-KCl experienced almost no corrosion below 40°C, but pitting corrosion was observed at temperatures above 60°C. As the duration of the experiment was increased, the rate of corrosion accelerated in proportion to the temperature. The 316 type stainless steel exhibited better corrosion resistance than did the 304 type. In the case of copper, the rate of corrosion accelerated in proportion to the duration and temperature but, unlike the case of stainless steel, the corrosion was more general. As a result, the extent of copper corrosion was about three times that of stainless steel.

  20. Potassium co-transport and antiport during the uptake of sucrose and glutamic acid from the xylem vessels

    NARCIS (Netherlands)

    Bel, A.J.E. van; Erven, A.J. van

    1979-01-01

    Perfusion experiments with excised internodes of tomato (Lycopersicon esculentum cv Moneymaker) showed that the uptake of glutamic acid and sucrose from the xylem vessels is accompanied with coupled proton co-transport and potassium antiport at low pH (<5.5). At high pH (5.5) both proton and potassi

  1. Potassium co-transport and antiport during the uptake of sucrose and glutamic acid from the xylem vessels

    NARCIS (Netherlands)

    Bel, A.J.E. van; Erven, A.J. van

    1979-01-01

    Perfusion experiments with excised internodes of tomato (Lycopersicon esculentum cv Moneymaker) showed that the uptake of glutamic acid and sucrose from the xylem vessels is accompanied with coupled proton co-transport and potassium antiport at low pH (<5.5). At high pH (5.5) both proton and potassi

  2. Hydrochlorothiazide treatment increases the abundance of the NaCl cotransporter in urinary extracellular vesicles of essential hypertensive patients.

    NARCIS (Netherlands)

    Pathare, G.T.; Tutakhel, O.A.Z.; Wel, M.C. van der; Shelton, L.M.; Deinum, J.; Lenders, J.W.M.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2017-01-01

    The thiazide-sensitive NaCl cotransporter (NCC), located apically in distal convoluted tubule epithelia, regulates the fine-tuning of renal sodium excretion. Three isoforms of NCC are generated through alternative splicing of the transcript, of which the third isoform has been the most extensively

  3. Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of Sodium-Glucose Cotransporter 2 Inhibitor Treatment

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Bagger, Jonatan I; Knop, Filip K

    2016-01-01

    Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have...

  4. Contribution of Na+,HCO3--cotransport to cellular pH control in human breast cancer

    DEFF Research Database (Denmark)

    Bødtkjer, Ebbe; Moreira, José; Mele, Marco

    2013-01-01

    H-sensitive fluorophores, we showed that Na(+) ,HCO(3) (-) -cotransport is the predominant mechanism of acid extrusion and is inhibited 34 ± 9% by 200 µM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid in human primary breast carcinomas. At intracellular pH (pH(i) ) levels >6.6, CO(2) /HCO(3) (-) -dependent mechanisms...

  5. Interaction of human organic anion transporter 2 (OAT2) and sodium taurocholate cotransporting polypeptide (NTCP) with antineoplastic drugs.

    Science.gov (United States)

    Marada, Venkata V V R; Flörl, Saskia; Kühne, Annett; Müller, Judith; Burckhardt, Gerhard; Hagos, Yohannes

    2015-01-01

    The ability of an antineoplastic drug to exert its cytostatic effect depends largely on the balance between its uptake into and extrusion from the cancer cells. ATP driven efflux transporter proteins drive the export of antineoplastic drugs and play a pivotal role in the development of chemoresistance. As regards uptake transporters, comparably less is known on their impact in drug action. In the current study, we characterized the interactions of two uptake transporter proteins, expressed mainly in the liver; the organic anion transporter 2 (OAT2, encoded by the SLC22A7 gene) and the sodium taurocholate cotransporting polypeptide (NTCP, encoded by the SLC10A1 gene), stably transfected in human embryonic kidney cells, with some antineoplastic agents that are routinely being used in cancer chemotherapy. Whereas NTCP did not show any strong interactions with the cytostatics tested, we observed a very strong inhibition of OAT2 mediated [(3)H] cGMP uptake in the presence of bendamustine, irinotecan and paclitaxel. The Ki values of OAT2 for bendamustine, irinotecan and paclitaxel were determined to be 43.3±4.33μM, 26.4±2.34μM and 10.4±0.45μM, respectively. Incubation of bendamustine with OAT2 expressing cells increased the caspase-3 activity, and this increase was inhibited by simultaneous incubation with bendamustine and probenecid, a well-known inhibitor of OATs, suggesting that bendamustine is a substrate of OAT2. A higher accumulation of irinotecan was observed in OAT2 expressing cells compared to control pcDNA cells by HPLC analysis of cell lysates. The accumulation was diminished in the presence of cGMP, the substrate we used to functionally characterize OAT2, suggesting specificity of this uptake and the fact that OAT2 mediates uptake of irinotecan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Skeletal muscle sodium glucose co-transporters in older adults with type 2 diabetes undergoing resistance training

    Directory of Open Access Journals (Sweden)

    Francisco Castaneda, Jennifer E. Layne, Carmen Castaneda

    2006-01-01

    Full Text Available We examined the expression of the sodium-dependent glucose co-transporter system (hSGLT3 in skeletal muscle of Hispanic older adults with type 2 diabetes. Subjects (65±8 yr were randomized to resistance training (3x/wk, n=13 or standard of care (controls, n=5 for 16 weeks. Skeletal muscle hSGLT3 and GLUT4 mRNA transcript levels were determined by real time RT-PCR. hSGLT3 transcripts increased by a factor of ten following resistance training compared to control subjects (0.10, P=0.03. There were no differences in GLUT4 mRNA expression levels between groups. Protein expression levels of these transporters were confirmed by immunohistochemistry and Western blotting. hSGLT3 after resistance exercise was found not to be co-localized with the nicotinic acetylcholine receptor. The change in hSGLT3 transcript levels in the vastus lateralis muscle was positively correlated with glucose uptake, as measured by the change in muscle glycogen stores (r=0.53, P=0.02; and with exercise intensity, as measured by the change in muscle strength (r=0.73, P=0.001. Group assignment was be the only independent predictor of hSGLT3 transcript levels, explaining 68% of its variability (P=0.01. Our data show that hSGLT3, but not GLTU4, expression was enhanced in skeletal muscle after 16 weeks of resistance training. This finding suggests that hSGLT3, an insulin-independent glucose transporter, is activated with exercise and it may play a significant role in glycemic control with muscle contraction. The hSGLT3 exact mechanism is not well understood and requires further investigation. However its functional significance regarding a reduction of glucose toxicity and improvement of insulin resistance is the subject of ongoing research.

  7. Ipragliflozin: A novel sodium-glucose cotransporter 2inhibitor developed in Japan

    Institute of Scientific and Technical Information of China (English)

    Tsuyoshi Ohkura

    2015-01-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitioninduces glucosuria and decreases blood glucose levelsin diabetic patients and lowers hypoglycemic risk.SGLT1 is expressed in the kidney and intestine; SGLT1inhibition causes abdominal symptoms such as diarrheaand reduces incretin secretion. Therefore, SGLT2selectivity is important. Ipragliflozin is highly selectivefor SGLT2. In type 2 diabetes mellitus (T2DM), urinaryglucose excretion increased to 90 g/24 h after 28 d oftreatment with ipragliflozin 300 mg/d. Twelve weeksof ipragliflozin 50 mg/d vs placebo reduced glycatedhemoglobin and body weight by 0.65% and 0.66kg, respectively, in Western T2DM patients, and by1.3% and 1.89 kg, respectively, in Japanese patients.Ipragliflozin (highly selective SGLT2 inhibitor) improvesglycemic control and reduces body weight andlowers hypoglycemic risk and abdominal symptoms.Ipragliflozin can be a novel anti-diabetic and antiobesityagent.

  8. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors for patients with Type 2 diabetes

    DEFF Research Database (Denmark)

    Røder, Michael Einar; Storgaard, Heidi; Rungby, Jørgen;

    2016-01-01

    problem. Extremely rare cases of ketoacidosis are reported, mostly in patients with Type 1 diabetes. One SGLT-2i, empagliflozin, has been shown to reduce cardiovascular mortality and progression of kidney disease in patients with Type 2 diabetes and cardiovascular disease. Outcome trials for other SGLT-2i......The sodium-glucose cotransporter 2 inhibitor (SGLT-2i)-class is efficacious as monotherapy and as add-on therapy with an expected lowering of the glycated haemoglobin (HbA1c) concentration of approximately 7 mmol/mol. Side effects relate to the mode of action, genital infections are the main...... are pending. SGLT-2i are now in guidelines as a possible second-line therapy or in case of metformin intolerance....

  9. Purification of used eutectic (LiCl-KCl) salt electrolyte from pyroprocessing

    Science.gov (United States)

    Cho, Yung-Zun; Lee, Tae-Kyo; Eun, Hee-Chul; Choi, Jung-Hoon; Kim, In-Tae; Park, Geun-Il

    2013-06-01

    The separation characteristics of surrogate rare-earth fission products in a eutectic (LiCl-KCl) molten salt were investigated. This system is based on the eutectic salt used for the pyroprocessing treatment of used nuclear fuel (UNF). The investigation was performed using an integrated rare-earth separation apparatus comprising a precipitation reactor, a solid detachment device, and a layer separation device. To separate rare-earth fission products, a phosphate precipitation method using both Li3PO4 and K3PO4 as a precipitant was performed. The use of an equivalent phosphate precipitant composed of 0.408 molar ratio-K3PO4 and 0.592 molar ratio-Li3PO4 can preserve the original eutectic ratio, LiCl-0.592 molar ratio (or 45.2 wt%), as well as provide a high separation efficiency of over 99.5% under conditions of 550 °C and Ar sparging when using La, Nd, Ce, and Pr chlorides. The mixture of La, Nd, Ce, and Pr phosphate had a typical monoclinic (or monazite) structure, which has been proposed as a reliable host matrix for the permanent disposal of a high-level waste form. To maximize the reusability of purified eutectic waste salt after rare-earth separation, the successive rare-earth separation process, which uses both phosphate precipitation and an oxygen sparging method, were introduced and tested with eight rare-earth (Y, La, Ce, Pr, Nd, Sm, Eu and Gd) chlorides. In the successive rare-earth separation process, the phosphate reaction was terminated within 1 h at 550 °C, and a 4-8 h oxygen sparging time were required to obtain over a 99% separation efficiency at 700-750 °C. The mixture of rare-earth precipitates separated by the successive rare-earth separation process was found to be phosphate, oxychloride, and oxide. Through the successive rare-earth separation process, the eutectic ratio of purified salt maintained its original value, and impurity content including the residual precipitant of purified salt can be minimized.

  10. Balanço de potássio e desempenho de frangos de corte suplementados com KCl no verão Potassium balance and performance of broilers supplemented with KCl in summer

    Directory of Open Access Journals (Sweden)

    Bonifácio Benicio de Souza

    2004-10-01

    Full Text Available Objetivou-se com o presente trabalho avaliar o efeito da suplementação de cloreto de potássio (KCl sobre o balanço de potássio e o desempenho de frangos de corte no verão. Foram utilizados 288 frangos de corte, da linhagem Hubbard, sexados, alojados em baterias no período de 28 a 49 dias de idade, distribuídos segundo um delineamento inteiramente casualizado em esquema fatorial 6 x 2, com 6 níveis de KCl (0,0; 0,4; 0,8; 1,2; 1,6; 2,0% e 2 sexos, com 4 repetições de 6 aves cada uma. As temperaturas máxima e mínima, umidade relativa do ar e o índice de temperatura do globo negro e umidade (ITGU, durante o período experimental, foram de 31,5ºC e 20,5ºC, 68% e 77%, respectivamente. As aves receberam ração "ad libitum", com dietas formuladas à base de milho e farelo de soja. Quando as aves atingiram a idade de 35 dias, foi realizado o balanço de potássio, durante um período de 96 horas. A elevação na suplementação de KCl na dieta aumentou linearmente (PThis experiment was conducted to verify the effect of KCl on potassium balance and performance of broilers in summer. A total of 288 broiler chickens aged 28 to 49 days was utilized, allocated according to a completely randomized design in a 6 x 2 factorial scheme 6 levels of KCl (0,0; 0,4; 0,8; 1,2; 1,6; 2,0 % and 2 sexes, with four replications of 6 birds each. The maximum and minimum temperatures, relative humidity and black globe-humidity index (BGHI were of 31,5ºC and 20ºC, 68% and of 73%, respectability. With the growing supplementation of KCl, there was a linear increase (P<0.01 in the intake, excretion and retention of the potassium, concentration of potassium in the plasma and water consumption. There was a linear reduction (P<0.01 of the excreta dry matter. The males overcame the females (P<0.01 in the intake and excretion of potassium. However, the females overcame the males (P<0.01 in the retention of the potassium. There was a positive balance of potassium for

  11. Modulation of NCC activity by low and high K+ intake: insights into the signaling pathways involved

    Science.gov (United States)

    Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika

    2014-01-01

    Modulation of Na+-Cl− cotransporter (NCC) activity is essential to adjust K+ excretion in the face of changes in dietary K+ intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K+ diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K+-citrate diets for 4 days. The low-K+ diet decreased and high-K+ diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr44/Thr48/Thr53) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser383/Ser325). The effect of the low-K+ diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K+ diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K+ diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K+-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K+ increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K+ diet. PMID:24761002

  12. Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved.

    Science.gov (United States)

    Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika; Gamba, Gerardo

    2014-06-15

    Modulation of Na(+)-Cl(-) cotransporter (NCC) activity is essential to adjust K(+) excretion in the face of changes in dietary K(+) intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K(+) diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K(+)-citrate diets for 4 days. The low-K(+) diet decreased and high-K(+) diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr(44)/Thr(48)/Thr(53)) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser(383)/Ser(325)). The effect of the low-K(+) diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K(+) diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K(+) diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K(+)-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K(+) increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K(+) diet. Copyright © 2014 the American Physiological Society.

  13. Extensive Gustatory Cortex Lesions Significantly Impair Taste Sensitivity to KCl and Quinine but Not to Sucrose in Rats.

    Science.gov (United States)

    Bales, Michelle B; Schier, Lindsey A; Blonde, Ginger D; Spector, Alan C

    2015-01-01

    Recently, we reported that large bilateral gustatory cortex (GC) lesions significantly impair taste sensitivity to salts in rats. Here we extended the tastants examined to include sucrose and quinine in rats with ibotenic acid-induced lesions in GC (GCX) and in sham-operated controls (SHAM). Presurgically, immediately after drinking NaCl, rats received a LiCl or saline injection (i.p.), but postsurgical tests indicated a weak conditioned taste aversion (CTA) even in controls. The rats were then trained and tested in gustometers to discriminate a tastant from water in a two-response operant taste detection task. Psychometric functions were derived for sucrose, KCl, and quinine. Our mapping system was used to determine placement, size, and symmetry of the lesions (~91% GC damage on average). For KCl, there was a significant rightward shift (ΔEC50 = 0.57 log10 units; pquinine sensitivity. Surprisingly, taste sensitivity to sucrose was unaffected by the extensive lesions and was comparable between GCX and SHAM rats. The fact that such large bilateral GC lesions did not shift sucrose psychometric functions relative to SHAM, but did significantly compromise quinine and KCl sensitivity suggests that the neural circuits responsible for the detection of specific taste stimuli are partially dissociable. Lesion-induced impairments were observed in expression of a postsurgical CTA to a maltodextrin solution as assessed in a taste-oriented brief-access test, but were not reflected in a longer term 46-h two-bottle test. Thus, deficits observed in rats after extensive damage to the GC are also dependent on the test used to assess taste function. In conclusion, the degree to which the GC is necessary for the maintenance of normal taste detectability apparently depends on the chemical and/or perceptual features of the stimulus.

  14. Generation of KCL025 research grade human embryonic stem cell line carrying a mutation in NF1 gene

    Directory of Open Access Journals (Sweden)

    Heema Hewitson

    2016-03-01

    Full Text Available The KCL025 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation in the NF1 gene encoding neurofibromin (c.3739–3742 ΔTTTG. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro assays.

  15. Deep sub-threshold $\\Xi^-$ production in Ar+KCl reactions at 1.76A GeV

    CERN Document Server

    Agakichiev, G; Bassini, R; Belver, D; Belyaev, A V; Blanco, A; Böhmer, M; Boyard, J L; Braun-Munzinger, P; Cabanelas, P; Castro, E; Chernenko, S; Christ, T; Destefanis, M; Díaz, J; Dohrmann, F; Dybczak, A; Eberl, T; Fabbietti, L; Fateev, O V; Finocchiaro, P; Fonte, P; Friese, J; Fröhlich, I; Galatyuk, T; Garzón, J A; Gernhäuser, R; Gil, A; Gilardi, C; Golubeva, M; González-Díaz, D; Guber, F; Hennino, T; Holzmann, R; Iori, I; Ivashkin, A; Jurkovic, M; Kämpfer, B; Kanaki, K; Karavicheva, T; Kirschner, D; König, I; König, W; Kolb, B W; Kotte, R; Krizek, F; Krücken, R; Kühn, W; Kugler, A; Kurepin, A; Lang, S; Lange, J S; Lapidus, K; Liu, T; Lopes, L; Lorenz, M; Maier, L; Mangiarotti, A; Markert, J; Metag, V; Michalska, B; Michel, J; Mishra, D; Morinière, E; Mousa, J; Müntz, C; Naumann, L; Otwinowski, J; Pachmayer, Y C; Palka, M; Parpottas, Y; Pechenov, V; Pechenova, O; Pietraszko, J; Przygoda, W; Ramstein, B; Reshetin, A; Roy-Stephan, M; Rustamov, A; Sadovskii, A; Sailer, B; Salabura, P; Schmah, A; Sobolev, Yu G; Spataro, S; Spruck, B; Ströbele, H; Stroth, J; Sturm, C; Sudol, M; Tarantola, A; Teilab, K; Tlustý, P; Traxler, M; Trebacz, R; Tsertos, H; Wagner, V; Weber, M; Wisniowski, M; Wojcik, T; Wüstenfeld, J; Yurevich, S; Zanevsky, Yu V; Zhou, P

    2009-01-01

    We report first results on a deep sub-threshold production of the doubly strange hyperon $\\Xi^-$ in a heavy-ion reaction. At a beam energy of 1.76A GeV the reaction Ar+KCl was studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18/GSI. A high-statistics and high-purity $\\Lambda$ sample was collected, allowing for the investigation of the decay channel $\\Xi^- \\to \\Lambda \\pi^-$. The deduced $\\Xi^-/(\\Lambda+\\Sigma^0)$ production ratio of $(5.6 \\pm 1.2 ^{+1.8}_{-1.7})\\cdot 10^{-3}$ is significantly larger than available model predictions.

  16. An upper limit on hypertriton production in collisions of Ar(1.76 A GeV) + KCl

    Energy Technology Data Exchange (ETDEWEB)

    Agakishiev, G.; Chernenko, S.; Fateev, O.; Zanevsky, Y. [Joint Institute of Nuclear Research, Dubna (Russian Federation); Belver, D.; Cabanelas, P.; Castro, E.; Garzon, J.A. [Univ. de Santiago de Compostela, LabCAF. F. Fisica, Santiago de Compostela (Spain); Blanco, A.; Fonte, P.; Lopes, L.; Mangiarotti, A. [LIP-Laboratorio de Instrumentacao e Fisica Experimental de Particulas, Coimbra (Portugal); Boehmer, M.; Friese, J.; Gernhaeuser, R.; Jurkovic, M.; Kruecken, R.; Maier, L.; Weber, M. [Technische Universitaet Muenchen, Physik Department E12, Garching (Germany); Boyard, J.L.; Hennino, T.; Liu, T.; Moriniere, E.; Ramstein, B. [Universite Paris Sud, Institut de Physique Nucleaire (UMR 8608), CNRS/IN2P3, Orsay Cedex (France); Destefanis, M.; Gilardi, C.; Kuehn, W.; Lange, J.S.; Metag, V.; Spruck, B. [Justus Liebig Universitaet Giessen, II. Physikalisches Institut, Giessen (Germany); Dohrmann, F.; Kaempfer, B.; Kotte, R.; Naumann, L.; Wendisch, C.; Wuestenfeld, J. [Helmholtz-Zentrum Dresden-Rossendorf, Institut fuer Strahlenphysik, Dresden (Germany); Dybczak, A.; Michalska, B.; Palka, M.; Przygoda, W.; Salabura, P.; Trebacz, R.; Wisniowski, M. [Jagiellonian University of Cracow, Smoluchowski Institute of Physics, Krakow (Poland); Epple, E.; Fabbietti, L.; Lapidus, K.; Siebenson, J. [Excellence Cluster ' ' Origin and Structure of the Universe' ' , Garching (Germany); Finocchiaro, P.; Schmah, A.; Spataro, S. [Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare, Catania (Italy); Froehlich, I.; Lorenz, M.; Markert, J.; Michel, J.; Muentz, C.; Pachmayer, Y.C.; Pechenova, O.; Rehnisch, L.; Rustamov, A.; Scheib, T.; Schuldes, H.; Stroebele, H.; Tarantola, A.; Teilab, K. [Goethe-Universitaet, Institut fuer Kernphysik, Frankfurt (Germany); Galatyuk, T.; Gonzalez-Diaz, D. [Technische Universitaet Darmstadt, Darmstadt (Germany); Golubeva, M.; Guber, F.; Ivashkin, A.; Karavicheva, T.; Kurepin, A.; Reshetin, A.; Sadovsky, A. [Russian Academy of Science, Institute for Nuclear Research, Moscow (Russian Federation); Gumberidze, M. [Technische Universitaet Darmstadt, Darmstadt (Germany); Universite Paris Sud, Institut de Physique Nucleaire (UMR 8608), CNRS/IN2P3, Orsay Cedex (France); Heinz, T.; Holzmann, R.; Koenig, I.; Koenig, W.; Kolb, B.W.; Lang, S.; Pechenov, V.; Pietraszko, J.; Schwab, E.; Sturm, C.; Traxler, M.; Yurevich, S. [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany); Iori, I. [Istituto Nazionale di Fisica Nucleare, Sezione di Milano, Milano (Italy); Krasa, A.; Krizek, F.; Kugler, A.; Sobolev, Yu.G.; Tlusty, P.; Wagner, V. [Academy of Sciences of Czech Republic, Nuclear Physics Institute, Rez (Czech Republic); Kuc, H. [Jagiellonian University of Cracow, Smoluchowski Institute of Physics, Krakow (Poland); Universite Paris Sud, Institut de Physique Nucleaire (UMR 8608), CNRS/IN2P3, Orsay Cedex (France); Mousa, J.; Tsertos, H. [University of Cyprus, Department of Physics, Nicosia (Cyprus); Stroth, J. [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany); Goethe-Universitaet, Institut fuer Kernphysik, Frankfurt (Germany); Collaboration: HADES Collaboration

    2013-11-15

    A high-statistic data sample of Ar(1.76 AGeV)+KCl events recorded with HADES is used to search for a hypertriton signal. An upper production limit per centrality-triggered event of 1.04 x 10{sup -3} on the 3 {sigma} level is derived. Comparing this value with the number of successfully reconstructed {Lambda} hyperons allows to determine an upper limit on the ratio N{sub 3{sub {Lambda}H}}/N{sub {Lambda}}, which is confronted with statistical and coalescence-type model calculations. (orig.)

  17. An upper limit on hypertriton production in collisions of Ar(1.76 AGeV)+KCl

    CERN Document Server

    Agakishiev, G; Blanco, A; Böhmer, M; Boyard, J L; Cabanelas, P; Castro, E; Chernenko, S; Destefanis, M; Dohrmann, F; Dybczak, A; Epple, E; Fabbietti, L; Fateev, O; Finocchiaro, P; Fonte, P; Friese, J; Fröhlich, I; Galatyuk, T; Garzón, J A; Gernhäuser, R; Gilardi, C; Golubeva, M; González-Díaz, D; Guber, F; Gumberidze, M; Heinz, T; Hennino, T; Holzmann, R; Iori, I; Ivashkin, A; Jurkovic, M; Kämpfer, B; Karavicheva, T; Koenig, I; Koenig, W; Kolb, B W; Kotte, R; Krása, A; Krizek, F; Krücken, R; Kuc, H; Kühn, W; Kugler, A; Kurepin, A; Lang, S; Lange, J S; Lapidus, K; Liu, T; Lopes, L; Lorenz, M; Maier, L; Mangiarotti, A; Markert, J; Metag, V; Michalska, B; Miche, J; Morinière, E; Mousa, J; Müntz, C; Naumann, L; Pachmayer, Y C; Palka, M; Pechenov, V; Pechenova, O; Pietraszko, J; Przygoda, W; Ramstein, B; Rehnisch, L; Reshetin, A; Rustamov, A; Sadovsky, A; Salabura, P; Scheib, T; Schmah, A; Schuldes, H; Schwab, E; Siebenson, J; Sobolev, Yu G; Spatarof, S; Spruck, B; Ströbele, H; Stroth, J; Sturm, C; Tarantola, A; Teilab, K; Tlusty, P; Traxler, M; Trebacz, R; Tsertos, H; Wagner, V; Weber, M; Wendisch, C; Wisniowski, M; Wüstenfeld, J; Yurevich, S; Zanevsky, Y

    2013-01-01

    A high-statistic data sample of Ar(1.76 AGeV)+KCl events recorded with HADES is used to search for a hypertriton signal. An upper production limit per centrality-triggered event of 1.04 x $10^{-3}$ on the $3\\sigma$ level is derived. Comparing this value with the number of successfully reconstructed $\\Lambda$ hyperons allows to determine an upper limit on the ratio $N_{_{\\Lambda}^3H}/N_{\\Lambda}$, which is confronted with statistical and coalescence-type model calculations.

  18. Composition dependence of glow peak temperature in KCl{sub 1-x}Br{sub x} doped with divalent cations

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Salas, R [Departamento de Investigacion en FIsica, Universidad de Sonora, Apartado Postal 5-088 Hermosillo, Sonora, 83190 (Mexico); Aceves, R [Departamento de Investigacion en FIsica, Universidad de Sonora, Apartado Postal 5-088 Hermosillo, Sonora, 83190 (Mexico); RodrIguez-Mijangos, R [Departamento de Investigacion en FIsica, Universidad de Sonora, Apartado Postal 5-088 Hermosillo, Sonora, 83190 (Mexico); Riveros, H G [Instituto de FIsica, UNAM, Apartado Postal 20/364, Mexico, DF 01000, Mexico (Mexico); Duarte, C [Departamento de GeologIa, Universidad de Sonora, Rosales y Boulevard Luis E, Hermosillo, Sonora, 83000 (Mexico)

    2004-01-28

    Thermoluminescence measurements of {beta}-irradiated Eu{sup 2+} - and Ca{sup 2+} - doped KCl{sub 1-x}KBr{sub x} solid solutions excited at room temperature have been carried out to identify the effect of composition on the glow peaks. A typical glow peak has been distinguished for each composition. A linear dependence of its temperature on the composition x has been found. These results indicate that for divalent impurity-doped alkali halide solid solutions these glow peak temperatures are mostly dependent on the lattice constant of the host than on the size of the anion or impurity cation.

  19. Generation of KCL018 research grade human embryonic stem cell line carrying a mutation in the DMPK gene

    Directory of Open Access Journals (Sweden)

    Cristian Miere

    2016-03-01

    Full Text Available The KCL018 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting one allele of the DMPK gene encoding the dystrophia myotonica protein kinase (2200 trinucleotide repeats; 14 for the normal allele. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro assays.

  20. Generation of KCL028 research grade human embryonic stem cell line carrying a mutation in the HTT gene

    Directory of Open Access Journals (Sweden)

    Laureen Jacquet

    2016-03-01

    Full Text Available The KCL028 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting one allele of the HTT gene encoding huntingtin (43 trinucleotide repeats; 21 for the normal allele. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro and in vivo assays.

  1. Characteristics of K2TiCl6 synthesis from KCl and TiCl4; KCl to TiCl4 kara no K2TiCl6 no gosei hanno tokusei

    Energy Technology Data Exchange (ETDEWEB)

    Kumagai, T.; Konda, S.; Sasaki, T.; Ishikawa, T. [Hokkaido University, Sapporo (Japan); Chiba, T. [Hokkaido University, Sapporo (Japan). Center for Advanced Research of Energy Technology

    1997-07-10

    Reaction characteristics were examined for synthesis of K2TiCl6 from KCl particles and TiCl4 gas. The reaction experiments were carried out exposing different sizes of KCI particles to a TiCl4 gas stream at 683 K. The mass gain due to formation of K2TiCl6 was measured as a function of time and morphology of the product was observed by SEM and EPMA. The apparent reaction rate decreases rapidly with the progress of the reaction, and the reaction is virtually terminated before its completion EPMA analysis on the particle cross-section reveals that the products are distributed around an unreacted KCl core within the particle, and the termination of the reaction takes place when the thickness of the outer product layer grows up to about 6{mu}m. The reaction kinetics are explained well on the basis of an unreacted-core model which assumes that the rate determining step is the intra-particle TiCl4 gas diffusion. 14 refs., 6 figs., 1 tab.

  2. NaCl-KCl-Na2WO4共融体系的方波伏安法分析%Square wave voltammetry analysis of NaCl-KCl-Na 2WO4 communion system

    Institute of Scientific and Technical Information of China (English)

    廖春发; 房孟钊; 王旭; 汤浩; 罗林生

    2015-01-01

    采用三电极体系,应用方波伏安法分析NaCl-KCl-Na2WO4共融体系的电化学特性,重点研究了钨(Ⅵ)离子的电化学行为,结果表明:W(Ⅵ)→W(Ⅳ)还原过程的特征峰与 W(Ⅳ)→W的特征峰发生相互重叠, W(Ⅵ)离子的还原过程分2步,即:W(Ⅵ)→W(Ⅳ)→W,其中第1步W(Ⅵ)→W(Ⅳ)过程可逆,第2步W(Ⅳ)→W 过程不可逆。%Characteristics of NaCl-KCl-Na2WO4 communion system was analyzed by three-electrode system and square wave voltammetry, focusing on the electrochemical behavior of the tungsten ion (VI). The results show that the characteristic peak of reduction process of W (Ⅵ)→W (Ⅳ)and W (Ⅳ)→W is overlapping, and the reduction process of tungsten ion(VI) is divided into two steps, that is W (Ⅵ)→W(Ⅳ)→W, of which the first step is reversible, while the second step,W(IV)→W, is irreversible.

  3. Taurine Inhibits K+-Cl− Cotransporter KCC2 to Regulate Embryonic Cl− Homeostasis via With-no-lysine (WNK) Protein Kinase Signaling Pathway*

    Science.gov (United States)

    Inoue, Koichi; Furukawa, Tomonori; Kumada, Tatsuro; Yamada, Junko; Wang, Tianying; Inoue, Rieko; Fukuda, Atsuo

    2012-01-01

    GABA inhibits mature neurons and conversely excites immature neurons due to lower K+-Cl− cotransporter 2 (KCC2) expression. We observed that ectopically expressed KCC2 in embryonic cerebral cortices was not active; however, KCC2 functioned in newborns. In vitro studies revealed that taurine increased KCC2 inactivation in a phosphorylation-dependent manner. When Thr-906 and Thr-1007 residues in KCC2 were substituted with Ala (KCC2T906A/T1007A), KCC2 activity was facilitated, and the inhibitory effect of taurine was not observed. Exogenous taurine activated the with-no-lysine protein kinase 1 (WNK1) and downstream STE20/SPS1-related proline/alanine-rich kinase (SPAK)/oxidative stress response 1 (OSR1), and overexpression of active WNK1 resulted in KCC2 inhibition in the absence of taurine. Phosphorylation of SPAK was consistently higher in embryonic brains compared with that of neonatal brains and down-regulated by a taurine transporter inhibitor in vivo. Furthermore, cerebral radial migration was perturbed by a taurine-insensitive form of KCC2, KCC2T906A/T1007A, which may be regulated by WNK-SPAK/OSR1 signaling. Thus, taurine and WNK-SPAK/OSR1 signaling may contribute to embryonic neuronal Cl− homeostasis, which is required for normal brain development. PMID:22544747

  4. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters

    OpenAIRE

    2008-01-01

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored th...

  5. Sodium Glucose Co-transporter Type 2 (SGLT2) Inhibitors: Targeting the Kidney to Improve Glycemic Control in Diabetes Mellitus

    OpenAIRE

    Bays, Harold

    2013-01-01

    Although hyperglycemia is a key therapeutic focus in the management of patients with type 2 diabetes mellitus (T2DM), many patients experience sub-optimal glycemic control. Current glucose-lowering agents involve the targeting of various body organs. Sodium glucose co-transporter type 2 (SGLT2) inhibitors target the kidney, reduce renal glucose reabsorption, and increase urinary glucose elimination, thus lowering glucose blood levels. This review examines some of the key efficacy and safety d...

  6. Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Gluud, Lise L; Bennett, Cathy

    2016-01-01

    OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND STUDY...... increased risk in non-serious adverse events. The analyses may overestimate the intervention benefit due bias....

  7. Determinants of Substrate and Cation Transport in the Human Na+/Dicarboxylate Cotransporter NaDC3*

    OpenAIRE

    Schlessinger, A; Sun, NN; Colas, C; Pajor, AM

    2014-01-01

    Metabolic intermediates, such as succinate and citrate, regulate important processes ranging from energy metabolism to fatty acid synthesis. Cytosolic concentrations of these metabolites are controlled, in part, by members of the SLC13 gene family. The molecular mechanism underlying Na+-coupled di- and tricarboxylate transport by this family is understood poorly. The human Na+/dicarboxylate cotransporter NaDC3 (SLC13A3) is found in various tissues, including the kidney, liver, and brain. In a...

  8. Synthesis of novel l-rhamnose derived acyclic C-nucleosides with substituted 1,2,3-triazole core as potent sodium-glucose co-transporter (SGLT) inhibitors.

    Science.gov (United States)

    Putapatri, Siddamal Reddy; Kanwal, Abhinav; Banerjee, Sanjay K; Kantevari, Srinivas

    2014-03-15

    Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes by preventing renal glucose reabsorption. In our efforts to identify novel inhibitors of SGLT, we synthesized a series of l-rhamnose derived acyclic C-nucleosides with 1,2,3-triazole core. The key β-ketoester building block 4 prepared from l-rhamnose in five steps, was reacted with various aryl azides to produce the respective 1,2,3-triazole derivatives in excellent yields. Deprotection of acetonide group gave the desired acyclic C-nucleosides 7a-o. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using recently developed cell-based nonradioactive fluorescence glucose uptake assay. Among them, 7m with IC50: 125.9nM emerged as the most potent SGLT2 inhibitor. On the other hand compound 7d exhibited best selectivity for inhibition of SGLT2 (IC50: 149.1nM) over SGLT1 (IC50: 693.2nM). The results presented here demonstrated the utility of acyclic C-nucleosides as novel SGLT inhibitors for future investigations.

  9. Exploring Io's atmospheric composition with APEX: first measurement of 34SO2 and tentative detection of KCl

    CERN Document Server

    Moullet, A; Moreno, R; Gurwell, M; Black, J; Butler, B

    2013-01-01

    The composition of Io's tenuous atmosphere is poorly constrained. Only the major species SO2 and a handful of minor species have been positively identified, but a variety of other molecular species should be present, based on thermochemical equilibrium models of volcanic gas chemistry and the composition of Io's environment. This paper focuses on the spectral search for expected yet undetected molecular species (KCl, SiO, S2O) and isotopes (34SO2). We analyze a disk-averaged spectrum of a potentially line-rich spectral window around 345 GHz, obtained in 2010 at the APEX-12m antenna (Atacama Pathfinder EXperiment). Using different models assuming either extended atmospheric distributions or a purely volcanically-sustained atmosphere, we tentatively measure the KCl relative abundance with respect to SO2 and derive a range of 4x10^{-4}-8x10^{-3}. We do not detect SiO or S2O and present new upper limits on their abundances. We also present the first measurement of the 34S/32S isotopic ratio in gas phase on Io, wh...

  10. Statistical hadronization model analysis of hadron yields in p + Nb and Ar + KCl at SIS18 energies

    Science.gov (United States)

    Agakishiev, G.; Arnold, O.; Balanda, A.; Belver, D.; Belyaev, A.; Berger-Chen, J. C.; Blanco, A.; Böhmer, M.; Boyard, J. L.; Cabanelas, P.; Castro, E.; Chernenko, S.; Destefanis, M.; Dohrmann, F.; Dybczak, A.; Epple, E.; Fabbietti, L.; Fateev, O.; Finocchiaro, P.; Fonte, P.; Friese, J.; Fröhlich, I.; Galatyuk, T.; Garzón, J. A.; Gernhäuser, R.; Gilardi, C.; Göbel, K.; Golubeva, M.; González-Díaz, D.; Guber, F.; Gumberidze, M.; Heinz, T.; Hennino, T.; Holzmann, R.; Ierusalimov, A.; Iori, I.; Ivashkin, A.; Jurkovic, M.; Kämpfer, B.; Karavicheva, T.; Koenig, I.; Koenig, W.; Kolb, B. W.; Kornakov, G.; Kotte, R.; Krása, A.; Krizek, F.; Krücken, R.; Kuc, H.; Kühn, W.; Kugler, A.; Kurepin, A.; Ladygin, V.; Lalik, R.; Lange, J. S.; Lang, S.; Lapidus, K.; Lebedev, A.; Liu, T.; Lopes, L.; Lorenz, M.; Maier, L.; Mangiarotti, A.; Markert, J.; Metag, V.; Michalska, B.; Mihaylov, D.; Michel, J.; Morinière, E.; Mousa, J.; Müntz, C.; Münzer, R.; Naumann, L.; Pachmayer, Y. C.; Palka, M.; Parpottas, Y.; Pechenov, V.; Pechenova, O.; Pietraszko, J.; Przygoda, W.; Ramstein, B.; Rehnisch, L.; Reshetin, A.; Rustamov, A.; Sadovsky, A.; Salabura, P.; Scheib, T.; Schmah, A.; Schuldes, H.; Schwab, E.; Siebenson, J.; Sobolev, Yu. G.; Spataro, S.; Spruck, B.; Ströbele, H.; Stroth, J.; Sturm, C.; Tarantola, A.; Teilab, K.; Tlusty, P.; Traxler, M.; Trebacz, R.; Tsertos, H.; Vasiliev, T.; Wagner, V.; Weber, M.; Wendisch, C.; Wirth, J.; Wisniowski, M.; Wüstenfeld, J.; Yurevich, S.; Zanevsky, Y.

    2016-06-01

    The HADES data from p + Nb collisions at a center-of-mass energy of √{s_{NN}} = 3.2 GeV are analyzed employing a statistical hadronization model. The model can successfully describe the production yields of the identified hadrons π0, η, Λ, K 0 s, ω with parameters T_{chem} = (99± 11) MeV and μb = (619± 34) MeV, which fit well into the chemical freeze-out systematics found in heavy-ion collisions. In addition, we reanalyze our previous HADES data from Ar + KCl collisions at √{s_{NN}} = 2.6 GeV with an updated version of the model. We address equilibration in heavy-ion collisions by testing two aspects: the description of yields and the regularity of freeze-out parameters from a statistical model fit as a function of colliding energy and system size. Despite its success, the model fails to describe the observed Ξ- yields in both, p + Nb and Ar + KCl . Special emphasis is put on feed-down contributions from higher-lying resonance states as a possible explanation for the observed excess.

  11. Comparison of gaseous oxidized Hg measured by KCl-coated denuders, and nylon and cation exchange membranes.

    Science.gov (United States)

    Huang, Jiaoyan; Miller, Matthieu B; Weiss-Penzias, Peter; Gustin, Mae Sexauer

    2013-07-02

    The chemical compounds that make up gaseous oxidized mercury (GOM) in the atmosphere, and the reactions responsible for their formation, are not well understood. The limitations and uncertainties associated with the current method applied to measure these compounds, the KCl-coated denuder, are not known due to lack of calibration and testing. This study systematically compared the uptake of specific GOM compounds by KCl-coated denuders with that collected using nylon and cation exchange membranes in the laboratory and field. In addition, a new method for identifying different GOM compounds using thermal desorption is presented. Different GOM compounds (HgCl2, HgBr2, and HgO) were found to have different affinities for the denuder surface and the denuder underestimated each of these compounds. Membranes measured 1.3 to 3.7 times higher GOM than denuders in laboratory and field experiments. Cation exchange membranes had the highest collection efficiency. Thermodesorption profiles for the release of GOM compounds from the nylon membrane were different for HgO versus HgBr2 and HgCl2. Application of the new field method for collection and identification of GOM compounds demonstrated these vary as a function of location and time of year. Understanding the chemistry of GOM across space and time has important implications for those developing policy regarding this environmental contaminant.

  12. Effects of temperature, concentration, and uranium chloride mixture on zirconium electrochemical studies in LiClsbnd KCl eutectic salt

    Science.gov (United States)

    Hoover, Robert O.; Yoon, Dalsung; Phongikaroon, Supathorn

    2016-08-01

    Experimental studies were performed to provide measurement and analysis of zirconium (Zr) electrochemistry in LiClsbnd KCl eutectic salt at different temperatures and concentrations using cyclic voltammetry (CV). An additional experimental set with uranium chloride added into the system forming UCl3sbnd ZrCl4sbnd LiClsbnd KCl was performed to explore the general behavior of these two species together. Results of CV experiments with ZrCl4 show complicated cathodic and anodic peaks, which were identified along with the Zr reactions. The CV results reveal that diffusion coefficients (D) of ZrCl4 and ZrCl2 as the function of temperature can be expressed as DZr(IV) = 0.00046exp(-3716/T) and DZr(II) = 0.027exp(-5617/T), respectively. The standard rate constants and apparent standard potentials of ZrCl4 at different temperatures were calculated. Furthermore, the results from the mixture of UCl3 and ZrCl4 indicate that high concentrations of UCl3 hide the features of the smaller concentration of ZrCl4 while Zr peaks become prominent as the concentration of ZrCl4 increases.

  13. Effects of temperature, concentration, and uranium chloride mixture on zirconium electrochemical studies in LiCl−KCl eutectic salt

    Energy Technology Data Exchange (ETDEWEB)

    Hoover, Robert O. [Department of Chemical and Materials Engineering and Nuclear Engineering Program, University of Idaho, Center for Advanced Energy Studies, 995 University Blvd, Idaho Falls, ID 8340 (United States); Yoon, Dalsung [Department of Mechanical & Nuclear Engineering, Virginia Commonwealth University, 401 West Main St., Richmond, VA 23284 (United States); Phongikaroon, Supathorn, E-mail: sphongikaroon@vcu.edu [Department of Mechanical & Nuclear Engineering, Virginia Commonwealth University, 401 West Main St., Richmond, VA 23284 (United States)

    2016-08-01

    Experimental studies were performed to provide measurement and analysis of zirconium (Zr) electrochemistry in LiCl−KCl eutectic salt at different temperatures and concentrations using cyclic voltammetry (CV). An additional experimental set with uranium chloride added into the system forming UCl{sub 3}−ZrCl{sub 4}−LiCl−KCl was performed to explore the general behavior of these two species together. Results of CV experiments with ZrCl{sub 4} show complicated cathodic and anodic peaks, which were identified along with the Zr reactions. The CV results reveal that diffusion coefficients (D) of ZrCl{sub 4} and ZrCl{sub 2} as the function of temperature can be expressed as D{sub Zr(IV)} = 0.00046exp(−3716/T) and D{sub Zr(II)} = 0.027exp(−5617/T), respectively. The standard rate constants and apparent standard potentials of ZrCl{sub 4} at different temperatures were calculated. Furthermore, the results from the mixture of UCl{sub 3} and ZrCl{sub 4} indicate that high concentrations of UCl{sub 3} hide the features of the smaller concentration of ZrCl{sub 4} while Zr peaks become prominent as the concentration of ZrCl{sub 4} increases.

  14. Rancang Bangun Dan Pengujian Alat Penjatah (Metering Device Tipe Edge Cell Untuk Penyaluran Pupuk Butiran Urea, TSP dan KCl

    Directory of Open Access Journals (Sweden)

    Syafriandi Syafriandi

    2015-04-01

    Abstract. This study aims to design a fertilizer granules allotment (metering device type of cell edge that can control the fertilizer output by regulating the rotational speed of the motor is assembled with electronic circuits and test the prototypes performance using a metering device with 3 types of fertilizers ie Urea, TSP and KCl. Research tools are designed only able to drain urea and TSP , while KCL fertilizer have trouble escaping from the gap hopper . The average amount of urea metering device 1 output to the voltage 12.16 and 20 volts, respectively for 81.33 g /min, 130.33 g/min and 169.00 g/min. In metering device 2 each fertilizer output voltage feed all values in a row at 75,67 g/min, 129.00 g/min and 168.20 g/min. The average number of TSP output to metering device 1 at the 12.16 and 20 volts, respectively for 121.20 g/min, 181.53 g/min and 244.67 g/min. In metering device 2 each fertilizer output voltage feed all values in a row of 119.27 g/min, 180.53 g/min and 243.73 g/min.

  15. Determination of the E-pO{sup 2-} stability diagram of plutonium in the molten LiCl-KCl eutectic at 450 deg. C

    Energy Technology Data Exchange (ETDEWEB)

    Caravaca, Concha [CIEMAT, DE/DFN/URR, Avda. Complutense 22, Madrid 28040 (Spain)], E-mail: c.caravaca@ciemat.es; Laplace, Annabelle; Vermeulen, Jackie; Lacquement, Jerome [Commissariat a l' Energie Atomique, Site de Marcoule, DEN/DRCP/SCPS/LPP, Batiment 399, BP 17171, 30207 Bagnols sur Ceze (France)

    2008-07-01

    Plutonium trichloride solution in the molten LiCl-KCl eutectic was prepared by carbochlorination of plutonium oxide. Kinetics of this reaction was compared in different conditions in the range of 443-550 deg. C. Using this molten salt solution, the redox potential of the Pu(III)/Pu couple at inert tungsten electrode was measured at 450 deg. C by electromotive force measurement and was found to be E'{sup o} = -2.76 V vs. the Cl{sub 2(g)}(1 atm)/Cl{sup -} reference electrode (molar fraction scale). Reaction between plutonium trichloride and oxide ions was studied by potentiometric titration, using yttria stabilized electrodes. In our experimental conditions, the titration curves indicate the precipitation of the sesquioxide Pu{sub 2}O{sub 3}. The solubility product cologarithm calculated from these curves is found to be pK{sub s}(Pu{sub 2}O{sub 3}) = 22.8 {+-} 1.1 (molality scale). Using the experimentally obtained values for E'{sup o}, activity coefficient and pK{sub s} joined to the published thermodynamic data, the stability phase diagram of the Pu-O species was then drawn.

  16. Effect of Size-Selective Retention on the Cotransport of Hydroxyapatite and Goethite Nanoparticles in Saturated Porous Media.

    Science.gov (United States)

    Wang, Dengjun; Jin, Yan; Jaisi, Deb P

    2015-07-21

    Attributable to their nanoscale size and slow phosphorus (P) release kinetics, hydroxyapatite nanoparticles (HANPs) are increasingly advocated as a promising P nanofertilizer. Additionally, HANPs have been extensively used to remediate soils, groundwater, and nuclear wastewaters contaminated with metals and radionuclides. Increasing application of HANPs for agronomic and environmental advantages will expedite their dissemination in subsurface environments. Because the biogeochemical cycling of P is intimately coupled with iron, it is anticipated that HANPs and released P from HANPs interact with iron oxides, particularly naturally occurring goethite nanoparticles (GNPs) because of their nanoscale size and high reactivity toward P. Here, we investigated the cotransport and retention of HANPs and GNPs in water-saturated sand columns under environmentally relevant transport conditions (pH and natural organic matter type and concentration). Our results indicated that the "size-selective retention", i.e., preferential retention of larger particles near the column inlet and elution of smaller particles occurred during cotransport of HANPs and GNPs, and the cotransport of both NPs is highly sensitive to solution chemistry that determines NPs dissolution, homo- and heteroaggregation, and co- and competitive-retention. These findings have important insights into application of HANPs as a promising P nanofertilizer and an in situ amendment for contaminated site remediation.

  17. Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.

    Directory of Open Access Journals (Sweden)

    Naziha Bakouh

    Full Text Available BACKGROUND: A growing number of proteins, including ion transporters, have been shown to interact with Cystic Fibrosis Transmembrane conductance Regulator (CFTR. CFTR is an epithelial chloride channel that is involved in Cystic Fibrosis (CF when mutated; thus a better knowledge of its functional interactome may help to understand the pathophysiology of this complex disease. In the present study, we investigated if CFTR and the sodium-phosphate co-transporter type 2a (NPT2a functionally interact after heterologous expression of both proteins in Xenopus laevis oocytes. METHODOLOGY/FINDINGS: NPT2a was expressed alone or in combination with CFTR in X. laevis oocytes. Using the two-electrode voltage-clamp technique, the inorganic phosphate-induced current (IPi was measured and taken as an index of NPT2a activity. The maximal IPi for NPT2a substrates was reduced when CFTR was co-expressed with NPT2a, suggesting a decrease in its expression at the oolemna. This was consistent with Western blot analysis showing reduced NPT2a plasma membrane expression in oocytes co-expressing both proteins, whereas NPT2a protein level in total cell lysate was the same in NPT2a- and NPT2a+CFTR-oocytes. In NPT2a+CFTR- but not in NPT2a-oocytes, IPi and NPT2a surface expression were increased upon PKA stimulation, whereas stimulation of Exchange Protein directly Activated by cAMP (EPAC had no effect. When NPT2a-oocytes were injected with NEG2, a short amino-acid sequence from the CFTR regulatory domain that regulates PKA-dependent CFTR trafficking to the plasma membrane, IPi values and NPT2a membrane expression were diminished, and could be enhanced by PKA stimulation, thereby mimicking the effects of CFTR co-expression. CONCLUSION/PERSPECTIVES: We conclude that when both CFTR and NPT2a are expressed in X. laevis oocytes, CFTR confers to NPT2a a cAMPi-dependent trafficking to the membrane. This functional interaction raises the hypothesis that CFTR may play a role in

  18. Functional role of a putative carbonic anhydrase II-binding domain in the electrogenic Na+ -HCO₃- cotransporter NBCe1 expressed in Xenopus oocytes.

    Science.gov (United States)

    Yamada, Hideomi; Horita, Shoko; Suzuki, Masashi; Fujita, Toshiro; Seki, George

    2011-01-01

    The electrogenic Na+ -HCO₃⁻ cotransporter NBCe1 plays essential roles in the regulation of systemic and/or local pH. Homozygous inactivating mutations in NBCe1 cause proximal renal tubular acidosis associated with ocular abnormalities. We recently showed that defective membrane expression of NBCe1, caused by several mutations such as Delta65bp (S982NfsX4), is also associated with familial migraine. The Delta65bp mutant is quite unique in that it lacks a putative carbonic anhydrase (CA) II-binding domain but still shows an apparently normal transport activity in Xenopus oocytes. In this addendum, we show that the co-expression of CAII together with the wild-type NBCe1 or the Delta65bp mutant does not enhance the NBCe1 activities in oocytes. Moreover, a carbonic anhydrase inhibitor acetazolamide fails to inhibit the wild-type or the Delta65bp activities co-expressed with CAII. These results indicate that a bicarbonate transport metabolon proposed for the interaction between CAII and NBCe1 does not work at least in Xenopus oocytes.

  19. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Kim Y

    2012-08-01

    Full Text Available Yoojin Kim, Ambika R BabuDivision of Endocrinology, John Stroger Jr Hospital of Cook County and Rush University, Chicago, IL, USABackground: The kidney plays an important role in glucose metabolism, and has been considered a target for therapeutic intervention. The sodium-glucose cotransporter type 2 (SGLT2 mediates most of the glucose reabsorption from the proximal renal tubule. Inhibition of SGLT2 leads to glucosuria and provides a unique mechanism to lower elevated blood glucose levels in diabetes. The purpose of this review is to explore the physiology of SGLT2 and discuss several SGLT2 inhibitors which have clinical data in patients with type 2 diabetes.Methods: We performed a PubMed search using the terms "SGLT2" and "SGLT2 inhibitor" through April 10, 2012. Published articles, press releases, and abstracts presented at national and international meetings were considered.Results: SGLT2 inhibitors correct a novel pathophysiological defect, have an insulin-independent action, are efficacious with glycosylated hemoglobin reduction ranging from 0.5% to 1.5%, promote weight loss, have a low incidence of hypoglycemia, complement the action of other antidiabetic agents, and can be used at any stage of diabetes. They are generally well tolerated. However, due to side effects, such as repeated urinary tract and genital infections, increased hematocrit, and decreased blood pressure, appropriate patient selection for drug initiation and close monitoring after initiation will be important. Results of ongoing clinical studies of the effect of SGLT2 inhibitors on diabetic complications and cardiovascular safety are crucial to determine the risk-benefit ratio. A recent decision by the Committee for Medicinal Products for Human Use of the European Medicines Agency has recommended approval of dapagliflozin for the treatment of type 2 diabetes as an adjunct to diet and exercise, in combination with other glucose-lowering medicinal products, including

  20. Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

    Directory of Open Access Journals (Sweden)

    Sheila G Crewther

    Full Text Available Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/-10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5 mM Ba(2+ and 10(-5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba(2+ but significant change only for negative lens defocus with bumetanide (Rx(SAL(-10D = -8.6 +/- .9 D; Rx(Ba2+(-10D = -2.9 +/- .9 D; Rx(Bum(-10D = -2.9 +/- .9 D; Rx(SAL(+10D = +8.2 +/- .9 D; Rx(Ba2+(+10D = +2.8 +/- 1.3 D; Rx(Bum(+10D = +8.0 +/- .7 D. Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba(2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a

  1. Simulation of NaCl and KCl mass transfer during salting of Prato cheese in brine with agitation: a numerical solution

    Directory of Open Access Journals (Sweden)

    E. Bona

    2007-09-01

    Full Text Available The association of dietary NaCl with arterial hypertension has led to a reduction in the levels of this salt in cheeses. For salting, KCl has been used as a partial substitute for NaCl, which cannot be completely substituted without affecting product acceptability. In this study a sensorially adequate saline solution (NaCl/KCl was simultaneously diffused during salting of Prato cheese in brine with agitation. The simultaneous multicomponent diffusion during the process was modeled with Fick’s second generalized law. The system of partial differential equations formed was solved by the finite element method (FEM. In the experimental data concentration the deviation for NaCl was of 7.3% and for KCl of 5.4%, both of which were considered acceptable. The simulation of salt diffusion will allow control and modulation of salt content in Prato cheese, permitting the prediction of final content from initial conditions.

  2. Single-dose Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Selective Inhibitor of Sodium Glucose Cotransporter 2, in Healthy Indian Participants.

    Science.gov (United States)

    Devineni, Damayanthi; Polidori, David; Curtin, Christopher; Stieltjes, Hans; Tian, Hong; Wajs, Ewa

    2016-01-01

    Canagliflozin, an orally active selective inhibitor of sodium glucose cotransporter 2, has been approved in several countries for the treatment of type 2 diabetes mellitus. This study assessed the pharmacokinetic (PK) and pharmacodynamic (PD) properties and tolerability of single-dose canagliflozin 200 or 300 mg in healthy Indian participants. In this Phase 1, single-center, open-label, 2-period crossover study, healthy adult participants were randomly assigned to receive a single dose of canagliflozin 200 mg in period 1, followed by canagliflozin 300 mg in period 2, or vice versa. The 2 periods were separated by a washout interval of 14 days. The PK and PD properties and tolerability of canagliflozin were assessed at prespecified time points. Of 15 randomized participants, 14 completed the study. After the administration of single doses of 200 and 300 mg, the mean (SD) Cmax values were 1792 (430) ng/mL and 2789 (941) ng/mL, respectively; AUC0-∞, values were 18,706 (3818) ng·h/mL and 28,207 (5901) ng·h/mL, respectively. The Tmax and t½ of canagliflozin were independent of dose (Tmax, 1.5 hours at both doses; t½, 13.0 and 12.6 hours with 200 and 300 mg). Over the first 4 hours, mean (SD) renal threshold for glucose (RTG) values were 60.8 (8.90) and 61.2 (7.04) mg/dL with the 200- and 300-mg doses, respectively. No effect on plasma glucose concentrations over 0 to 4 hours relative to baseline was observed with either dose. The only treatment-emergent adverse event (TEAE) reported in >1 participant was dizziness (2 participants with the 200-mg dose). None of the participants in the 300-mg group reported any TEAEs. No deaths, discontinuations due to TEAEs, or hypoglycemic episodes were reported. The mean plasma exposure (Cmax and AUC) to canagliflozin increased in a dose-dependent manner after the administration of single-dose oral canagliflozin 200 and 300 mg in these healthy Indian participants. The Tmax and t½ of canagliflozin appeared to be independent of

  3. Effect of Sodium Glucose Cotransporter 2 Inhibitors With Low SGLT2/SGLT1 Selectivity on Circulating Glucagon-Like Peptide 1 Levels in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Takebayashi, Kohzo; Inukai, Toshihiko

    2017-09-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1. Recent evidence shows that these SGLT2 inhibitors with low SGLT2/SGLT1 selectivity elevate the level of circulating glucagon like peptide-1 (GLP-1), an incretin hormone that promotes insulin secretion in pancreatic β cells. This effect probably occurs partly via inhibition of intestinal SGLT1, and the elevation of active GLP-1 levels is especially apparent when these drugs are co-administered with dipeptidyl peptidase 4 (DPP4) inhibitors. These findings suggest that a combination of canagliflozin or sotagliflozin and a DPP4 inhibitor can provide a beneficial effect associated with elevation of circulating active GLP-1 and may serve as a treatment for patients with type 2 diabetes.

  4. CD8(+) T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension.

    Science.gov (United States)

    Liu, Yunmeng; Rafferty, Tonya M; Rhee, Sung W; Webber, Jessica S; Song, Li; Ko, Benjamin; Hoover, Robert S; He, Beixiang; Mu, Shengyu

    2017-01-09

    Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8(+) T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8(+) T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8(+) T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K(+) channel Kir4.1, and stimulation of the Cl(-) channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.

  5. CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension

    Science.gov (United States)

    Liu, Yunmeng; Rafferty, Tonya M.; Rhee, Sung W.; Webber, Jessica S.; Song, Li; Ko, Benjamin; Hoover, Robert S.; He, Beixiang; Mu, Shengyu

    2017-01-01

    Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl− channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension. PMID:28067240

  6. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Scheen, André J

    2015-01-01

    Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin

  7. Sodium-glucose cotransporter 2 inhibitors with insulin in type 2 diabetes: Clinical perspectives

    Directory of Open Access Journals (Sweden)

    Mathew John

    2016-01-01

    Full Text Available The treatment of type 2 diabetes is a challenging problem. Most subjects with type 2 diabetes have progression of beta cell failure necessitating the addition of multiple antidiabetic agents and eventually use of insulin. Intensification of insulin leads to weight gain and increased risk of hypoglycemia. Sodium-glucose cotransporter 2 (SGLT2 inhibitors are a class of antihyperglycemic agents which act by blocking the SGLT2 in the proximal tubule of the kidney. They have potential benefits in terms of weight loss and reduction of blood pressure in addition to improvements in glycemic control. Further, one of the SGLT2 inhibitors, empagliflozin has proven benefits in reducing adverse cardiovascular (CV outcomes in a CV outcome trial. Adding SGLT2 inhibitors to insulin in subjects with type 2 diabetes produced favorable effects on glycemic control without the weight gain and hypoglycemic risks associated with insulin therapy. The general risks of increased genital mycotic infections, urinary tract infections, volume, and osmosis-related adverse effects in these subjects were similar to the pooled data of individual SGLT2 inhibitors. There are subsets of subjects with type 2 diabetes who may have insulin deficiency, beta cell autoimmunity, or is prone to diabetic ketoacidosis. In these subjects, SGLT2 inhibitors should be used with caution to prevent the rare risks of ketoacidosis.

  8. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-03-01

    Full Text Available The sodium-glucose cotransporter (SGLT 2 offer a novel approach to treating type 2 diabetes by reducing hyperglycaemia via increased urinary glucose excretion. In the present study, the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six SGLT2 inhibitors commercially available in Japan were investigated and compared. Based on findings in normal and diabetic mice, the six drugs were classified into two categories, long-acting: ipragliflozin and dapagliflozin, and intermediate-acting: tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. Long-acting SGLT2 inhibitors exerted an antihyperglycemic effect with lower variability of blood glucose level via a long-lasting increase in urinary glucose excretion. In addition, ipragliflozin and luseogliflozin exhibited superiority over the others with respect to fast onset of pharmacological effect. Duration and onset of the pharmacologic effects seemed to be closely correlated with the pharmacokinetic properties of each SGLT2 inhibitor, particularly with respect to high distribution and long retention in the target organ, the kidney. While all six SGLT2 inhibitors were significantly effective in increasing urinary glucose excretion and reducing hyperglycemia, our findings suggest that variation in the quality of daily blood glucose control associated with duration and onset of pharmacologic effects of each SGLT2 inhibitor might cause slight differences in rates of improvement in type 2 diabetes.

  9. Sodium glucose co-transporter inhibitors – A new class of old drugs

    Science.gov (United States)

    Malhotra, Aneeta; Kudyar, Surbhi; Gupta, Anil K.; Kudyar, Rattan P.; Malhotra, Pavan

    2015-01-01

    Sodium glucose co-transporter (SGLT) inhibitors are a new class of drugs which are used in the pharmacotherapy of Type-II diabetes, which happens to be a major risk factor for developing both micro as well as macro-vascular complications. These drugs inhibit the glucose reabsorption by inhibiting SGLT, which exhibits a novel and promising mechanism of action by promoting the urinary glucose excretion hence providing a basis of therapeutic intervention. Results of SGLT-II inhibitors are very encouraging as there is a significant elevation of GLP-1 level, which forms the basis of relevance in treatment of diabetes. It targets the HbA1C and keeps a check on its levels. It also exerts other positive benefits such as weight loss, reduction in blood glucose levels, reduction in blood pressure and improvement in insulin resistance and β-cell dysfunction: All contributing to effective glycemic control. SGLT inhibition will develop as effective modality as it has the capability of inhibiting reabsorption of greater percentage of filtered glucose load. PMID:26539362

  10. Blocking effect of colloids on arsenate adsorption during co-transport through saturated sand columns.

    Science.gov (United States)

    Ma, Jie; Guo, Huaming; Lei, Mei; Wan, Xiaoming; Zhang, Hanzhi; Feng, Xiaojuan; Wei, Rongfei; Tian, Liyan; Han, Xiaokun

    2016-06-01

    Transport of environmental pollutants through porous media is influenced by colloids. Co-transport of As(V) and soil colloids at different pH were systematically investigated by monitoring breakthrough curves (BTCs) in saturated sand columns. A solute transport model was applied to characterize transport and retention sites of As(V) in saturated sand in the presence of soil colloids. A colloid transport model and the DLVO theory were used to reveal the mechanism and hypothesis of soil colloid-promoted As(V) transport in the columns. Results showed that rapid transport of soil colloids, regulated by pH and ionic strength, promoted As(V) transport by blocking As(V) adsorption onto sand, although soil colloids had low adsorption for As(V). The promoted transport was more significant at higher concentrations of soil colloids (between 25 mg L(-1) and 150 mg L(-1)) due to greater blocking effect on As(V) adsorption onto the sand surfaces. The blocking effect of colloids was explained by the decreases in both instantaneous (equilibrium) As adsorption and first-order kinetic As adsorption on the sand surface sites. The discovery of this blocking effect improves our understanding of colloid-promoted As transport in saturated porous media, which provides new insights into role of colloids, especially colloids with low As adsorption capacity, in As transport and mobilization in soil-groundwater systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Abnormal expression of cerebrospinal fluid cation chloride cotransporters in patients with Rett syndrome.

    Directory of Open Access Journals (Sweden)

    Sofia Temudo Duarte

    Full Text Available OBJECTIVE: Rett Syndrome is a progressive neurodevelopmental disorder caused mainly by mutations in the gene encoding methyl-CpG-binding protein 2. The relevance of MeCP2 for GABAergic function was previously documented in animal models. In these models, animals show deficits in brain-derived neurotrophic factor, which is thought to contribute to the pathogenesis of this disease. Neuronal Cation Chloride Cotransporters (CCCs play a key role in GABAergic neuronal maturation, and brain-derived neurotrophic factor is implicated in the regulation of CCCs expression during development. Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group. METHODS: The presence of bumetanide sensitive NKCC1 and KCC2 was analysed in cerebrospinal fluid samples from a control pediatric population (1 day to 14 years of life and from Rett syndrome patients (2 to 19 years of life, by immunoblot analysis. RESULTS: Both proteins were detected in the cerebrospinal fluid and their levels are higher in the early postnatal period. However, Rett syndrome patients showed significantly reduced levels of KCC2 and KCC2/NKCC1 ratio when compared to the control group. CONCLUSIONS: Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective.

  12. Renal Expression and Urinary Excretion of Na-K-2Cl Cotransporter in Obstructive Nephropathy

    Directory of Open Access Journals (Sweden)

    Anabel Brandoni

    2017-01-01

    Full Text Available Renal damage due to urinary tract obstruction accounts for up to 30% of acute kidney injury in paediatrics and adults. Bilateral ureteral obstruction (BUO is associated with polyuria and reduced urinary concentrating capacity. We investigated the renal handling of water and electrolytes together with the renal expression and the urinary excretion of the Na-K-Cl cotransporter (NKCC2 after 1 (BUO-1, 2 (BUO-2, and 7 (BUO-7 days of release of BUO. Immunoblotting and immunohistochemical studies showed that NKCC2 expression was upregulated in apical membranes both from BUO-2 and from BUO-7 rats. The apical membrane expression, where NKCC2 is functional, may be sufficient to normalize water, potassium, sodium, and osmolytes tubular handling. NKCC2 abundance in homogenates and mRNA levels of NKCC2 was significantly decreased in almost all groups suggesting a decrease in the synthesis of the transporter. Urinary excretion of NKCC2 was increased in BUO-7 groups. These data suggest that the upregulation in the expression of NKCC2 in apical membranes during the postobstructive phase of BUO could contribute to improving the excretion of sodium and consequently also the excretion of potassium, osmolytes, and water. Moreover, the increase in urinary excretion of NKCC2 in BUO-7 group could be a potential additional biomarker of renal function recovery.

  13. Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill

    Science.gov (United States)

    Breves, Jason P.; Serizier, Sandy B.; Goffin, Vincent; McCormick, Stephen D.; Karlstrom, Rolf O.

    2013-01-01

    Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na+/Cl− cotransporter (ncc; slc12a10.2), Na+/H+ exchanger (nhe3b; slc9a3.2), and epithelial Ca2+ channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl− uptake in zebrafish for the first time.

  14. Co-transport of metal complexes by the green mussel Perna viridis.

    Science.gov (United States)

    Chuang, Chia-Ying; Wang, Wen-Xiong

    2006-07-15

    We examined the uptake of ligand-bound metals (Cd and Zn) by the green mussel Perna viridis using defined artificial seawater. Different free ion concentrations (1 pM to 10 microM) in uptake solutions were created by adding different amounts of total metals (Cd 0.1 nM to 0.1 mM; Zn 0.5 nM to 0.05 mM) and ligands (EDTA, NTA, citric acid). Our results showed that Cd and Zn uptake could not be fully explained by the free Cd and Zn concentrations in the presence of different ligands, indicating that metal-ligand complexes were at least partially available for uptake by the mussels. Total Zn concentrations appeared to be a better predictor of metal uptake than the free Zn ion concentrations in the presence of different ligands. Uptake of lipophilic organic metal complexes was substantially greater than the hydrophilic metal complexes, even though the free ion concentration was comparable or lower. Moreover, the radiolabeled ligand compounds were directly accumulated by the mussels. The accumulation of metal complexes may explain the increased metal uptake with increasing ligand and total metal concentration, even though the free ion metal concentration was constant. Overall, our experimental results indicated that free metal ion cannot fully explain metal uptake since metal complex species were also available to the mussels to some extent, apparently through a co-transport process.

  15. Osmoregulation Requires Brain Expression of the Renal Na-K-2Cl Cotransporter NKCC2

    Science.gov (United States)

    Konopacka, Agnieszka; Qiu, Jing; Yao, Song T.; Greenwood, Michael P.; Greenwood, Mingkwan; Lancaster, Thomas; Inoue, Wataru; de Souza Mecawi, Andre; Vechiato, Fernanda M.V.; de Lima, Juliana B.M.; Coletti, Ricardo; Hoe, See Ziau; Martin, Andrew; Lee, Justina; Joseph, Marina; Hindmarch, Charles; Paton, Julian; Antunes-Rodrigues, Jose; Bains, Jaideep

    2015-01-01

    The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution—rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats. PMID:25834041

  16. Renal glucose handling in diabetes and sodium glucose cotransporter 2 inhibition

    Directory of Open Access Journals (Sweden)

    Resham Raj Poudel

    2013-01-01

    Full Text Available The kidneys play a major role in glucose homeostasis through its utilization, gluconeogenesis, and reabsorption via sodium glucose cotransporters (SGLTs. The defective renal glucose handling from upregulation of SGLTs, mainly the SGLT2, plays a fundamental role in the pathogenesis of type 2 diabetes mellitus. Genetic mutations in a SGLT2 isoform that results in benign renal glycosuria, as well as clinical studies with SGLT2 inhibitors in type 2 diabetes support the potential of this approach. These studies indicate that inducing glycosuria by suppressing SGLT2 can reduce plasma glucose and A1c levels, as well as decrease weight, resulting in improved β-cell function and enhanced insulin sensitivity in liver and muscle. Because the mechanism of SGLT2 inhibition is independent of insulin secretion and sensitivity, these agents can be combined with other antidiabetic agents, including exogenous insulin. This class represents a novel therapeutic approach with potential for the treatment of both type 2 and type 1 diabetes.

  17. Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Raskin, Philip

    2013-07-01

    Results from randomized controlled trials have demonstrated that the risk of microvascular complications can be reduced by intensive glycaemic control in patients with type 2 diabetes mellitus (T2DM). However, only about half of patients with diagnosed diabetes achieve recommended glycaemic goals. New therapies with complementary mechanisms of action that are independent of insulin secretion or action may provide additional therapeutic options to enable patients to achieve glycaemic control. The kidney plays an important role in glucose homeostasis, primarily by the reabsorption of filtered glucose. The sodium-glucose cotransporter 2 (SGLT2), located in the proximal convoluted tubule, is responsible for the majority of glucose reabsorption by the kidney. SGLT2 inhibitors offer a novel approach to treat T2DM and reduce hyperglycaemia by increasing urinary excretion of glucose. Dapagliflozin, an SGLT2 inhibitor recently approved in Europe for the treatment of T2DM, improves glycaemic control in patients with T2DM when used as monotherapy or when added to other diabetes medications, such as metformin, sulfonylureas, pioglitazone, and insulin. As a class, SGLT2 inhibitors are well tolerated and have a low propensity to cause hypoglycaemia. An increase in signs, symptoms, and other events suggestive of genital and, in some studies, urinary tract infections has been reported with SGLT2 inhibitors. Results from ongoing and future clinical trials will help define the role for this new class of investigational compounds, with its unique mechanism of action, as a treatment option for reducing hyperglycaemia in patients with T2DM.

  18. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

    Science.gov (United States)

    Buschur, Elizabeth O.; Buse, John B.; Cohan, Pejman; Diner, Jamie C.; Hirsch, Irl B.

    2015-01-01

    OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS Cases identified incidentally are described. RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. CONCLUSIONS SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes. PMID:26078479

  19. The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate.

    Science.gov (United States)

    Mistry, Abinash C; Wynne, Brandi M; Yu, Ling; Tomilin, Viktor; Yue, Qiang; Zhou, Yiqun; Al-Khalili, Otor; Mallick, Rickta; Cai, Hui; Alli, Abdel A; Ko, Benjamin; Mattheyses, Alexa; Bao, Hui-Fang; Pochynyuk, Oleh; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

    2016-10-01

    The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are coexpressed, the second part of the distal convoluted tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and coexpression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by blue native PAGE. Extensive coimmunoprecipitation experiments demonstrated a consistent interaction of NCC with α- and γ-ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence resonance energy transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting the function of ENaC. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  20. Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill.

    Science.gov (United States)

    Breves, Jason P; Serizier, Sandy B; Goffin, Vincent; McCormick, Stephen D; Karlstrom, Rolf O

    2013-04-30

    Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na(+)/Cl(-) cotransporter (ncc; slc12a10.2), Na(+)/H(+) exchanger (nhe3b; slc9a3.2), and epithelial Ca(2+) channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl(-) uptake in zebrafish for the first time. Copyright © 2013. Published by Elsevier Ireland Ltd.

  1. Expression of Pit2 sodium-phosphate cotransporter during murine odontogenesis is developmentally regulated.

    Science.gov (United States)

    Zhao, Dawei; Vaziri Sani, Forugh; Nilsson, Jeanette; Rodenburg, Michaela; Stocking, Carol; Linde, Anders; Gritli-Linde, Amel

    2006-12-01

    Different sodium-dependent inorganic phosphate (P(i)) uptake mechanisms play a major role in cellular P(i) homeostasis. The function and detailed distribution patterns of the type III Na(+)-phosphate cotransporter, PiT-2, in different organs during development are still largely unknown. We therefore examined the temporospatial expression patterns of Pit2 during murine odontogenesis. Odontoblasts were always devoid of Pit2 expression, whereas a transient, but strong, expression was detected in young secretory ameloblasts. However, the stratum intermedium and, later on, the papillary layer and cells of the subodontoblastic layer, exhibited high levels of Pit2 mRNA, which increased gradually as the tooth matured. Hormonal treatment or P(i) starvation of tooth germs in vitro did not alter Pit2 levels or patterns of expression, indicating mechanisms of regulation different from those of PiT-1 or other cell types. PiT-2 also functions as a retroviral receptor, and functional membrane-localized protein was confirmed throughout the dental papilla/pulp by demonstrating cellular permissiveness to infection by a gammaretrovirus that uses PiT-2 as a receptor. The distinct pattern of Pit2 expression during odontogenesis suggests that its P(i)-transporter function may be important for homeostasis of dental cells and not specifically for mineralization of the dental extracellular matrices. The expression of viral receptors in enamel-forming cells and the dental pulp may be of pathological significance.

  2. Direct control of Na(+)-K(+)-2Cl(-)-cotransport protein (NKCC1) expression with aldosterone.

    Science.gov (United States)

    Ding, Bo; Frisina, Robert D; Zhu, Xiaoxia; Sakai, Yoshihisa; Sokolowski, Bernd; Walton, Joseph P

    2014-01-01

    Sodium/potassium/chloride cotransporter (NKCC1) proteins play important roles in Na(+) and K(+) concentrations in key physiological systems, including cardiac, vascular, renal, nervous, and sensory systems. NKCC1 levels and functionality are altered in certain disease states, and tend to decline with age. A sensitive, effective way of regulating NKCC1 protein expression has significant biotherapeutic possibilities. The purpose of the present investigation was to determine if the naturally occurring hormone aldosterone (ALD) could regulate NKCC1 protein expression. Application of ALD to a human cell line (HT-29) revealed that ALD can regulate NKCC1 protein expression, quite sensitively and rapidly, independent of mRNA expression changes. Utilization of a specific inhibitor of mineralocorticoid receptors, eplerenone, implicated these receptors as part of the ALD mechanism of action. Further experiments with cycloheximide (protein synthesis inhibitor) and MG132 (proteasome inhibitor) revealed that ALD can upregulate NKCC1 by increasing protein stability, i.e., reducing ubiquitination of NKCC1. Having a procedure for controlling NKCC1 protein expression opens the doors for therapeutic interventions for diseases involving the mis-regulation or depletion of NKCC1 proteins, for example during aging.

  3. Extensive Gustatory Cortex Lesions Significantly Impair Taste Sensitivity to KCl and Quinine but Not to Sucrose in Rats.

    Directory of Open Access Journals (Sweden)

    Michelle B Bales

    Full Text Available Recently, we reported that large bilateral gustatory cortex (GC lesions significantly impair taste sensitivity to salts in rats. Here we extended the tastants examined to include sucrose and quinine in rats with ibotenic acid-induced lesions in GC (GCX and in sham-operated controls (SHAM. Presurgically, immediately after drinking NaCl, rats received a LiCl or saline injection (i.p., but postsurgical tests indicated a weak conditioned taste aversion (CTA even in controls. The rats were then trained and tested in gustometers to discriminate a tastant from water in a two-response operant taste detection task. Psychometric functions were derived for sucrose, KCl, and quinine. Our mapping system was used to determine placement, size, and symmetry of the lesions (~91% GC damage on average. For KCl, there was a significant rightward shift (ΔEC50 = 0.57 log10 units; p<0.001 in the GCX psychometric function relative to SHAM, replicating our prior work. There was also a significant lesion-induced impairment (ΔEC50 = 0.41 log10 units; p = 0.006 in quinine sensitivity. Surprisingly, taste sensitivity to sucrose was unaffected by the extensive lesions and was comparable between GCX and SHAM rats. The fact that such large bilateral GC lesions did not shift sucrose psychometric functions relative to SHAM, but did significantly compromise quinine and KCl sensitivity suggests that the neural circuits responsible for the detection of specific taste stimuli are partially dissociable. Lesion-induced impairments were observed in expression of a postsurgical CTA to a maltodextrin solution as assessed in a taste-oriented brief-access test, but were not reflected in a longer term 46-h two-bottle test. Thus, deficits observed in rats after extensive damage to the GC are also dependent on the test used to assess taste function. In conclusion, the degree to which the GC is necessary for the maintenance of normal taste detectability apparently depends on the chemical and

  4. Production of strangeness in Ar+KCl reactions at 1.756 AGeV with HADES; Produktion von Seltsamkeit in Ar+KCl Reaktionen bei 1.756 AGeV mit HADES

    Energy Technology Data Exchange (ETDEWEB)

    Schmah, Alexander Marc

    2008-05-15

    In september/october 2005 the first of heavier colliding systems was investigated with the HADES spectrometer by using an Ar projectile and a KCl target at a bombarding energy of 1.756 AGeV. With 850 million semi-central reactions in the colliding system Ar+KCl the opportunity was given for one of the most extensive hadron analyses in the SIS energy regime. The results of these analyses are presented in this thesis. The main focal point is the production of particles with strangeness content. The particle ratios of {lambda} and K{sup 0}{sub S} are comparable to those of other experiments. The corrections of acceptance, detector-, cut- and reconstruction efficiency is done using the simulation packages PLUTO, UrQMD and GEANT. With the corrected transverse mass spectra rapidity distributions and particle multiplicities are calculated. Due to the nearly full sample of reconstructed particles carrying strangeness, one can conclude to the missing part, which is connected to the charged {sigma}-hyperons. Within the error bars the fraction of {sigma}{sup {+-}}{sup ,0} is at least 12 % of the {lambda} multiplicity. The detection of the {phi} vector meson far below the nucleon-nucleon production threshold in the decay channel {phi} {yields} K{sup +}K{sup -} exceeds with 168 {+-} 18 the only up to now published data by more than a factor 7. The extracted effective temperature of T{sub eff}=80{+-}9{sup +2}{sub -3} is a brand-new result. The determined {phi}/K{sup -} ratio is 0.59{sup +0.30}{sub -0.29}. (orig.)

  5. KCl含量对乳化炸药压力减敏的影响%Influences of KCl content on pressure desensitization of emulsion explosives

    Institute of Scientific and Technical Information of China (English)

    杜明燃; 汪旭光; 颜事龙

    2015-01-01

    在相同的乳胶基质中分别添加0%、2%、4%、6%和8%的KCl,再分别用膨胀珍珠岩和化学发泡剂敏化制备2组乳化炸药.测试各乳化炸药水中爆炸冲击波,得出它们未受压和受压后的爆炸冲击波压力峰值,利用波峰值计算乳化炸药的压力减敏度.依据压力减敏度数值,分析KCl含量对乳化炸药压力减敏作用的影响,并测试不同KCl含量下分散相的析晶点,分析不同KCl含量造成压力减敏变化的原因.结果表明:KCl含量在0%~2%之间时,乳化炸药的压力减敏度无明显变化,KCl含量在2%~8%之间时,KCl含量对乳化炸药的压力减敏度有较大影响,而且呈现出正线形相关性.%An emulsion matrix was mixed with 0%, 2%, 4%, 6% and 8% by the mass of KCl separately, and then expanded perlite and chemical foaming agent as sensitizing agent were used separately to make two groups of emulsion explosives. Their explosion shock waves were tested in water before and after compression by shock waves produced by the host charge underwater. The pressure desensitization degrees of these emulsion explosives were calculated with the peak pressure values of tested shock waves and compared, and the influence of KCl content was analyzed. Results show that when KCl content is between 0% and 2%, the pressure desensitization degrees of the emulsion explosives are unchanged; when KCl content is between 2% and 8%, KCl content shows strong influence, desensitization degree increases with the KCl content. It means that the anti-pressing performance of explosives is worse with the increase of KCl content, the change of the quality and crystallization point of dispersed phase is a factor to change the pressure desensitization degree. These results can provide reference for coal mine blasting and further study on mechanism of pressure desensitization.

  6. IMPURITY EFFECTS AND RADIATION DAMAGE.Kinetics of U2 to H2O- defects conversion in OH- doped KCl and KBr

    OpenAIRE

    Morato,S.; Gomes, L.

    1980-01-01

    A stepwise annealing procedure after a UV photodecomposition of OH- defects in KCl and KBr showed that a U2 center assumes an intermediate configuration before finally forming a H2O- defect. This configuration is characterized by an optical absorption band at 45 000 cm-1 in KCl and at 40 000 cm-1 in KBr. From experimental observations it is proposed that this configuration is formed by a U2 · OH- pair with the U2 center having an independent characteristic optical absorption. A complete cycle...

  7. Hot Corrosion Behavior of High-Chromium, High-Carbon Cast Irons in NaCl-KCl Molten Salts

    Directory of Open Access Journals (Sweden)

    S. Vuelvas-Rayo

    2012-01-01

    Full Text Available A study on the corrosion behavior of a series of experimental high-chromium (18.53–30.48 wt.%, high-carbon (3.82–5.17% cast irons in NaCl-KCl (1 : 1 M at 670°C has been evaluated by using weight loss technique and compared with a 304-type stainless steel. It was found that all castings had a higher corrosion rate than conventional 304SS and that the addition of Cr increased the degradation rate of the cast irons. Additionally, corrosion rate increased by increasing the C contents up to 4.29%, but it decreased with a further increase in its contents. Results are discussed in terms of consumption of the Cr2O3 layer by the melt.

  8. Electrodeposition of Zr and electrochemical formation of Mg-Zr alloys from the eutectic LiCl-KCl

    Energy Technology Data Exchange (ETDEWEB)

    Chen Zeng [College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China); Zhang Milin [College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China)], E-mail: milinzhang@126.com; Han Wei; Wang Xiaolei; Tang Dingxiang [College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China)

    2008-07-14

    To investigate the electrodeposition mechanism of Zr(IV), the electrochemistry of a LiCl-KCl-K{sub 2}ZrF{sub 6} melt at molybdenum and tungsten electrodes was studied at the temperature between 773 K and 973 K. Transient eletrochemical techniques, such as cyclic volatmmetry and chronopotentiometry were used. The results showed that Zr(IV) was reduced to Zr metal by a two-step mechanism corresponding to the Zr(IV)/Zr(II) and Zr(II)/Zr transitions. The intermediate product was identified as ZrCl{sub 2} by X-ray diffraction. At a liquid magnesium electrode, Mg-Zr alloy was obtained by potentiostatic electrolysis, and the samples were characterized by scanning electron microscopy and energy dispersive X-ray detector. The zirconium concentration in samples was about 0.8 mass% determined by an inductively coupled plasma atomic emission spectrometer.

  9. Equilibrium between titanium ions and high-purity titanium electrorefining in a NaCl-KCl melt

    Institute of Scientific and Technical Information of China (English)

    Jian-xun Song; Qiu-yu Wang; Guo-jing Hu; Xiao-bo Zhu; Shu-qiang Jiao; Hong-min Zhu

    2014-01-01

    TiClx (x=2.17) was prepared by using titanium sponge to reduce the concentration of TiCl4 in a NaCl−KCl melt under negative pressure. The as-prepared NaCl−KCl−TiClx melt was employed as the electrolyte, and two parallel crude titanium plates and one high-purity titanium plate were used as the anode and cathode, respectively. A series of electrochemical tests were performed to investigate the influence of electrolytic parameters on the current efficiency and quality of cathodic products. The results indicated that the quality of cathodic prod-ucts was related to the current efficiency, which is significantly dependent on the current density and the initial concentration of titanium ions. The significance of this study is the attainment of high-purity titanium with a low oxygen content of 30 × 10−6.

  10. Electrochemical Study of Ni20Cr Coatings Applied by HVOF Process in ZnCl2-KCl at High Temperatures

    Science.gov (United States)

    Porcayo-Calderón, J.; Sotelo-Mazón, O.; Casales-Diaz, M.; Ascencio-Gutierrez, J. A.; Salinas-Bravo, V. M.; Martinez-Gomez, L.

    2014-01-01

    Corrosion behavior of Ni20Cr coatings deposited by HVOF (high velocity oxygen-fuel) process was evaluated in ZnCl2-KCl (1 : 1 mole ratio) molten salts. Electrochemical techniques employed were potentiodynamic polarization curves, open circuit potential, and linear polarization resistance (LPR) measurements. Experimental conditions included static air and temperatures of 350, 400, and 450°C. 304-type SS was evaluated in the same conditions as the Ni20Cr coatings and it was used as a reference material to assess the coatings corrosion resistance. Coatings were evaluated as-deposited and with a grinded surface finished condition. Results showed that Ni20Cr coatings have a better corrosion performance than 304-type SS. Analysis showed that Ni content of the coatings improved its corrosion resistance, and the low corrosion resistance of 304 stainless steel was attributed to the low stability of Fe and Cr and their oxides in the corrosive media used. PMID:25210645

  11. Thermoluminescence dependence on the wavelength of monochromatic UV-radiation in Cu-doped KCl and KBr at room temperature

    Energy Technology Data Exchange (ETDEWEB)

    Perez R, A.; Piters, T.; Aceves, R.; Rodriguez M, R.; Perez S, R., E-mail: rperez@cifus.uson.mx [Universidad de Sonora, Departamento de Investigaciones en Fisica, Apdo. Postal 5-088, 83190 Hermosillo, Sonora (Mexico)

    2014-08-15

    Thermoluminescence (Tl) dependence on the UV irradiation wavelengths from 200 to 500 nm in Cu-doped KCl and KBr crystals with different thermal treatment has been analyzed. Spectrum of the Tl intensity of each material show lower intensity at wavelengths longer than 420 nm. The Tl intensity depends on the irradiation wavelength. Structure of the Tl intensity spectrum of each sample is very similar to the structure of its optical absorption spectrum, indicating that at each wavelength, monochromatic radiation is absorbed to produce electronic transitions and electron hole pairs. Thermoluminescence of materials with thermal treatment at high temperature shows electron-hole trapping with less efficiency. The results show that Cu-doped alkali-halide materials are good detectors of a wide range of UV monochromatic radiations and could be used to measure UV radiation doses. (Author)

  12. Electrochemical studies and analysis of 1–10 wt% UCl{sub 3} concentrations in molten LiCl–KCl eutectic

    Energy Technology Data Exchange (ETDEWEB)

    Hoover, Robert O., E-mail: roberthoover@vandals.uidaho.edu [Chemical and Materials Engineering Department and Nuclear Engineering Program, University of Idaho, Idaho Falls, Center for Advanced Energy Studies, 995 University Blvd, Idaho Falls, ID 83401 (United States); Shaltry, Michael R., E-mail: mshaltry@uidaho.edu [Chemical and Materials Engineering Department and Nuclear Engineering Program, University of Idaho, Idaho Falls, Center for Advanced Energy Studies, 995 University Blvd, Idaho Falls, ID 83401 (United States); Martin, Sean, E-mail: Sean.martin@xenuclear.com [Department of Engineering Physics, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, WI 53706 (United States); Sridharan, Kumar, E-mail: kumar@engr.wisc.edu [Department of Engineering Physics, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, WI 53706 (United States); Phongikaroon, Supathorn, E-mail: supathor@uidaho.edu [Chemical and Materials Engineering Department and Nuclear Engineering Program, University of Idaho, Idaho Falls, Center for Advanced Energy Studies, 995 University Blvd, Idaho Falls, ID 83401 (United States)

    2014-09-15

    Three electrochemical methods – cyclic voltammetry (CV), chronopotentiometry (CP), and anodic stripping voltammetry (ASV) – were applied to solutions of up to 10 wt% UCl{sub 3} in the molten LiCl–KCl eutectic salt at 500 °C to determine electrochemical properties and behaviors and to help provide a scientific basis for the development of an in situ electrochemical probe for determining the concentration of uranium in a used nuclear fuel electrorefiner. Diffusion coefficients of UCl{sub 4} and UCl{sub 3} were calculated to be (6.72 ± 0.360) × 10{sup −6} cm{sup 2}/s and (1.04 ± 0.17) × 10{sup −5} cm{sup 2}/s, respectively. Apparent standard reduction potentials were determined to be (−0.381 ± 0.013) V and (−1.502 ± 0.076) V vs. 5 mol% Ag/AgCl or (−1.448 ± 0.013) V and (−2.568 ± 0.076) V vs. Cl{sub 2}/Cl{sup −} for the U(IV)/U(III) and U(III)/U redox couples, respectively. In comparing this data with supercooled thermodynamic data to determine activity coefficients, the thermodynamic database used was important with resulting activity coefficients ranging from 2.34 × 10{sup −3} to 1.08 × 10{sup −2} for UCl{sub 4} and 4.94 × 10{sup −5} to 4.50 × 10{sup −4} for UCl{sub 3}. Of anodic stripping voltammetry and cyclic voltammetry anodic or cathodic peaks, the CV cathodic peak height divided by square root of scan rate was shown to be the most reliable method of determining UCl{sub 3} concentration in the molten salt.

  13. High temperature corrosion of thermally sprayed NiCr- and amorphous Fe-based coatings covered with a KCl-K{sub 2}SO{sub 4} salt

    Energy Technology Data Exchange (ETDEWEB)

    Varis, T.; Suhonen, T.; Tuurna, S.; Ruusuvuori, K.; Holmstroem, S.; Salonen, J. [VTT, Espoo (Finland); Bankiewicz, D.; Yrjas, P. [Aabo Akademi Univ., Turku (Finland)

    2010-07-01

    New process conditions due to the requirement of higher efficiency together with the use of high-chlorine and alkali containing fuels such as biomass and waste fuels for heat and electricity production will challenge the resistance and life of tube materials. In conventional materials the addition of alloying elements to increase the corrosion resistance in aggressive combustion conditions increases costs relatively rapidly. Thermally sprayed coating offer promising, effective, flexible and cost efficient solutions to fulfill the material needs for the future. Some heat exchanger design alteractions before global commercialization have to be overcome, though. High temperature corrosion in combustion plants can occur by a variety of mechanisms including passive scale degradation with subsequent rapid scaling, loss of adhesion and scale detachment, attack by melted or partly melted deposits via fluxing reactions and intergranular-/interlamellar corrosion. A generally accepted model of the ''active oxidation'' attributes the responsibility for inducing corrosion to chlorine. The active oxidation mechanism plays a key role in the thermally sprayed coatings due to their unique lamellar structure. In this study, the corrosion behaviour of NiCr (HVOF and Wire Arc), amorphous Fe-based, and Fe13Cr (Wire Arc) thermally sprayed coatings, were tested in the laboratory under simplified biomass combustion conditions. The tests were carried out by using a KCl-K{sub 2}SO{sub 4} salt mixture as a synthetic biomass ash, which was placed on the materials and then heat treated for one week (168h) at two different temperatures (550{sup 0}C and 600 C) and in two different gas atmospheres (air and air+30%H{sub 2}O). After the exposures, the metallographic cross sections of the coatings were studied with SEM/EDX analyzer. The results showed that the coatings behaved relatively well at the lower test temperature while critical corrosion through the lamella boundaries

  14. Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption

    Institute of Scientific and Technical Information of China (English)

    Marco Montagnani; Anna Abrahamsson; Cecilia G(a)lman; G(o)sta Eggertsen; Hanns-Ulrich Marschall; Elisa Ravaioli; Curt Einarsson; Paul A Dawson

    2006-01-01

    The etiology of most cases of idiopathic bile acid malabsorption (TBAM) is unknown. Tn this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR)and peroxisome proliferator activated receptor alpha (PPARα). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine(SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one (C4). The ASBT,FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC,and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.

  15. N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection

    Science.gov (United States)

    Appelman, Monique D.; Chakraborty, Anindita; Protzer, Ulrike; McKeating, Jane A.

    2017-01-01

    The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT. The physiological function of NTCP, the uptake of bile acids, was also not affected in cells expressing these single glycosylation variants, consistent with their trafficking to the plasma membrane. However, glycosylation-deficient NTCP (NTCP-N5,11Q) failed to support HBV infection, showed minimal cellular expression and was degraded in the lysosome. This affected the physiological bile acid transporter function of NTCP-N5,11Q in a similar fashion. In conclusion, N-glycosylation is required for efficient NTCP localization at the plasma membrane and subsequent HBV infection and these characteristics are preserved in NTCP carrying a single carbohydrate moiety. PMID:28125599

  16. Immunolocalization of Na+/K+-ATPase and Na+/K+/2Cl- cotransporter in the tubular epithelia of sea snake salt glands.

    Science.gov (United States)

    Babonis, L S; Hyndman, K A; Lillywhite, H B; Evans, D H

    2009-12-01

    The sublingual salt gland is the primary site of salt excretion in sea snakes; however, little is known about the mechanisms mediating ion excretion. Na(+)/K(+)-ATPase (NKA) and Na(+)/K(+)/2Cl(-) cotransporter (NKCC) are two proteins known to regulate membrane potential and drive salt secretion in most vertebrate secretory cells. We hypothesized that NKA and NKCC would localize to the basolateral membranes of the principal cells comprising the tubular epithelia of sea snake salt glands. Although there is evidence of NKA activity in salt glands from several species of sea snake, the localization of NKA and NKCC and other potential ion transporters remains unstudied. Using histology and immunohistochemistry, we localized NKA and NKCC in salt glands from three species of laticaudine sea snake: Laticauda semifasciata, L. laticaudata, and L. colubrina. Antibody specificity was confirmed using Western blots. The compound tubular glands of all three species were found to be composed of serous secretory epithelia, and NKA and NKCC were abundant in the basolateral membranes. These results are consistent with the morphology of secretory epithelia found in the rectal salt glands of marine elasmobranchs, the nasal glands of marine birds and the gills of teleost fishes, suggesting a similar function in regulating ion secretion.

  17. Intramolecular and intermolecular fluorescence resonance energy transfer in fluorescent protein-tagged Na-K-Cl cotransporter (NKCC1): sensitivity to regulatory conformational change and cell volume.

    Science.gov (United States)

    Pedersen, Meike; Carmosino, Monica; Forbush, Biff

    2008-02-01

    To examine the structure and function of the Na-K-Cl cotransporter, NKCC1, we tagged the transporter with cyan (CFP) and yellow (YFP) fluorescent proteins and measured fluorescence resonance energy transfer (FRET) in stably expressing human embryonic kidney cell lines. Fluorescent protein tags were added at the N-terminal residue between the regulatory domain and the membrane domain and within a poorly conserved region of the C terminus. Both singly and doubly tagged NKCC1s were appropriately trafficked to the cell membrane and were fully functional; regulation was normal except when YFP was inserted near the regulatory domain, in which case activation occurred only upon incubation with calyculin A. Quenching of YFP fluorescence by Cl(-) provided a ratiometric indicator of intracellular [Cl(-)]. All of the CFP/YFP NKCC pairs exhibited some level of FRET, demonstrating the presence of dimers or higher multimers in functioning NKCC1. With YFP near the regulatory domain and CFP in the C terminus, we recorded a 6% FRET change signaling the regulatory phosphorylation event. On the other hand, when the probe was placed at the extreme N terminus, such changes were not seen, presumably due to the length and predicted flexibility of the N terminus. Substantial FRET changes were observed contemporaneous with cell volume changes, possibly reflective of an increase in molecular crowding upon cell shrinkage.

  18. KCNJ10 determines the expression of the apical Na-Cl cotransporter (NCC) in the early distal convoluted tubule (DCT1).

    Science.gov (United States)

    Zhang, Chengbiao; Wang, Lijun; Zhang, Junhui; Su, Xiao-Tong; Lin, Dao-Hong; Scholl, Ute I; Giebisch, Gerhard; Lifton, Richard P; Wang, Wen-Hui

    2014-08-12

    The renal phenotype induced by loss-of-function mutations of inwardly rectifying potassium channel (Kir), Kcnj10 (Kir4.1), includes salt wasting, hypomagnesemia, metabolic alkalosis and hypokalemia. However, the mechanism by which Kir.4.1 mutations cause the tubulopathy is not completely understood. Here we demonstrate that Kcnj10 is a main contributor to the basolateral K conductance in the early distal convoluted tubule (DCT1) and determines the expression of the apical Na-Cl cotransporter (NCC) in the DCT. Immunostaining demonstrated Kcnj10 and Kcnj16 were expressed in the basolateral membrane of DCT, and patch-clamp studies detected a 40-pS K channel in the basolateral membrane of the DCT1 of p8/p10 wild-type Kcnj10(+/+) mice (WT). This 40-pS K channel is absent in homozygous Kcnj10(-/-) (knockout) mice. The disruption of Kcnj10 almost completely eliminated the basolateral K conductance and decreased the negativity of the cell membrane potential in DCT1. Moreover, the lack of Kcnj10 decreased the basolateral Cl conductance, inhibited the expression of Ste20-related proline-alanine-rich kinase and diminished the apical NCC expression in DCT. We conclude that Kcnj10 plays a dominant role in determining the basolateral K conductance and membrane potential of DCT1 and that the basolateral K channel activity in the DCT determines the apical NCC expression possibly through a Ste20-related proline-alanine-rich kinase-dependent mechanism.

  19. Dapagliflozin Binds Specifically to Sodium-Glucose Cotransporter 2 in the Proximal Renal Tubule.

    Science.gov (United States)

    Ghezzi, Chiara; Yu, Amy S; Hirayama, Bruce A; Kepe, Vladimir; Liu, Jie; Scafoglio, Claudio; Powell, David R; Huang, Sung-Cheng; Satyamurthy, Nagichettiar; Barrio, Jorge R; Wright, Ernest M

    2017-03-01

    Kidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[(18)F]fluoro-dapagliflozin (F-Dapa). We detected prominent binding of intravenously injected F-Dapa in the kidney cortexes of rats and wild-type and Sglt1-knockout mice but not Sglt2-knockout mice, and injection of SGLT2 inhibitors prevented this binding. Furthermore, imaging revealed only low levels of F-Dapa in the urinary bladder, even after displacement of kidney binding with dapagliflozin. Microscopic ex vitro autoradiography of kidney showed F-Dapa binding to the apical surface of early proximal tubules. Notably, in vivo imaging did not show measureable specific binding of F-Dapa in heart, muscle, salivary glands, liver, or brain. We propose that F-Dapa is freely filtered by the kidney, binds to SGLT2 in the apical membranes of the early proximal tubule, and is subsequently reabsorbed into blood. The high density of functional SGLT2 transporters detected in the apical membrane of the proximal tubule but not detected in other organs likely accounts for the high kidney specificity of SGLT2 inhibitors. Overall, these data are consistent with data from clinical studies on SGLT2 inhibitors and provide a rationale for the mode of action of these drugs. Copyright © 2017 by the American Society of Nephrology.

  20. Mutations in the Na-Cl cotransporter reduce blood pressure in humans.

    Science.gov (United States)

    Cruz, D N; Simon, D B; Nelson-Williams, C; Farhi, A; Finberg, K; Burleson, L; Gill, J R; Lifton, R P

    2001-06-01

    The relationship between salt homeostasis and blood pressure has remained difficult to establish from epidemiological studies of the general population. Recently, mendelian forms of hypertension have demonstrated that mutations that increase renal salt balance lead to higher blood pressure, suggesting that mutations that decrease the net salt balance might have the converse effect. Gitelman's syndrome, caused by loss of function mutations in the Na-Cl cotransporter of the distal convoluted tubule (NCCT), features inherited hypokalemic alkalosis with so-called "normal" blood pressure. We hypothesized that the mild salt wasting of Gitelman's syndrome results in reduced blood pressure and protection from hypertension. We have formally addressed this question through the study of 199 members of a large Amish kindred with Gitelman's syndrome. Through genetic testing, family members were identified as inheriting 0 (n=60), 1 (n=113), or 2 (n=26) mutations in NCCT, permitting an unbiased assessment of the clinical consequences of inheriting these mutations by comparison of the phenotypes of relatives with contrasting genotypes. The results demonstrate high penetrance of hypokalemic alkalosis, hypomagnesemia, and hypocalciuria in patients inheriting 2 mutant NCCT alleles. In addition, the NCCT genotype was a significant predictor of blood pressure, with homozygous mutant family members having significantly lower age- and gender-adjusted systolic and diastolic blood pressures than those of their wild-type relatives. Moreover, both homozygote and heterozygote subjects had significantly higher 24-hour urinary Na(+) than did wild-type subjects, reflecting a self-selected higher salt intake. Finally, heterozygous children, but not adults, had significantly lower blood pressures than those of the wild-type relatives. These findings provide formal demonstration that inherited mutations that impair renal salt handling lower blood pressure in humans.

  1. Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure.

    Science.gov (United States)

    Hsu, Yu-Juei; Yang, Sung-Sen; Chu, Nain-Feng; Sytwu, Huey-Kang; Cheng, Chih-Jen; Lin, Shih-Hua

    2009-04-01

    Gitelman's syndrome (GS), which is caused by homozygous or compound heterozygous mutations of the thiazide-sensitive sodium chloride cotransporter (NCC), usually manifests in children and is associated with low blood pressure. However, the prevalence of heterozygous NCC mutations and their association with blood pressure in children have not yet been studied. Five hundred unrelated children from the Taipei Children Heart Study were enrolled. Genomic DNA was isolated from peripheral blood and the SLC12A3 gene was amplified by polymerase chain reaction (PCR). The 15 NCC mutations previously identified in Chinese patients with GS were evaluated using restriction fragment length polymorphism (RFLP) analysis. Blood pressure, biochemistry and urine pH were measured. The allelic frequency of heterozygous NCC mutations and their association with low blood pressure were also investigated. RFLP analysis for the 15 NCC mutations revealed heterozygous T60M in 1 child, T163M in 1, S283Y in 4, R642C in 2, W844X in 2, R928C in 9 and R959frameshift in 10 children. The overall incidence of positive heterozygous NCC mutations was approximately 2.9%. There were no significant differences in systolic or diastolic blood pressure, biochemical profiles or urine pH between children with heterozygous NCC mutations (n = 29) and non-affected controls (n = 471), except for slightly higher fasting plasma glucose concentrations in NCC-heterozygous children (91 +/- 2.3 versus 88 +/- 0.4 mg/dL, P pressures. We found a relatively high prevalence of heterozygous NCC mutations in Chinese children, suggesting that GS may not be rare in this population. Heterozygous NCC mutations were not associated with lower blood pressure in these Chinese children.

  2. Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter.

    Science.gov (United States)

    Carey, Robert M; Schoeffel, Cynthia D; Gildea, John J; Jones, John E; McGrath, Helen E; Gordon, Lindsay N; Park, Min Jeong; Sobota, Rafal S; Underwood, Patricia C; Williams, Jonathan; Sun, Bei; Raby, Benjamin; Lasky-Su, Jessica; Hopkins, Paul N; Adler, Gail K; Williams, Scott M; Jose, Pedro A; Felder, Robin A

    2012-11-01

    Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na(+) (10 mmol/d) and 7 days of high Na(+) (300 mmol/d) intake. Salt sensitivity was defined as a ≥ 7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na(+) diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0 × 10(-4) and 3.1 × 10(-4) with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9 × 10(-5) and 2.6 × 10(-4) and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2 × 10(-5)]; rs1017783 [P=1.1 × 10(-4)]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.

  3. Age-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters

    Directory of Open Access Journals (Sweden)

    Seok Kyu eKang

    2015-05-01

    Full Text Available Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB, with NKCC1 antagonist bumetanide (BTN as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in postnatal day 7, 10 and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

  4. Role of sodium glucose cotransporter-2 inhibitors in type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ahmadieh H

    2017-05-01

    Full Text Available Hala Ahmadieh,1 Nisrine Ghazal,2 Sami T Azar3 1Faculty of Medicine, Clinical Sciences Department, Beirut Arab University, 2Department of Endocrinology and Metabolism, American University of Beirut, Beirut, Lebanon; 3Department of Internal Medicine, Division of Endocrinology, American University of Beirut, New York, NY, USA Abstract: The burden of diabetes mellitus (DM in general has been extensively increasing over the past few years. Selective sodium glucose cotransporter-2 (SGLT2 inhibitors were extensively studied in type 2 DM and found to have sustained urinary glucose loss, improvement of glycemic control, in addition to their proven metabolic effects on weight, blood pressure, and cardiovascular benefits. Type 1 DM (T1D patients clearly depend on insulin therapy, which till today fails to achieve the optimal glycemic control and metabolic targets that are needed to prevent risk of complications. New therapies are obviously needed as an adjunct to insulin therapy in order to try to achieve optimal control in T1D. Many oral diabetic medications have been tried in T1D patients as an adjunct to insulin treatment and have shown conflicting results. Adjunctive use of SGLT2 inhibitors in addition to insulin therapies in T1D was found to have the potential to improve glycemic control along with decrease in the insulin doses, as has been shown in certain animal and short-term human studies. Furthermore, larger well-randomized studies are needed to better evaluate their efficacy and safety in patients with T1D. Euglycemic diabetic ketoacidosis incidences were found to be increased among users of SGLT2 inhibitors, although the incidence remains very low. Recent beneficial effects of ketone body production and this shift in fuel energetics have been suggested based on the findings of protective cardiovascular benefits associated with one of the SGLT2 inhibitors. Keywords: glycemic control, glycosylated hemoglobin, euglucemic diabetic ketoacidosis

  5. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats.

    Directory of Open Access Journals (Sweden)

    Sarika Kapoor

    Full Text Available The sodium-glucose-cotransporter-2 (SGLT2 inhibitor dapagliflozin (DAPA induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD, we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group. Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d. DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

  6. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Directory of Open Access Journals (Sweden)

    Reed JW

    2016-10-01

    control. Keywords: blood pressure, canagliflozin, dapagliflozin, empagliflozin, sodium–glucose cotransporter 2 inhibitors, type 2 diabetes

  7. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats.

    Science.gov (United States)

    Kapoor, Sarika; Rodriguez, Daniel; Riwanto, Meliana; Edenhofer, Ilka; Segerer, Stephan; Mitchell, Katharyn; Wüthrich, Rudolf P

    2015-01-01

    The sodium-glucose-cotransporter-2 (SGLT2) inhibitor dapagliflozin (DAPA) induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD), we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d) or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group). Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d) and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d). DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min) and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min) after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

  8. Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy.

    Science.gov (United States)

    Karlócai, Mária R; Wittner, Lucia; Tóth, Kinga; Maglóczky, Zsófia; Katarova, Zoja; Rásonyi, György; Erőss, Loránd; Czirják, Sándor; Halász, Péter; Szabó, Gábor; Payne, John A; Kaila, Kai; Freund, Tamás F

    2016-09-01

    Synaptic reorganization in the epileptic hippocampus involves altered excitatory and inhibitory transmission besides the rearrangement of dendritic spines, resulting in altered excitability, ion homeostasis, and cell swelling. The potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in neurons and hence will play a prominent role in determining the polarity of GABAA receptor-mediated chloride currents. In addition, KCC2 also interacts with the actin cytoskeleton which is critical for dendritic spine morphogenesis, and for the maintenance of glutamatergic synapses and cell volume. Using immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and compared them to control human tissue. We also studied the distribution of KCC2 in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression was found in epilepsy and confirmed by Western blots. The cellular and subcellular distributions in control mouse and human samples were largely similar; moreover, changes affecting KCC2-expression were also alike in chronic epileptic human and mouse hippocampi. At the subcellular level, we determined the neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue, staining became more intense in the immunopositive elements detected in control tissue, and profiles with subthreshold expression of KCC2 in control samples became labelled. Positive interneuron somata and dendrites were more numerous in epileptic hippocampi, despite severe interneuron loss. Whether the elevation of KCC2-expression is ultimately a pro- or anticonvulsive change, or both-behaving differently during ictal and interictal states in a context-dependent manner-remains to be established.

  9. Emerging roles of sodium-glucose cotransporter 2 inhibitors in cardiology.

    Science.gov (United States)

    Tanaka, Atsushi; Node, Koichi

    2017-03-01

    The ultimate goal of treatment in people with diabetes mellitus is to prevent development of cardiovascular (CV) disease, resulting in prolongation of healthy life expectancy. Although impaired glycemic metabolism has a central role in its pathology, a number of studies have demonstrated that remedy for its imbalance cannot necessarily be accomplished as a therapeutic goal. A comprehensive medical approach against multi-factorial pathologies in diabetes, such as insulin resistance, obesity, hypertension, and dyslipidemia, in addition to diet and exercise therapy should be rather performed in the routine clinical setting. Along with such conceptual transition, what is required in anti-diabetes agents has also changed, and several anti-diabetes agents have been newly placed on the market in this decade. Such agents are required to undergo global pre- or post-marketing clinical trials assessing CV safety. A growing body of clinical evidence from those trials is now accumulating, and empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has first demonstrated significant risk reduction, relative to placebo, in CV death, overall mortality, and hospitalization for worsened heart failure in high-risk patients with diabetes mellitus. An SGLT2 inhibitor is a unique glucose-lowering agent and at the same time has multifaceted effects on hemodynamic and metabolic parameters beyond glycemic control. A major mode of action of SGLT2 inhibitors appears to be 'glycosuria' and 'natriuresis,' leading to amelioration of systemic glycemic homeostasis and potential cardio-renal protection. However, the precise mechanisms by which SGLT2 inhibitors affect benefits on the CV systems are yet to be fully elucidated. Thus, although we are now facing several unanswered concerns lurking behind the successful trial, SGLT2 inhibitors surely play several important roles in high-quality management of not only diabetes, but also CV medicine. This review summarizes our current

  10. The role of aspartic acid residues 405 and 416 of the kidney isotype of sodium-bicarbonate cotransporter 1 in its targeting to the plasma membrane

    Science.gov (United States)

    Kucher, Volodymyr; Li, Emily Y.; Conforti, Laura; Zahedi, Kamyar A.

    2012-01-01

    The NH2 terminus of the sodium-bicarbonate cotransporter 1 (NBCe1) plays an important role in its targeting to the plasma membrane. To identify the amino acid residues that contribute to the targeting of NBCe1 to the plasma membrane, polarized MDCK cells were transfected with expression constructs coding for green fluorescent protein (GFP)-tagged NBCe1 NH2-terminal deletion mutants, and the localization of GFP-tagged proteins was analyzed by confocal microscopy. Our results indicate that the amino acids between residues 399 and 424 of NBCe1A contain important sequences that contribute to its localization to the plasma membrane. Site-directed mutagenesis studies showed that GFP-NBCe1A mutants D405A and D416A are retained in the cytoplasm of the polarized MDCK epithelial cells. Examination of functional activities of D405A and D416A reveals that their activities are reduced compared with the wild-type NBCe1A. Similarly, aspartic acid residues 449 and 460 of pancreatic NBCe1 (NBCe1B), which correspond to residues 405 and 416 of NBCe1A, are also required for its full functional activity and accurate targeting to the plasma membrane. In addition, while replacement of D416 with glutamic acid did not affect the targeting or functional activity of NBCe1A, substitution of D405 with glutamic acid led to the retention of the mutated protein in the intracellular compartment and impaired functional activity. These studies demonstrate that aspartic acid residues 405 and 416 in the NH2 terminus of NBCe1A are important in its accurate targeting to the plasma membrane. PMID:22442137

  11. On the impedance of galvanic cells—XVI The impedance of the dropping mercury electrode in aqueous 1 M KCl with K+ discharge

    NARCIS (Netherlands)

    Sluyters-Rehbach, M.; Sluyters, J.H.

    1966-01-01

    The discharge of K+ ions at the dropping mercury electrode (dme) in 1 M KCl solution at 25°C has been studied by means of analysis of the electrode impedance at different frequencies, using the complex plane method. It is shown that the electrode reaction is almost entirely diffusion-controlled, but

  12. The importance of SO{sub 2} and SO{sub 3} for sulphation of gaseous KCl - An experimental investigation in a biomass fired CFB boiler

    Energy Technology Data Exchange (ETDEWEB)

    Kassman, Haakan [Vattenfall Power Consultant AB, Nykoeping (Sweden); Chalmers University of Technology, Department of Energy and Environment, Division of Energy Technology, Gothenburg (Sweden); Baefver, Linda [Technical Research Institute of Sweden, Energy Technology, Boraas (Sweden); Aamand, Lars-Erik [Chalmers University of Technology, Department of Energy and Environment, Division of Energy Technology, Gothenburg (Sweden)

    2010-09-15

    This paper is based on results obtained during co-combustion of wood pellets and straw in a 12 MW circulating fluidised bed (CFB) boiler. Elemental sulphur (S) and ammonium sulphate ((NH{sub 4}){sub 2}SO{sub 4}) were used as additives to convert the alkali chlorides (mainly KCl) to less corrosive alkali sulphates. Their performance was then evaluated using several measurement tools including, IACM (on-line measurements of gaseous alkali chlorides), a low-pressure impactor (particle size distribution and chemical composition of extracted fly ash particles), and deposit probes (chemical composition in deposits collected). The importance of the presence of either SO{sub 2} or SO{sub 3} for gas phase sulphation of KCl is also discussed. Ammonium sulphate performed significantly better than elemental sulphur. A more efficient sulphation of gaseous KCl was achieved with (NH{sub 4}){sub 2}SO{sub 4} even when the S/Cl molar ratio was less than half compared to sulphur. Thus the presence of gaseous SO{sub 3} is of greater importance than that of SO{sub 2} for the sulphation of gaseous KCl. (author)

  13. On the impedance of galvanic cells XXIV. The impedance of the In3+/In(Hg) electrode reaction in KSCN and KCl solution

    NARCIS (Netherlands)

    Timmer, B.; Sluyters-Rehbach, M.; Sluyters, J.H.

    1968-01-01

    The In3+/In(Hg) system in KSCN and KCl solutions has been investigated using both d.c. and a.c. measurements. The experimental data are analysed and interpreted according to theoretical equations presented recently. It is shown that the specific adsorption of indium from 1 M KSCN follows a linear a

  14. Chemical mechanical planarization of amorphous Ge2Sb2Te5 using KClO4 as oxidizer in acidic slurry

    Science.gov (United States)

    He, Aodong; Song, Zhitang; Bo, Liu; Zhong, Min; Weili, Liu; Wang, Liangyong; Yan, Weixia; Lei, Yu; Wu, Guangping

    Amorphous Ge2Sb2Te5 (a-GST) chemical mechanical planarization (CMP) using KClO4 as the oxidizer in an acidicslurry is investigated in the present work. It is shown that the removal rate (RR ) of the a-GST firstly increases and thentends to saturate when the KClO4 concentration is greater than 0.8 wt%, but the static etch rate (SER) linearly increasesfrom low to high KClO4 concentration. To understand the oxidation-reaction capability of Ge, Sb and Te, depth profilesof composition of elements and etch morphology of a-GST immersed in the slurry for some time are measured,respectively. It is found that selective corrosion occurs among Ge, Sb and Te, and an accumulation of Te and loss of Gein a-GST surface region are obvious observed, especially at high KClO4 concentrations. Temperature dependent sheetresistance measurements of all the samples pre- and post-CMP reveal a similar trend, which implies a-GST CMP is ableto keep its characteristic well.

  15. Thermodynamic description of the AgCl–CoCl{sub 2}–InCl{sub 3}–KCl system

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Kun, E-mail: wangkun@sinap.ac.cn [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China); Fei, Zejie [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China); Wang, Jian [Center for Research in Computational Thermochemistry (CRCT), Dept. of Chemical Engineering, Ecole Polytechnique, Montréal, Québec, H3C 3A7 (Canada); Wu, Zhu [Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050 (China); Li, Chonghe [Shanghai Key Laboratory of Modern Metallurgy & Materials Processing, Shanghai University, Shanghai, 200072 (China); Xie, Leidong [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China)

    2015-08-01

    The present investigation is aimed at deriving a set of self-consistent thermodynamic functions for the AgCl–CoCl{sub 2}–InCl{sub 3}–KCl quaternary system within the framework of the CALPHAD approach. All the previous reported thermodynamic parameters for the binary subsystems were initially reviewed and adopted, and critical thermodynamic evaluations and optimizations were later performed on the unavailable AgCl–KCl and InCl{sub 3}–KCl systems in terms of the required phase equilibria and thermochemical data from experimental measurements and theoretical predictions (First-principles method and empirical equation). The Modified Quasi-Chemical model were applied to describing the molten salt phase, while all the intermediate phases were treated as the stoichiometric compounds due to no observation of the homogeneity composition range. Various phase equilibria and thermodynamic properties in the ternary and quaternary systems could be facilely calculated based upon the ultimate thermodynamic database established in this case, which will support beneficial instructions in the related industrial processes. - Highlights: • The modified quasi-chemical model was used to describe the liquid phase. • First principles method was applied to assist model parameters optimization of the intermediate phase. • The complete phase diagram of the InCl{sub 3}–KCl system was calculated for the first time in the present work.

  16. Application of the rotating cylinder electrode in molten LiCl-KCl eutectic containing uranium(III)- and magnesium(II)-chloride

    Science.gov (United States)

    Rappleye, Devin; Simpson, Michael F.

    2017-04-01

    The application of the rotating cylinder electrode (RCE) to molten LiCl-KCl eutectic mixtures for electroanalytical measurements is presented. This enabled the measurement of the limiting current which was observed to follow a linear trend with the rotational rate raised to 0.64-0.65 power on average, which closely agrees with existing RCE mass-transfer correlations. This is the first publication of electroanalytical RCE measurements in LiCl-KCl eutectic based molten salt mixtures, to our knowledge. These measurements were made in mixtures of molten LiCl-KCl eutectic containing UCl3 and MgCl2. Kinetic parameters were calculated for Mg2+ in LiCl-KCl eutectic. The exchange current density (io) of Mg2+ deposition varied with mole fraction (x) according to io(A cm-2) = 1.64x0.689. The parameters from RCE measurements were also applied in an electrochemical co-deposition model entitled DREP to detect and predict the deposition rate of U and Mg. DREP succeeded in detecting the co-deposition of U and Mg, even when Mg constituted less than 0.5 wt% of the deposit.

  17. Spectroscopy of virtual photons in Ar+KCl collisions at E{sub kin}=1.76 AGeV; Spektroskopie virtueller Photonen in Ar+KCl Stoessen bei E{sub kin}=1,76 AGeV

    Energy Technology Data Exchange (ETDEWEB)

    Jurkovic, Martin

    2010-01-14

    The objective of this thesis is the analysis of virtual photon emission originating from the decays of the short lived hadrons produced in Ar+KCl collisions at E{sub kin}=1.76 AGeV. The measured observables were the reconstructed e{sup +}e{sup -} pairs and their kinematic distributions. The data were recorded with the HADES spectrometer assembled at GSI Helmholtzzentrum fuer Schwerionenforschung GmbH in Darmstadt, Germany. Due to the considerably higher combinatorial background originating from the {gamma}-conversion as compared to that from light collision systems (p+p,C+C) investigated so far with HADES, a new method for identification and suppression of conversion electrons using the signal pattern in the RICH-detector was studied. An improvement of signal to background ratio (S/B) reaching 30% was achieved. For the procedure of calculating the e{sup +}/e{sup -} track efficiencies a detailed study of RICH detector signals was performed, leading to an overall improved description of ring observables in the simulation. In total, 32545pm 385 e{sup +}e{sup -} signal pairs with an opening angle {alpha}{sub ee} > 15 and 0.1 < p{sub e} < 1.1 GeV/c were identified, with 7402{+-}222 pairs in the so-called {eta} mass region (0.15 < M{sub ee} < 0.55 GeV/c{sup 2}) and 253{+-}25 for masses M{sub ee} > 0.55 GeV/c{sup 2}. A clear signal from direct {omega} decay with S/B {proportional_to}1 was identified for the first time in the SIS18 energy regime. The extraction of the {omega} yield per produced {pi}{sup 0} results in N({omega})/N({pi}{sup 0}) {approx} (4,5 {+-} 2,5(stat) {+-} 2(sys)) .10{sup -8}. The e{sup +}e{sup -} production in the {eta} mass region was compared to the expected {eta} Dalitz decay {eta}{yields}{gamma}e{sup +}e{sup -} contribution. The measured e{sup +}e{sup -} yield is higher by a factor F = 3.4{+-}0.2(stat){+-}0.6(sys){+-}0.9({eta}) as compared to the {eta} production. The excitation function of the extra e{sup +}/e{sup -} sources shows similar energy

  18. cAMP-dependent and cholinergic regulation of the electrogenic intestinal/pancreatic Na+/HCO3- cotransporter pNBC1 in human embryonic kidney (HEK293 cells

    Directory of Open Access Journals (Sweden)

    Soleimani Manoocher

    2008-12-01

    Full Text Available Abstract Background The renal (kNBC1 and intestinal (pNBC1 electrogenic Na+/HCO3- cotransporter variants differ in their primary structure, transport direction, and response to secretagogues. Previous studies have suggested that regulatory differences between the two subtypes can be partially explained by unique consensus phosphorylation sites included in the pNBC1, but not the kNBC1 sequence. After having shown activation of NBC by carbachol and forskolin in murine colon, we now investigated these pathways in HEK293 cells transiently expressing a GFP-tagged pNBC1 construct. Results Na+- and HCO3--dependent pHi recovery from an acid load (measured with BCECF was enhanced by 5-fold in GFP-positive cells compared to the control cells in the presence of CO2/HCO3-. Forskolin (10-5 M had no effect in untransfected cells, but inhibited the pHi recovery in cells expressing pNBC1 by 62%. After preincubation with carbachol (10-4 M, the pHi recovery was enhanced to the same degree both in transfected and untransfected cells, indicating activation of endogenous alkalizing ion transporters. Acid-activated Na+/HCO3- cotransport via pNBC1 expressed in renal cells is thus inhibited by cAMP and not affected by cholinergic stimulation, as opposed to the findings in native intestinal tissue. Conclusion Regulation of pNBC1 by secretagogues appears to be not solely dependent on its primary structure, but also on properties of the cell type in which it is expressed.

  19. Cotransport of H+, lactate and H2O by membrane proteins in retinal pigment epithelium of bullfrog

    DEFF Research Database (Denmark)

    Zeuthen, T; Hamann, S; la Cour, M

    1996-01-01

    solution concentration and/or osmolarity. 3. Two parallel pathways for water transport were identified across the retinal membrane, an osmotic one with a hydraulic water permeability of 3.2 x 10(-4) cm s-1 (osmol l-1)-1 and one which depended on the presence of lactate. 4. Addition of sodium lactate...... the effect. The influx of water could proceed against osmotic gradients elicited by mannitol. 6. The interdependence of the fluxes of H+, lactate and H2O can be described as cotransport: the fluxes had a fixed ratio of about 109 mmol of lactic acid per litre of water, the flux of one species was able...

  20. Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

    OpenAIRE

    Khan, Saeed R.; Glenton, Patricia A.

    2008-01-01

    The most common theories about the pathogenesis of idiopathic kidney stones consider precipitation of calcium phosphate (CaP) within the kidneys critical for the development of the disease. We decided to test the hypothesis that a CaP substrate can promote the deposition of calcium oxalate (CaOx) in the kidneys. Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with knockout (KO) of NaPi IIa (Npt2a), a sodium-phosphate cotransporter. Npt2a KO mice are hypercalciuric an...

  1. Synthesis of CaCrO{sub 4} powders for the cathode material of the thermal battery by GNP and electrochemical characteristics of Ca/LiCl-KCl/CaCrO{sub 4} thermal battery system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Whung Whoe

    2000-04-01

    Thermal batteries are one of the devices employing solid electrolyte that are not nonconductive at ambient temperature, and activated by electrochemical reaction when the sufficient heat is supplied to electrolyte to melt. The demand of thermal batteries would be increased because it is cost effective and highly reliable in that no maintenance is necessary, electric power can be generated as necessary and no self discharge unlike the other primary batteries. These thermal batteries are used to the military purposes and satellite communication systems and as an emergency power sources, applied to the important places where power supply should not be interrupted, such as hospital, powder plants, ships and portable communication devices. Therefore, the purpose of this study was focused to obtain the manufacturing technologies of thermal battery on our own, after manufacturing the CaCrO{sub 4} produced by GNP and investigating the electrochemical characteristics of Ca/LiCl-KCl+CaCrO{sub 4}/Ni.

  2. Investigating microstructural evolution during the electroreduction of UO2 to U in LiCl-KCl eutectic using focused ion beam tomography

    Science.gov (United States)

    Brown, L. D.; Abdulaziz, R.; Tjaden, B.; Inman, D.; Brett, D. J. L.; Shearing, P. R.

    2016-11-01

    Reprocessing of spent nuclear fuels using molten salt media is an attractive alternative to liquid-liquid extraction techniques. Pyroelectrochemical processing utilizes direct, selective, electrochemical reduction of uranium dioxide, followed by selective electroplating of a uranium metal. Thermodynamic prediction of the electrochemical reduction of UO2 to U in LiCl-KCl eutectic has shown to be a function of the oxide ion activity. The pO2- of the salt may be affected by the microstructure of the UO2 electrode. A uranium dioxide filled "micro-bucket" electrode has been partially electroreduced to uranium metal in molten lithium chloride-potassium chloride eutectic. This partial electroreduction resulted in two distinct microstructures: a dense UO2 and a porous U metal structure were characterised by energy dispersive X-ray spectroscopy. Focused ion beam tomography was performed on five regions of this electrode which revealed an overall porosity ranging from 17.36% at the outer edge to 3.91% towards the centre, commensurate with the expected extent of reaction in each location. The pore connectivity was also seen to reduce from 88.32% to 17.86% in the same regions and the tortuosity through the sample was modelled along the axis of propagation of the electroreduction, which was seen to increase from a value of 4.42 to a value of infinity (disconnected pores). These microstructural characteristics could impede the transport of O2- ions resulting in a change in the local pO2- which could result in the inability to perform the electroreduction.

  3. 氯化钾团簇的成核和重结晶的分子动力学模拟%Molecular Dynamics Simulation of Nucleation and Recrystalization of KCl Clusters

    Institute of Scientific and Technical Information of China (English)

    王国勋; 朱小蕾; 邵景玲; 杨操

    2009-01-01

    利用Born-Mayer-Huggins 势函数对(KCl)256、(KCl)500和(KCl)864团簇的成核和重结晶进行了分子动力学(MD)模拟.根据MD模拟结果和经典成核理论估算和讨论了KCl团簇的熔化温度、熔化焓、平均离子扩散系数、成核速率、固液界面自由能和临界核大小.另一方面,在MD模拟中,观察到了(KCl)864的热退火过程中的固态重结晶,并获得了250~400K温度范围内(KCl)864团簇重结晶的成核速率.

  4. Cotransport of hydroxyapatite nanoparticles and hematite colloids in saturated porous media: Mechanistic insights from mathematical modeling and phosphate oxygen isotope fractionation

    Science.gov (United States)

    Wang, Dengjun; Jin, Yan; Jaisi, Deb P.

    2015-11-01

    The fate and transport of individual type of engineered nanoparticles (ENPs) in porous media have been studied intensively and the corresponding mechanisms controlling ENPs transport and deposition are well-documented. However, investigations regarding the mobility of ENPs in the concurrent presence of another mobile colloidal phase such as naturally occurring colloids (colloid-mediated transport of ENPs) are largely lacking. Here, we investigated the cotransport and retention of engineered hydroxyapatite nanoparticles (HANPs) with naturally occurring hematite colloids in water-saturated sand columns under environmentally relevant transport conditions, i.e., pH, ionic strength (IS), and flow rate. Particularly, phosphate oxygen isotope fractionation of HANPs during cotransport was explored at various ISs and flow rates to examine the mechanisms controlling the isotope fractionation of HANPs in abiotic transport processes (physical transport). During cotransport, greater mobility of both HANPs and hematite occurred at higher pHs and flow rates, but at lower ISs. Intriguingly, the mobility of both HANPs and hematite was substantially lower during cotransport than the individual transport of either, attributed primarily to greater homo- and hetero-aggregation when both particles are copresent in the suspension. The shapes of breakthrough curves (BTCs) and retention profiles (RPs) during cotransport for both particles evolved from blocking to ripening with time and from flat to hyperexponential with depth, respectively, in response to decreases in pH and flow rate, and increases in IS. The blocking BTCs and RPs that are flat or hyperexponential can be well-approximated by a one-site kinetic attachment model. Conversely, a ripening model that incorporates attractive particle-particle interaction has to be employed to capture the ripening BTCs that are impacted by particle aggregation during cotransport. A small phosphate oxygen isotope fractionation (≤ 1.8

  5. Physiology and pathophysiology of Na+/H+ exchange and Na+-K+-2Cl- cotransport in the heart, brain, and blood

    DEFF Research Database (Denmark)

    Pedersen, S. F.; O´Donnell, M. E.; Anderson, S. E.

    2006-01-01

    . The aim is to provide a comprehensive overview of the mechanisms and consequences of stress-induced stimulation of these transporters with focus on the heart, brain, and blood. The physiological stressors reviewed are metabolic/exercise stress, osmotic stress, and mechanical stress, conditions in which......Maintenance of a stable cell volume and intracellular pH is critical for normal cell function. Arguably, two of the most important ion transporters involved in these processes are the Na+/H+ exchanger isoform 1 (NHE1) and Na+-K+-2Cl- cotransporter isoform 1 (NKCC1). Both NHE1 and NKCC1...... are stimulated by cell shrinkage and by numerous other stimuli, including a wide range of hormones and growth factors, and for NHE1, intracellular acidification. Both transporters can be important regulators of cell volume, yet their activity also, directly or indirectly, affects the intracellular concentrations...

  6. Thermoluminescent monitoring of the solar ultraviolet radiation with KCl: Eu{sup 2+} crystals; Monitoreo termoluminiscente de la radiacion solar ultravioleta con cristales de KCl: Eu{sup 2+}

    Energy Technology Data Exchange (ETDEWEB)

    Chernov, V.; Melendrez, R.; Barboza F, M. [Centro de Investigacion en Fisica, Universidad de Sonora, A.P. 5-88, Hermosillo, Sonora (Mexico)

    2000-07-01

    In this work it has been investigating the Tl properties of KCl: Eu{sup 2+} subjected to solar direct radiation. Also it was realized irradiation with the Deuterium and Xenon lamps. It was used a set of filters and a Katos monochromator 0.25 M to determine the spectral response to Tl peaks and a study of them with respect to the duration of the Sun irradiation. After of the Sun irradiation the Tl curves show several peaks between the ambient temperature and 673 K. The relation between peaks depends strongly of the irradiation time and the different solar light wavelength. It is possible to divide the Tl peaks in two groups. The first one (T<473 K) is very sensitive to ultraviolet radiation but it is strongly affected by visible light. The second one (T>473 K) is not too sensitive but is more stable under optical whitening. Here the obtained results are discussed with respect to UV dosemeters development for environment which facilitate to obtain direct measurements of the UV index. (Author)

  7. Fructose-1,6-diphosphate protects against epileptogenesis by modifying cation-chloride co-transporters in a model of amygdaloid-kindling temporal epilepticus.

    Science.gov (United States)

    Ding, Yao; Wang, Shan; Jiang, Yan; Yang, Yi; Zhang, Manman; Guo, Yi; Wang, Shuang; Ding, Mei-ping

    2013-11-20

    Fructose-1,6-diphosphate (FDP) shifts the metabolism of glucose from glycolysis to the pentose phosphate pathway and has anticonvulsant activity in several acute seizure animal models. In the present study, we investigated the anti-epileptogenic effects of FDP in an amygdaloid-kindling seizure model, which is an animal model of the most common form of human temporal lobe epilepsy. We found that 1.0 g/kg FDP slowed seizure progression and shortened the corresponding after-discharge duration (ADD). FDP increased the number of stimulations needed to reach seizure stages 2-5 and prolonged the cumulative ADD prior to reaching stages 3-5. It also shortened staying days and cumulative ADD in stages 4-5. However, it demonstrated no significant protective effect when administered after the animals were fully kindled. In hippocampal neurons, cation-chloride co-transporters (CCCs) are suggested to play interesting roles in epilepsy by modulating γ-aminobutyric acid (GABA)ergic activity through controlling GABAA receptor-mediated reversal potential. We examined the potential link between FDP and the hippocampal expression of two main members of the CCCs: the neuron-specific K(+)-Cl(-)co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-)co-transporter 1 (NKCC1). FDP inhibited the kindling-induced downregulation of KCC2 expression and decreased NKCC1 expression during the kindling session. Taken together, our data reveal that FDP may have protective activity against epileptogenesis, from partial to generalized tonic-clonic seizures. Furthermore, our findings suggest that the FDP-induced imbalance between KCC2 and NKCC1 expression may be involved in the neuroprotective effect.

  8. The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon.

    Science.gov (United States)

    Wang, X Y; Masilamani, S; Nielsen, J; Kwon, T H; Brooks, H L; Nielsen, S; Knepper, M A

    2001-07-01

    The kidneys "escape" from the Na-retaining effects of aldosterone when circulating levels of aldosterone are inappropriately elevated in the setting of normal or expanded extracellular fluid volume, e.g., in primary aldosteronism. Using a targeted proteomics approach, we screened renal protein extracts with rabbit polyclonal antibodies directed to each of the major Na transporters expressed along the nephron to determine whether escape from aldosterone-mediated Na retention is associated with decreased abundance of one or more of renal Na transporters. The analysis revealed that the renal abundance of the thiazide-sensitive Na-Cl cotransporter (NCC) was profoundly and selectively decreased. None of the other apical solute-coupled Na transporters displayed decreases in abundance, nor were the total abundances of the three ENaC subunits significantly altered. Immunocytochemistry showed a strong decrease in NCC labeling in distal convoluted tubules of aldosterone-escape rats with no change in the cellular distribution of NCC. Ribonuclease protection assays (RPAs) revealed that the decrease in NCC protein abundance was not associated with altered NCC mRNA abundance. Thus, the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule appears to be the chief molecular target for regulatory processes responsible for mineralocorticoid escape, decreasing in abundance via a posttranscriptional mechanism.

  9. The Renal Sodium Bicarbonate Cotransporter NBCe2: Is It a Major Contributor to Sodium and pH Homeostasis?

    Science.gov (United States)

    Felder, Robin A; Jose, Pedro A; Xu, Peng; Gildea, John J

    2016-09-01

    The sodium bicarbonate cotransporter (NBCe2, aka NBC4) was originally isolated from the human testis and heart (Pushkin et al. IUBMB Life 50:13-19, 2000). Subsequently, NBCe2 was found in diverse locations where it plays a role in regulating sodium and bicarbonate transport, influencing intracellular, extracellular, interstitial, and ultimately plasma pH (Boron et al. J Exp Biol. 212:1697-1706, 2009; Parker and Boron, Physiol Rev. 93:803-959, 2013; Romero et al. Mol Asp Med. 34:159-182, 2013). NBCe2 is located in human and rodent renal-collecting duct and proximal tubule. While much is known about the two electrogenic sodium bicarbonate cotransporters, NBCe1 and NBCe2, in the regulation of sodium homeostasis and pH balance in the rodent kidney, little is known about their roles in human renal physiology. NBCe2 is located in the proximal tubule Golgi apparatus under basal conditions and then disperses throughout the cell, but particularly into the apical membrane microvilli, during various maneuvers that increase intracellular sodium. This review will summarize our current understanding of the distribution and function of NBCe2 in the human kidney and how genetic variants of its gene, SLC4A5, contribute to salt sensitivity of blood pressure.

  10. Immunohistochemical localization of the Na-K-Cl co-transporter (NKCC1) in the gerbil inner ear.

    Science.gov (United States)

    Crouch, J J; Sakaguchi, N; Lytle, C; Schulte, B A

    1997-06-01

    We mapped the cellular and subcellular distribution of the Na-K-Cl co-transporter (NKCC) in the adult gerbil inner ear by immunostaining with a monoclonal antibody (MAb T4) generated against human colon NKCC. Heavy immunolabeling was seen in the basolateral plasma membrane of marginal cells in the stria vascularis and dark cells in the vestibular system. Subpopulations of fibrocytes in the cochlear spiral ligament and limbus and underlying the vestibular neurosensory epithelium also stained with moderate to strong intensity, apparently along their entire plasmalemma. Because MAb T4 recognizes both the basolateral secretory (NKCC1) and the apical absorptive (NKCC2) isoforms of the co-transporter, we employed reverse transcription and the polymerase chain reaction (RT-PCR) to explore isoform diversity in inner ear tissues. Using NKCC1 and NKCC2 isoform-specific PCR primers based on mouse and human sequences, only transcripts for NKCC1 were detected in the gerbil inner ear. The presence of abundant NKCC1 in the basolateral plasmalemma of strial marginal and vestibular dark cells confirms conclusions drawn from pharmacological and physiological data. The co-expression of NKCC1 and Na,K-ATPase in highly specialized subpopulations of cochlear and vestibular fibrocytes provides further evidence for their role in recycling K+ leaked or effluxed through hair cells into perilymph back to endolymph, as postulated in current models of inner ear ion homeostasis.

  11. The single-electrode Peltier heats of Li-Al alloy electrodes in LiCl-KCl eutectic system

    Energy Technology Data Exchange (ETDEWEB)

    Amezawa, Koji; Ito, Yasuhiko; Tomii, Yoichi (Kyoto Univ. (Japan))

    1994-11-01

    This paper presents the single-electrode Peltier heat of cathodic (or anodic) reaction of Li-Al alloy electrode in a coexisting phase state, or an intermetallic compound phase state estimated by thermoelectric-power measurement. The thermoelectric-power measurements of Li-Al alloys in various coexisting phase states were carried out with both potentiometric and potential-sweep methods in the LiCl-KCl eutectic system between 673 and 843 K. The values of the thermoelectric power of Li-Al alloys calculated by using thermodynamic literature data were in good agreement with those obtained by experiment. The single-electrode Peltier heat changes drastically with change of its phase state, and it was found that the formation reactions of [beta] (Li[sub 0.5]Al[sub 0.5]) and [gamma] (Li[sub 0.6]Al[sub 0.4]) phases are exothermic, and those of liquid phase from [beta] and [gamma] phase are endothermic. The single-electrode Peltier heat for the cathodic formation reaction of Li-Al alloy in intermetallic compound [gamma] phase is estimated to be exothermic by using the measured values of thermoelectric powers of Li-Al alloys in ([beta] + [gamma]) and ([gamma] + liq.) regions.

  12. Vibrational-rotational dependence of molecular properties. Electric field gradients for HCl, LiCl, NaCl and KCl

    Science.gov (United States)

    Seth, Michael; Pernpointner, Markus; Bowmaker, Graham A.; Schwerdtfeger, Peter

    The vibrational-rotational dependence of the nuclear quadrupole coupling constant (NQCC) for the isotopes 2H, 7Li, 23Na, 39K, and 35Cl is analysed in detail for the diatomic Group 1 chlorides HCl, LiCl, NaCl and KCl. The potential energy curves were calculated pointwise by using coupled cluster techniques. The electric field gradients (EFGs) and dipole moments were obtained analytically from a QCISD procedure using the Z vector method. Generally the calculated spectroscopic properties are in very good agreement with experimental data. Relativistic effects taken into account by a coupled cluster Douglas-Kroll procedure can safely be neglected for the electric field gradients up to potassium. The Inglis model which explains the trend and magnitudes of EFGs within an ionic model of weakly polarized atoms is analysed. According to this model the derivatives of the EFG, ∂nq (R)/∂Rn , with respect to the internuclear distance R should show alternating sign behaviour with increasing power n. Hence, the mechanical anharmonicity (deviation from Hooke's law potential) and the electrical anharmonicity (curvature of q(R)) are of different sign, and we expect partial cancellation of anharmonicity effects in the vibrational dependence of the NQCCs. Nevertheless, a perturbative vibrational-rotational analysis reveals a strong dependence of the chlorine and Group 1 element NQCCs on the vibrational level due to dominating mechanical anharmonicity.

  13. Lambda-p femtoscopy in collisions of Ar+KCl at 1.76 AGeV

    CERN Document Server

    Agakishiev, G; Bassini, R; Belver, D; Belyaev, A V; Blanco, A; Böhmer, M; Boyard, J L; Braun-Munzinger, P; Cabanelas, P; Castro, E; Chernenko, S; Christ, T; Destefanis, M; Díaz, J; Dohrmann, F; Dybczak, A; Eberl, T; Fabbietti, L; Fateev, O V; Finocchiaro, P; Fonte, P; Friese, J; Fröhlich, I; Galatyuk, T; Garzón, J A; Gernhäuser, R; Gil, A; Gilardi, C; Golubeva, M; González-Díaz, D; Guber, F; Hennino, T; Holzmann, R; Iori, I; Ivashkin, A; Jurkovic, M; Kämpfer, B; Kanaki, K; Karavicheva, T; Kirschner, D; Koenig, I; Koenig, W; Kolb, B W; Kotte, R; Krizek, F; Krücken, R; Kühn, W; Kugler, A; Kurepin, A; Lang, S; Lange, J S; Lapidus, K; Liu, T; Lopes, L; Lorenz, M; Maier, L; Mangiarotti, A; Markert, J; Metag, V; Michalska, B; Michel, J; Mishra, D; Morinière, E; Mousa, J; Müntz, C; Naumann, L; Otwinowski, J; Pachmayer, Y C; Palka, M; Parpottas, Y; Pechenov, V; Pechenova, O; Pietraszko, J; Przygoda, W; Ramstein, B; Reshetin, A; Roy-Stephan, M; Rustamov, A; Sadovsky, A; Sailer, B; Salabura, P; Schmah, A; Sobolev, Yu G; Spataro, S; Spruck, B; Ströbele, H; Stroth, J; Sturm, C; Sudol, M; Tarantola, A; Teilab, K; Tlusty, P; Traxler, M; Trebacz, R; Tsertos, H; Wagner, V; Weber, M; Wendisch, C; Wisniowski, M; Wojcik, T; Wüstenfeld, J; Yurevich, S; Zanevsky, Y V; Zhou, P; Zumbruch, P

    2010-01-01

    Results on $\\Lambda$p femtoscopy are reported at the lowest energy so far. At a beam energy of 1.76A~GeV, the reaction Ar+KCl was studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18/GSI. A high-statistics and high-purity $\\Lambda$ sample was collected, allowing for the investigation of $\\Lambda$ p correlations at small relative momenta. The experimental correlation function is compared to corresponding model calculations allowing the determination of the space-time extent of the $\\Lambda$p emission source. The $\\Lambda$p source radius is found slightly smaller than the pp correlation radius for a similar collis ion system. The present $\\Lambda$p radius is significantly smaller than that found for Au+Au/Pb+Pb collisio ns in the AGS, SPS and RHIC energy domains, but larger than that observed for electroproduction from He. Taking into account all available data, we find the $\\Lambda$p source radius to increase almost linearly with the number of participants to the power of one-third.

  14. Electrochemical Study of Ni20Cr Coatings Applied by HVOF Process in ZnCl2-KCl at High Temperatures

    Directory of Open Access Journals (Sweden)

    J. Porcayo-Calderón

    2014-01-01

    Full Text Available Corrosion behavior of Ni20Cr coatings deposited by HVOF (high velocity oxygen-fuel process was evaluated in ZnCl2-KCl (1 : 1 mole ratio molten salts. Electrochemical techniques employed were potentiodynamic polarization curves, open circuit potential, and linear polarization resistance (LPR measurements. Experimental conditions included static air and temperatures of 350, 400, and 450°C. 304-type SS was evaluated in the same conditions as the Ni20Cr coatings and it was used as a reference material to assess the coatings corrosion resistance. Coatings were evaluated as-deposited and with a grinded surface finished condition. Results showed that Ni20Cr coatings have a better corrosion performance than 304-type SS. Analysis showed that Ni content of the coatings improved its corrosion resistance, and the low corrosion resistance of 304 stainless steel was attributed to the low stability of Fe and Cr and their oxides in the corrosive media used.

  15. Estimation of the composition of intermetallic compounds in LiCl-KCl molten salt by cyclic voltammetry.

    Science.gov (United States)

    Liu, Ya L; Liu, Kui; Yuan, Li Y; Chai, Zhi F; Shi, Wei Q

    2016-08-15

    In this work, the compositions of Ce-Al, Er-Al and La-Bi intermetallic compounds were estimated by the cyclic voltammetry (CV) technique. At first, CV measurements were carried out at different reverse potentials to study the co-reduction processes of Ce-Al, Er-Al and La-Bi systems. The CV curves obtained were then re-plotted with the current as a function of time, and the coulomb number of each peak was calculated. By comparing the coulomb number of the related peaks, the compositions of the Ce-Al, Er-Al and La-Bi intermetallic compounds formed in the co-reduction process could be estimated. The results showed that Al11Ce3, Al3Ce, Al2Ce and AlCe could be formed by the co-reduction of Ce(iii) and Al(iii). For the co-reduction of Er(iii) and Al(iii), Al3Er2, Al2Er and AlEr were formed. In a La(iii) and Bi(iii) co-existing system in LiCl-KCl melts, LaBi2, LaBi and Li3Bi were the major products as a result of co-reduction.

  16. A Glial K/Cl Transporter Controls Neuronal Receptive Ending Shape by Chloride Inhibition of an rGC.

    Science.gov (United States)

    Singhvi, Aakanksha; Liu, Bingqian; Friedman, Christine J; Fong, Jennifer; Lu, Yun; Huang, Xin-Yun; Shaham, Shai

    2016-05-05

    Neurons receive input from the outside world or from other neurons through neuronal receptive endings (NREs). Glia envelop NREs to create specialized microenvironments; however, glial functions at these sites are poorly understood. Here, we report a molecular mechanism by which glia control NRE shape and associated animal behavior. The C. elegans AMsh glial cell ensheathes the NREs of 12 neurons, including the thermosensory neuron AFD. KCC-3, a K/Cl transporter, localizes specifically to a glial microdomain surrounding AFD receptive ending microvilli, where it regulates K(+) and Cl(-) levels. We find that Cl(-) ions function as direct inhibitors of an NRE-localized receptor-guanylyl-cyclase, GCY-8, which synthesizes cyclic guanosine monophosphate (cGMP). High cGMP mediates the effects of glial KCC-3 on AFD shape by antagonizing the actin regulator WSP-1/NWASP. Components of this pathway are broadly expressed throughout the nervous system, suggesting that ionic regulation of the NRE microenvironment may be a conserved mechanism by which glia control neuron shape and function.

  17. Electrochemical extraction of neodymium by co-reduction with aluminum in LiCl–KCl molten salt

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yong-De, E-mail: y5d2006@hrbeu.edu.cn [Key Discipline Laboratory of Nuclear Safety and Simulation Technology, Harbin Engineering University, Harbin 150001 (China); Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China); Xu, Yan-Lu [Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China); Zhang, Mi-Lin, E-mail: zhangmilin@hrbeu.edu.cn [Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China); Xue, Yun [Key Discipline Laboratory of Nuclear Safety and Simulation Technology, Harbin Engineering University, Harbin 150001 (China); Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China); Han, Wei; Huang, Ying; Chen, Qiong [Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China); Zhang, Zhi-Jian [Key Discipline Laboratory of Nuclear Safety and Simulation Technology, Harbin Engineering University, Harbin 150001 (China)

    2013-02-15

    The electrochemical behavior of Nd(III) ions in LiCl–KCl and LiCl–KCl–AlCl{sub 3} melts on a Mo electrode at 723 K was studied by various electrochemical techniques. The results showed that Nd(III) ions are reduced to Nd(0) through two consecutive steps, and the underpotential deposition of neodymium on pre-deposited Al electrode formed two kinds of Al–Nd intermetallic compounds in LiCl–KCl–AlCl{sub 3} solutions. The electrochemical extraction of neodymium was carried out in LiCl–KCl–AlCl{sub 3} melts on a Mo electrode at 873 K by potentiostatic and galvanostatic electrolysis. The extraction efficiency was 99.25% after potentiostatic electrolysis for 30 h. Al–Li–Nd bulk alloy was obtained by galvanostatic electrolysis. X-ray diffraction (XRD) suggested that Al{sub 2}Nd and Al{sub 3}Nd phases were formed in Al–Li–Nd alloy. The microstructure and micro-zone chemical analysis of Al–Li–Nd alloy were characterized by scanning electron microscopy (SEM) with energy dispersive spectrometry (EDS), respectively.

  18. Following the electroreduction of uranium dioxide to uranium in LiCl–KCl eutectic in situ using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Brown, L.D.; Abdulaziz, R.; Jervis, R.; Bharath, V.J. [Electrochemical Innovation Lab, Dept. Chemical Engineering, UCL, London WC1E 7JE (United Kingdom); Atwood, R.C.; Reinhard, C.; Connor, L.D. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Simons, S.J.R.; Inman, D.; Brett, D.J.L. [Electrochemical Innovation Lab, Dept. Chemical Engineering, UCL, London WC1E 7JE (United Kingdom); Shearing, P.R., E-mail: p.shearing@ucl.ac.uk [Electrochemical Innovation Lab, Dept. Chemical Engineering, UCL, London WC1E 7JE (United Kingdom)

    2015-09-15

    Highlights: • We investigated the electroreduction of UO{sub 2} to U in LiCl/KCL eutectic molten salt. • Combined electrochemical measurement and in situ XRD is utilised. • The electroreduction appears to occur in a single, 4-electron-step, process. • No intermediate compounds were observed. - Abstract: The electrochemical reduction of uranium dioxide to metallic uranium has been investigated in lithium chloride–potassium chloride eutectic molten salt. Laboratory based electrochemical studies have been coupled with in situ energy dispersive X-ray diffraction, for the first time, to deduce the reduction pathway. No intermediate phases were identified using the X-ray diffraction before, during or after electroreduction to form α-uranium. This suggests that the electrochemical reduction occurs via a single, 4-electron-step, process. The rate of formation of α-uranium is seen to decrease during electrolysis and could be a result of a build-up of oxygen anions in the molten salt. Slow transport of O{sup 2−} ions away from the UO{sub 2} working electrode could impede the electrochemical reduction.

  19. Liquidus Temperatures and Thermodynamic Properties of the KCl-{KNO}2

    Science.gov (United States)

    Peng, Qiang; Ding, Jing; Yang, Xiaoxi; Wei, Xiaolan; Yang, Jianping

    2013-05-01

    Potassium nitrite is very sensitive to temperature, humidity, and the atmosphere, so few studies have been made in this field for the thermodynamic properties of molten salt with nitrite salt. In this article, the liquidus curves of NaCl-{NaNO}2 are calculated by a simple "hard-sphere" ionic interaction model. The calculated liquidus temperatures show good agreement with experimental values, which implies an ideal mixing enthalpy and entropy for the liquid binary systems. In addition to the phase equilibrium data and experimental thermochemical properties of molten salt systems, the activities of these binary systems are determined by the phase diagrams and the analytical integration of the classical Gibbs-Duhem equation.

  20. Interactions between Na+ channels and Na+-HCO3- cotransporters in the freshwater fish gill MR cell: a model for transepithelial Na+ uptake.

    Science.gov (United States)

    Parks, Scott K; Tresguerres, Martin; Goss, Greg G

    2007-02-01

    Isolated mitochondria-rich (MR) cells from the rainbow trout gill epithelium were subjected to intracellular pH (pH(i)) imaging with the pH-sensitive dye BCECF-AM. MR cells were categorized into two distinct functional subtypes based on their ability to recover pH(i) from an NH(4)Cl-induced acidification in the absence of Na(+). An apparent link between resting pH(i) and Na(+)-independent pH(i) recovery was made. We observed a unique pH(i) acidification event that was induced by extracellular Na(+) addition. This further classified the mixed MR cell population into two functional subtypes: the majority of cells (77%) demonstrated the Na(+)-induced pH(i) acidification, whereas the minority (23%) demonstrated an alkalinization of pH(i) under the same circumstances. The focus of this study was placed on the Na(+)-induced acidification and pharmacological analysis via the use of amiloride and phenamil, which revealed that Na(+) uptake was responsible for the intracellular acidification. Further experiments revealed that pH(i) acidification could be abolished when Na(+) was allowed entry into the cell, but the activity of an electrogenic Na(+)-HCO(3)(-) cotransporter (NBC) was inhibited by DIDS. The electrogenic NBC activity was supported by a DIDS-sensitive, Na(+)-induced membrane potential depolarization as observed via imaging of the voltage-sensitive dye bis-oxonol. We also demonstrated NBC immunoreactivity via Western blotting and immunohistochemistry in gill tissue. We propose a model for transepithelial Na(+) uptake occurring via an apical Na(+) channel linked to a basolateral, electrogenic NBC in one subpopulation of MR cells.

  1. Effect of vasopressin on Na(+)-K(+)-2Cl(-) cotransporter (NKCC) and the signaling mechanisms on the murine late distal colon.

    Science.gov (United States)

    Xue, Hong; Tang, Xudong

    2016-01-15

    It has been demonstrated that the antidiuretic hormone vasopressin is able to regulate the expression of Na-K-Cl cotransporters (NKCC1 and NKCC2) in the kidney. The present study investigated the effects of long- and short-term administration of vasopressin on NKCC and the possible signaling mechanism of vasopressin in the mouse distal colon using the siRNA, real-time PCR, western blotting and Ussing chambers method. The results showed the presence of NKCC2 expression in the colon, which was verified with a siRNA technique. The mRNA and protein expression level of NKCC2 significantly increased by about 40% and 90% respectively in response to restricting water intake to 1ml/day/20g for 7 days. In contrast, the NKCC1 expression level was unchanged in the colon. To determine the short-term activation of NKCC2 by vasopressin in vitro, we found that the administration of vasopressin caused a 3-fold increase in mouse colon NKCC2 phosphorylation, which was detected with phosphospecific antibody R5. In addition, the Ussing chamber results showed that NKCC2, cAMP and Ca(2+) signaling pathway may be involved in the vasopressin-induced response. Further, adenylate cyclase inhibitor MDL-12330A and PKA inhibitor H89 and Ca(2+) chelator BAPTA-AM reversed the vasopressin induced NKCC2 phosphorylation level increase by about 35%, 28% and 42% respectively suggesting vasopressin stimulate NKCC2 phosphorylation increase mediated by cAMP-PKA and Ca(2+) signaling in the colon. Collectively, these data suggest that the expression and phosphorylation of NKCC2 are increased in the colon by vasopressin stimulation, in association with enhanced activity of the vasopressin/cAMP and Ca(2+) pathways.

  2. Thiazide-sensitive Na+ -Cl- cotransporter (NCC) gene inactivation results in increased duodenal Ca2+ absorption, enhanced osteoblast differentiation and elevated bone mineral density.

    Science.gov (United States)

    Hsu, Yu-Juei; Yang, Sung-Sen; Cheng, Chih-Jen; Liu, Shu-Ting; Huang, Shih-Ming; Chau, Tom; Chu, Pauling; Salter, Donald M; Lee, Herng-Sheng; Lin, Shih-Hua

    2015-01-01

    Inactivation of the thiazide-sensitive sodium chloride cotransporter (NCC) due to genetic mutations in Gitelman's syndrome (GS) or pharmacological inhibition with thiazide diuretics causes hypocalciuria and increased bone mineral density (BMD) with unclear extrarenal calcium (Ca(2+) ) regulation. We investigated intestinal Ca(2+) absorption and bone Ca(2+) metabolism in nonsense Ncc Ser707X (S707X) homozygous knockin mice (Ncc(S707X/S707X) mice). Compared to wild-type and heterozygous knockin littermates, Ncc(S707X/S707X) mice had increased intestinal absorption of (45) Ca(2+) and expression of the active Ca(2+) transport machinery (transient receptor potential vanilloid 6, calbindin-D9K , and plasma membrane Ca(2+) ATPase isoform 1b). Ncc(S707X/S707X) mice had also significantly increased Ca(2+) content accompanied by greater mineral apposition rate (MAR) in their femurs and higher trabecular bone volume, cortical bone thickness, and BMD determined by μCT. Their osteoblast differentiation markers, such as bone alkaline phosphatase, procollagen I, osteocalcin, and osterix, were also significantly increased while osteoclast activity was unaffected. Analysis of marrow-derived bone cells, either treated with thiazide or directly cultured from Ncc S707X knockin mice, showed that the differentiation of osteoblasts was associated with increased phosphorylation of mechanical stress-induced focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). In conclusion, NCC inhibition stimulates duodenal Ca(2+) absorption as well as osteoblast differentiation and bone Ca(2+) storage, possibly through a FAK/ERK dependent mechanism. © 2014 American Society for Bone and Mineral Research.

  3. Efficacy and Safety of Canagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2, When Used in Conjunction With Insulin Therapy in Patients With Type 2 Diabetes

    NARCIS (Netherlands)

    Neal, Bruce; Perkovic, Vlado; de Zeeuw, Dick; Mahaffey, Kenneth W.; Fulcher, Greg; Ways, Kirk; Desai, Mehul; Shaw, Wayne; Capuano, George; Alba, Maria; Jiang, Joel; Vercruysse, Frank; Meininger, Gary; Matthews, David

    OBJECTIVE There are limited data about the effects of sodium-glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS The CANagliflozin CardioVascular Assessment Study is

  4. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Belhage, Bo; Zeuthen, Emil

    2005-01-01

    and osmosis at the membrane with diffusion in the cytoplasm. The combination of high resolution measurements and precise modelling showed that water transport across the membrane can be explained by cotransport of water in the membrane proteins and that intracellular unstirred layers effects are minute....

  5. Autosomal recessive hypophosphataemic rickets with hypercalciuria is not caused by mutations in the type II renal sodium/phosphate cotransporter gene.

    NARCIS (Netherlands)

    Heuvel, L.P.W.J. van den; Koul, K. Op de; Knots, E.; Knoers, N.V.A.M.; Monnens, L.A.H.

    2001-01-01

    BACKGROUND: At present the genetic defect for autosomal recessive and autosomal dominant hypophosphataemic rickets with hypercalciuria (HHRH) is unknown. Type II sodium/phosphate cotransporter (NPT2) gene is a serious candidate for being the causative gene in either or both autosomal recessive and a

  6. Relative contributions of Na+/H+ exchange and Na+/HCO3- cotransport to ischemic Na-i(+) overload in isolated rat hearts

    NARCIS (Netherlands)

    Ten Hove, M; Nederhoff, MGJ; Van Echteld, CJA

    2005-01-01

    The Na+/H+ exchanger (NHE) and/or the Na+/HCO3- cotransporter (NBC) were blocked during ischemia in isolated rat hearts. Intracellular Na+ concentration ([Na+](i)), intracellular pH (pH(i)), and energy-related phosphates were measured by using simultaneous Na-23 and P-31 NMR spectroscopy. Hearts wer

  7. Efficacy and Safety of Canagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2, When Used in Conjunction With Insulin Therapy in Patients With Type 2 Diabetes

    NARCIS (Netherlands)

    Neal, Bruce; Perkovic, Vlado; de Zeeuw, Dick; Mahaffey, Kenneth W.; Fulcher, Greg; Ways, Kirk; Desai, Mehul; Shaw, Wayne; Capuano, George; Alba, Maria; Jiang, Joel; Vercruysse, Frank; Meininger, Gary; Matthews, David

    2015-01-01

    OBJECTIVE There are limited data about the effects of sodium-glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS The CANagliflozin CardioVascular Assessment Study is

  8. 氯化钾施用量在烤烟生产上研究%Study on Consumption of KCl in Flue-Cured Tobacco Production

    Institute of Scientific and Technical Information of China (English)

    刘坤华; 谭雪庆; 张文建; 谢孔华

    2012-01-01

    2010年余庆县开展了氯化钾肥料施用量的田间试验工作,结果表明:氯化钾施用量为45.0~60.0 kg/hm2范围内,能显著提高烟叶产量和经济效益,烟叶外观质量、内在质量明显改善,化学成分较为协调,评吸质量较优。%The work of consumption of KCl in flue-cured tobacco production in Yuqing county in 2010 was carried out.The result showed that when fertilizing amount of KCl was 45.0~60.0 kg/hm2,it could increase tobacco production and economic benefits,improve appearance and quality of tobacco leaves,make chemical composition more harmonious and smoking quality more excellent

  9. Dynamic Fluctuation of U(3+) Coordination Structure in the Molten LiCl-KCl Eutectic via First Principles Molecular Dynamics Simulations.

    Science.gov (United States)

    Li, Xuejiao; Song, Jia; Shi, Shuping; Yan, Liuming; Zhang, Zhaochun; Jiang, Tao; Peng, Shuming

    2017-01-26

    The dynamic fluctuation of the U(3+) coordination structure in a molten LiCl-KCl mixture was studied using first principles molecular dynamics (FPMD) simulations. The radial distribution function, probability distribution of coordination numbers, fluctuation of coordination number and cage volume, self-diffusion coefficient and solvodynamic mean radius of U(3+), dynamics of the nearest U-Cl distances, and van Hove function were evaluated. It was revealed that fast exchange of Cl(-) occurred between the first and second coordination shells of U(3+) accompanied with fast fluctuation of coordination number and rearrangement of coordination structure. It was concluded that 6-fold coordination structure dominated the coordination structure of U(3+) in the molten LiCl-KCl-UCl3 mixture and a high temperature was conducive to the formation of low coordinated structure.

  10. Experimental investigation on moving chemical reaction boundary theory for weak-acid-strong-base system with background electrolyte KCl in large concentration.

    Science.gov (United States)

    Cao, C X; Zhou, S L; Qian, Y A; He, Y Z; Yang, L; Qu, Q S; Chen, W K

    2001-07-13

    In this report, the moving chemical reaction boundary (MCRB) was formed with the weak acid of acetic acid (HAc) and the strong alkali of NaOH, coupled with the excess of background electrolyte KCl. The experiments were compared with the predictions by the moving chemical reaction boundary equation (MCRBE). It is very interesting that (1) the experimental results are in good agreement with the predictions with the original MCRBE if the MCRB is an anodic moving boundary, (2) however, the experiments are extremely far away from the predictions with the original MCRBE if a cathodic moving boundary. Hence, the original MCRBE must be corrected under the later situation of cathodic moving MCRB. The corrected MCRBE was well quantitatively proved to be valid for the cathodic moving MNRB formed with the same electrolytes of HAc, NaOH and KCl.

  11. INTERACTION OF LASER RADIATION WITH MATTER: Influence of Ca and Pb impurities on the bulk optical strength of ultrapure NaCl and KCl crystals

    Science.gov (United States)

    Vinogradov, An V.; Voszka, R.; Kovalev, Valerii I.; Faĭzullov, F. S.; Janszky, J.

    1987-06-01

    A significant increase (by a factor of about 3) of the bulk damage threshold in the case of interaction of CO2 laser radiation pulses with ultrapure NaCl and KCl crystals grown in a reactive atmosphere was observed on introduction of divalent metal ions Ca and Pb in concentrations of 10-5-10-6 mol/mol. Impurities were introduced in concentrations of 10-8-10-3 and 2×10-7-10-4 mol/mol into the melts of KCl and NaCl, respectively. The concentration of other impurities (including OH) did not exceed ~10-6 mol/mol. A physical model was developed to account for the observed dependence on the basis of an analogy between a system of colloidal particles and F centers in a crystal and a liquid-vapor system.

  12. The chemical stability of L-isoleucine, L-threonine, and L-serine in aqueous solutions of KCl at 298.15 K

    Science.gov (United States)

    Roy, Sanjay; Dolui, Bijoy Krishna

    2016-06-01

    The experimental saturated solubilities of L-isoleucine, L-threonine, and L-serine in aqueous mixtures of a KCl solution at 298.15 K are presented in this article. The solubilities are measured by gravimetric method. In the present study the theoretical calculation of the standard transfer Gibbs free energy, cavity forming enthalpy of transfer, cavity forming transfer Gibbs free energy, dipole-dipole interaction effect have been computed. The chemical effects of the transfer Gibbs energies for the present amino acids have been obtained by subtracting the cavity effects and dipole-dipole interaction effects from the Δ G t 0 ( i). The stability of the experimental amino acids in aqueous KCl in terms of thermodynamic parameters is explained.

  13. I-NERI ANNUAL TECHNICAL PROGRESS REPORT: 2006-002-K, Separation of Fission Products from Molten LiCl-KCl Salt Used for Electrorefining of Metal Fuels

    Energy Technology Data Exchange (ETDEWEB)

    S. Frank

    2009-09-01

    An attractive alternative to the once-through disposal of electrorefiner salt is to selectively remove the active fission products from the salt and recycle the salt back to the electrorefiner (ER). This would allow salt reuse for some number of cycles before ultimate disposal of the salt in a ceramic waste form. Reuse of ER salt would, thus, greatly reduce the volume of ceramic waste produced during the pyroprocessing of spent nuclear fuel. This final portion of the joint I-NERI research project is to demonstrate the separation of fission products from molten ER salt by two methods previously selected during phase two (FY-08) of this project. The two methods selected were salt/zeolite contacting and rare-earth fission product precipitation by oxygen bubbling. The ER salt used in these tests came from the Mark-IV electrorefiner used to anodically dissolved driver fuel from the EBR-II reactor on the INL site. The tests were performed using the Hot Fuel Dissolution Apparatus (HFDA) located in the main cell of the Hot Fuels Examination Facility (HFEF) at the Materials and Fuels complex on the INL site. Results from these tests were evaluated during a joint meeting of KAERI and INL investigators to provide recommendations as to the future direction of fission product removal from electrorefiner salt that accumulate during spent fuel treatment. Additionally, work continued on kinetic measurements of surrogate quaternary salt systems to provide fundamental kinetics on the ion exchange system and to expand the equilibrium model system developed during the first two phases of this project. The specific objectives of the FY09 I-NERI research activities at the INL include the following: • Perform demonstration tests of the selected KAERI precipitation and INL salt/zeolite contacting processes for fission product removal using radioactive, fission product loaded ER salt • Continue kinetic studies of the quaternary Cs/Sr-LiCl-KCl system to determine the rate of ion

  14. Cyclic Voltammetric Experiment - Simulation. Comparisons of the Complex Mechanism Associated with Electrochemical Reduction of Zr4+ in LiCl-KCl Eutectic Molten Salt

    OpenAIRE

    Fabian, Cesimiro P.; Luca, Vittorio; Le, Than H.; Bond, Alan M.; Chamelot, Pierre; Massot, Laurent; Caravaca, Concepción; Hanley, Tracey L.; Lumpkin, Gregory R.

    2012-01-01

    International audience; Nuclear energy increasingly represents an important option for generating largely clean CO2-free electricity and zirconium is a fission product that is expected to be present in irradiated fuels. The present investigation addresses the electrochemical reduction of Zr4+ to Zro in LiCl - KCl eutectic molten salt in the temperature range 425-550◦C using cyclic voltammetry (CV), square-wave voltammetry (SWV) and bulk electrolysis. Simulations of the CV data indicate that t...

  15. Sensory characterisation and consumer acceptability of small calibre fermented sausages with 50% substitution of NaCl by mixtures of KCl and potassium lactate.

    Science.gov (United States)

    Guàrdia, M D; Guerrero, L; Gelabert, J; Gou, P; Arnau, J

    2008-12-01

    The effect of six mixtures with 50% molar substitution of KCl (0-50%) and potassium lactate (0-50%) as NaCl substitutes in small calibre fermented sausages on some sensory parameters and on the acceptability was studied. Also, the relationship between sensory profile and consumer acceptability using external preference mapping was investigated. The results showed that as the K-lactate substitution increased, pH, sweetness, crumbliness and pastiness also increased, and piquantness, hardness, cohesiveness, ripened flavour, acid taste and saltiness decreased. However, the treatments prepared with a high level of salt substitution by KCl showed scores of sensory attributes similar to those of the control. Consumer segmentation showed differences in acceptability between genders, place of residence, educational level and age group. Consumers rejected fermented sausages with high K-lactate substitution but not those with a high KCl substitution. External preference mapping split consumers up into four clusters with different preference patterns. According to these results and from a sensory point of view, it is possible to achieve a reduction of 50% of NaCl in small calibre fermented sausages and to obtain a product acceptable to most consumers.

  16. 1090K下MgCl2-KCl-CaCl2三元熔盐体系的密度预测

    Institute of Scientific and Technical Information of China (English)

    赵飞; 陈志远; 陈洪智; 赵世强

    2014-01-01

    镁电解工艺中使用的电解质需要具有合适的密度范围.MgCl2-KCl-CaCl2三元熔盐体系是镁电解质的重要基础三元系.使用了新一代溶液几何模型,预测了这一三元系在1 090 K下的密度.首先勘正了标准数据库中的MgCl2-CaCl2熔盐二元系的密度表达式.对已知3个二元系KCl-CaCl2、MgCl2-CaCl2、KCl-MgCl2数据,采用三次式表达的Redlich-Kister关系式拟合得到了它们的超额密度函数.并计算各组分之间的相似系数.最终获得全组分范围内的三元熔盐体系密度分布图.已知成分点的实验值与预测值之间相对误差在2.21%~0.99%之间,这表明了预测结果的可靠性.

  17. Interplay between structure and transport properties of molten salt mixtures of ZnCl2-NaCl-KCl: A molecular dynamics study.

    Science.gov (United States)

    Manga, Venkateswara Rao; Swinteck, Nichlas; Bringuier, Stefan; Lucas, Pierre; Deymier, Pierre; Muralidharan, Krishna

    2016-03-01

    Molten mixtures of network-forming covalently bonded ZnCl2 and network-modifying ionically bonded NaCl and KCl salts are investigated as high-temperature heat transfer fluids for concentrating solar power plants. Specifically, using molecular dynamics simulations, the interplay between the extent of the network structure, composition, and the transport properties (viscosity, thermal conductivity, and diffusion) of ZnCl2-NaCl-KCl molten salts is characterized. The Stokes-Einstein/Eyring relationship is found to break down in these network-forming liquids at high concentrations of ZnCl2 (>63 mol. %), while the Eyring relationship is seen with increasing KCl concentration. Further, the network modification due to the addition of K ions leads to formation of non-bridging terminal Cl ions, which in turn lead to a positive temperature dependence of thermal conductivity in these melts. This new understanding of transport in these ternary liquids enables the identification of appropriate concentrations of the network formers and network modifiers to design heat transfer fluids with desired transport properties for concentrating solar power plants.

  18. Inhibition of the Na/bicarbonate cotransporter NBCe1-A by diBAC oxonol dyes relative to niflumic acid and a stilbene.

    Science.gov (United States)

    Liu, Xiaofen; Williams, Jennifer B; Sumpter, Brandon R; Bevensee, Mark O

    2007-02-01

    Na/HCO(3) cotransporters (NBCs) are important regulators of intracellular pH (pH(i) in a variety of organ systems where acid-base status is critical for tissue function. To characterize the pharmacology of NBCs in more detail, we used the two-electrode voltage-clamp technique to examine the effect of previously identified inhibitors of anion exchanger 1 (AE1) on the activity of rat NBCe1-A expressed in Xenopus laevis oocytes. NBC-expressing oocytes voltage-clamped at -60 mV and exposed to a 5% CO(2)/33 mM HCO(3)(-) solution displayed NBC-mediated outward currents that were inhibited by either niflumic acid or one of the two bis-oxonol dyes diBA(3)C4 and diBA(5)C4. NBCe1-A was less sensitive to niflumic acid (apparent K(i) of 100 microM) than 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, apparent K(i) of 36 microM) but more sensitive to the diBAC dyes (apparent K(i) of approximately 10 microM). Based on current-voltage relationships, the diBAC dyes inhibited HCO(3)(-) -induced NBCe1-mediated inward currents more so than outward currents. NBCe1 sensitivity to the dyes was (1) lower in the presence of 40 microM DIDS, (2) unaffected by changes in external HCO(3)(-) concentration and (3) only modestly higher at an external Na(+) concentration of 5, but not 15 or 33, mM. Therefore, the diBAC dyes compete with DIDS but not appreciably with Na(+) or HCO(3)(-) for binding. The mechanism of diBAC inhibition of NBCe1 appears similar to that previously reported for AE1.

  19. Phorbol 12-myristate 13-acetate-induced endocytosis of the Na-K-2Cl cotransporter in MDCK cells is associated with a clathrin-dependent pathway.

    Science.gov (United States)

    Mykoniatis, Andreas; Shen, Le; Fedor-Chaiken, Mary; Tang, Jun; Tang, Xu; Worrell, Roger T; Delpire, Eric; Turner, Jerrold R; Matlin, Karl S; Bouyer, Patrice; Matthews, Jeffrey B

    2010-01-01

    In secretory epithelial cells, the basolateral Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) plays a major role in salt and fluid secretion. Our laboratory has identified NKCC1 surface expression as an important regulatory mechanism for Cl(-) secretion in the colonic crypt cell line T84, a process also present in native human colonic crypts. We previously showed that activation of protein kinase C (PKC) by carbachol and phorbol 12-myristate 13-acetate (PMA) decreases NKCC1 surface expression in T84 cells. However, the specific endocytic entry pathway has not been defined. We used a Madin-Darby canine kidney (MDCK) cell line stably transfected with enhanced green fluorescent protein (EGFP)-NKCC1 to map NKCC1 entry during PMA exposure. At given times, we fixed and stained the cells with specific markers (e.g., dynamin II, clathrin heavy chain, and caveolin-1). We also used chlorpromazine, methyl-beta-cyclodextrin, amiloride, and dynasore, blockers of the clathrin, caveolin, and macropinocytosis pathways and the vesicle "pinchase" dynamin, respectively. We found that PMA caused dose- and time-dependent NKCC1 endocytosis. After 2.5 min of PMA exposure, approximately 80% of EGFP-NKCC1 endocytic vesicles colocalized with clathrin and approximately 40% colocalized with dynamin II and with the transferrin receptor, the uptake of which is also mediated by clathrin-coated vesicles. We did not observe significant colocalization of EGFP-NKCC1 endocytic vesicles with caveolin-1, a marker of the caveolae-mediated endocytic pathway. We quantified the effect of each inhibitor on PMA-induced EGFP-NKCC1 endocytosis and found that only chlorpromazine and dynasore caused significant inhibition compared with the untreated control (61% and 25%, respectively, at 2.5 min). Together, these results strongly support the conclusion that PMA-stimulated NKCC1 endocytosis is associated with a clathrin pathway.

  20. Essential role for NHERF in cAMP-mediated inhibition of the Na+-HCO3- co-transporter in BSC-1 cells.

    Science.gov (United States)

    Weinman, E J; Evangelista, C M; Steplock, D; Liu, M Z; Shenolikar, S; Bernardo, A

    2001-11-01

    Prior studies have indicated a requirement for the PDZ domain-containing protein, Na(+)/H(+) Exchanger Regulatory Factor (NHERF), for protein kinase A (PKA)-mediated inhibition of the renal basolateral Na(+)-HCO(3)(-) co-transporter (NBC). The present studies explore the potential mechanisms by which NHERF transduces cAMP signals to inhibit NBC. In BSC-1 cells, cells that express NBC but lack NHERF, 8-bromo-cAMP (100 microm for 15 min) failed to inhibit transport until wild-type mNHERF-(1-355) was expressed. mNHERF-(116-355) containing PDZ II and C-terminal ezrin-binding sequences or a mutant unphosphorylated form of rabbit NHERF effectively transduced the cAMP signals that inhibited NBC. By contrast, mNHERF-(1-126) encompassing N-terminal PDZ I and mNHERF-(1-325), which lacks ezrin-binding, failed to support cAMP inhibition of NBC activity. NBC and NHERF did not associate with each other in yeast two-hybrid or co-immunoprecipitation assays, and confocal microscopy indicated distinct subcellular localization of the two proteins. NBC was phosphorylated in BSC-1 cells, but its phosphorylation was not increased by cAMP nor was immunoprecipitated NBC phosphorylated by PKA in vitro. Acute exposure of mNHERF-(1-355)-expressing BSC-1 cells to cAMP did not change cell surface expression of NBC. Although these results established an essential role for NHERF in cAMP-mediated inhibition of NBC in BSC-1 cells, they also suggest a novel mechanism for NHERF-mediated signal transduction distinct from that previously characterized from studies of other NHERF targets.

  1. Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1.

    Science.gov (United States)

    Vallon, Volker; Schroth, Jana; Lang, Florian; Kuhl, Dietmar; Uchida, Shinichi

    2009-09-01

    The Na-Cl cotransporter NCC is expressed in the distal convoluted tubule, activated by phosphorylation, and has been implicated in renal NaCl and K(+) homeostasis. The serum and glucocorticoid inducible kinase 1 (SGK1) contributes to renal NaCl retention and K(+) excretion, at least in part, by stimulating the epithelial Na(+) channel and Na(+)-K(+)-ATPase in the downstream segments of aldosterone-sensitive Na(+)/K(+) exchange. In this study we confirmed in wild-type mice (WT) that dietary NaCl restriction increases renal NCC expression and its phosphorylation at Thr(53), Thr(58), and Ser(71), respectively. This response, however, was attenuated in mice lacking SGK1 (Sgk1(-/-)), which may contribute to impaired NaCl retention in those mice. Total renal NCC expression and phosphorylation at Thr(53), Thr(58), and Ser(71) in WT were greater under low- compared with high-K(+) diet. This finding is consistent with a regulation of NCC to modulate Na(+) delivery to downstream segments of Na(+)/K(+) exchange, thereby modulating K(+) excretion. Dietary K(+)-dependent variation in renal expression of total NCC and phosphorylated NCC were not attenuated in Sgk1(-/-) mice. In fact, high-K(+) diet-induced NCC suppression was enhanced in Sgk1(-/-) mice. The hyperkalemia induced in Sgk1(-/-) mice by a high-K(+) diet may have augmented NCC suppression, thereby increasing Na(+) delivery and facilitating K(+) excretion in downstream segments of impaired Na(+)/K(+) exchange. In summary, changes in NaCl and K(+) intake altered NCC expression and phosphorylation, an observation consistent with a role of NCC in NaCl and K(+) homeostasis. The two maneuvers dissociated plasma aldosterone levels from NCC expression and phosphorylation, implicating additional regulators. Regulation of NCC expression and phosphorylation by dietary NaCl restriction appears to involve SGK1.

  2. Expression of Na+/glucose co-transporter 1 (SGLT1) is enhanced by supplementation of the diet of weaning piglets with artificial sweeteners.

    Science.gov (United States)

    Moran, Andrew W; Al-Rammahi, Miran A; Arora, Daleep K; Batchelor, Daniel J; Coulter, Erin A; Daly, Kristian; Ionescu, Catherine; Bravo, David; Shirazi-Beechey, Soraya P

    2010-09-01

    In an intensive livestock production, a shorter suckling period allows more piglets to be born. However, this practice leads to a number of disorders including nutrient malabsorption, resulting in diarrhoea, malnutrition and dehydration. A number of strategies have been proposed to overcome weaning problems. Artificial sweeteners, routinely included in piglets' diet, were thought to enhance feed palatability. However, it is shown in rodent models that when included in the diet, they enhance the expression of Na+/glucose co-transporter (SGLT1) and the capacity of the gut to absorb glucose. Here, we show that supplementation of piglets' feed with a combination of artificial sweeteners saccharin and neohesperidin dihydrochalcone enhances the expression of SGLT1 and intestinal glucose transport function. Artificial sweeteners are known to act on the intestinal sweet taste receptor T1R2/T1R3 and its partner G-protein, gustducin, to activate pathways leading to SGLT1 up-regulation. Here, we demonstrate that T1R2, T1R3 and gustducin are expressed together in the enteroendocrine cells of piglet intestine. Furthermore, gut hormones secreted by the endocrine cells in response to dietary carbohydrates, glucagon-like peptides (GLP)-1, GLP-2 and glucose-dependent insulinotrophic peptide (GIP), are co-expressed with type 1 G-protein-coupled receptors (T1R) and gustducin, indicating that L- and K-enteroendocrine cells express these taste elements. In a fewer endocrine cells, T1R are also co-expressed with serotonin. Lactisole, an inhibitor of human T1R3, had no inhibitory effect on sweetener-induced SGLT1 up-regulation in piglet intestine. A better understanding of the mechanism(s) involved in sweetener up-regulation of SGLT1 will allow the identification of nutritional targets with implications for the prevention of weaning-related malabsorption.

  3. Disrupting Na+,HCO3--cotransporter NBCn1 (Slc4a7) delays murine breast cancer development

    DEFF Research Database (Denmark)

    Lee, S.; Axelsen, T. V.; Andersen, Anne Poder

    2016-01-01

    ) mice. Breast cancer histopathology in NBCn1 KO mice differed from that in WT mice and included less aggressive tumor types. The extracellular tumor microenvironment in NBCn1 KO mice contained higher concentrations of glucose and lower concentrations of lactate than that in WT mice. Independently......Increased metabolism and insufficient blood supply cause acidic waste product accumulation in solid cancers. During carcinogenesis, cellular acid extrusion is upregulated but the underlying molecular mechanisms and their consequences for cancer growth and progression have not been established....... Genome-wide association studies have indicated a possible link between the Na(+),HCO3(-)-cotransporter NBCn1 (SLC4A7) and breast cancer. We tested the functional consequences of NBCn1 knockout (KO) for breast cancer development. NBCn1 protein expression increased 2.5-fold during breast carcinogenesis...

  4. The effects of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Gluud, Lise Lotte; Christensen, Mikkel

    2014-01-01

    to the knowledge regarding the beneficial and harmful effects of SGLT-2i in patients with type 2 diabetes. We plan to publish the study irrespective of the results. RESULTS: The study will be disseminated by peer-review publication and conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014008960......INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes. METHODS AND ANALYSIS: A systematic review with meta......-analyses of randomised clinical trials on SGLT-2i versus placebo, other oral glucose lowering drugs or insulin for patients with type 2 diabetes will be performed. The primary end point will be the glycated haemoglobin. Secondary end points will include changes in body weight, body mass index, fasting plasma glucose...

  5. Mutation of the Na-K-Cl co-transporter gene Slc12a2 results in deafness in mice.

    Science.gov (United States)

    Dixon, M J; Gazzard, J; Chaudhry, S S; Sampson, N; Schulte, B A; Steel, K P

    1999-08-01

    Hearing impairment is a common human condition, but we know little about the molecular basis of cochlear function. Shaker-with-syndactylism (sy) is a classic deaf mouse mutant and we show here that a second allele, sy(ns), is associated with abnormal production of endolymph, the fluid bathing sensory hair cells. Using a positional candidate approach, we demonstrate that mutations in the gene encoding the basolateral Na-K-Cl co-transporter Slc12a2 (Nkcc1, mBSC2) cause the deafness observed in sy and sy(ns) mice. This finding provides the molecular basis of another link in the chain of K+recycling in the cochlea, a process essential for normal cochlear function.

  6. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    Directory of Open Access Journals (Sweden)

    Mizerski Grzegorz

    2015-09-01

    Full Text Available The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1, and sodium-glucose co-transporter type type 2 (SGLT2 - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the administration of dapagliflozin, a selective SGLT2 inhibitor, in patients with type 2 diabetes, is associated with the reduction of HbA1c concentration by 0.45-1.11%. Additional benefits from the treatment with dapagliflozin are the reduction of arterial blood pressure and a permanent reduction of body weight. This outcome is related to the effect of osmotic diuresis and to the considerable loss of the glucose load by way of urine excretion. Dapagliflozin may be successfully applied in type 2 diabetes monotherapy, as well as in combined therapy (including insulin, where it is equally effective as other oral anti-diabetic drugs. Of note: serious adverse effects of dapagliflozin administration are rarely observed. What is more, episodes of severe hypoglycaemia related with the treatment occur only sporadically, most often in the course of diabetes polytherapy. The most frequent effects of the SGLT2 inhibitors are inseparably associated with the mechanism of their action (the glucuretic effect, and cover urogenital infections with a mild clinical course. At present, clinical trials are being continued of the administration of several subsequent drugs from this group, the most advanced of these being the use of canagliflozin and empagliflozin.

  7. Cotransport of clay colloids and viruses through water-saturated vertically oriented columns packed with glass beads: Gravity effects.

    Science.gov (United States)

    Syngouna, Vasiliki I; Chrysikopoulos, Constantinos V

    2016-03-01

    The cotransport of clay colloids and viruses in vertically oriented laboratory columns packed with glass beads was investigated. Bacteriophages MS2 and ΦX174 were used as model viruses, and kaolinite (ΚGa-1b) and montmorillonite (STx-1b) as model clay colloids. A steady flow rate of Q=1.5 mL/min was applied in both vertical up (VU) and vertical down (VD) flow directions. In the presence of KGa-1b, estimated mass recovery values for both viruses were higher for VD than VU flow direction, while in the presence of STx-1b the opposite was observed. However, for all cases examined, the produced mass of viruses attached onto suspended clay particles were higher for VD than VU flow direction, suggesting that the flow direction significantly influences virus attachment onto clays, as well as packed column retention of viruses attached onto suspended clays. KGa-1b hindered the transport of ΦX174 under VD flow, while STx-1b facilitated the transport of ΦX174 under both VU and VD flow directions. Moreover, KGa-1b and STx-1b facilitated the transport of MS2 in most of the cases examined except of the case where KGa-1b was present under VD flow. Also, the experimental data were used for the estimation of virus surface-coverages and virus surface concentrations generated by virus diffusion-limited attachment, as well as virus attachment due to sedimentation. Both sedimentation and diffusion limited virus attachment were higher for VD than VU flow, except the case of MS2 and STx-1b cotransport. The diffusion-limited attachment was higher for MS2 than ΦΧ174 for all cases examined. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Analysis of electron pair production in the collision system Ar+KCl at 1.76 AGeV; Analyse der Elektronpaarproduktion im Stosssystem Ar+KCl bei 1,76 AGeV

    Energy Technology Data Exchange (ETDEWEB)

    Lang, Simon Martin

    2008-06-30

    The HADES-spectrometer at GSI is used to measure the production of the light vector mesons {rho}, {omega} and {phi} at SIS energies. Therefore, the medium sized collision system Ar+KCl was measured at 1.76 AGeV kinetic energy of beam particles. In this system the density of particle tracks is much larger as compared to the formerly used collision system C+C, making it necessary to upgrade the data analysis. The previous method of hard-cuts - used for particle identification - was replaced by a newly developed multi-variate analysis based on an artificial neural network. This algorithm has the benefit, that it is more robust against fluctuations in one or more of the used detector observables. This increases the overall efficiency and purity of the analysis procedure. Furthermore, the reconstruction of particle tracks inside the HADES spectrometer is based on a few position information, only. During analysis of raw data, these information are combined to a artificially large manifold of tracks. This leads to the general problem that one has to select the maximum number of true physical tracks out of this set of tracks per event. A new method of track selection is used to filter the data not only to select single tracks, but also to identify electron pairs created during Dalitz-decay of {pi}{sup 0} mesons, which build the bulk of combinatorial background. The result of the analysis is an efficiency corrected invariant mass spectrum of electron pairs, normalized to the mean number of pions per event. The spectrum consists of more than 16,000 pairs with an invariant mass larger than 150 MeV. In total more than 150000 pairs were found. A first comparison with the spectra calculated by using the old analysis approach shows a 30% enhancement in yield of reconstructed electron pairs. A first comparison with a simple thermal model implemented by the Pluto event generator, opens the possibility to compare the measured pair yield of {omega} and {phi} mesons via m{sub T

  9. Characterization of incomplete fusion in the reactions Ar + KCl at 32,40,52 and 74 MeV/u; Caracterisation de la fusion incomplete dans les reactions Ar + KCl a 32,40,52 et 74 Mev/u

    Energy Technology Data Exchange (ETDEWEB)

    Bisquer, E. [Lyon-1 Univ., 69 - Villeurbanne (France). Inst. de Physique Nucleaire]|[Universite Claude Bernard, 69 - Lyon (France)

    1996-12-20

    Heavy ion collisions at intermediate energies (10 to 100 A.MeV) have been investigated and gave evidence to the persistence of so-called low energy mechanisms such as incomplete fusion. This thesis aims at determining the energy threshold beyond which such a mechanism does not occur any more. First we investigated the so-called conventional incomplete fusion. This mechanism is well known from low energy studies: a thermalized compound nucleus is formed which further de-excites by evaporating particles. Residues will be therefore detected in coincidence with mainly light particles. Ar + KCl at incident energies of 32, 40, 52 and 74 A.MeV has been selected for this analysis. These experiments have been performed using the INDRA multidetector in GANIL (Caen). The detection performance of INDRA allowed to use new analysis methods via global variables. In a first step, global variables have been compared in order to find the one that is the most appropriate to our study. Then incomplete fusion events have been extracted from raw events recorded at incident energies of 32, 40 and 52 A.MeV. It turned out that the contribution of this mechanisms was very weak at 52. A.MeV. It turned out that the contribution of this mechanism was very weak at 52 A.MeV and even zero at 74 A.MeV. We then investigated events in which three fragments were detected which could possibly sign multifragmentation. We did not find instantaneous multifragmentation with any expansion contribution. We also performed BNV simulations in order to compare our experimental results to model predictions, solving in a semi-classical way the Vlasov transport equation. A good agreement has been obtained on the size of the compound nucleus formed. However the excitation energy has not been reproduced, as the code seems to overestimate the energy taken away by preequilibrium particles. Incomplete fusion decreases as a function of energy but is not replaced by instantaneous multifragmentation with any expansion

  10. Reversible stress softening in layered rat esophagus in vitro after potassium chloride activation.

    Science.gov (United States)

    Jiang, Hongbo; Liao, Donghua; Zhao, Jingbo; Wang, Guixue; Gregersen, Hans

    2017-01-23

    Significant stress softening recovery after potassium chloride (KCl) administration was previously demonstrated in the intact rat esophageal wall. The aim of this study is to investigate the effect of KCl activation on stress softening recovery in the separated mucosa-submucosa layer and muscle layer of rat esophagus. Three series of loading-unloading distensions were carried out on 10 rat esophagi where the two separated layers were distended at luminal pressure levels 0.5, 1.0 and 2.0 kPa. Numerous distension cycles were done in [Formula: see text]-free Krebs solution before and after activation with KCl (110 mmol) for 3 min in calcium-containing media. The diameter and luminal pressure were recorded for stress and strain calculation. During KCl activation, the muscle layer responded with a high-amplitude contraction, and the mucosa-submucosa layer responded with a longer-lasting low-amplitude contraction. The hysteresis loop areas from the muscle layer were significantly bigger than those from the mucosa-submucosa layer at distension pressures 1.0 and 2.0 kPa ([Formula: see text]). The calculated stiffness in the mucosa-submucosa layer was significantly higher than that in the muscle layer ([Formula: see text]). After activation with KCl, the stored energy and the stiffness after the stress and viscoelasticity softening increased in both layers, indicating that the reversible stress softening in esophagus after KCl activation is existed in both layers.

  11. Changes in Mice Brain Spontaneous Electrical Activity during Cortical Spreading Depression due to Mobile Phone Radiation

    Science.gov (United States)

    Sallam, Samera M.; Mohamed, Ehab I.; Dawood, Abdel-Fattah B.

    2008-01-01

    The objective of the present study was to investigate changes in spontaneous EEG activity during cortical spreading depression (CSD) in mice brain. The cortical region of anaesthetized mice were exposed to the electromagnetic fields (EMFs) emitted from a mobile phone (MP, 935.2-960.2 MHz, 41.8 mW/cm2). The effect of EMFs on EEG was investigated before and after exposure to different stimuli (MP, 2% KCl, and MP & 2% KCl). The records of brain spontaneous EEG activity, slow potential changes (SPC), and spindle shaped firings were obtained through an interfaced computer. The results showed increases in the amplitude of evoked spindles by about 87%, 17%, and 226% for MP, 2% KCl, and MP & 2% KCl; respectively, as compared to values for the control group. These results showed that the evoked spindle is a more sensitive indicator of the effect of exposure to EMFs from MP. PMID:23675079

  12. Acute Aerobic Swimming Exercise Induces Distinct Effects in the Contractile Reactivity of Rat Ileum to KCl and Carbachol

    Science.gov (United States)

    Araujo, Layanne C. da Cunha; de Souza, Iara L. L.; Vasconcelos, Luiz H. C.; Brito, Aline de Freitas; Queiroga, Fernando R.; Silva, Alexandre S.; da Silva, Patrícia M.; Cavalcante, Fabiana de Andrade; da Silva, Bagnólia A.

    2016-01-01

    Aerobic exercise promotes short-term physiological changes in the intestinal smooth muscle associated to the ischemia-reperfusion process; however, few studies have demonstrated its effect on the intestinal contractile function. Thus, this work describes our observations regarding the influence of acute aerobic swimming exercise in the contractile reactivity, oxidative stress, and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and acutely exercised (EX-AC) groups. Animals were acclimated by 10, 10, and 30 min of swimming exercise in intercalated days 1 week before exercise. Then they were submitted to forced swimming for 1 h with a metal of 3% of their body weight attached to their body. Animals were euthanized immediately after the exercise section and the ileum was suspended in organ baths for monitoring isotonic contractions. The analysis of lipid peroxidation was performed in order to determinate the malondialdehyde (MDA) levels as a marker of oxidative stress, and intestinal smooth muscle morphology by histological staining. Cumulative concentration-response curves to KCl were altered in the EX-AC with an increase in both its efficacy and potency (Emax = 153.2 ± 2.8%, EC50 = 1.3 ± 0.1 × 10−2 M) compared to the SED group (Emax = 100%, EC50 = 1.8 ± 0.1 × 10−2 M). Interestingly, carbachol had its efficacy and potency reduced in the EX-AC (Emax = 67.1 ± 1.4%, EC50 = 9.8 ± 1.4 × 10−7 M) compared to the SED group (Emax = 100%, EC50 = 2.0 ± 0.2 × 10−7 M). The exercise did not alter the MDA levels in the ileum (5.4 ± 0.6 μ mol/mL) in the EX-AC compared to the SED group (8.4 ± 1.7 μ mol/mL). Moreover, neither the circular nor the longitudinal smooth muscle layers thickness were modified by the exercise (66.2 ± 6.0 and 40.2 ± 2.6 μm, respectively), compared to the SED group (61.6 ± 6.4 and 34.8 ± 3.7 μm, respectively). Therefore, the ileum sensitivity to contractile agents is differentially altered by the acute aerobic

  13. Determination of Exchange Current Density of U{sup 3+}/U Couple in LiCl-KCl Eutectic Mixture

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Inkyu [Korea Atomic Energy Research Institute, 1045 Daedeok-Daero, Yuseong, Daejeon (Korea, Republic of); Serrano, Brenda E.; Li, Selly X.; Hermann, Steven [Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415 (United States); Phongikaroon, Supathorn [University of Idaho, Idaho Falls, 1776 Science Center Dr. Idaho Falls, ID 83402 (United States)

    2009-06-15

    During the spent metallic fuel electrorefining process, uranium is electrochemically dissolved from the anode basket to produce U{sup 3+} ion, which are then selectively reduced at the solid cathode. These anodic and cathodic reactions are assumed to be simple oxidation and reduction reactions of the U{sup 3+}/U couple. Despite numerous studies in this area, the basic electrochemical properties of this redox couple such as the exchange current density and charge transfer coefficient have not been thoroughly investigated, thus providing a motivation for this study. In the reported experiment, the exchange current density of the U{sup 3+}/U couple was measured in LiCl-KCl eutectic mixture at 500 deg. C by applying a linear polarization resistance technique. The UCl{sub 3} concentration was 1.54 x 10{sup -4} mol/cm{sup 3} and 0.51 wt% of Cd was present in the salt. This is due to the reaction of U metal with CdCl{sub 2} used to generate UCl{sub 3} in the salt. Four different metal wires - tungsten, carbon steel, stainless steel, and zirconium - were employed as the working electrode. Since the U{sup 3+}/U couple was assumed to be a one step reaction, obtained exchange current density values were anticipated to be almost identical. However, the results indicated that they were 584, 398, 204, and 202 A/m{sup 2} for tungsten, carbon steel, stainless steel, and zirconium, respectively. Though it is still not clear why these values were different, it may be due to the differences in the interaction between electrode materials and uranium metal. To evaluate the charge transfer coefficient of the U{sup 3+}/U couple, Tafel measurements were also carried out for each electrode material, but there were difficulties encountered with calculating the exact values. By applying the exchange current densities to Tafel results, however, the charge transfer coefficients of this couple for each electrode material could be calculated and were found to be in the range of 0.3 to 0.5. In

  14. Neuronal chloride accumulation and excitatory GABA underlie aggravation of neonatal epileptiform activities by phenobarbital.

    Science.gov (United States)

    Nardou, Romain; Yamamoto, Sumii; Chazal, Geneviève; Bhar, Asma; Ferrand, Nadine; Dulac, Olivier; Ben-Ari, Yehezkel; Khalilov, Ilgam

    2011-04-01

    Phenobarbital produces its anti-epileptic actions by increasing the inhibitory drive of γ-aminobutyric acid. However, following recurrent seizures, γ-aminobutyric acid excites neurons because of a persistent increase of chloride raising the important issue of whether phenobarbital could aggravate persistent seizures. Here we compared the actions of phenobarbital on initial and established ictal-like events in an in vitro model of mirror focus. Using the in vitro three-compartment chamber preparation with the two hippocampi and their commissural fibres placed in three different chambers, kainate was applied to one hippocampus and phenobarbital contralaterally, either after one ictal-like event or after many recurrent ictal-like events that produce an epileptogenic mirror focus. Field, perforated patch and single-channel recordings were used to determine the effects of γ-aminobutyric acid and their modulation by phenobarbital, and alterations of the chloride cotransporters were investigated using sodium-potassium-chloride cotransporter 1 and potassium chloride cotransporter 2 antagonists, potassium chloride cotransporter 2 immunocytochemistry and sodium-potassium-chloride cotransporter 1 knockouts. Phenobarbital reduced initial ictal-like events and prevented the formation of a mirror focus when applied from the start. In contrast, phenobarbital aggravated epileptiform activities when applied after many ictal-like events by enhancing the excitatory actions of γ-aminobutyric acid due to increased chloride. The accumulation of chloride and the excitatory actions of γ-aminobutyric acid in mirror foci neurons are mediated by the sodium-potassium-chloride cotransporter 1 chloride importer and by downregulation and internalization of the chloride-exporter potassium-chloride cotransporter 2. Finally, concomitant applications of the sodium-potassium-chloride cotransporter 1 antagonist bumetanide and phenobarbital decreased excitatory actions of γ-aminobutyric acid and

  15. Prediction of the density of molten MgCl2-KCl-CaCl2 ternary at 1 090 K%1090 K下MgCl2-KCl-CaCl2三元熔盐体系的密度预测

    Institute of Scientific and Technical Information of China (English)

    赵飞; 陈志远; 陈洪智; 赵世强

    2014-01-01

    Electrolyte used for magnesium production should be maintained in a proper range of densities. MgCl2-KCl-CaCl2 ternary is one of the important basal melts of the electrolyte. The new generational geometric model is employed to predict the density of the ternary at the temperature of 1 090 K. Before the prediction , the density functions of molten MgCl2-CaCl2 binary to temperature are revised based on the data of NSRDS. The excess density functions of KCl-CaCl2,MgCl2-CaCl2,KCl-MgCl2 are fitted with Redlich-Kister equation. And the similarity coefficients of the three components in the ternary are worked out. The calculation results of the model are compared with the known experimental data. The relative errors of the predicted data are in the range of 2.21%~0.99%. Therefore, it is proposed that the prediction results are reliable.%镁电解工艺中使用的电解质需要具有合适的密度范围.MgCl2-KCl-CaCl2三元熔盐体系是镁电解质的重要基础三元系.使用了新一代溶液几何模型,预测了这一三元系在1090 K下的密度.首先勘正了标准数据库中的 MgCl2-CaCl2熔盐二元系的密度表达式.对已知3个二元系KCl-CaCl2、MgCl2-CaCl2、KCl-MgCl2数据,采用三次式表达的Redlich-Kister关系式拟合得到了它们的超额密度函数.并计算各组分之间的相似系数.最终获得全组分范围内的三元熔盐体系密度分布图.已知成分点的实验值与预测值之间相对误差在2.21%~0.99%之间,这表明了预测结果的可靠性.

  16. An overview of the effect of sodium glucose cotransporter 2 inhibitor monotherapy on glycemic and other clinical laboratory parameters in type 2 diabetes patients

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-07-01

    Full Text Available Yaowen Wang,1 Xueting Hu,2 Xueying Liu,3 Zengqi Wang2 1Department of Clinical Laboratory, Weifang People’s Hospital, 2Department of Clinical Laboratory, Weifang Traditional Chinese Hospital, Weifang, 3Department of Clinical Laboratory, The Third Hospital of Jinan, Jinan, People’s Republic of China Objectives: We aimed to determine the effect of sodium glucose cotransporter 2 (SGLT2 inhibitor monotherapy on glycemic and other clinical laboratory parameters versus other antidiabetic medications or placebo therapy in patients with type 2 diabetes mellitus. In addition, we aimed to investigate the risk of diabetic ketoacidosis associated with SGLT2 inhibitor therapy and evaluate its weight-sparing ability. Design: Meta-analysis. Materials and methods: PubMed and MEDLINE were searched to identify eligible studies up to December 2015. Randomized controlled trials that assessed the efficacy and safety of SGLT2 inhibitor monotherapy versus placebo therapy or active control were considered. The Cochrane Collaboration Risk of Bias Tool was used to evaluate quality and bias. The mean ­difference was used to evaluate the glycemic and other clinical laboratory parameters for SGLT2 inhibitor intervention versus control by drugs or placebo. Similarly, the risk ratio was used to assess adverse events, and the I2 was used to evaluate heterogeneity. Results: SGLT2 inhibitors significantly decreased glycated hemoglobin (HbA1c (P<0.001, weight (P<0.001, and the low-density lipoprotein/high-density lipoprotein ratio (P=0.03 compared with placebo therapy. No statistically significant changes were found in fasting plasma glucose, 2-hour postprandial glucose, or lipid parameters. Significant changes in the uric acid level were found for SGLT2 inhibitors versus placebo therapy (P=0.005 or active control (P<0.001. Although no significant change in levels of ketones occurred (P=0.93, patients receiving SGLT2 inhibitors were at greater risk of increased ketone bodies

  17. a Modified Denitrifying Bacteria Method for Dual Stable Isotopic Analysis of of Soil Nitrate in Kcl Extracts: Identification of Bioindicators of Nitrogen Deposition Along a Gradient in the Sonoran Desert

    Science.gov (United States)

    Bell, M. D.; Sickman, J. O.; Allen, E. B.

    2011-12-01

    Previous studies performing dual isotopic analysis of nitrate in KCl soil extracts using denitrifying bacteria have not incorporated alterations in the method to compensate for the increased N2O blank produced when the bacteria are exposed to KCl in solution. When 1M KCl is used as a blank, the amount of N2O released from the concentrated bacteria solution is more than four times as high as when using a DI water blank. The excess N2O produced is not an artifact of nitrate impurity in the KCl, although the blank increases with the molarity of KCl up to 1M. The introduction of N2O gas is significant enough to alter the values of IAEA USGS standards (3 μg in 3ml KCl) which in turn results in an inaccurate regression for unknown samples. We reduced the size of the KCl blank and its effect on the standards by adding 3ml of KCl to the bacteria solution prior to purging the sample with He gas. This removes the N2O gas which is released by the bacteria when they initially come in contact with the KCl, and allows for standards to be calibrated to a precision of ± 0.1 % δ15N and ± 0.2 % δ18O. Using this new method, we measured δ15N and δ18O of nitrate in 1M KCl soil extracts taken from surface soil (5cm cores) along a nitrogen deposition gradient spanning the Coachella Valley in the western Sonoran Desert during the summer. Early germinating winter annual plant species (Schismus barbatus, Chaenactic fremontii, and Malacothrix glabrata) were collected as seedlings early in the growing season and again in late spring before senescence. Leaves from the dominant shrub, Larrea tridentata, were also collected from each site. Soil nitrogen from sites on the eastern edge of the valley had δ18O values between +30 and +41%, indicating an influence of atmospheric nitrate in plant available nitrate. There was an inverse correlation (r2=0.907) between soil δ18O and the δ15N of the C.fremontii leaf tissue, which suggests that in areas of high N deposition, some seedlings are

  18. Pharmacodynamic Effects of Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, from a Randomized Study in Patients with Type 2 Diabetes

    OpenAIRE

    Sue Sha; Damayanthi Devineni; Atalanta Ghosh; David Polidori; Marcus Hompesch; Sabine Arnolds; Linda Morrow; Heike Spitzer; Keith Demarest; Paul Rothenberg

    2014-01-01

    INTRODUCTION: This randomized, double-blind, placebo-controlled, single and multiple ascending-dose study evaluated the pharmacodynamic effects and safety/tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes. METHODS: Patients (N = 116) discontinued their antihyperglycemic medications 2 weeks before randomization. Patients received canagliflozin 30, 100, 200, or 400 mg once daily or 300 mg twice daily, or placebo at 2 study centers in th...

  19. Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin

    OpenAIRE

    Bader, Nimrah; Mirza, Lubna

    2016-01-01

    We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin. The clinical history, physical examination findings and laboratory values are described. Other causes of acidosis such as salicylate toxicity or alcohol intoxication were excluded. Ketoacidosis resolved after increasing dextrose and insulin doses supporting the hypothesis that SGLT-2 inhibitors may lead to hypoin...

  20. Preparation of Mg-Yb alloy film by electrolysis in the molten LiCl-KCl-YbCl_3 system at low temperature

    Institute of Scientific and Technical Information of China (English)

    陈野; 叶克; 张密林

    2010-01-01

    The electrochemical behavior of Yb3+ and electrodeposition of Mg-Yb alloy film at solid magnesium cathode in the molten LiCl-KCl-YbCl3(2 wt.%) system at 773 K was investigated.Transient electrochemical techniques,such as cyclic voltammetry,chronopotentiometry and chronoamperometry were used in order to explore the deposition mechanism of Yb.The reduction process of Yb3+ is stepwise reactions which are single-electron and double-electron reversible charge transfer reactions.The speed control step was a diffu...

  1. Preparing different phases of Mg-Li-Sm alloys by molten salt electrolysis in LiCl-KCl-MgCl_2-SmCl_3 melts

    Institute of Scientific and Technical Information of China (English)

    韩伟; 田阳; 张密林; 叶克; 赵全友; 魏树权

    2010-01-01

    Different phases of Mg-Li-Sm alloys were prepared by galvanostatic electrolysis in LiCl-KCl-MgCl2-SmCl3 melts at 670 °C.The electrolysis process and phase control of Mg-Li-Sm alloys were studied.The microstructures of α,α+β,β phases of Mg-Li-Sm alloys were characterized by X-ray diffraction(XRD) and optical microscope(OM).Analysis of scanning electron microscopy(SEM) and EDS mapping analysis showed that Mg distributed homogeneously in Mg-Li-Sm alloys.EDS result showed that the distribution of Sm was more at...

  2. Involvement of functional groups on the surface of carboxyl group-terminated polyamidoamine dendrimers bearing arbutin in inhibition of Na⁺/glucose cotransporter 1 (SGLT1)-mediated D-glucose uptake.

    Science.gov (United States)

    Sakuma, Shinji; Kanamitsu, Shun; Teraoka, Yumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Shirasaka, Yoshiyuki; Tamai, Ikumi; Muraoka, Masahiro; Nakatsuji, Yohji; Kida, Toshiyuki; Akashi, Mitsuru

    2012-04-01

    A carboxyl group-terminated polyamidoamine dendrimer (generation: 3.0) bearing arbutin, which is a substrate of Na⁺/glucose cotransporter 1 (SGLT1), via a nonbiodegradable ω-amino triethylene glycol linker (PAMAM-ARB), inhibits SGLT1-mediated D-glucose uptake, as does phloridzin, which is a typical SGLT1 inhibitor. Here, since our previous research revealed that the activity of arbutin was dramatically improved through conjugation with the dendrimer, we examined the involvement of functional groups on the dendrimer surface in inhibition of SGLT1-mediated D-glucose uptake. PAMAM-ARB, with a 6.25% arbutin content, inhibited in vitro D-glucose uptake most strongly; the inhibitory effect decreased as the arbutin content increased. In vitro experiments using arbutin-free original dendrimers indicated that dendrimer-derived carboxyl groups actively participated in SGLT1 inhibition. However, the inhibitory effect was much less than that of PAMAM-ARB and was equal to that of glucose moiety-free PAMAM-ARB. Data supported that the glucose moiety of arbutin was essential for the high activity of PAMAM-ARB in SGLT1 inhibition. Analysis of the balance of each domain further suggested that carboxyl groups anchored PAMAM-ARB to SGLT1, and the subsequent binding of arbutin-derived glucose moieties to the target sites on SGLT1 resulted in strong inhibition of SGLT1-mediated D-glucose uptake.

  3. Influence of CNTs on Thermal Behavior and Light Radiation Properties of Zr/KClO 4 Pyrotechnics%碳纳米管对Zr/KClO4烟火剂的热行为和光辐射性能的影响

    Institute of Scientific and Technical Information of China (English)

    刘黎明; 康晓丽; 易勇; 张红芳; 罗江山; 唐永建

    2014-01-01

    To improve the pump efficiency of Zr/KClO4 pyrotechnic reagent used in Solid state laser pump sources,the carbon nanotubes(CNTs)with catalytic property,high specific surface area,strong adsorption capacity and high strength were intro-duced in pyrotechnic reagent Zr/KClO4 . The effect of carbon nanotubes on the thermal decomposition and light radiation perform-ance of Zr/KClO4(60/40)pyrotechnic reagent used in the pump sources was studied by differential thermal analysis technology and photoelectric detection technology. The results show that the addition of CNTs has a significant impact on the thermal decom-position characteristics and light radiation energy of Zr/KClO4 . With increasing of the CNTs,the combustion rate and exothermic quantity of the pyrotechnic reagent gradually increase,and the melting endothermic peak of the pyrotechnic reagent decrease and tend to disappear. However,the light radiation energies reveal the trend of firstly increases and then decreases. When the mass percentage of CNTs in the pyrotechnic reagent is 0.50%,the total radiation energy of the pyrotechnics can reach 1830 J·g-1. The effective radiation energy within the three strong absorption bands of Nd:Yttrium Aluminum Garnet( YAG)laser gain medium, that is(590 ±10)nm,(750±10)nm and(808±10)nm,can be increased by 41%,25% and 31%,respectively.%为了提高烟火固体激光器泵浦源 Zr/KClO4的泵浦效率,在烟火剂 Zr/KClO4中引入具有催化性能、高比表面积、强吸附能力、高强度的碳纳米管(CNTs),借助差热分析技术和光电探测技术研究了碳纳米管对泵浦源用烟火剂 Zr/KClO4(60/40)的热分解和光辐射性能的影响。结果表明:CNTs的加入对 Zr/KClO4的热分解特性和光辐射能均有显著的影响。随着 CNTs 添加量的增加,烟火剂的燃烧速率和放热量均逐渐增加,药剂的融化吸热峰减弱,甚至趋于消失,药剂的光辐射能量却呈现出先

  4. The effect of mixed HCl-KCl competitive adsorbate on Pt adsorption and catalytic properties of Pt-Sn/Al2O3 catalysts in propane dehydrogenation

    Science.gov (United States)

    Zangeneh, Farnaz Tahriri; Taeb, Abbas; Gholivand, Khodayar; Sahebdelfar, Saeed

    2015-12-01

    The effect of competitive adsorbate concentration and combination on the adsorption of H2PtCl6 onto γ-Al2O3 in the preparation and performance of PtSnK/γ-Al2O3 catalyst for propane dehydrogenation was investigated. The catalysts were prepared by sequential impregnation of Sn and Pt precursors. The effect of competitor concentration on Pt adsorption was studied by using hydrochloric acid (0.1-0.3 M) and the effect of pH was studied by using KCl/HCl mixtures at constant (0.1 M) total chloride ion concentration. The catalysts were characterized by nitrogen adsorption/desorption, XRD, XRF, SEM and CO chemisorption. The catalytic performance tests were carried out in a fixed-bed quartz reactor under kinetic controlled condition for proper catalyst screening. It was found that the corrosive competitor HCl could be partially substituted with KCl without appreciable impact on catalyst performance with the advantage of lower acid attack on the support and reduced leaching of the deposited tin. A model based on initial concentration and uptake of the adsorbates was developed to obtain the adsorption parameters. Values of 890 μmol/g and 600 lit/mol were obtained for adsorption site concentration of the tin-impregnated support and equilibrium constant for Pt adsorption, respectively, for HCl concentration range of 0.1-0.3 M.

  5. Corrosion Behavior of Yttria-Stabilized Zirconia-Coated 9Cr-1Mo Steel in Molten UCl3-LiCl-KCl Salt

    Science.gov (United States)

    Jagadeeswara Rao, Ch.; Venkatesh, P.; Prabhakara Reddy, B.; Ningshen, S.; Mallika, C.; Kamachi Mudali, U.

    2017-02-01

    For the electrorefining step in the pyrochemical reprocessing of spent metallic fuels of future sodium cooled fast breeder reactors, 9Cr-1Mo steel has been proposed as the container material. The electrorefining process is carried out using 5-6 wt.% UCl3 in LiCl-KCl molten salt as the electrolyte at 500 °C under argon atmosphere. In the present study, to protect the container vessel from hot corrosion by the molten salt, 8-9% yttria-stabilized zirconia (YSZ) ceramic coating was deposited on 9Cr-1Mo steel by atmospheric plasma spray process. The hot corrosion behavior of YSZ-coated 9Cr-1Mo steel specimen was investigated in molten UCl3-LiCl-KCl salt at 600 °C for 100-, 500-, 1000- and 2000-h duration. The results revealed that the weight change in the YSZ-coated specimen was insignificant even after exposure to molten salt for 2000 h, and delamination of coating did not occur. SEM examination showed the lamellar morphology of the YSZ coating after the corrosion test with occluded molten salt. The XRD analysis confirmed the presence of tetragonal and cubic phases of ZrO2, without any phase change. Formation of UO2 in some regions of the samples was evident from XRD results.

  6. Separation of actinides from irradiated An–Zr based fuel by electrorefining on solid aluminium cathodes in molten LiCl–KCl

    Energy Technology Data Exchange (ETDEWEB)

    Souček, P., E-mail: Pavel.Soucek@ec.europa.eu [European Commission, Joint Research Centre (JRC), Institute for Transuranium Elements (ITU), Postfach 2340, 76125 Karlsruhe (Germany); Murakami, T. [Central Research Institute of Electric Power Industry (CRIEPI), Komae-shi, Tokyo 201-8511 (Japan); Claux, B.; Meier, R.; Malmbeck, R. [European Commission, Joint Research Centre (JRC), Institute for Transuranium Elements (ITU), Postfach 2340, 76125 Karlsruhe (Germany); Tsukada, T. [Central Research Institute of Electric Power Industry (CRIEPI), Komae-shi, Tokyo 201-8511 (Japan); Glatz, J.-P. [European Commission, Joint Research Centre (JRC), Institute for Transuranium Elements (ITU), Postfach 2340, 76125 Karlsruhe (Germany)

    2015-04-15

    Highlights: • Electrorefining process in molten LiCl-KCl using solid Al electrodes was demonstrated. • High separation factors of actinides over lanthanides were achieved. • Efficient recovery of actinides from irradiated nuclear fuel was achieved. • Uniform, dense and well adhered deposits were obtained and characterised. • Kinetic parameters of actinide–aluminium alloy formation were evaluated. - Abstract: An electrorefining process for metallic spent nuclear fuel treatment is being investigated in ITU. Solid aluminium cathodes are used for homogeneous recovery of all actinides within the process carried out in molten LiCl–KCl eutectic salt at a temperature of 500 °C. As the selectivity, efficiency and performance of solid Al has been already shown using un-irradiated An–Zr alloy based test fuels, the present work was focused on laboratory-scale demonstration of the process using irradiated METAPHIX-1 fuel composed of U{sub 67}–Pu{sub 19}–Zr{sub 10}–MA{sub 2}–RE{sub 2} (wt.%, MA = Np, Am, Cm, RE = Nd, Ce, Gd, Y). Different electrorefining techniques, conditions and cathode geometries were used during the experiment yielding evaluation of separation factors, kinetic parameters of actinide–aluminium alloy formation, process efficiency and macro-structure characterisation of the deposits. The results confirmed an excellent separation and very high efficiency of the electrorefining process using solid Al cathodes.

  7. Electrochemical Formation of Al-Li Alloys by Codeposition of Al and Li from LiCl-KCl-AlF3 Melts at 853 K

    Institute of Scientific and Technical Information of China (English)

    SUN Yi; ZHANG Mi-lin; HAN Wei; LI Mei; YANG Yu-sheng

    2013-01-01

    The electrochemical behavior of Al(Ⅲ) ions was studied in molten LiCl-KCl melts on a molybdenum electrode.Cyclic voltammetry,chronopotentiometry and chronoamperometry were used to explore the deposition mechanism of Al and Li.Cyclic voltammetry expriment indicates that under potential deposition(UPD) of lithium on pre-deposited aluminium led to the formation of liquid Al-Li alloys at 853 K.The diffusion coefficient of Al(Ⅲ) ions at 853 K in LiCl-KCl-AlF3(1%,mass fraction) melts was determined to be (2.79±0.05)× 10-5 cm2/s.Chronopotentiograms and chronoamperograms demonstrate that the codeposition of Al(Ⅲ) and Li(Ⅰ) ions formed Al-Li alloys at cathodic current densities higher than-0.28 A/cm2 or cathodic potentials more negative than-2.20 V.X-Ray diffraction(XRD) pattern indicates that Al-Li alloys with different phases formed via galvanostatic electrolysis.Inductively coupled plasma(ICP) analyses of the samples obtained by electrolysis show that lithium and aluminium contents of Al-Li alloys could be controlled by AlF3 concentration and current intensity.

  8. Fluorescence Resonance Energy Transfer of the Tb(III)-Nd(III) Binary System in Molten LiCl-KCl Eutectic Salt

    Energy Technology Data Exchange (ETDEWEB)

    Kim, B. Y. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Yun, J. I. [KAIST, Daejeon (Korea, Republic of)

    2015-05-15

    The lanthanides act as a neutron poison in nuclear reactor with large neutron absorption cross section. For that reason, very low amount of lanthanides is required in the recovered U/TRU ingot product from pyrochemical process. In view of that, the investigation of thermodynamic properties and chemical behaviors of lanthanides in molten chloride salt are necessary to estimate the performance efficiency of pyrochemical process. However, there are uncertainties about knowledge and understanding of basic mechanisms in pyrochemical process, such as chemical speciation and redox behaviors due to the lack of in-situ monitoring methods for high temperature molten salt. The spectroscopic analysis is one of the probable techniques for in-situ qualitative and quantitative analysis. Recently, a few fluorescence spectroscopic measurements on single lanthanide element in molten LiCl-KCl eutectic have been investigated. The fluorescence intensity and the fluorescence lifetime of Tb(III) were decreased as increasing the concentration of Nd(III), demonstrating collisional quenching between donor ions and acceptor ions. The Forster distance (..0) of Tb(III)-Nd(III) binary system in molten LiCl-KCl eutectic was determined in the specific range of .... (0.1-1.0) and .. (1.387-1.496)

  9. Electroanalytical measurements of binary-analyte mixtures in molten LiCl-KCl eutectic: Uranium(III)- and Magnesium(II)-Chloride

    Science.gov (United States)

    Rappleye, Devin; Newton, Matthew L.; Zhang, Chao; Simpson, Michael F.

    2017-04-01

    The electrochemical behavior of MgCl2 in molten LiCl-KCl eutectic was investigated to evaluate its suitability as a surrogate for PuCl3 in studies related to the eletrorefining of used nuclear fuel. The reduction of Mg2+ was found to be electrochemically reversible up to 300 mV s-1 at 773 K. The diffusion coefficient for Mg2+ was calculated to be 1.74 and 2.17 × 10-5 cm2 s-1 with and without U3+ present, respectively, at 773 K using cyclic voltammetry (CV). Upon comparison to literature data, the diffusion coefficient of Mg2+ differs by only 8.8% (with U3+ present) from that of Pu3+ and the difference in peak potentials was only 79 mV. Binary-analyte mixtures of UCl3 and MgCl2 in eutectic LiCl-KCl were further investigated using CV, normal pulse voltammetry (NPV), chronoamperometry (CA) and open-circuit potential (OCP) measurements for the purpose of comparing each technique's accuracy in measuring U3+ and Mg2+ concentrations. Of all the techniques tested, NPV resulted in the lowest error which was, on average, 11.4% and 9.81% for U3+ and Mg2+, respectively.

  10. Electrochemical deposition of Al–Mg alloys on tungsten wires from AlCl{sub 3}–NaCl–KCl melts

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yaling; Zhao, Peng; Dai, Yinhai; Yao, Mengqi; Gan, Haibo; Hu, Wencheng, E-mail: huwc@uestc.edu.cn

    2016-02-15

    Highlights: • The method of electrochemical deposition is used to prepare Al–Mg alloys on tungsten wires. • AlCl{sub 3}–NaCl–KCl melts as a non-aqueous electrolyte is used in electrochemical deposition. • The effects of deposition voltage and molten salt temperature on the surface morphology and magnesium content of the Al–Mg deposits are studied. • Al–Mg alloys with 9.14 at.% Mg are obtained. - Abstract: This paper studies the electrochemical method that obtains the Al–Mg alloys on tungsten wires from AlCl{sub 3}–NaCl–KCl melts containing a mass fraction of 3% MgCl{sub 2}. Electrochemical experiments are performed with a three electrode system. Linear sweep voltammetry is used to determine the electrodeposition potential of Al–Mg alloys in molten salts. X-ray diffraction is employed to examine the crystallographic structure of Al–Mg alloy electrodeposits. Results show that the Al–Mg alloy coating consists of an Al (Mg) solid solution and the amorphous phase. The effects of the electrodeposition potential and temperature on the morphology of Al–Mg electrodeposits are demonstrated by scanning electron microscopy.

  11. A novel method for increasing the frequency of somatic embryogenesis in wheat tissue culture by NaCl and KCl supplementation.

    Science.gov (United States)

    Galiba, G; Yamada, Y

    1988-01-01

    The effect of NaCl, KCl and LiCl on the growth and morphogeneis of tissue cultures originating from immature embryos of four wheat (Triticum aestivum L.) and one triticale (Triticosecale)varieties was investigated. The morphogenetic pathway to plant regeneration in Chinese Spring wheat was determined as incomplete somatic embryogenesis because the differentiation and subsequent germination of the shoot apices happened in the early phase of embryo development. Culture medium supplemented by NaCl suppressed the differentiation of shoot apices resulting in the development of more typical somatic embryoids. Forty mM concentrations of both NaCl or KCl increased the formation of somatic embryos in Chinese Spring. Arthur and GK Kincso wheat varieties while Lasko triticale regenerated well without the addition. The salts inhibited plantlet formation from somatic embryoids so the salts supplement should be omitted. Forty mM LiCl inhibited growth while 10mM LiCl had no effect on growth or embryogenesis.

  12. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies.

    Science.gov (United States)

    Nyirjesy, Paul; Sobel, Jack D; Fung, Albert; Mayer, Cristiana; Capuano, George; Ways, Kirk; Usiskin, Keith

    2014-06-01

    To characterize genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) using pooled data from Phase 3 studies. Genital mycotic infections with canagliflozin 100 and 300 mg were evaluated in Population 1 (N = 2313; mean exposure [weeks]: canagliflozin, 24.3; placebo, 23.8), including patients from four placebo-controlled studies, and Population 2 (N = 9439; mean exposure [weeks]: canagliflozin, 68.1; control, 64.4), including patients from eight placebo/active-controlled studies (including older patients and those with renal impairment or high cardiovascular disease risk). ClinicalTrials.gov, NCT01081834; NCT01106625; NCT01106677; NCT01106690; NCT01032629; NCT01064414; NCT01106651; NCT00968812. Adverse events suggestive of genital mycotic infections were recorded, with additional information collected using supplemental electronic case report forms. In Population 1, genital mycotic infection incidence was higher with canagliflozin 100 and 300 mg than placebo (95% confidence intervals excluded zero) in females (10.4%, 11.4%, 3.2%) and males (4.2%, 3.7%, 0.6%). These were generally mild to moderate in intensity, none were serious, and few led to discontinuation. Most events with canagliflozin were treated with antifungal therapies, and median symptom duration following treatment initiation was similar across groups; few patients had >1 event (females, 2.3%; males, 0.9%). Findings with canagliflozin 100 and 300 mg versus control were similar in Population 2 (females: 14.7%, 13.9%, 3.1%; males: 7.3%, 9.3%, 1.6%); a low proportion of males underwent circumcision across groups. Most events with canagliflozin occurred within the first 4 months in females and first year in males; no consistent evidence of dose dependence was observed. Key limitations included lack of laboratory confirmation for most events and variable treatment methods. Genital mycotic infection incidences

  13. Na+/K+-ATPase β1-subunit is recruited in Na-K-2Cl co-transporter isoform 2 multiprotein complexes in rat kidneys: possible role in blood pressure regulation.

    Science.gov (United States)

    Carmosino, Monica; Torretta, Silvia; Procino, Giuseppe; Timperio, Annamaria; Zolla, Lello; Svelto, Maria

    2014-09-01

    The progression from prehypertensive to hypertensive state in spontaneous hypertensive rats (SHRs) is accompanied by a significant increase in membrane expression of Na-K-2Cl co-transporter isoform 2 (NKCC2), suggesting that the altered NKCC2 trafficking and activity are directly related with the development of hypertension in this strain. The aim of this work is to gain insights on the molecular mechanism that underlies this phenomenon. We performed a comparative analysis of NKCC2 multiprotein complexes (MPCs) in the kidney of SHRs versus Wistar Kyoto rats by Blue Native difference gel electrophoresis combined with mass spectrometry. We found that the recruitment of the β-subunit isoform 1 of the Na(+)-K(+)-ATPase (β1NK) in NKCC2 MPCs was significantly increased in the kidneys of SHR compared with Wistar Kyoto rat control strain. Co-immunoprecipitation experiments showed that β1NK actually interacts with NKCC2 in the native tissue. The analysis of the physiological role of β1NK-NKCC2 interaction in human embryonic kidney cells showed that β1NK increased the steady-state membrane expression and activity of NKCC2 enhancing NKCC2 trafficking toward the plasma membrane. We identify a new NKCC2-interacting partner involved in the modulation of NKCC2 intracellular trafficking and possibly involved in the regulation of blood pressure.

  14. Sodium-glucose co-transporter 2 (SGLT2 inhibitors: a growing class of anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Eva M Vivian

    2014-12-01

    Full Text Available Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM. The renal sodium-glucose co-transporter 2 (SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic parameters in patients with T2DM when used as monotherapy or in combination with other antihyperglycemic agents. Treatment with SGLT2 inhibitors is associated with weight reduction, lowered blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall, canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients compared with those receiving placebo. Evidence from clinical trials suggests that SGLT2 inhibitors are a promising new treatment option for T2DM.

  15. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors: Part 2. Antidiabetic effects in type 2 diabetic mice

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-07-01

    Full Text Available Previously we investigated the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six sodium-glucose cotransporter (SGLT 2 inhibitors commercially available in Japan using normal and diabetic mice. We classified the SGLT2 inhibitors with respect to duration of action as either long-acting (ipragliflozin and dapagliflozin or intermediate-acting (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. In the present study, antidiabetic effects of repeated administration of these SGLT2 inhibitors in type 2 diabetic mice were investigated. When repeatedly administered for 4 weeks, all SGLT2 inhibitors significantly exhibited antihyperglycemic, antihyperinsulinemic, and pancreas-protective effects, as well as insulin resistance-improving effects. When compared at doses producing comparable reduction in hyperglycemia across all drugs, the antidiabetic effects of ipragliflozin and dapagliflozin were more potent than those of the other four drugs, but these differences among the six drugs were not statistically significant. Further, an oral glucose tolerance test performed after repeated administration demonstrated significant improvement in glucose tolerance only with ipragliflozin and dapagliflozin, implying improved insulin resistance and secretion. Taken together, these findings demonstrate that, although all SGLT2 inhibitors exert antidiabetic effects in type 2 diabetic mice, these pharmacologic effects might be slightly superior with the long-acting drugs, which are able to provide favorable blood glucose control throughout the day.

  16. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters

    Science.gov (United States)

    Jolivalt, Corinne G.; Lee, Corinne A.; Ramos, Khara M.; Calcutt, Nigel A.

    2008-01-01

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored the role of the GABAA receptor in rats with painful diabetic neuropathy. KCC2 protein levels were significantly reduced in the spinal cord of diabetic rats while levels of NKCC1 and the GABAA receptor were unchanged. Spinal delivery of the GABAA receptor antagonist bicuculline reduced formalin-evoked flinching in diabetic rats and also dose-dependently alleviated tactile allodynia. GABAA receptor-mediated rate-dependent depression of the spinal H reflex was absent in the spinal cord of diabetic rats. Control rats treated with the KCC2 blocker DIOA, mimicked diabetes by showing increased formalin-evoked flinching and diminished rate dependent depression. The ability of bicuculline to alleviate allodynia and formalin-evoked hyperalgesia in diabetic rats is consistent with a reversal of the properties of GABA predicted by reduced spinal KCC2 and suggests that reduced KCC2 expression and increased GABA release contribute to spinally-mediated hyperalgesia in diabetes. PMID:18755547

  17. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters.

    Science.gov (United States)

    Jolivalt, Corinne G; Lee, Corinne A; Ramos, Khara M; Calcutt, Nigel A

    2008-11-15

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored the role of the GABA(A) receptor in rats with painful diabetic neuropathy. KCC2 protein levels were significantly reduced in the spinal cord of diabetic rats, while levels of NKCC1 and the GABA(A) receptor were unchanged. Spinal delivery of the GABA(A) receptor antagonist bicuculline reduced formalin-evoked flinching in diabetic rats and also dose-dependently alleviated tactile allodynia. GABA(A) receptor-mediated rate-dependent depression of the spinal H reflex was absent in the spinal cord of diabetic rats. Control rats treated with the KCC2 blocker DIOA, mimicked diabetes by showing increased formalin-evoked flinching and diminished rate- dependent depression. The ability of bicuculline to alleviate allodynia and formalin-evoked hyperalgesia in diabetic rats is consistent with a reversal of the properties of GABA predicted by reduced spinal KCC2 and suggests that reduced KCC2 expression and increased GABA release contribute to spinally mediated hyperalgesia in diabetes.

  18. Co-transport of polycyclic aromatic hydrocarbons by motile microorganisms leads to enhanced mass transfer under diffusive conditions.

    Science.gov (United States)

    Gilbert, Dorothea; Jakobsen, Hans H; Winding, Anne; Mayer, Philipp

    2014-04-15

    The environmental chemodynamics of hydrophobic organic chemicals (HOCs) are often rate-limited by diffusion in stagnant boundary layers. This study investigated whether motile microorganisms can act as microbial carriers that enhance mass transfer of HOCs through diffusive boundary layers. A new experimental system was developed that allows (1) generation of concentration gradients of HOCs under the microscope, (2) exposure and direct observation of microorganisms in such gradients, and (3) quantification of HOC mass transfer. Silicone O-rings were integrated into a Dunn chemotaxis chamber to serve as sink and source for polycyclic aromatic hydrocarbons (PAHs). This resulted in stable concentration gradients in water (>24 h). Adding the model organism Tetrahymena pyriformis to the experimental system enhanced PAH mass transfer up to hundred-fold (benzo[a]pyrene). Increasing mass transfer enhancement with hydrophobicity indicated PAH co-transport with the motile organisms. Fluorescence microscopy confirmed such transport. The effective diffusivity of T. pyriformis, determined by video imaging microscopy, was found to exceed molecular diffusivities of the PAHs up to four-fold. Cell-bound PAH fractions were determined to range from 28% (naphthalene) to 92% (pyrene). Motile microorganisms can therefore function as effective carriers for HOCs under diffusive conditions and might significantly enhance mobility and availability of HOCs.

  19. Review. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence?

    Science.gov (United States)

    Meredith, David

    2009-01-27

    The proton-coupled di- and tripeptide transporter PepT1 (SLC15a1) is the major route by which dietary nitrogen is taken up from the small intestine, as well as being the route of entry for important therapeutic (pro)drugs such as the beta-lactam antibiotics, angiotensin-converting enzyme inhibitors and antiviral and anti-cancer agents. PepT1 is a member of the major facilitator superfamily of 12 transmembrane domain transporter proteins. Expression studies in Xenopus laevis on rabbit PepT1 that had undergone site-directed mutagenesis of a conserved arginine residue (arginine282 in transmembrane domain 7) to a glutamate revealed that this residue played a role in the coupling of proton and peptide transport and prevented the movement of non-coupled ions during the transporter cycle. Mutations of arginine282 to other non-positive residues did not uncouple proton-peptide cotransport, but did allow additional ion movements when substrate was added. By contrast, mutations to positive residues appeared to function the same as wild-type. These findings are discussed in relation to the functional role that arginine282 may play in the way PepT1 operates, together with structural information from the homology model of PepT1 based on the Escherichia coli lactose permease crystal structure.

  20. Place of sodium-glucose co-transporter type 2 inhibitors for treatment of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Nasser; Mikhail

    2014-01-01

    Inhibitors of sodium-glucose co-transporter type 2(SGLT2), such as canagliflozin and dapagliflozin, are recently approved for treatment of type 2 diabetes. These agents lower blood glucose mainly by increasing urinary glucose excretion. Compared with placebo, SGLT2 inhibitors reduce hemoglobin A1c(Hb A1c) levels by an average of 0.5%-0.8% when used as monotherapy or add-on therapy. Advantages of this drug class include modest weight loss of approximately 2 kg, low risk of hypoglycemia, and decrease blood pressure of approximately 4 mm Hg systolic and 2 mm Hg diastolic. These characteristics make these agents potential add-on therapy in patients with Hb A1 c levels close to 7%-8.0%, particularly if these patients are obese, hypertensive, and/or prone for hypoglycemia. Meanwhile, these drugs are limited by high frequency of genital mycotic infections. Less common adverse effects include urinary tract infections, hypotension, dizziness, and worsening renal function. SGLT2 inhibitors should be used with caution in the elderly because of increased adverse effects, and should not be used in chronic kidney disease due to decreased or lack of efficacy and nephrotoxicity. Overall, SGLT2 inhibitors are useful addition for treatment of select groups of patients with type 2 diabetes,but their efficacy and safety need to be established in long-term clinical trials.

  1. Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone.

    Science.gov (United States)

    Chiga, Motoko; Rai, Tatemitsu; Yang, Sung-Sen; Ohta, Akihito; Takizawa, Toichiro; Sasaki, Sei; Uchida, Shinichi

    2008-12-01

    Pseudohypoaldosteronism type II (PHAII) is caused by mutations in the WNK1 and WNK4 genes (WNK with-no-lysine kinase). In a mouse model of this disease where a mutant of Wnk4 D561A was knocked in, increased phosphorylation of the sodium chloride cotransporter (NCC) was found and the transporter was concentrated on the apical membrane of the distal tubules. In addition, we recently found that other kinases, such as the oxidative stress response kinase-1/STE20/SPS1-related proline alanine-rich kinase (OSR1/SPAK), also showed increased phosphorylation in these mice. Here we determined whether this kinase cascade is regulated by dietary salt intake. We found that the phosphorylation states of NCC and OSR1/SPAK were increased by low-salt diets and decreased by high-salt diets; a regulation completely lost in the knock-in mice. Increased phosphorylation was reversed by spironolactone and this decreased phosphorylation was reversed by administration of exogenous aldosterone. These studies suggest that that the WNK-OSR1/SPAK-NCC cascade may be a novel effector system of aldosterone action in the kidney.

  2. Circadian exosomal expression of renal thiazide-sensitive NaCl cotransporter (NCC) and prostasin in healthy individuals.

    Science.gov (United States)

    Castagna, Annalisa; Pizzolo, Francesca; Chiecchi, Laura; Morandini, Francesca; Channavajjhala, Sarath Kiran; Guarini, Patrizia; Salvagno, Gianluca; Olivieri, Oliviero

    2015-06-01

    A circadian timing system is involved in the maintenance of fluid and electrolyte balance and blood pressure control. Aldosterone and vasopressin modulate ion transporters and channels crucial in sodium (Na) and water reabsorption such as the epithelium Na channel and the renal thiazide-sensitive NaCl cotransporter (NCC). We analyzed in urinary exosomes the intraday variations of NCC and prostasin expression and the association with electrolytes and water balance parameters. Blood and urine samples were collected at five time points during the day from five healthy subjects. Blood renin, aldosterone, cortisol, ACTH, and plasmatic and urinary Na, potassium, creatinine, adiuretin (ADH), NCC, and prostasin were evaluated. ACTH and cortisol showed a circadian pattern, similarly to aldosterone, while exosomal NCC and prostasin pattern were similar to urinary ADH, decreased in the morning and subsequently increased in the afternoon and evening. In urinary exosomes, NCC and prostasin had a diurnal pattern parallel to ADH and aquaporin 2, confirming that, in healthy subjects, both prostasin and NCC relate to water balance. These results provide suggestions for a possible chronotherapeutic approach in patients treated with thiazides, diuretic drugs acting as specific inhibitors of NCC-mediated Na reabsorption. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The K–Cl Cotransporter KCC3 as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Atsushi Shiozaki

    2014-01-01

    Full Text Available The objectives of the present study were to investigate the role of K–Cl cotransporter 3 (KCC3 in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC. Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN, and the survival rate of patients with a CN>MT score was lower than that of patients with a CN≤MT score. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.

  4. Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin: rationale and evidences.

    Science.gov (United States)

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    Sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are recently approved class of anti-hyperglycaemic agents for the treatment of type 2 diabetes mellitus (T2DM). SGLT-2I inhibits renal glucose reabsorption, thereby ensuing urinary glucose excretion in a dose-dependent manner. This caloric loss and osmotic diuresis, secondary to increased urinary glucose excretion, has a unique potential to counter insulin induced weight gain and fluid retention, with little potential of hypoglycemic exacerbation. Also, as these agents act independently of insulin secretion or action, they are effective even in long-standing diabetes with depleted β-cell reserve. Improvement in insulin sensitivity, as observed with SGLT-2I can also facilitate insulin action. Furthermore, significant reduction in total daily insulin dosage and reduction of body weight as observed during combination therapy renders SGLT-2I, a near-ideal partner to insulin. This review aims to evaluate the safety and efficacy of currently used SGLT-2I as an add-on to insulin therapy in the treatment of T2DM.

  5. Impact of lysine and liquid smoke as flavor enhancers on the quality of low-fat Bologna-type sausages with 50% replacement of NaCl by KCl.

    Science.gov (United States)

    Dos Santos Alves, Larissa Aparecida Agostinho; Lorenzo, José Manuel; Gonçalves, Carlos Antonio Alvarenga; Dos Santos, Bibiana Alves; Heck, Rosane Teresinha; Cichoski, Alexandre José; Campagnol, Paulo Cezar Bastianello

    2017-01-01

    Low-fat Bologna-type sausages were produced with 50% of NaCl replaced by KCl and with addition of lysine and/or liquid smoke as flavor enhancers. The influence of sodium reduction on technological, physicochemical, and microbiological properties was determined. In addition, the sensory properties were evaluated using a Check all that apply questionnaire (CATA) and a consumer study. The partial replacement of NaCl by KCl did not have negative impacts on physicochemical, technological, and microbiological properties. However, the addition of KCl affected the sensory acceptance, as consumers identified by CATA questionnaire a reduction in salty taste and an increase in bitter, astringent, and metallic taste. The isolated or combined addition of lysine and liquid smoke reduced the sensory quality defects caused by the addition of KCl. Therefore, high quality low-fat Bologna-type sausages with sodium reduction close to 50% can be produced by replacing 50% NaCl by KCl and with addition of 1% lysine and/or 0.1% liquid smoke. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. KCL22/NOD-SCID 小鼠慢性粒细胞白血病移植瘤模型的建立及其鉴定%Establishment and verification of a KCL22/NOD-SCID mouse transplantation tumor model of chronic myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    文良雪; 刘鑫; 李会; 黄宁姝; 黄峥兰; 冯文莉

    2015-01-01

    Objective To investigate the potential of chronic myeloid leukemia ( CML) cell line KCL22 in indu-cing leukemia in NOD-SCID mice for setting up a basis for constructing a CML mouse transplantation tumor model. Methods 2 ×107 KCL22 cells in logarithmic growth phase were injected via the tail vein into experimental NOD-SCID mice whereas PBS was injected to the mice of control group.General condition of the mice of both groups was observed.Wright staining was used to observe the changes of blood and bone marrow smears.PCR was conducted to detect the transcription level of BCR-ABL, and histology with HE staining was used to evaluate the tumor cell invasion in the liver and spleen. Results Four weeks after the injection of KCL22 cells, the mice in experimental group showed physical signs of decreased reactivity, depression, swollen hindlimb muscles and petechia on the hindlimb femur.Peripheral white blood cells ( WBC) began to increase after 5 weeks, with a significantly increased quantity compared with the control group (P90 days) (P<0.05).Conclusions A NOD-SCID mouse model of CML transplantation tumor is successfully established with leukemia KCL22 cells.%目的:研究人慢性粒细胞白血病细胞株KCL22在NOD-SCID小鼠体内致白血病的能力,为慢性粒细胞白血病血液移植瘤模型鼠的建立奠定基础。方法取对数生长期的KCL22细胞2×107个,经尾静脉注射入NOD-SCID小鼠,对照组小鼠注射无菌PBS。观察小鼠一般情况,瑞氏染色监测血象和骨髓象变化,PCR检测骨髓细胞BCR-ABL基因转录水平,HE染色观察肝、脾组织肿瘤细胞浸润情况。结果实验组小鼠于注射细胞后约4周开始出现反应力下降、精神萎靡、股骨肌肿大、后肢骨节出血点等体征,外周血白细胞从第5周逐渐增多,计数较对照组显著升高( P<0.05),血涂片可见幼稚粒细胞,肝、脾、骨髓组织切片可见白血病细胞浸润,骨髓细胞高表达BCR

  7. Relação entre o alumínio extraível com KCl e oxalato de amônio e a mineralogia da fração argila, em solos ácidos brasileiros

    Directory of Open Access Journals (Sweden)

    Gabriel Octávio de Mello Cunha

    2014-10-01

    Full Text Available Em solos ácidos de ambiente mais tropical com esmectitas, assim como em solos altamente tamponados de ambiente subtropical, contendo esmectita com hidroxi-Al entrecamadas (EHE e, ou, vermiculita com hidroxi-Al entrecamadas (VHE, os teores de Al-KCl podem ser excepcionalmente altos; entretanto, em alguns casos não se manifestam efeitos fitotóxicos do elemento nas culturas. O Al "trocável" é tradicionalmente quantificado no extrato da solução de KCl 1 mol L-1 (Al-KCl, mas nem sempre esse elemento provém unicamente de formas trocáveis. Este trabalho objetivou investigar relações entre o Al extraído com solução de KCl e de oxalato de amônio com a mineralogia da fração argila. A quantificação do Al nos extratos de KCl e oxalato de amônio foi feita, respectivamente, por titulação com NaOH 0,02 mol L-1 padronizado e por espectrofotometria de absorção atômica. Foram utilizadas amostras de dois horizontes (A e B de 12 perfis de solo de cinco estados brasileiros (AC, PE, BA, RS e SC, com diferentes características mineralógicas, todos com teores de Al-KCl superior a 4 cmol c kg-1 no horizonte B. Dois perfis de SC (Rancho Queimado e Curitibanos, com níveis mais baixos de Al-KCl, foram incluídos para comparação. Os altos teores de Al-KCl evidenciaram-se relacionados com a mineralogia dos solos estudados. Nos solos ácidos com mais esmectitas, drenagem moderada ou imperfeita e oscilação do lençol freático houve evidências morfológicas, confirmadas pelas análises mineralógicas, de que no clima atual ocorre um processo de destruição de argilas, liberando Al que precipita como compostos amorfos. A alta concentração salina da solução de KCl dissolve parcialmente tais compostos, superestimando as formas trocáveis desse elemento, principalmente nos horizontes subsuperficiais. Nos solos ácidos do ambiente subtropical, os teores de Al-KCl também foram altos, embora com valores mais baixos do que nos com predomínio de

  8. Effect of potassium sources on the antioxidant activity of eggplant¹

    Directory of Open Access Journals (Sweden)

    Douglas José Marques

    2014-12-01

    Full Text Available Potassium participates in the essential processes in plant physiology, however, the effects of K sources on plant metabolism have been little studied. Also, in certain cases, K sources and concentrations may cause undesirable effects, e.g., soil salinization. The objective was to evaluate the effect of K sources and levels on the enzyme activity of the antioxidant system and protein content in eggplant (Solanum melongena L. leaves and to determine the most suitable K sources for these physiological characteristics. The experiment was conducted in randomized blocks, in a 2 × 4 factorial design, consisting of two K sources (KCl and K2SO4 and rates (250, 500, 750, and 1000 kg ha-1 K2O, with four replications. The following variables were evaluated: plant height, number of leaves per plant, superoxide dismutase (SOD, catalase (CAT, and leaf protein content. There was an increase in CAT activity with increasing K levels until 30 days after transplanting (DAT, when K2SO4 was applied and until 60 DAT, when KCl was used; after this period, the enzyme activity decreased under both sources. The activity of SOD increased in the presence of KCl, but was reduced with the application of K2SO4. For both K sources, increasing rates reduced the protein content and number of leaves per plant, and this reduction was greater under KCl application. Thus it was concluded that KCl tends more strongly to salinize the soil than K2SO4. Both for KCl and for K2SO4, the increasing rates adversely affected the activities of CAT and SOD and the levels of leaf protein in eggplant. The potential of KCl to reduce the enzyme activity of SOD and CAT, leaf protein content and plant growth of eggplant was stronger than that of K2SO4.

  9. Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2 inhibitor for the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Joshua J Neumiller

    2014-06-01

    Full Text Available Type 2 diabetes is increasing in prevalence worldwide, and hyperglycemia is often poorly controlled despite a number of therapeutic options. Unlike previously available agents, sodium-glucose co-transporter 2 (SGLT2 inhibitors offer an insulin-independent mechanism for improving blood glucose levels, since they promote urinary glucose excretion (UGE by inhibiting glucose reabsorption in the kidney. In addition to glucose control, SGLT2 inhibitors are associated with weight loss and blood pressure reductions, and do not increase the risk of hypoglycemia. Empagliflozin is a selective inhibitor of SGLT2, providing dose-dependent UGE increases in healthy volunteers, with up to 90 g of glucose excreted per day. It can be administered orally, and studies of people with renal or hepatic impairment indicated empagliflozin needed no dose adjustment based on pharmacokinetics. In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure. As add-on to basal insulin, empagliflozin not only improved HbA1c levels but also reduced insulin doses. Across studies, empagliflozin was generally well tolerated with a similar rate of hypoglycemia to placebo; however, patients had a slightly increased frequency of genital infections, but not urinary tract infections, versus placebo. Phase III studies have also reported a good safety profile along with significant improvements in HbA1c, weight and blood pressure, with no increased risk of hypoglycemia versus placebo. Based on available data, it appears that empagliflozin may be a useful option in a range of patients; however, clinical decisions will be better informed by the results of ongoing studies, in particular, a large cardiovascular outcome study (EMPA-REG OUTCOME™.

  10. Safety of Sodium-Glucose Co-Transporter 2 Inhibitors during Ramadan Fasting: Evidence, Perceptions and Guidelines

    Directory of Open Access Journals (Sweden)

    Salem A. Beshyah

    2016-06-01

    Full Text Available Sodium-glucose co-transporter 2 (SGLT2 inhibitors are a new glucose-lowering therapy for T2DM with documented benefits on blood glucose, hypertension, weight reduction and long term cardiovascular benefit. They have an inherent osmotic diuretic effect and lead to some volume loss and possible dehydration. There is some concern about the safety of using SGLT2 inhibitors in Muslim type 2 diabetes mellitus (T2DM patients during the fast during Ramadan. Currently, there is a dearth of research data to help guide physicians and reassure patients.  One study confirmed good glycemic control with less risk of hypoglycemia and no marked volume depletion. Data in the elderly and in combination with diuretics are reassuring of their safe to use in Ramadan in general. SGLT2 inhibitor-related diabetic ketoacidosis has not been reported during Ramadan and is unlikely to be relevant. Survey of physicians revealed that the majority felt that SGLT2 inhibitors are generally safe in T2DM patients during Ramadan fasting but should be discontinued in certain high risk patients. Some professional groups with interest in diabetes and Ramadan fasting included SGLT2 inhibitors in their guidelines on management of diabetes during Ramadan. They acknowledged the lack of trial data, recommended caution in high risk groups, advised regular monitoring and emphasized pre-Ramadan patients’ education. In conclusion, currently, knowledge, data and experience with SGLT2 inhibitors in Ramadan are limited. Nonetheless, stable patients with normal kidney function and low risk of dehydration may safely use the SGLT2 inhibitors therapy. Higher risk patients should be observed carefully and managed on individual basis.

  11. Interaction of the Sodium/Glucose Cotransporter (SGLT) 2 inhibitor Canagliflozin with SGLT1 and SGLT2.

    Science.gov (United States)

    Ohgaki, Ryuichi; Wei, Ling; Yamada, Kazunori; Hara, Taiki; Kuriyama, Chiaki; Okuda, Suguru; Ueta, Kiichiro; Shiotani, Masaharu; Nagamori, Shushi; Kanai, Yoshikatsu

    2016-07-01

    Canagliflozin, a selective sodium/glucose cotransporter (SGLT) 2 inhibitor, suppresses the renal reabsorption of glucose and decreases blood glucose level in patients with type 2 diabetes. A characteristic of canagliflozin is its modest SGLT1 inhibitory action in the intestine at clinical dosage. To reveal its mechanism of action, we investigated the interaction of canagliflozin with SGLT1 and SGLT2. Inhibition kinetics and transporter-mediated uptake were examined in human SGLT1- or SGLT2-expressing cells. Whole-cell patch-clamp recording was conducted to examine the sidedness of drug action. Canagliflozin competitively inhibited SGLT1 and SGLT2, with high potency and selectivity for SGLT2. Inhibition constant (Ki) values for SGLT1 and SGLT2 were 770.5 and 4.0 nM, respectively. (14)C-canagliflozin was suggested to be transported by SGLT2; however, the transport rate was less than that of α-methyl-d-glucopyranoside. Canagliflozin inhibited α-methyl-d-glucopyranoside-induced SGLT1- and SGLT2-mediated inward currents preferentially from the extracellular side and not from the intracellular side. Based on the Ki value, canagliflozin is estimated to sufficiently inhibit SGLT2 from the urinary side in renal proximal tubules. The Ki value for SGLT1 suggests that canagliflozin suppresses SGLT1 in the small intestine from the luminal side, whereas it does not affect SGLT1 in the heart and skeletal muscle, considering the maximal concentration of plasma-unbound canagliflozin. Similarly, SGLT1 in the kidney would not be inhibited, thereby aiding in the prevention of hypoglycemia. After binding to SGLT2, canagliflozin may be reabsorbed by SGLT2, which leads to the low urinary excretion and prolonged drug action of canagliflozin. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Effect of hepatic or renal impairment on the pharmacokinetics of canagliflozin, a sodium glucose co-transporter 2 inhibitor.

    Science.gov (United States)

    Devineni, Damayanthi; Curtin, Christopher R; Marbury, Thomas C; Smith, William; Vaccaro, Nicole; Wexler, David; Vandebosch, An; Rusch, Sarah; Stieltjes, Hans; Wajs, Ewa

    2015-03-01

    Canagliflozin is a sodium-glucose cotransporter 2 inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM). Because T2DM is often associated with renal or hepatic impairment, understanding the effects of these comorbid conditions on the pharmacokinetics of canagliflozin, and further assessing its safety, in these special populations is essential. Two open-label studies evaluated the pharmacokinetics, pharmacodynamics (renal study only), and safety of canagliflozin in participants with hepatic or renal impairment. Participants in the hepatic study (8 in each group) were categorized based on their Child-Pugh score (normal hepatic function, mild impairment [Child-Pugh score of 5 or 6], and moderate impairment [Child-Pugh score of 7-9]) and received a single oral dose of canagliflozin 300 mg. Participants in the renal study (8 in each group) were categorized based on their creatinine clearance (CLCR) (normal renal function [CLCR ≥80 mL/min]; mild [CLCR 50 to canagliflozin 200 mg; the exception was those with ESRD, who received 1 dose postdialysis and 1 dose predialysis (10 days later). Canagliflozin's pharmacokinetics and pharmacodynamics (urinary glucose excretion [UGE] and renal threshold for glucose excretion [RTG]) were assessed at predetermined time points. Mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinite (AUC)0-∞ values differed by Canagliflozin's pharmacokinetics were not affected by mild or moderate hepatic impairment. Systemic exposure to canagliflozin increased in the renal impairment groups relative to participants with normal renal function. Pharmacodynamic response to canagliflozin, measured by using UGE and RTG, declined with increasing severity of renal impairment. A single oral dose of canagliflozin was well tolerated by participants in both studies. ClinicalTrials.gov identifiers: NCT01186588 and NCT01759576. Copyright © 2015 Elsevier HS Journals, Inc. All rights

  13. Genistein affects parathyroid gland and NaPi 2a cotransporter in an animal model of the andropause.

    Science.gov (United States)

    Pantelic, J; Ajdzanovic, V; Medigovic, I; Mojic, M; Trifunovic, S; Milosevic, V; Filipovic, B

    2013-06-01

    This study aimed to examine the effects of genistein on the structural and functional changes in parathyroid glands (PTG) and sodium phosphate cotransporter 2a (NaPi 2a) in orchidectomized rats. Sixteen-month-old Wistar rats were divided into sham-operated (SO), orchidectomized (Orx) and genistein-treated orchidectomized (Orx+G) groups. Genistein (30 mg/kg/day) was administered subcutaneously for 3 weeks, while the controls received vehicle alone. PTG was analyzed histomorphometrically, while the expressions of NaPi 2a mRNA/protein levels from kidneys were determined by real time PCR and Western blots. Serum and urine parameters were determined biochemically. The PTG volume in Orx rats was increased by 30% (p<0.05), compared to the SO group. Orx+G treatment increased the PTG volume by 35% and 75% (p<0.05) respectively, comparing to Orx and SO animals. Orchidectomy led to increment of serum PTH by 27% (p<0.05) compared to the SO group, Orx+G decreased it by 18% (p<0.05) comparing to Orx animals. NaPi 2a expression in Orx animals was reduced in regards to its abundance in SO animals, although it was increased in Orx+G group compared to the Orx. Phosphorus urine content of Orx animals was raised by 12% (p<0.05) compared to that for the SO group, while Orx+G induced a 17% reduction (p<0.05) in regards to Orx animals. Our study shows that Orx increases PTG volume and serum PTH level, while protein expression of NaPi 2a is reduced. Application of genistein attenuates the orchidectomy-induced changes in serum PTH level, stimulates the expression of NaPi 2a and reduces urinary Pi excretion, implying potential beneficial effects on andropausal symptoms.

  14. Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure.

    Science.gov (United States)

    Fava, C; Montagnana, M; Rosberg, L; Burri, P; Almgren, P; Jönsson, A; Wanby, P; Lippi, G; Minuz, P; Hulthèn, L U; Aurell, M; Melander, O

    2008-02-01

    Gitelmańs syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1,000,000, in Sweden, suggesting that approximately 1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 +/- 16.4 versus 123.2 +/- 19.4 mmHg; diastolic 62.5 +/- 10.5 versus 73.1 +/- 9.4 mmHg; P pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case-control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies.

  15. Inhibition of Sodium-GlucoseCotransporter 2 with Dapagliflozin in Han: SPRD Rats with Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Daniel Rodriguez

    2015-12-01

    Full Text Available Background/Aims: Dapagliflozin (DAPA is a selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2 which induces glucosuria and osmotic diuresis. The therapeutic effect of DAPA in progressing stages of polycystic kidney disease (PKD has not been studied. Methods: We examined the effect of DAPA in the Han: SPRD rat model of PKD. DAPA (10 mg/kg/day or vehicle (VEH was administered orally via gavage to 5 week old male Han: SPRD (Cy/+ or control (+/+ rats (n = 8-9 per group for 5 weeks. Blood and urine were collected at baseline and after 2.5 and 5 weeks of treatment to assess renal function and albuminuria. At the end of the treatment, rats were sacrificed and kidneys were excised for histological analysis. Results: After 5 weeks of treatment, DAPA-treated Cy/+ and +/+ rats exhibited significantly higher glucosuria, water intake and urine output than VEH-treated rats. DAPA-treated Cy/+ rats also exhibited significantly higher clearances for creatinine and BUN and less albuminuria than VEH-treated Cy/+ rats. DAPA treatment for 5 weeks resulted in a significant increase of the kidney weight in Cy/+ rats but no change in cyst growth. The degree of tubular epithelial cell proliferation, macrophage infiltration and interstitial fibrosis was also similar in DAPA-and VEH-treated Cy/+ rats. Conclusion: The induction of glucosuria with the SGLT2-specific inhibitor DAPA was associated with improved renal function and decreased albuminuria, but had no effect on cyst growth in Cy/+ rats. Overall the beneficial effects of DAPA in this PKD model were weaker than the previously described effects of the combined SGLT1/2 inhibitor phlorizin.

  16. Use of sodium-glucose cotransporter 2 inhibitors in older patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kambara, Takahiro; Shibata, Rei; Osanai, Hiroyuki; Nakashima, Yoshihito; Asano, Hiroshi; Sakai, Kazuyoshi; Murohara, Toyoaki; Ajioka, Masayoshi

    2017-09-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. The mean age of the patients was 73.7 ± 10.0 years. During the follow-up period (mean 289.3 days), there was no event associated with oral administration of SGLT2 inhibitors. These drugs significantly lowered fasting blood glucose and glycosylated hemoglobin levels at 6 months, and did not affect the creatinine level, blood urea nitrogen/creatinine ratio or estimated glomerular filtration rate during treatment. Although the treatment significantly increased hemoglobin and hematocrit levels, it did not affect the ultrasonographically determined diameter of the inferior vena cava, and no signs of intravascular collapse were observed. Changes in brain natriuretic peptide levels during the follow-up period were assessed in 78 patients with a brain natriuretic peptide level exceeding the normal upper limit before treatment with SGLT2 inhibitors. The brain natriuretic peptide levels significantly decreased after 6 months of treatment. In older Japanese patients with diabetes, treatment with SGLT2 inhibitors for 6 months exerted a favorable hypoglycemic effect, while no sign of dehydration was observed. Geriatr Gerontol Int 2017; ••: ••-••. © 2017 Japan Geriatrics Society.

  17. Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by targeting a NaCl cotransporter in bone

    Science.gov (United States)

    Dvorak, Melita M; De Joussineau, Cyrille; Carter, D Howard; Pisitkun, Trairak; Knepper, Mark A; Gamba, Gerardo; Kemp, Paul J; Riccardi, Daniela

    2008-01-01

    Thiazide diuretics are used, worldwide, as the first-choice drug for patients with uncomplicated hypertension. In addition to their anti-hypertensive actions, they increase bone mineral density and reduce the prevalence of fractures, indicating that thiazides may have a role in the management of postmenopausal osteoporosis. Traditionally, the bone-protective effects of thiazides have been attributed to an increase in renal calcium reabsorption, secondary to the inhibition of the sodium chloride cotransporter, NCC, expressed in the kidney distal tubule. Whether thiazides exert a direct osteoanabolic effect independently of their renal action is controversial. Here we demonstrate that freshly frozen sections of human and rat bone express NCC, principally in bone-forming cells, the osteoblasts. In primary and established culture models of osteoblasts, fetal rat calvarial (FRC) and human MG63 cells, NCC protein is virtually absent in proliferating cells while its expression is dramatically increased during differentiation. Thiazides directly stimulate the production of osteoblast markers, runt-related transcription factor 2 (runx2) and osteopontin, in the absence of a proliferative effect. Using overexpression/knockdown studies in FRC cells, we show that thiazides, but not loop diuretics, increase mineralized nodule formation acting on NCC. Overall, our study demonstrates that thiazides stimulate osteoblast differentiation and bone mineral formation independently of their renal actions. In addition to their use as part of a therapeutic treatment plan for elderly, hypertensive individuals, our discovery opens up the possibility that bone-specific drug targeting by thiazides may be developed for the prevention and treatment of osteoporosis in the patient population as a whole. PMID:17656470

  18. 钠-葡萄糖协同转运蛋白与糖尿病%Sodium-glucose cotransporters and diabetes

    Institute of Scientific and Technical Information of China (English)

    朱蕾; 杨怡

    2011-01-01

    Sodium-glucose cotransporters (SGLTs) are carrier proteins which can help glucose to enter eukaryotic cells.Among them,the SGLT1 and SGLT2 are the most important ones and play major roles in dietary glucose absorption and renal glucose reabsorption respectively.In the state of diabetes,increased expression of SGLT1 in the intestine will enhance the glucose absorption and therefore accelerate hyperglycemia.Through decreasing salivary secretion,increased expression of SGLT1 in salivary glands will promote the development of diabetic oral complications.Meanwhile the expression of SGLT1 and SGLT2 in kidney are also increased which will enhance the glucose reabsorption and therefore accelerate hyperglycemia and deteriorate dial.tic nephropathy.At present,selective inhibitor of SGLT2 is becoming a new drug for diabetes.%钠-葡萄糖协同转运蛋白(SGLTs)在葡萄糖的跨细胞转运中发挥重要作用,其中SGLT1负责膳食葡萄糖的吸收,SGLT2负责肾脏中葡萄糖的重吸收.在糖尿病状态下,肠道SGLT1表达的增加将促进葡萄糖的吸收,从而加重了高血糖,而涎腺导管SGLT1表达的增加则使唾液分泌减少,促进了口腔并发症的发生;肾脏SGLT2和SGLT1表达的增加使葡萄糖的重吸收增加,加重了高血糖,并促进了糖尿病肾病的进展.目前,选择性SLGT2抑制剂已经成为新型的抗糖尿病药物.

  19. Prenatal hypoxia-ischemia induces abnormalities in CA3 microstructure, potassium chloride cotransporter 2 expression and inhibitory tone

    Directory of Open Access Journals (Sweden)

    Lauren L Jantzie

    2015-09-01

    Full Text Available Infants who suffer perinatal brain injury, including those with encephalopathy of prematurity, are prone to chronic neurological deficits including epilepsy, cognitive impairment, and behavioral problems such as anxiety, inattention and poor social interaction. These deficits, especially in combination, pose the greatest hindrance to these children becoming independent adults. Cerebral function depends on adequate development of essential inhibitory neural circuits and the appropriate amount of excitation and inhibition at specific stages of maturation. Early neuronal synaptic responses to γ-amino butyric acid (GABA are initially excitatory. During the early postnatal period, GABAAR responses switch to inhibitory with the upregulation of potassium-chloride co-transporter KCC2. With extrusion of chloride by KCC2, the Cl- reversal potential shifts and GABA and glycine responses become inhibitory. We hypothesized that prenatal hypoxic-ischemic brain injury chronically impairs the developmental upregulation of KCC2 that is essential for cerebral circuit formation. Following late gestation hypoxia-ischemia, diffusion tensor imaging in juvenile rats shows poor microstructural integrity in the hippocampal CA3 subfield, with reduced fractional anisotropy and elevated radial diffusivity. The loss of microstructure correlates with early reduced KCC2 expression on NeuN-positive pyramidal neurons, and decreased monomeric and oligomeric KCC2 protein expression in the CA3 subfield. Together with decreased IPSCs during a critical window of development, we document for the first time that prenatal transient systemic hypoxia-ischemia in rats impairs hippocampal CA3 inhibitory tone. Failure of timely development of inhibitory tone likely contributes to a lower seizure threshold and impaired cognitive function in children who suffer perinatal brain injury.

  20. Double knockout of carbonic anhydrase II (CAII) and Na(+)-Cl(-) cotransporter (NCC) causes salt wasting and volume depletion.

    Science.gov (United States)

    Xu, Jie; Barone, Sharon; Brooks, Mary-Beth; Soleimani, Manoocher

    2013-01-01

    The thiazide-sensitive Na(+)-Cl(-) cotransporter NCC and the Cl(-)/HCO3(-)exchanger pendrin are expressed on apical membranes of distal cortical nephron segments and mediate salt absorption, with pendrin working in tandem with the epithelial Na(+) channel (ENaC) and the Na(+)-dependent chloride/bicarbonate exchanger (NDCBE), whereas NCC is working by itself. A recent study showed that NCC and pendrin compensate for loss of each other under basal conditions, therefore masking the role that each plays in salt reabsorption. Carbonic anhydrase II (CAII, CA2 or CAR2) plays an important role in acid-base transport and salt reabsorption in the proximal convoluted tubule and acid-base transport in the collecting duct. Animals with CAII deletion show remodeling of intercalated cells along with the downregulation of pendrin. NCC KO mice on the other hand show significant upregulation of pendrin and ENaC. Neither model shows any significant salt wasting under baseline conditions. We hypothesized that the up-regulation of pendrin is essential for the prevention of salt wasting in NCC KO mice. To test this hypothesis, we generated NCC/CAII double KO (dKO) mice by crossing mice with single deletion of NCC and CAII. The NCC/CAII dKO mice displayed significant downregulation of pendrin, along with polyuria and salt wasting. As a result, the dKO mice developed volume depletion, which was associated with the inability to concentrate urine. We conclude that the upregulation of pendrin is essential for the prevention of salt and water wasting in NCC deficient animals and its downregulation or inactivation will result in salt wasting, impaired water conservation and volume depletion in the setting of NCC inactivation or inhibition. © 2014 S. Karger AG, Basel.

  1. Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles.

    Science.gov (United States)

    Lee, Donna H; Riquier, Anne D M; Yang, Li E; Leong, Patrick K K; Maunsbach, Arvid B; McDonough, Alicia A

    2009-04-01

    When blood pressure (BP) is elevated above baseline, a pressure natriuresis-diuresis response ensues, critical to volume and BP homeostasis. Distal convoluted tubule Na(+)-Cl(-) cotransporter (NCC) is regulated by trafficking between the apical plasma membrane (APM) and subapical cytoplasmic vesicles (SCV). We aimed to determine whether NCC trafficking contributes to pressure diuresis by decreasing APM NCC or compensates for increased volume flow to the DCT by increasing APM NCC. BP was raised 50 mmHg (high BP) in rats by arterial constriction for 5 or 20-30 min, provoking a 10-fold diuresis at both times. Kidneys were excised, and NCC subcellular distribution was analyzed by 1) sorbitol density gradient fractionation and immunoblotting and 2) immunoelectron microscopy (immuno-EM). NCC distribution did not change after 5-min high BP. After 20-30 min of high BP, 20% of NCC redistributed from low-density, APM-enriched fractions to higher density, endosome-enriched fractions, and, by quantitative immuno-EM, pool size of APM NCC decreased 14% and SCV pool size increased. Because of the time lag of the response, we tested the hypothesis that internalization of NCC was secondary to the decrease in ANG II that accompanies high BP. Clamping ANG II at a nonpressor level by coinfusion of captopril (12 microg/min) and ANG II (20 ng.kg(-1).min(-1)) during 30-min high BP reduced diuresis to eightfold and prevented redistribution of NCC from APM- to SCV-enriched fractions. We conclude that DCT NCC may participate in pressure natriuresis-diuresis by retraction out of apical plasma membranes and that the retraction is, at least in part, driven by the fall in ANG II that accompanies acute hypertension.

  2. Determinants of substrate and cation transport in the human Na+/dicarboxylate cotransporter NaDC3.

    Science.gov (United States)

    Schlessinger, Avner; Sun, Nina N; Colas, Claire; Pajor, Ana M

    2014-06-13

    Metabolic intermediates, such as succinate and citrate, regulate important processes ranging from energy metabolism to fatty acid synthesis. Cytosolic concentrations of these metabolites are controlled, in part, by members of the SLC13 gene family. The molecular mechanism underlying Na(+)-coupled di- and tricarboxylate transport by this family is understood poorly. The human Na(+)/dicarboxylate cotransporter NaDC3 (SLC13A3) is found in various tissues, including the kidney, liver, and brain. In addition to citric acid cycle intermediates such as α-ketoglutarate and succinate, NaDC3 transports other compounds into cells, including N-acetyl aspartate, mercaptosuccinate, and glutathione, in keeping with its dual roles in cell nutrition and detoxification. In this study, we construct a homology structural model of NaDC3 on the basis of the structure of the Vibrio cholerae homolog vcINDY. Our computations are followed by experimental testing of the predicted NaDC3 structure and mode of interaction with various substrates. The results of this study show that the substrate and cation binding domains of NaDC3 are composed of residues in the opposing hairpin loops and unwound portions of adjacent helices. Furthermore, these results provide a possible explanation for the differential substrate specificity among dicarboxylate transporters that underpin their diverse biological roles in metabolism and detoxification. The structural model of NaDC3 provides a framework for understanding substrate selectivity and the Na(+)-coupled anion transport mechanism by the human SLC13 family and other key solute carrier transporters.

  3. pp and {pi}{pi} intensity interferometry in collisions of Ar+KCl at 1.76A GeV

    Energy Technology Data Exchange (ETDEWEB)

    Agakishiev, G.; Destefanis, M.; Gilardi, C.; Kirschner, D.; Kuehn, W.; Lange, J.S.; Metag, V.; Mishra, D.; Pechenova, O.; Perez Cavalcanti, T.; Spruck, B. [Justus Liebig Universitaet Giessen, II.Physikalisches Institut, Giessen (Germany); Balanda, A.; Dybczak, A.; Michalska, B.; Otwinowski, J.; Przygoda, W.; Salabura, P.; Trebacz, R.; Wisniowski, M.; Wojcik, T. [Jagiellonian University of Cracow, Smoluchowski Institute of Physics, Krakow (Poland); Bannier, B.; Dohrmann, F.; Kanaki, K.; Kotte, R.; Naumann, L.; Wendisch, C.; Wuestenfeld, J.; Zhou, P. [Helmholtz-Zentrum Dresden-Rossendorf, Institut fuer Strahlenphysik, Dresden (Germany); Bassini, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Milano, Milano (Italy); Belver, D.; Cabanelas, P.; Castro, E.; Garzon, J.A. [Universidad de Santiago de Compostela, Departamento de Fisica de Particulas, Santiago de Compostela (Spain); Belyaev, A.V.; Chernenko, S.; Fateev, O.V.; Zanevsky, Y.V. [Joint Institute of Nuclear Research, Dubna (Russian Federation); Blanco, A.; Lopes, L.; Mangiarotti, A. [LIP-Laboratorio de Instrumentacao e Fisica Experimental de Particulas, Coimbra (Portugal); Boehmer, M.; Christ, T.; Eberl, T.; Epple, E.; Friese, J.; Gernhaeuser, R.; Huck, P.; Jurkovic, M.; Kruecken, R.; Maier, L.; Sailer, B.; Siebenson, J.; Weber, M. [Technische Universitaet Muenchen, Physik Department E12, Muenchen (Germany); Boyard, J.L.; Gumberidze, M.; Hennino, T.; Liu, T.; Moriniere, E.; Ramstein, B.; Roy-Stephan, M. [CNRS/IN2P3 - Universite Paris Sud, Institut de Physique Nucleaire (UMR 8608), Orsay Cedex (France); Diaz, J.; Gil, A. [Universidad de Valencia-CSIC, Instituto de Fisica Corpuscular, Valencia (Spain); Fabbietti, L. [Technische Universitaet Muenchen, Physik Department E12, Muenchen (Germany); Technische Universitaet Muenchen, Excellence Cluster Universe, Garching (Germany); Finocchiaro, P. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Catania (Italy)] [and others

    2011-05-15

    Results on pp, {pi}{sup +}{pi}{sup +}, and {pi}{sup -}{pi}{sup -} intensity interferometry are reported for collisions of Ar+KCl at 1.76A GeV beam energy, studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18/GSI. The experimental correlation functions as a function of the relative momentum are compared to model calculations allowing the determination of the space-time extent of the corresponding emission sources. The {pi}{pi} source radii are found significantly larger than the pp emission radius. The present radii do well complement the beam-energy dependences of Gaussian source radii of the collision system of size A + A {approx_equal} 40 + 40. The pp source radius at fixed beam energy is found to increase linearly with the cube root of the number of participants. From this trend, a lower limit of the pp correlation radius is deduced. (orig.)

  4. NaCl-KCl-Na_2WO_4共融体系的方波伏安法分析

    Institute of Scientific and Technical Information of China (English)

    廖春发; 房孟钊; 王旭; 汤浩; 罗林生

    2015-01-01

    采用三电极体系,应用方波伏安法分析NaCl-KCl-Na2WO4共融体系的电化学特性,重点研究了钨(Ⅵ)离子的电化学行为,结果表明:W(Ⅵ)→W(Ⅳ)还原过程的特征峰与W(Ⅳ)→W的特征峰发生相互重叠,W(Ⅵ)离子的还原过程分2步,即:W(Ⅵ)→W(Ⅳ)→W,其中第1步W(Ⅵ)→W(Ⅳ)过程可逆,第2步W(Ⅳ)→W过程不可逆.

  5. pp and ππ intensity interferometry in collisions of Ar+KCl at 1.76A GeV

    Science.gov (United States)

    Agakishiev, G.; Balanda, A.; Bannier, B.; Bassini, R.; Belver, D.; Belyaev, A. V.; Blanco, A.; Böhmer, M.; Boyard, J. L.; Cabanelas, P.; Castro, E.; Chernenko, S.; Christ, T.; Destefanis, M.; Dıaz, J.; Dohrmann, F.; Dybczak, A.; Eberl, T.; Epple, E.; Fabbietti, L.; Fateev, O. V.; Finocchiaro, P.; Fonte, P.; Friese, J.; Fröhlich, I.; Galatyuk, T.; Garzón, J. A.; Gernhäuser, R.; Gil, A.; Gilardi, C.; Golubeva, M.; González-Dıaz, D.; Guber, F.; Gumberidze, M.; Heilmann, M.; Heinz, T.; Hennino, T.; Holzmann, R.; Huck, P.; Iori, I.; Ivashkin, A.; Jurkovic, M.; Kämpfer, B.; Kanaki, K.; Karavicheva, T.; Kirschner, D.; Koenig, I.; Koenig, W.; Kolb, B. W.; Kotte, R.; Krizek, F.; Krücken, R.; Kühn, W.; Kugler, A.; Kurepin, A.; Lang, S.; Lange, J. S.; Lapidus, K.; Liu, T.; Lopes, L.; Lorenz, M.; Maier, L.; Mangiarotti, A.; Markert, J.; Metag, V.; Michalska, B.; Michel, J.; Mishra, D.; Morinière, E.; Mousa, J.; Müntz, C.; Naumann, L.; Otwinowski, J.; Pachmayer, Y. C.; Palka, M.; Parpottas, Y.; Pechenov, V.; Pechenova, O.; Pérez Cavalcanti, T.; Pietraszko, J.; Przygoda, W.; Ramstein, B.; Reshetin, A.; Roy-Stephan, M.; Rustamov, A.; Sadovsky, A.; Sailer, B.; Salabura, P.; Schmah, A.; Schwab, E.; Siebenson, J.; Sobolev, Yu. G.; Spataro, S.; Spruck, B.; Ströbele, H.; Stroth, J.; Sturm, C.; Tarantola, A.; Teilab, K.; Tlusty, P.; Traxler, M.; Trebacz, R.; Tsertos, H.; Wagner, V.; Weber, M.; Wendisch, C.; Wisniowski, M.; Wojcik, T.; Wüstenfeld, J.; Yurevich, S.; Zanevsky, Y. V.; Zhou, P.; Zumbruch, P.

    2011-05-01

    Results on pp, π+π+, and π-π- intensity interferometry are reported for collisions of Ar+KCl at 1.76 A GeV beam energy, studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18/GSI. The experimental correlation functions as a function of the relative momentum are compared to model calculations allowing the determination of the space-time extent of the corresponding emission sources. The ππ source radii are found significantly larger than the pp emission radius. The present radii do well complement the beam-energy dependences of Gaussian source radii of the collision system of size A + A ≃ 40 + 40 . The pp source radius at fixed beam energy is found to increase linearly with the cube root of the number of participants. From this trend, a lower limit of the pp correlation radius is deduced.

  6. Consequence of condensed-phase formation in transient burning of TiH/sub x//KClO/sub 4/ in a closed system

    Energy Technology Data Exchange (ETDEWEB)

    Razani, A.; Shahinpoor, M.; Hingorani-Norenberg, S.L.

    1989-01-01

    Transient burning of TiH/sub X//KClO/sub 4/ in a closed system is formulated including the effect of condensed species. Thermodynamic properties are evaluated using both BLAKE and TIGER computer codes. Three different equations of state for gaseous species are used and their effect on the burning rate is evaluated. For more accurate transient burning analysis, a pressure dependent covolume for gaseous species is generated. The effect of pressure dependent covolume as well as the condensed species on transient burning is evaluated. Both parameters are found to be important when the burning rate at high loading densities in a closed system is considered. At high loading densities, condensed species become important not only because of the their effect on thermodynamic properties but also due to the volume occupied by these species. 11 refs., 2 figs., 2 tabs.

  7. Experimental Study of Codeposition Electrochemistry Using Mixtures of ScCl3 and YCl3 in LiCl-KCl Eutectic Salt at 500°C