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Sample records for 00-0127 product citrate

  1. Total synthesis of alkyl citrate natural products.

    PubMed

    Rizzacasa, Mark A; Sturgess, Dayna

    2014-03-07

    This review highlights the synthesis of members of the alkyl citrate family of natural products. The focus is on the stereoselective construction of the alkyl citrate moiety common to these compounds.

  2. Effects of pH and Sugar on Acetoin Production from Citrate by Leuconostoc lactis.

    PubMed

    Cogan, T M; O'dowd, M; Mellerick, D

    1981-01-01

    The relationship between acetoin production and citrate utilization in Leuconostoc lactis NCW1 was studied. In a complex medium the organism utilized citrate at neutral pH (initial pH, 6.3) and at acid pH (initial pH, 4.5) but produced nine times more acetoin at the latter pH. In resting cells the utilization of citrate was optimum at pH 5.3. Production of acetoin as a function of citrate utilization increased as the pH decreased, and at pH 4.3 all of the citrate utilized was recovered as acetoin. Glucose (10 mM) and lactose (10 mM) markedly stimulated citrate utilization but totally inhibited acetoin production in glucose- and lactose-grown cells. Addition of glucose to cells actively metabolizing citrate caused an immediate increase in citrate uptake and a reduction in the level of acetoin. The apparent K(m) values of lactic dehydrogenase for pyruvate were 1.05, 0.25, and 0.15 mM at pH 7.5, 6.5, and 5.0, respectively. Several heterofermentation intermediates inhibited alpha-acetolactate synthetase and decarboxylase activities. The implications of these results in regulating acetoin formatin are discussed.

  3. Comparative genomics and transcriptome analysis of Aspergillus niger and metabolic engineering for citrate production

    PubMed Central

    Yin, Xian; Shin, Hyun-dong; Li, Jianghua; Du, Guocheng; Liu, Long; Chen, Jian

    2017-01-01

    Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains—namely, A. niger H915-1 (citrate titer: 157 g L−1), A1 (117 g L−1), and L2 (76 g L−1)—to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis. Furthermore, transcriptome analysis of A. niger H915-1 revealed that the transcription levels of 479 genes changed between the cell growth stage (6 h) and the citrate synthesis stage (12 h, 24 h, 36 h, and 48 h). In the glycolysis pathway, triosephosphate isomerase was up-regulated, whereas pyruvate kinase was down-regulated. Two cytosol ATP-citrate lyases, which take part in the cycle of citrate synthesis, were up-regulated, and may coordinate with the alternative oxidases in the alternative respiratory pathway for energy balance. Finally, deletion of the oxaloacetate acetylhydrolase gene in H915-1 eliminated oxalate formation but neither influence on pH decrease nor difference in citrate production were observed. PMID:28106122

  4. Citrate catabolism and production of acetate and succinate by Lactobacillus helveticus ATCC 15807.

    PubMed

    Torino, M I; Taranto, M P; Font de Valdez, G

    2005-11-01

    The citrate metabolism of Lactobacillus helveticus ATCC 15807 was studied under controlled-pH fermentations at pH 4.5 and pH 6.2. The micro-organism was able to co-metabolize citrate and lactose at both pH from the beginning of growth, which enhanced the rate of lactose consumption and lactic acid production, compared with cultures without citrate. The effect of citrate on cell growth was dependent on the balance between the ratio of dissociated to non-dissociated forms of the acetic acid produced and the extra ATP gained by the cells, both facts related to the citrate metabolism. The citrate catabolism determined a change in the fermentation pattern of L. helveticus ATCC 15807 from homolactic to a mixed-acid profile, regardless of the external pH. Within this new fermentation pattern, acetate was the major product formed (13-20 mM), followed by succinate (2.4-3.7 mM), while acetoine, dyacetile or butanediol were not detected. The mixed-acid profile displayed by L. helveticus ATCC 15807 was linked to NADH(2) oxidase activity rather than the acetate kinase enzyme.

  5. Formation of amide- and imide-linked degradation products between the peptide drug oxytocin and citrate in citrate-buffered formulations.

    PubMed

    Poole, Robert A; Kasper, Piotr Tomasz; Jiskoot, Wim

    2011-07-01

    Citric acid is widely used to buffer pharmaceutical formulations including protein pharmaceuticals. In accelerated stability studies of the small cyclic peptide oxytocin, we have noted that additional degradation products form when oxytocin is formulated in citrate that do not form in other common buffers such as acetate and phosphate. Using high-pressure liquid chromatography combined with high-resolution and tandem mass spectrometry, we identified these degradation products as amide- and imide-linked adducts of oxytocin and citrate. The site of reaction was shown to be the N-terminal amine of cysteine. The adducts have been found to form for oxytocin formulated in citrate buffer over the pH range of 3-6; the extent of formation is greatest at a pH of 4-4.5. We have additionally identified these same adducts in samples of oxytocin formulated in citrate buffer that had been stored in the dark for 3 months at room temperature. Altogether, these results demonstrate that reaction between citrate and oxytocin leads to the formation of covalent amide- and imide-linked adducts. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  6. Diacetyl and acetoin production from the co-metabolism of citrate and xylose by Leuconostoc mesenteroides subsp. mesenteroides.

    PubMed

    Schmitt, P; Vasseur, C; Phalip, V; Huang, D Q; Diviès, C; Prévost, H

    1997-06-01

    The co-metabolism of citrate plus xylose by Leuconostoc mesenteroides subsp. mesenteroides results in a growth stimulation, an increase in D-lactate and acetate production and repression of ethanol production. This correlated well with the levels of key enzymes involved. A partial repression of alcohol dehydrogenase and a marked stimulation of acetate kinase were observed. High citrate bioconversion yields in diacetyl plus acetoin were obtained at pH 5.2 in batch (11.5%) or in chemostat (up to 17.4%) culture. In contrast, no diacetyl or acetoin was detected in citrate plus glucose fermentation.

  7. Properties of Aspergillus niger citrate synthase and effects of citA overexpression on citric acid production.

    PubMed

    Ruijter, G J; Panneman, H; Xu, D; Visser, J

    2000-03-01

    Using a combination of dye adsorption and affinity elution we purified Aspergillus niger citrate synthase to homogeneity using a single column and characterised the enzyme. An A. niger citrate synthase cDNA was isolated by immunological screening and used to clone the corresponding citA gene. The deduced amino acid sequence showed high similarity to other fungal citrate synthases. After processing upon mitochondrial import, the calculated M(r) of A. niger citrate synthase is 48501, which agrees well with the estimated molecular mass of the purified protein (48 kDa). In addition to an N-terminal mitochondrial import signal, a peroxisomal target sequence (AKL) was found at the C-terminus of the protein. Whether both signals are functional in vivo is not clear. Strains overexpressing citA were made by transformation and cultured under citric acid-producing conditions. Up to 11-fold overproduction of citrate synthase did not increase the rate of citric acid production by the fungus, suggesting that citrate synthase contributes little to flux control in the pathway involved in citric acid biosynthesis by a non-commercial strain.

  8. Controlling Citrate Synthase Expression by CRISPR/Cas9 Genome Editing for n-Butanol Production in Escherichia coli.

    PubMed

    Heo, Min-Ji; Jung, Hwi-Min; Um, Jaeyong; Lee, Sang-Woo; Oh, Min-Kyu

    2017-02-17

    Genome editing using CRISPR/Cas9 was successfully demonstrated in Esherichia coli to effectively produce n-butanol in a defined medium under microaerobic condition. The butanol synthetic pathway genes including those encoding oxygen-tolerant alcohol dehydrogenase were overexpressed in metabolically engineered E. coli, resulting in 0.82 g/L butanol production. To increase butanol production, carbon flux from acetyl-CoA to citric acid cycle should be redirected to acetoacetyl-CoA. For this purpose, the 5'-untranslated region sequence of gltA encoding citrate synthase was designed using an expression prediction program, UTR designer, and modified using the CRISPR/Cas9 genome editing method to reduce its expression level. E. coli strains with decreased citrate synthase expression produced more butanol and the citrate synthase activity was correlated with butanol production. These results demonstrate that redistributing carbon flux using genome editing is an efficient engineering tool for metabolite overproduction.

  9. ATP citrate lyase mediated cytosolic acetyl-CoA biosynthesis increases mevalonate production in Saccharomyces cerevisiae.

    PubMed

    Rodriguez, Sarah; Denby, Charles M; Van Vu, T; Baidoo, Edward E K; Wang, George; Keasling, Jay D

    2016-03-03

    With increasing concern about the environmental impact of a petroleum based economy, focus has shifted towards greener production strategies including metabolic engineering of microbes for the conversion of plant-based feedstocks to second generation biofuels and industrial chemicals. Saccharomyces cerevisiae is an attractive host for this purpose as it has been extensively engineered for production of various fuels and chemicals. Many of the target molecules are derived from the central metabolite and molecular building block, acetyl-CoA. To date, it has been difficult to engineer S. cerevisiae to continuously convert sugars present in biomass-based feedstocks to acetyl-CoA derived products due to intrinsic physiological constraints-in respiring cells, the precursor pyruvate is directed away from the endogenous cytosolic acetyl-CoA biosynthesis pathway towards the mitochondria, and in fermenting cells pyruvate is directed towards the byproduct ethanol. In this study we incorporated an alternative mode of acetyl-CoA biosynthesis mediated by ATP citrate lyase (ACL) that may obviate such constraints. We characterized the activity of several heterologously expressed ACLs in crude cell lysates, and found that ACL from Aspergillus nidulans demonstrated the highest activity. We employed a push/pull strategy to shunt citrate towards ACL by deletion of the mitochondrial NAD(+)-dependent isocitrate dehydrogenase (IDH1) and engineering higher flux through the upper mevalonate pathway. We demonstrated that combining the two modifications increases accumulation of mevalonate pathway intermediates, and that both modifications are required to substantially increase production. Finally, we incorporated a block strategy by replacing the native ERG12 (mevalonate kinase) promoter with the copper-repressible CTR3 promoter to maximize accumulation of the commercially important molecule mevalonate. By combining the push/pull/block strategies, we significantly improved mevalonate

  10. ATP citrate lyase mediated cytosolic acetyl-CoA biosynthesis increases mevalonate production in Saccharomyces cerevisiae

    SciTech Connect

    Rodriguez, Sarah; Denby, Charles M.; Van Vu, T.; Baidoo, Edward E. K.; Wang, George; Keasling, Jay D.

    2016-03-03

    With increasing concern about the environmental impact of a petroleum based economy, focus has shifted towards greener production strategies including metabolic engineering of microbes for the conversion of plant-based feedstocks to second generation biofuels and industrial chemicals. Saccharomyces cerevisiae is an attractive host for this purpose as it has been extensively engineered for production of various fuels and chemicals. Many of the target molecules are derived from the central metabolite and molecular building block, acetyl-CoA. To date, it has been difficult to engineer S. cerevisiae to continuously convert sugars present in biomass-based feedstocks to acetyl-CoA derived products due to intrinsic physiological constraints—in respiring cells, the precursor pyruvate is directed away from the endogenous cytosolic acetyl-CoA biosynthesis pathway towards the mitochondria, and in fermenting cells pyruvate is directed towards the byproduct ethanol. In this study we incorporated an alternative mode of acetyl-CoA biosynthesis mediated by ATP citrate lyase (ACL) that may obviate such constraints. We characterized the activity of several heterologously expressed ACLs in crude cell lysates, and found that ACL from Aspergillus nidulans demonstrated the highest activity. We employed a push/pull strategy to shunt citrate towards ACL by deletion of the mitochondrial NAD+-dependent isocitrate dehydrogenase (IDH1) and engineering higher flux through the upper mevalonate pathway. We demonstrated that combining the two modifications increases accumulation of mevalonate pathway intermediates, and that both modifications are required to substantially increase production. Finally, we incorporated a block strategy by replacing the native ERG12 (mevalonate kinase) promoter with the copper-repressible CTR3 promoter to maximize accumulation of the commercially important molecule mevalonate. In conclusion, by combining the push/pull/block strategies, we significantly improved

  11. Concentration-dependent Sildenafil citrate (Viagra) effects on ROS production, energy status, and human sperm function.

    PubMed

    Sousa, Maria Inês; Amaral, Sandra; Tavares, Renata Santos; Paiva, Carla; Ramalho-Santos, João

    2014-04-01

    Literature regarding the effects of sildenafil citrate on sperm function remains controversial. In the present study, we specifically wanted to determine if mitochondrial dysfunction, namely membrane potential, reactive oxygen species production, and changes in energy content, are involved in in vitro sildenafil-induced alterations of human sperm function. Sperm samples of healthy men were incubated in the presence of 0.03, 0.3, and 3 μM sildenafil citrate in a phosphate buffered saline (PBS)-based medium for 2, 3, 12, and 24 hours. Sperm motility and viability were evaluated and mitochondrial function, i.e., mitochondrial membrane potential and mitochondrial superoxide production were assessed using flow-cytometry. Additionally, adenosine triphosphate (ATP) levels were determined by high performance liquid chromatography (HPLC) analysis. Results show a decrease in sperm motility correlated with the level of mitochondria-generated superoxide, without a visible effect on mitochondrial membrane potential or viability upon exposure to sildenafil. The effect on both motility and superoxide production was higher for the intermediate concentration of sildenafil (0.3 µM) indicating that the in vitro effects of sildenafil on human sperm do not vary linearly with drug concentration. Adenosine triphosphate levels also decreased following sildenafil exposure, but this decrease was only detected after a decrease in motility was already evident. These results suggest that along with the level of ATP and mitochondrial function other factors are involved in the early sildenafil-mediated decline in sperm motility. However, the further decrease in ATP levels and increase in mitochondria-generated reactive oxygen species after 24 hours of exposure might further contribute towards declining sperm motility.

  12. ATP citrate lyase mediated cytosolic acetyl-CoA biosynthesis increases mevalonate production in Saccharomyces cerevisiae

    DOE PAGES

    Rodriguez, Sarah; Denby, Charles M.; Van Vu, T.; ...

    2016-03-03

    With increasing concern about the environmental impact of a petroleum based economy, focus has shifted towards greener production strategies including metabolic engineering of microbes for the conversion of plant-based feedstocks to second generation biofuels and industrial chemicals. Saccharomyces cerevisiae is an attractive host for this purpose as it has been extensively engineered for production of various fuels and chemicals. Many of the target molecules are derived from the central metabolite and molecular building block, acetyl-CoA. To date, it has been difficult to engineer S. cerevisiae to continuously convert sugars present in biomass-based feedstocks to acetyl-CoA derived products due to intrinsicmore » physiological constraints—in respiring cells, the precursor pyruvate is directed away from the endogenous cytosolic acetyl-CoA biosynthesis pathway towards the mitochondria, and in fermenting cells pyruvate is directed towards the byproduct ethanol. In this study we incorporated an alternative mode of acetyl-CoA biosynthesis mediated by ATP citrate lyase (ACL) that may obviate such constraints. We characterized the activity of several heterologously expressed ACLs in crude cell lysates, and found that ACL from Aspergillus nidulans demonstrated the highest activity. We employed a push/pull strategy to shunt citrate towards ACL by deletion of the mitochondrial NAD+-dependent isocitrate dehydrogenase (IDH1) and engineering higher flux through the upper mevalonate pathway. We demonstrated that combining the two modifications increases accumulation of mevalonate pathway intermediates, and that both modifications are required to substantially increase production. Finally, we incorporated a block strategy by replacing the native ERG12 (mevalonate kinase) promoter with the copper-repressible CTR3 promoter to maximize accumulation of the commercially important molecule mevalonate. In conclusion, by combining the push/pull/block strategies, we significantly

  13. Final report on the safety assessment of acetyl triethyl citrate, acetyl tributyl citrate, acetyl trihexyl citrate, and acetyl trioctyl citrate.

    PubMed

    Johnson, Wilbur

    2002-01-01

    Acetyl Triethyl Citrate, Acetyl Tributyl Citrate, Acetyl Trihexyl Citrate, and Acetyl Trioctyl Citrate all function as plasticizers in cosmetics. Additionally, the Trihexyl and Trioctyl forms are described as skin-conditioning agents-emollients, although there are currently no reported uses of Acetyl Trihexyl Citrate or Acetyl Trioctyl Citrate. Acetyl Triethyl Citrate and Acetyl Tributyl Citrate are used in nail products at concentrations up to 7%. Recognizing that there are no reported uses of Acetyl Trihexyl or Trioctyl Citrate, if they were to be used in the future, their concentration of use is expected to be no higher than that reported for Acetyl Triethyl and Tributyl Citrate. These ingredients were sufficiently similar in structure that safety test data on one were considered applicable to all. Approximately 99% of orally administered Acetyl Tributyl Citrate is excreted-intermediate metabolites include acetyl citrate, monobutyl citrate, acetyl monobutyl citrate, dibutyl citrate, and acetyl dibutyl citrate. In acute, short-term, subchronic, and chronic feeding studies, these ingredients were relatively nontoxic. Differences from controls were either not statistically significant or not related to any organ toxicity. Ocular exposures produced moderate reactions that cleared by 48 hours after instillation. Dermal application was not toxic in rabbits. In a guinea pig maximization test, Acetyl Triethyl Citrate was a sensitizer whereas Acetyl Tributyl Citrate was not. Limited clinical testing of Acetyl Triethyl Citrate and Acetyl Tributyl Citrate was negative for both skin irritation and sensitization. These clinical data were considered more relevant than the guinea pig maximization data, suggesting to the Cosmetic Ingredient Review Expert Panel that none of these ingredients would be a sensitizer. Physiologic effects noted with intravenous delivery of Acetyl Triethyl Citrate or Acetyl Tributyl Citrate include dose-related decreases in blood pressure and

  14. Increased cyclic guanosine monophosphate production and endothelial nitric oxide synthase level in mononuclear cells from sildenafil citrate-treated patients with erectile dysfunction.

    PubMed

    García-Cardoso, J; Vela, R; Mahillo, E; Mateos-Cáceres, P J; Modrego, J; Macaya, C; López-Farré, A J

    2010-01-01

    Mononuclear cells express enzymes involved in the NO/cyclic guanosine monophosphate (cGMP) generating system, as well as PDE5. The objective of the study was to determine the effect of sildenafil citrate administration on the level of proteins involved in the NO/cGMP generating system in mononuclear cells from patients with ED. Twenty-one patients with ED (International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) 17.9+/-0.8) were enrolled and 100 mg sildenafil citrate on-demand was administered during 12 weeks. All patients showed cardiovascular risk factors. After sildenafil citrate administration, IIEF-EFD score was improved (26+/-1.2 P<0.05). In the mononuclear cells, the protein level of endothelial NO synthase (eNOS) was higher after sildenafil citrate treatment. It was accompanied by reduction in the circulating plasma levels of both high-sensitive C-reactive protein and soluble intercellular adhesive molecule-1. The protein level of soluble guanylate cyclase and PDE5 did not change in the mononuclear cells after sildenafil citrate treatment. However, in the mononuclear cells exogenous NO induced a higher cGMP production after 12-weeks sildenafil citrate administration. In conclusion, in mononuclear cells from patients with ED sildenafil citrate administration increased the level of eNOS protein and increased cGMP production in response to NO. Moreover, sildenafil citrate administration reduced the plasma circulating levels of two biomarkers associated with inflammation.

  15. Citrate Metabolism by Pediococcus halophilus

    PubMed Central

    Kanbe, Chiyuki; Uchida, Kinji

    1987-01-01

    Several strains of non-citrate-metabolizing Pediococcus halophilus have previously been isolated from soy sauce mash or moromi. The factors controlling the metabolism of citrate in soy pediococci were studied. All the soy pediococcal strains tested which failed to decompose citrate did not possess citrate lyase [citrate (pro-3S)-lyase; EC 4.1.3.6] activity. In P. halophilus, citrate lyase was an inducible enzyme, and the optimum pH for activity was 7.0. The metabolism of citrate in P. halophilus was different from that observed in lactic streptococci. The main products from citrate were acetate and formate, and this bacterium produced no acetoin or diacetyl. Formate production from citrate was greatly reduced in the presence of glucose. P. halophilus 7117 (Cit+) was proved to contain citrate lyase, pyruvate formate-lyase (EC 2.3.1.54) phosphotransacetylase (phosphate acetyltransferase; EC 2.3.1.8), and acetate kinase (EC 2.7.2.1), i.e., all the enzymes necessary to convert citrate to acetate and formate. PMID:16347358

  16. Immunomodulatory effect of diethylcarbamazine citrate plus filarial excretory-secretory product on rat hepatocarcinogenesis.

    PubMed

    Abdel-Latif, Mahmoud; Sakran, Thabet; El-Shahawi, Gamal; El-Fayoumi, Hoda; El-Mallah, Al-Mahy

    2015-02-01

    Diethylcarbamazine citrate (DEC) had a significance in anti-filarial chemotherapy, while excretory-secretory product (ES) is released from adult filarial females. The target of the current study was to examine the immunomodulatory effect of DEC, Setaria equina ES or a combination of them on rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN). In vitro effect of combined DEC and ES or ES alone on lipopolysaccharide (LPS)-stimulated rat peripheral blood mononuclear cells (PBMCs) was tested through IFN-γ assay in culture supernatants. In addition, single or repeated doses of DEC, ES or DEC+ES have been applied in white albino rats to test the effect on HCC. Levels of IFN-γ and anti-ES IgG antibodies in rat serum were assayed using ELISA. Hemolytic complement activity (CH50) was determined in serum while the concentration of nitric oxide (NO) was assayed in liver tissue. The infiltration of NK cells as well as the expression of MHC Iproliferating cell nuclear antigen (PCNA), inducible NO synthase (iNOS), Bcl2 and p53 were determined using immunohistochemistry. There was a dose-dependent increase in IFN-γ after in vitro exposure to DEC+ES. Repeated ES doses increased NO concentration (p<0.05) and expression of iNOS but reduced CH50 (p<0.001), while repeated DEC+ES doses could increase anti-ES IgG (p<0.01), IFN-γ level (p<0.05) and NK cell infiltration. The same treatments could also reduce the expression of MHC I expression, PCNA, Bcl2 and p53. This study has shown immunomodulatory and protective effects of DEC+ES repeated doses on rat HCC.

  17. Enhancement of L-lactic acid production in Lactobacillus casei from Jerusalem artichoke tubers by kinetic optimization and citrate metabolism.

    PubMed

    Ge, Xiang-Yang; Qian, He; Zhang, Wei-Guo

    2010-01-01

    Efficient L-lactic acid production from Jerusalem artichoke tubers by Lactobacillus casei G-02 using simultaneous saccharification and fermentation (SSF) in fed-batch culture is demonstrated. The kinetic analysis in the SSF signified that the inulinase activity was subjected to product inhibition, while the fermentation activity of G-02 was subjected to substrate inhibition. It was also found that the intracellularly NOX activity was enhanced by the citrate metabolism, which increased the carbon flux of Embden-Meyerhof-Parnas (EMP) pathway dramatically, and resulted more ATP production. As a result, when the SSF was carried out at 40 degrees after the initial hydrolysis of 1 h with supplemented sodium citrate of 10g/L, L-lactic acid concentration of 141.5 g/L was obtained in 30 h with a volumetric productivity of 4.7 g/L/h. The conversion efficiency and product yield were 93.6% of the theoretical lactic acid yield and 52.4 g lactic acid/100 g Jerusalem artichoke flour, respectively. Such a high concentration of lactic acid with high productivity from Jerusalem artichoke has not been reported previously, and hence G-02 could be a potential candidate for economical production of L-lactic acid from Jerusalem artichoke at a commercial scale.

  18. The nitroxide Tempo inhibits hydroxyl radical production from the Fenton-like reaction of iron(II)-citrate with hydrogen peroxide.

    PubMed

    Shi, Fengqiang; Zhang, Peifeng; Mao, Yujia; Wang, Can; Zheng, Meiqing; Zhao, Zhongwei

    2017-01-29

    In vivo physiological ligand citrate can bind iron(II) ions to form the iron(II)-citrate complex. Inhibition of hydroxyl radical (OH) production from the Fenton-like reaction of iron(II)-citrate with H2O2 is biologically important, as this reaction may account for one of the mechanisms of the labile iron pool in vivo to induce oxidative stress and pathological conditions. Nitroxides have promising potentials as therapeutic antioxidants. However, there are controversial findings indicating that they not only act as antioxidants but also as pro-oxidants when engaged in Fenton reactions. Although the underlying mechanisms are proposed to be the inhibition or enhancement of the OH production by nitroxides, the proposed elucidations are only based on assessing biological damages and not demonstrated directly by measuring the OH production in the presence of nitroxides. In this study, therefore, we employed EPR and fluorescence spectroscopies to show direct evidence that nitroxide 2,2,6,6-tetramethyl-piperidine-1-oxyl (Tempo) inhibited OH production from the Fenton-like reaction of iron(II)-citrate with H2O2 by up to 90%. We also demonstrated spectrophotometrically, for the first time, that this inhibition was due to oxidation of the iron(II)-citrate by Tempo with a stoichiometry of Tempo:Iron(III)-citrate = 1.1:1.0. A scheme was proposed to illustrate the roles of nitroxides engaged in Fenton/Fenton-like reactions.

  19. 21 CFR 582.1195 - Calcium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Additives § 582.1195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or feeding practice. ...

  20. Lactic acid bacteria involved in cocoa beans fermentation from Ivory Coast: Species diversity and citrate lyase production.

    PubMed

    Ouattara, Hadja D; Ouattara, Honoré G; Droux, Michel; Reverchon, Sylvie; Nasser, William; Niamke, Sébastien L

    2017-09-01

    Microbial fermentation is an indispensable process for high quality chocolate from cocoa bean raw material. lactic acid bacteria (LAB) are among the major microorganisms responsible for cocoa fermentation but their exact role remains to be elucidated. In this study, we analyzed the diversity of LAB in six cocoa producing regions of Ivory Coast. Ribosomal 16S gene sequence analysis showed that Lactobacillus plantarum and Leuconostoc mesenteroides are the dominant LAB species in these six regions. In addition, other species were identified as the minor microbial population, namely Lactobacillus curieae, Enterococcus faecium, Fructobacillus pseudoficulneus, Lactobacillus casei, Weissella paramesenteroides and Weissella cibaria. However, in each region, the LAB microbial population was composed of a restricted number of species (maximum 5 species), which varied between the different regions. LAB implication in the breakdown of citric acid was investigated as a fundamental property for a successful cocoa fermentation process. High citrate lyase producer strains were characterized by rapid citric acid consumption, as revealed by a 4-fold decrease in citric acid concentration in the growth medium within 12h, concomitant with an increase in acetic acid and lactic acid concentration. The production of citrate lyase was strongly dependent on environmental conditions, with optimum production at acidic pH (pH<5), and moderate temperature (30-40°C), which corresponds to conditions prevailing in the early stage of natural cocoa fermentation. This study reveals that one of the major roles of LAB in the cocoa fermentation process involves the breakdown of citric acid during the early stage of cocoa fermentation through the activity of citrate lyase. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. 21 CFR 582.6751 - Sodium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium citrate. 582.6751 Section 582.6751 Food and..., FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 2 § 582.6751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is generally recognized...

  2. 21 CFR 582.6751 - Sodium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sodium citrate. 582.6751 Section 582.6751 Food and..., FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 2 § 582.6751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is generally recognized...

  3. 21 CFR 582.6751 - Sodium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium citrate. 582.6751 Section 582.6751 Food and..., FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 2 § 582.6751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is generally recognized...

  4. 21 CFR 582.6751 - Sodium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium citrate. 582.6751 Section 582.6751 Food and..., FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 2 § 582.6751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is generally recognized...

  5. 21 CFR 582.6751 - Sodium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium citrate. 582.6751 Section 582.6751 Food and..., FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 2 § 582.6751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is generally recognized...

  6. Correlation of ATP citrate lyase and acetyl CoA levels with trichothecene production in Fusarium graminearum.

    PubMed

    Sakamoto, Naoko; Tsuyuki, Rie; Yoshinari, Tomoya; Usuma, Jermnak; Furukawa, Tomohiro; Nagasawa, Hiromichi; Sakuda, Shohei

    2013-11-21

    The correlation of ATP citrate lyase (ACL) and acetyl CoA levels with trichothecene production in Fusarium graminearum was investigated using an inhibitor (precocene II) and an enhancer (cobalt chloride) of trichothecene production by changing carbon sources in liquid medium. When precocene II (30 µM) was added to inhibit trichothecene production in a trichothecene high-production medium containing sucrose, ACL expression was reduced and ACL mRNA level as well as acetyl CoA amount in the fungal cells were reduced to the levels observed in a trichothecene trace-production medium containing glucose or fructose. The ACL mRNA level was greatly increased by addition of cobalt chloride in the trichothecene high-production medium, but not in the trichothecene trace-production medium. Levels were reduced to those level in the trichothecene trace-production medium by addition of precocene II (300 µM) together with cobalt chloride. These results suggest that ACL expression is activated in the presence of sucrose and that acetyl CoA produced by the increased ALC level may be used for trichothecene production in the fungus. These findings also suggest that sucrose is important for the action of cobalt chloride in activating trichothecene production and that precocene II may affect a step down-stream of the target of cobalt chloride.

  7. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  8. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  9. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  10. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  11. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  12. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  13. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  14. 21 CFR 582.6625 - Potassium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium citrate. 582.6625 Section 582.6625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This substance is generally...

  15. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  16. 21 CFR 582.1625 - Potassium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium citrate. 582.1625 Section 582.1625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1625 Potassium citrate. (a) Product. Potassium citrate. (b) Conditions of use. This...

  17. 21 CFR 582.5449 - Manganese citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Manganese citrate. 582.5449 Section 582.5449 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5449 Manganese citrate. (a) Product. Manganese citrate. (b) Conditions of use. This...

  18. 21 CFR 582.5449 - Manganese citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Manganese citrate. 582.5449 Section 582.5449 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5449 Manganese citrate. (a) Product. Manganese citrate. (b) Conditions of use. This...

  19. 21 CFR 582.5449 - Manganese citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Manganese citrate. 582.5449 Section 582.5449 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5449 Manganese citrate. (a) Product. Manganese citrate. (b) Conditions of use. This...

  20. 21 CFR 582.1751 - Sodium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium citrate. 582.1751 Section 582.1751 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is...

  1. 21 CFR 582.1751 - Sodium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium citrate. 582.1751 Section 582.1751 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is...

  2. 21 CFR 582.1751 - Sodium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium citrate. 582.1751 Section 582.1751 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is...

  3. 21 CFR 582.1751 - Sodium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium citrate. 582.1751 Section 582.1751 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1751 Sodium citrate. (a) Product. Sodium citrate. (b) Conditions of use. This substance is...

  4. 21 CFR 582.5195 - Calcium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium citrate. 582.5195 Section 582.5195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance...

  5. 21 CFR 582.5449 - Manganese citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Manganese citrate. 582.5449 Section 582.5449 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5449 Manganese citrate. (a) Product. Manganese citrate. (b) Conditions of use. This...

  6. 21 CFR 582.5449 - Manganese citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Manganese citrate. 582.5449 Section 582.5449 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5449 Manganese citrate. (a) Product. Manganese citrate. (b) Conditions of use. This...

  7. 21 CFR 582.5195 - Calcium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Calcium citrate. 582.5195 Section 582.5195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance...

  8. 21 CFR 582.5195 - Calcium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Calcium citrate. 582.5195 Section 582.5195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance...

  9. 21 CFR 582.5195 - Calcium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Calcium citrate. 582.5195 Section 582.5195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance...

  10. Determination of sildenafil citrate and related substances in the commercial products and tablet dosage form using HPLC.

    PubMed

    Daraghmeh, N; Al-Omari, M; Badwan, A A; Jaber, A M

    2001-06-01

    This study aimed at developing and validating an HPLC method for the assay of sildenafil citrate and its related substances that might coexist in the drug commercial products and in tablets' formulation as impurities that originate from synthesis processes or degradation. A chromatographic system comprising a microBondapak C(18) (10 microm) column, a mobile phase of ammonium acetate (pH 7.0, 0.2 M)-acetonitrile (1:1, v/v), a flow rate of 1 ml/min and a UV detector set at 240 nm has shown good chromatographic separation for sildenfil and the other related substances. The degree of linearity of the calibration curves, the percent recoveries of sildenafil and related substances, the limit of detection, LOD, and limit of quantitation, LOQ for the HPLC method have been determined. The HPLC method under study was found to be specific, precise, accurate, reproducible indicating stability and robust.

  11. Effect of the Food Additives Sodium Citrate and Disodium Phosphate on Shiga Toxin-Producing Escherichia coli and Production of stx-Phages and Shiga toxin

    PubMed Central

    Lenzi, Lucas J.; Lucchesi, Paula M. A.; Medico, Lucía; Burgán, Julia; Krüger, Alejandra

    2016-01-01

    Induction and propagation of bacteriophages along the food production chain can represent a significant risk when bacteriophages carry genes for potent toxins. The aim of this study was to evaluate the effect of different compounds used in the food industry on the growth of Shiga toxin-producing Escherichia coli (STEC) and the production of stx-phage particles and Shiga toxin. We tested the in vitro effect of lactic acid, acetic acid, citric acid, disodium phosphate, and sodium citrate on STEC growth. A bacteriostatic effect was observed in most of treated cultures. The exceptions were those treated with sodium citrate and disodium phosphate in which similar growth curves to the untreated control were observed, but with reduced OD600 values. Evaluation of phage production by plaque-based assays showed that cultures treated with sodium citrate and disodium phosphate released phages in similar o lower levels than untreated cultures. However, semi-quantification of Stx revealed higher levels of extracellular Stx in STEC cultures treated with 2.5% sodium citrate than in untreated cultures. Our results reinforce the importance to evaluate if additives and other treatments used to decrease bacterial contamination in food induce stx-phage and Stx production. PMID:27446032

  12. Effect of the Food Additives Sodium Citrate and Disodium Phosphate on Shiga Toxin-Producing Escherichia coli and Production of stx-Phages and Shiga toxin.

    PubMed

    Lenzi, Lucas J; Lucchesi, Paula M A; Medico, Lucía; Burgán, Julia; Krüger, Alejandra

    2016-01-01

    Induction and propagation of bacteriophages along the food production chain can represent a significant risk when bacteriophages carry genes for potent toxins. The aim of this study was to evaluate the effect of different compounds used in the food industry on the growth of Shiga toxin-producing Escherichia coli (STEC) and the production of stx-phage particles and Shiga toxin. We tested the in vitro effect of lactic acid, acetic acid, citric acid, disodium phosphate, and sodium citrate on STEC growth. A bacteriostatic effect was observed in most of treated cultures. The exceptions were those treated with sodium citrate and disodium phosphate in which similar growth curves to the untreated control were observed, but with reduced OD600 values. Evaluation of phage production by plaque-based assays showed that cultures treated with sodium citrate and disodium phosphate released phages in similar o lower levels than untreated cultures. However, semi-quantification of Stx revealed higher levels of extracellular Stx in STEC cultures treated with 2.5% sodium citrate than in untreated cultures. Our results reinforce the importance to evaluate if additives and other treatments used to decrease bacterial contamination in food induce stx-phage and Stx production.

  13. Citrate and renal calculi: an update

    NASA Technical Reports Server (NTRS)

    Pak, C. Y.

    1994-01-01

    Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease.

  14. Citrate and renal calculi: an update

    NASA Technical Reports Server (NTRS)

    Pak, C. Y.

    1994-01-01

    Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease.

  15. Production of itaconate by whole-cell bioconversion of citrate mediated by expression of multiple cis-aconitate decarboxylase (cadA) genes in Escherichia coli

    PubMed Central

    Kim, Junyoung; Seo, Hyung-Min; Bhatia, Shashi Kant; Song, Hun-Seok; Kim, Jung-Ho; Jeon, Jong-Min; Choi, Kwon-Young; Kim, Wooseong; Yoon, Jeong-Jun; Kim, Yun-Gon; Yang, Yung-Hun

    2017-01-01

    Itaconate, a C5 unsaturated dicarboxylic acid, is an important chemical building block that is used in manufacturing high-value products, such as latex and superabsorbent polymers. Itaconate is produced by fermentation of sugars by the filamentous fungus Aspergillus terreus. However, fermentation by A. terreus involves a long fermentation period and the formation of various byproducts, resulting in high production costs. E. coli has been developed as an alternative for producing itaconate. However, fermentation of glucose gives low conversion yields and low productivity. Here, we report the whole-cell bioconversion of citrate to itaconate with enhanced aconitase and cis-aconitate decarboxylase activities by controlling the expression of multiple cadA genes. In addition, this bioconversion system does not require the use of buffers, which reduces the production cost and the byproducts released during purification. Using this whole-cell bioconversion system, we were able to catalyze the conversion of 319.8 mM of itaconate (41.6 g/L) from 500 mM citrate without any buffer system or additional cofactors, with 64.0% conversion in 19 h and a productivity of 2.19 g/L/h. Our bioconversion system suggests very high productivity for itaconate production. PMID:28051098

  16. 21 CFR 573.580 - Iron-choline citrate complex.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.580 Iron-choline citrate complex. Iron-choline citrate complex made by... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Iron-choline citrate complex. 573.580 Section 573...

  17. 21 CFR 573.580 - Iron-choline citrate complex.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.580 Iron-choline citrate complex. Iron-choline citrate complex made by... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Iron-choline citrate complex. 573.580 Section 573...

  18. 21 CFR 573.580 - Iron-choline citrate complex.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.580 Iron-choline citrate complex. Iron-choline citrate complex made by... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Iron-choline citrate complex. 573.580 Section 573...

  19. Evidence that Osteoblasts are Specialized Citrate-producing Cells that Provide the Citrate for Incorporation into the Structure of Bone

    PubMed Central

    Franklin, Renty B.; Chellaiah, Meena; Zou, Jing; Reynolds, Mark A.; Costello, Leslie C.

    2015-01-01

    Citrate is a major component of bone in all vertebrates, but its implications in bone have remained largely unknown. Recent studies identified that citrate is incorporated into the structure of the hydroxyapatite nanocrystal/collagen complex; and is essential for the important biomechanical properties of bone. This raises the important question, “What is the source of citrate for incorporation into bone?”; A question that heretofore had remained unresolved. Studies in this report were designed to determine the plausibility of our concept that the osteoblasts are specialized citrate-producing cells, which provide the citrate that is incorporated into the structure of bone; and that osteogenic differentiation of mesenchyme cells leads to the development of the citrate-producing osteoblasts. The results demonstrated that primary human osteoblasts exhibit the capability of citrate-production. Undifferentiated mesenchyme cells do not exhibit the capability of citrate production; and osteogenic differentiation results in citrate-producing osteoblasts. The up-regulation of zinc uptake transporter ZIP1 is essential for the manifestation of the citrate-producing capability of the osteoblasts. We determined that osteoblast transport of citrate from plasma is not a likely source of citrate in bone. Thus, this study establishes for the first time that the osteoblasts are specialized citrate-producing cells that provide the citrate for incorporation into the structure of bone; and that mesenchyme cell osteogenesis leads to differentiated citrate-producing osteoblasts. This is a new understanding; which must include the osteogenic development of citrate-producing osteoblasts, and the process of “citration” in concert with mineralization during bone formation. It also provides a new understanding of the role of bone in the homeostatic maintenance of plasma citrate concentration. PMID:25745519

  20. Citrate Anticoagulation: Are Blood Donors Donating Bone?

    PubMed Central

    Bialkowski, Walter; Bruhn, Roberta; Edgren, Gustaf; Papanek, Paula

    2015-01-01

    An estimated 2.4 million volunteer apheresis blood donation procedures were performed in the United States in 2010 and increases in the proportion of transfused blood products derived from apheresis blood collections have been consistently reported. Anticoagulation is required during apheresis and is achieved with citrate. Donor exposure to citrate causes an acute physiological response in the donor maintaining serum mineral homeostasis. Some data are available on the sequelae of this acute response in the days and weeks following exposure, raising questions about bone mineral density in regular apheresis donors. New research is emerging that addresses the potential long term health outcomes of repeated citrate exposure. This article reviews the acute physiological response to citrate anticoagulation in volunteer blood donors, presents contrasting perspectives on the potential effects of citrate exposure on bone density, and identifies key knowledge gaps in our understanding of long term health outcomes in apheresis donors. PMID:26607494

  1. Physicochemical action of potassium-magnesium citrate in nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Pak, C. Y.; Koenig, K.; Khan, R.; Haynes, S.; Padalino, P.

    1992-01-01

    Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS).

  2. Physicochemical action of potassium-magnesium citrate in nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Pak, C. Y.; Koenig, K.; Khan, R.; Haynes, S.; Padalino, P.

    1992-01-01

    Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS).

  3. The distribution of plasmids determining citrate utilization in citrate-positive variants of Escherichia coli from humans, domestic animals, feral birds and environments.

    PubMed

    Ishiguro, N; Sato, G

    1979-10-01

    Sixty-seven isolates of citrate-positive variants of Escherichia coli were isolated from human, domestic animal, feral bird and environmental sources. With the exception of citrate utilization, all isolates were identified as typical E. coli by their biochemical reactions. The transmission of the ability to utilize citrate on Simmons' citrate agar was demonstrated in 53 (79.1%) out of the 67 citrate-positive E. coli variants obtained from various sources. Drug resistance determinants and citrate utilizing character were co-transmitted into E. coli K-12 by conjugation among citrate-positive E. coli isolates carrying R plasmids except for that isolated from horses. The other characters (haemolysin or colicin production, raffinose or sucrose fermentation) were not transmitted together with the citrate utilizing character. These facts suggested that the structural gene responsible for citrate utilizing ability in citrate-positive variants of E. coli was located on a conjugative plasmid.

  4. Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses

    PubMed Central

    Ashbrook, M J; McDonough, K L; Pituch, J J; Christopherson, P L; Cornell, T T; Selewski, D T; Shanley, T P; Blatt, N B

    2015-01-01

    Citrate, a central component of cellular metabolism, is a widely used anti-coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)-citrate lyase, which metabolizes citrate, has been shown to be essential for inflammation, but the ability of exogenous citrate to impact inflammatory signalling cascades remains largely unknown. We hypothesized that citrate would modulate inflammatory responses as both a cellular metabolite and calcium chelator, and tested this hypothesis by determining how clinically relevant levels of citrate modulate monocyte proinflammatory responses to lipopolysaccharide (LPS) in a human acute monocytic leukaemia cell line (THP-1). In normal medium (0·4 mM calcium), citrate inhibited LPS-induced tumour necrosis factor (TNF)-α and interleukin (IL)-8 transcripts, whereas in medium supplemented with calcium (1·4 mM), TNF-α and IL-8 levels increased and appeared independent of calcium chelation. Using an IL-8–luciferase plasmid construct, the same increased response was observed in the activation of the IL-8 promoter region, suggesting transcriptional regulation. Tricarballylic acid, an inhibitor of ATP-citrate lyase, blocked the ability of citrate to augment TNF-α, linking citrate's augmentation effect with its metabolism by ATP-citrate lyase. In the presence of citrate, increased histone acetylation was observed in the TNF-α and IL-8 promoter regions of THP-1 cells. We observed that citrate can both augment and inhibit proinflammatory cytokine production via modulation of inflammatory gene transactivation. These findings suggest that citrate anti-coagulation may alter immune function through complex interactions with the inflammatory response. PMID:25619261

  5. Gastrointestinal citrate absorption in nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Fegan, J.; Khan, R.; Poindexter, J.; Pak, C. Y.

    1992-01-01

    Gastrointestinal absorption of citrate was measured in stone patients with idiopathic hypocitraturia to determine if citrate malabsorption could account for low urinary citrate. Citrate absorption was measured directly from recovery of orally administered potassium citrate (40 mEq.) in the intestinal lavage fluid, using an intestinal washout technique. In 7 stone patients citrate absorption, serum citrate levels, peak citrate concentration in serum and area under the curve were not significantly different from those of 7 normal subjects. Citrate absorption was rapid and efficient in both groups, with 96 to 98% absorbed within 3 hours. The absorption of citrate was less efficient from a tablet preparation of potassium citrate than from a liquid preparation, probably due to a delayed release of citrate from wax matrix. However, citrate absorption from solid potassium citrate was still high at 91%, compared to 98% for a liquid preparation. Thus, hypocitraturia is unlikely to be due to an impaired gastrointestinal absorption of citrate in stone patients without overt bowel disease.

  6. Gastrointestinal citrate absorption in nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Fegan, J.; Khan, R.; Poindexter, J.; Pak, C. Y.

    1992-01-01

    Gastrointestinal absorption of citrate was measured in stone patients with idiopathic hypocitraturia to determine if citrate malabsorption could account for low urinary citrate. Citrate absorption was measured directly from recovery of orally administered potassium citrate (40 mEq.) in the intestinal lavage fluid, using an intestinal washout technique. In 7 stone patients citrate absorption, serum citrate levels, peak citrate concentration in serum and area under the curve were not significantly different from those of 7 normal subjects. Citrate absorption was rapid and efficient in both groups, with 96 to 98% absorbed within 3 hours. The absorption of citrate was less efficient from a tablet preparation of potassium citrate than from a liquid preparation, probably due to a delayed release of citrate from wax matrix. However, citrate absorption from solid potassium citrate was still high at 91%, compared to 98% for a liquid preparation. Thus, hypocitraturia is unlikely to be due to an impaired gastrointestinal absorption of citrate in stone patients without overt bowel disease.

  7. In Vivo Validation of In Silico Predicted Metabolic Engineering Strategies in Yeast: Disruption of α-Ketoglutarate Dehydrogenase and Expression of ATP-Citrate Lyase for Terpenoid Production

    PubMed Central

    Gruchattka, Evamaria; Kayser, Oliver

    2015-01-01

    Background Engineering of the central carbon metabolism of Saccharomyces cerevisiae to redirect metabolic flux towards cytosolic acetyl-CoA has become a central topic in yeast biotechnology. A cell factory with increased flux into acetyl-CoA can be used for heterologous production of terpenoids for pharmaceuticals, biofuels, fragrances, or other acetyl-CoA derived compounds. In a previous study, we identified promising metabolic engineering targets in S. cerevisiae using an in silico stoichiometric metabolic network analysis. Here, we validate selected in silico strategies in vivo. Results Patchoulol was produced by yeast via a heterologous patchoulol synthase of Pogostemon cablin. To increase the metabolic flux from acetyl-CoA towards patchoulol, a truncated HMG-CoA reductase was overexpressed and farnesyl diphosphate synthase was fused with patchoulol synthase. The highest increase in production could be achieved by modifying the carbon source; sesquiterpenoid titer increased from glucose to ethanol by a factor of 8.4. Two strategies predicted in silico were chosen for validation in this work. Disruption of α-ketoglutarate dehydrogenase gene (KGD1) was predicted to redirect the metabolic flux via the pyruvate dehydrogenase bypass towards acetyl-CoA. The metabolic flux was redirected as predicted, however, the effect was dependent on cultivation conditions and the flux was interrupted at the level of acetate. High amounts of acetate were produced. As an alternative pathway to synthesize cytosolic acetyl-CoA, ATP-citrate lyase was expressed as a polycistronic construct, however, in vivo performance of the enzyme needs to be optimized to increase terpenoid production. Conclusions Stoichiometric metabolic network analysis can be used successfully as a metabolic prediction tool. However, this study highlights that kinetics, regulation and cultivation conditions may interfere, resulting in poor in vivo performance. Main sites of regulation need to be released and

  8. In Vivo Validation of In Silico Predicted Metabolic Engineering Strategies in Yeast: Disruption of α-Ketoglutarate Dehydrogenase and Expression of ATP-Citrate Lyase for Terpenoid Production.

    PubMed

    Gruchattka, Evamaria; Kayser, Oliver

    2015-01-01

    Engineering of the central carbon metabolism of Saccharomyces cerevisiae to redirect metabolic flux towards cytosolic acetyl-CoA has become a central topic in yeast biotechnology. A cell factory with increased flux into acetyl-CoA can be used for heterologous production of terpenoids for pharmaceuticals, biofuels, fragrances, or other acetyl-CoA derived compounds. In a previous study, we identified promising metabolic engineering targets in S. cerevisiae using an in silico stoichiometric metabolic network analysis. Here, we validate selected in silico strategies in vivo. Patchoulol was produced by yeast via a heterologous patchoulol synthase of Pogostemon cablin. To increase the metabolic flux from acetyl-CoA towards patchoulol, a truncated HMG-CoA reductase was overexpressed and farnesyl diphosphate synthase was fused with patchoulol synthase. The highest increase in production could be achieved by modifying the carbon source; sesquiterpenoid titer increased from glucose to ethanol by a factor of 8.4. Two strategies predicted in silico were chosen for validation in this work. Disruption of α-ketoglutarate dehydrogenase gene (KGD1) was predicted to redirect the metabolic flux via the pyruvate dehydrogenase bypass towards acetyl-CoA. The metabolic flux was redirected as predicted, however, the effect was dependent on cultivation conditions and the flux was interrupted at the level of acetate. High amounts of acetate were produced. As an alternative pathway to synthesize cytosolic acetyl-CoA, ATP-citrate lyase was expressed as a polycistronic construct, however, in vivo performance of the enzyme needs to be optimized to increase terpenoid production. Stoichiometric metabolic network analysis can be used successfully as a metabolic prediction tool. However, this study highlights that kinetics, regulation and cultivation conditions may interfere, resulting in poor in vivo performance. Main sites of regulation need to be released and improved enzymes are essential to

  9. The vital role of citrate buffer in acetone-butanol-ethanol (ABE) fermentation using corn stover and high-efficient product recovery by vapor stripping-vapor permeation (VSVP) process.

    PubMed

    Xue, Chuang; Wang, Zixuan; Wang, Shudong; Zhang, Xiaotong; Chen, Lijie; Mu, Ying; Bai, Fengwu

    2016-01-01

    Butanol is not only an important solvent and chemical intermediate in food and pharmaceutical industries, but also considered as an advanced biofuel. Recently, there have been resurging interests in producing biobutanol especially using low-cost lignocellulosic biomass, but the process still suffers from low titer and productivity. The challenge for the bioconversion approach is to find an effective way of degrading materials into simple sugars that can then be converted into fuels by microorganisms. The pretreatment of lignocellulosic biomass is the great important process in influencing butanol production and recovery, finally determining its eco-feasibility in commercialization. The effects of various strengths of citrate buffer on enzymatic hydrolysis and acetone-butanol-ethanol fermentation using corn stover or glucose as feedstock were investigated. The strengths of citrate buffer in the range of 20-100 mM had no effect on enzymatic hydrolysis, but greatly influenced the performance of ABE fermentation using corn stover hydrolysate. When 30 mM citrate buffer was used for enzymatic hydrolysis, the fermentation broth with the maximum butanol and ABE concentrations of 11.2 and 19.8 g/L were obtained from 30.9 g/L glucose and 9.7 g/L xylose, respectively, which was concentrated to 100.4 g/L butanol and 153.5 g/L ABE by vapor stripping-vapor permeation process. Furthermore, using glucose as sole carbon source, there were no cell growth and ABE production in the P2 medium with 80 or 100 mM citrate buffer, indicating that higher concentrations of citrate buffer had deleterious effect on cell growth and metabolism due to the variation of cells internal pH and cell membrane permeability. To mimic in situ product recovery for ABE fermentation, the VSVP process produced the condensate containing 212.0-232.0 g/L butanol (306.6-356.1 g/L ABE) from fermentation broth containing ~10 g/L butanol (~17 g/L ABE), the performance of which was more effective than

  10. Characterization of ATP citrate lyase from Chlorobium limicola.

    PubMed Central

    Antranikian, G; Herzberg, C; Gottschalk, G

    1982-01-01

    ATP citrate lyase (EC 4.1.3.8) from Chlorobium limicola was partially purified. It was established that the consumption of substrates and the formation of products proceeded stoichiometrically and that citrate cleavage was of the si-type. ADP and oxaloacetate inhibited enzyme activity. Oxaloacetate also inhibited the growth of C. limicola. PMID:7142107

  11. Citrate anticoagulation: Are blood donors donating bone?

    PubMed

    Bialkowski, Walter; Bruhn, Roberta; Edgren, Gustaf; Papanek, Paula

    2016-10-01

    An estimated 2.4 million volunteer apheresis blood donation procedures were performed in the United States in 2010, and increases in the proportion of transfused blood products derived from apheresis blood collections have been consistently reported. Anticoagulation is required during apheresis and is achieved with citrate. Donor exposure to citrate causes an acute physiological response to maintain serum mineral homeostasis. Some data are available on the sequelae of this acute response in the days and weeks following exposure, raising questions about bone mineral density in regular apheresis donors. New research is emerging that addresses the potential long-term health outcomes of repeated citrate exposure. This article reviews the acute physiological response to citrate anticoagulation in volunteer blood donors, presents contrasting perspectives on the potential effects of citrate exposure on bone density, and identifies key knowledge gaps in our understanding of long-term health outcomes in apheresis donors. J. Clin. Apheresis 31:459-463, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  12. Production of 68Ga-citrate Based on a SnO2 Generator for Short-Term Turpentine Oil-Induced Inflammation Imaging in Rats.

    PubMed

    Mirzaei, Alireza; Jalilian, Amir R; Akhlaghi, Mehdi; Beiki, Davood

    2016-01-01

    Gallium-68 citrate has been successfully applied in the PET imaging of infections and inflammation in some centers; however further evaluation of the tracer in inflammation models is of great importance. 68Ga-citrate prepared from [68Ga]GaCl3 (eluted form an SnO2 based 68Ge/68Ga generator) and sodium citrate at optimized conditions followed by quality control tests was injected to normal and turpentine-oil induced rats PET/CT imaging studies up to 290 min. 68Ga-citrate was prepared with acceptable radiochemical purity (>99 ITLC, >99% HPLC), specific activity (28-30 GBq/mM), chemical purity (Sn, Fe <0.3 ppm; Zn<0.2 ppm) in 15 min at 50°C. PET/CT imaging of the tracer demonstrated early detection of inflamed site in animal models in 60-80 min. This study demonstrated possible early detection of inflammation foci in vivo using 68Ga-citrate prepared using commercially available 68Ge/68Ga generators for PET imaging. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Anaerobic degradation of citrate under sulfate reducing and methanogenic conditions.

    PubMed

    Gámez, Victor M; Sierra-Alvarez, Reyes; Waltz, Rebecca J; Field, James A

    2009-07-01

    Citrate is an important component of metal processing effluents such as chemical mechanical planarization wastewaters of the semiconductor industry. Citrate can serve as an electron donor for sulfate reduction applied to promote the removal of metals, and it can also potentially be used by methanogens that coexist in anaerobic biofilms. The objective of this study was to evaluate the degradation of citrate with sulfate-reducing and methanogenic biofilms. During batch bioassays, the citrate, acetate, methane and sulfide concentrations were monitored. The results indicate that independent of the biofilm or incubation conditions used, citrate was rapidly fermented with specific rates ranging from 566 to 720 mg chemical oxygen demand (COD) consumed per gram volatile suspended solids per day. Acetate was found to be the main fermentation product of citrate degradation, which was later degraded completely under either methanogenic or sulfate reducing conditions. However, if either sulfate reduction or methanogenesis was infeasible due to specific inhibitors (2-bromoethane sulfonate), absence of sulfate or lack of adequate microorganisms in the biofilm, acetate accumulated to levels accounting for 90-100% of the citrate-COD consumed. Based on carbon balances measured in phosphate buffered bioassays, acetate, CO(2) and hydrogen are the main products of citrate fermentation, with a molar ratio of 2:2:1 per mol of citrate, respectively. In bicarbonate buffered bioassays, acetogenesis of H(2) and CO(2) increased the yield of acetate. The results taken as a whole suggest that in anaerobic biofilm systems, citrate is metabolized via the formation of acetate as the main metabolic intermediate prior to methanogenesis or sulfate reduction. Sulfate reducing consortia must be enriched to utilize acetate as an electron donor in order to utilize the majority of the electron-equivalents in citrate.

  14. 21 CFR 582.5195 - Calcium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Calcium citrate. 582.5195 Section 582.5195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

  15. 78 FR 34338 - Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-07

    ... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of... administrative review of the antidumping duty order on citric acid and certain citrate salts (citric acid) from... is citric acid and certain citrate salts. The product is currently classified in the Harmonized...

  16. Citrate synthesis in intact rat-liver mitochondria is irreversible.

    PubMed

    Greksák, M; Lopes-Cardozo, M; van den Bergh, S G

    1982-02-01

    Rat-liver mitochondria were incubated with [1,5-14C]citrate in the presence of fluorocitrate to block its oxidation in the Krebs cycle. The reaction products were analysed enzymatically and by anion-exchange chromatography. Incorporation of 14C into acetyl-L-carnitine or ketone bodies via a backward action of citrate synthase was not observed. The optimal rate of citrate synthesis from pyruvate and malate in the presence of fluorocitrate was 15 nmol . mg-1 min-1. In the absence of fluorocitrate, but in the presence of malonate, citrate was oxidized to succinate at a rate of 4 nmol . mg-1 . min-1. We conclude that the synthesis of citrate by intact rat liver mitochondria is an irreversible process. The possible mechanism underlying this phenomenon and the consequence for metabolic regulation are discussed.

  17. Citrate as a siderophore in Bradyrhizobium japonicum.

    PubMed Central

    Guerinot, M L; Meidl, E J; Plessner, O

    1990-01-01

    Under iron-limiting conditions, many bacteria secrete ferric iron-specific ligands, generically termed siderophores, to aid in the sequestering and transport of iron. One strain of the nitrogen-fixing soybean symbiont Bradyrhizobium japonicum, 61A152, was shown to produce a siderophore when 20 B. japonicum strains were screened with all six chemical assays commonly used to detect such production. Production by strain 61A152 was detected via the chrome azurol S assay, a general test for siderophores which is independent of siderophore structure. The iron-chelating compound was neither a catechol nor a hydroxamate and was ninhydrin negative. It was determined to be citric acid via a combination of thin-layer chromatography and high-voltage paper electrophoresis; this identification was verified by a specific enzymatic assay for citric acid. The inverse correlation which was observed between citric acid release and the iron content of the medium suggested that ferric citrate could serve as an iron source. This was confirmed via growth and transport assays. Exogenously added ferric citrate could be used to overcome iron starvation, and iron-deficient cells actively transported radiolabeled ferric citrate. These results, taken together, indicate a role for ferric citrate in the iron nutrition of this strain, which has been shown to be an efficient nitrogen-fixing strain on a variety of soybean cultivars. PMID:2140566

  18. Citrate Uptake in Exchange with Intermediates in the Citrate Metabolic Pathway in Lactococcus lactis IL1403▿

    PubMed Central

    Pudlik, Agata M.; Lolkema, Juke S.

    2011-01-01

    Carbohydrate/citrate cometabolism in Lactococcus lactis results in the formation of the flavor compound acetoin. Resting cells of strain IL1403(pFL3) rapidly consumed citrate while producing acetoin when substoichiometric concentrations of glucose or l-lactate were present. A proton motive force was generated by electrogenic exchange of citrate and lactate catalyzed by the citrate transporter CitP and proton consumption in decarboxylation reactions in the pathway. In the absence of glucose or l-lactate, citrate consumption was biphasic. During the first phase, hardly any citrate was consumed. In the second phase, citrate was converted rapidly, but without the formation of acetoin. Instead, significant amounts of the intermediates pyruvate and α-acetolactate, and the end product acetate, were excreted from the cells. It is shown that the intermediates and acetate are excreted in exchange with the uptake of citrate catalyzed by CitP. The availability of exchangeable substrates in the cytoplasm determines both the rate of citrate consumption and the end product profile. It follows that citrate metabolism in L. lactis IL1403(pFL3) splits up in two routes after the formation of pyruvate, one the well-characterized route yielding acetoin and the other a new route yielding acetate. The flux distribution between the two branches changes from 85:15 in the presence of l-lactate to 30:70 in the presence of pyruvate. The proton motive force generated was greatest in the presence of l-lactate and zero in the presence of pyruvate, suggesting that the pathway to acetate does not generate proton motive force. PMID:21115655

  19. Ca2+-citrate uptake and metabolism in Lactobacillus casei ATCC 334.

    PubMed

    Mortera, Pablo; Pudlik, Agata; Magni, Christian; Alarcón, Sergio; Lolkema, Juke S

    2013-08-01

    The putative citrate metabolic pathway in Lactobacillus casei ATCC 334 consists of the transporter CitH, a proton symporter of the citrate-divalent metal ion family of transporters CitMHS, citrate lyase, and the membrane-bound oxaloacetate decarboxylase complex OAD-ABDH. Resting cells of Lactobacillus casei ATCC 334 metabolized citrate in complex with Ca(2+) and not as free citrate or the Mg(2+)-citrate complex, thereby identifying Ca(2+)-citrate as the substrate of the transporter CitH. The pathway was induced in the presence of Ca(2+) and citrate during growth and repressed by the presence of glucose and of galactose, most likely by a carbon catabolite repression mechanism. The end products of Ca(2+)-citrate metabolism by resting cells of Lb. casei were pyruvate, acetate, and acetoin, demonstrating the activity of the membrane-bound oxaloacetate decarboxylase complex OAD-ABDH. Following pyruvate, the pathway splits into two branches. One branch is the classical citrate fermentation pathway producing acetoin by α-acetolactate synthase and α-acetolactate decarboxylase. The other branch yields acetate, for which the route is still obscure. Ca(2+)-citrate metabolism in a modified MRS medium lacking a carbohydrate did not significantly affect the growth characteristics, and generation of metabolic energy in the form of proton motive force (PMF) was not observed in resting cells. In contrast, carbohydrate/Ca(2+)-citrate cometabolism resulted in a higher biomass yield in batch culture. However, also with these cells, no generation of PMF was associated with Ca(2+)-citrate metabolism. It is concluded that citrate metabolism in Lb. casei is beneficial when it counteracts acidification by carbohydrate metabolism in later growth stages.

  20. Ca2+-Citrate Uptake and Metabolism in Lactobacillus casei ATCC 334

    PubMed Central

    Mortera, Pablo; Pudlik, Agata; Magni, Christian; Alarcón, Sergio

    2013-01-01

    The putative citrate metabolic pathway in Lactobacillus casei ATCC 334 consists of the transporter CitH, a proton symporter of the citrate-divalent metal ion family of transporters CitMHS, citrate lyase, and the membrane-bound oxaloacetate decarboxylase complex OAD-ABDH. Resting cells of Lactobacillus casei ATCC 334 metabolized citrate in complex with Ca2+ and not as free citrate or the Mg2+-citrate complex, thereby identifying Ca2+-citrate as the substrate of the transporter CitH. The pathway was induced in the presence of Ca2+ and citrate during growth and repressed by the presence of glucose and of galactose, most likely by a carbon catabolite repression mechanism. The end products of Ca2+-citrate metabolism by resting cells of Lb. casei were pyruvate, acetate, and acetoin, demonstrating the activity of the membrane-bound oxaloacetate decarboxylase complex OAD-ABDH. Following pyruvate, the pathway splits into two branches. One branch is the classical citrate fermentation pathway producing acetoin by α-acetolactate synthase and α-acetolactate decarboxylase. The other branch yields acetate, for which the route is still obscure. Ca2+-citrate metabolism in a modified MRS medium lacking a carbohydrate did not significantly affect the growth characteristics, and generation of metabolic energy in the form of proton motive force (PMF) was not observed in resting cells. In contrast, carbohydrate/Ca2+-citrate cometabolism resulted in a higher biomass yield in batch culture. However, also with these cells, no generation of PMF was associated with Ca2+-citrate metabolism. It is concluded that citrate metabolism in Lb. casei is beneficial when it counteracts acidification by carbohydrate metabolism in later growth stages. PMID:23709502

  1. Synthesis and Antimicrobial Activity of Silver Citrate Complexes

    PubMed Central

    Djokić, Stojan

    2008-01-01

    Formation of silver citrate/citric acid complexed solutions was investigated. Although, silver citrate is minimally soluble in water, it can successfully be dissolved in citric acid solutions. The maximum concentration of Ag(I) in solution is estimated at 23 to 25 g/L if the concentration of citric acid is at least 4 mol/L or higher. The dissolution of silver citrate in citric acid solutions was attributed to the formation of silver citrate complexes of a general formula [Ag3(C6H5O7)n+1]3n−. The silver citrate/citric acid solutions, containing more than about 13 g/L Ag+ ion, have exhibited a decrease in Ag(I) concentration in solution over time, due to crystallization. The crystallization product was attributed to the formation of [Ag3C6H5O7]x·nH2O. Importantly, the diluted silver citrate/citric acid complexed solutions have exhibited very strong bacteriostatic and bactericidal activities. PMID:19079586

  2. Aroma compounds generation in citrate metabolism of Enterococcus faecium: Genetic characterization of type I citrate gene cluster.

    PubMed

    Martino, Gabriela P; Quintana, Ingrid M; Espariz, Martín; Blancato, Victor S; Magni, Christian

    2016-02-02

    Enterococcus is one of the most controversial genera belonging to Lactic Acid Bacteria. Research involving this microorganism reflects its dual behavior as regards its safety. Although it has also been associated to nosocomial infections, natural occurrence of Enterococcus faecium in food contributes to the final quality of cheese. This bacterium is capable of fermenting citrate, which is metabolized to pyruvate and finally derives in the production of the aroma compounds diacetyl, acetoin and 2,3 butanediol. Citrate metabolism was studied in E. faecium but no data about genes related to these pathways have been described. A bioinformatic approach allowed us to differentiate cit(-) (no citrate metabolism genes) from cit(+) strains in E. faecium. Furthermore, we could classify them according to genes encoding for the transcriptional regulator, the oxaloacetate decarboxylase and the citrate transporter. Thus we defined type I organization having CitI regulator (DeoR family), CitM cytoplasmic soluble oxaloacetate decarboxylase (Malic Enzyme family) and CitP citrate transporter (2-hydroxy-carboxylate transporter family) and type II organization with CitO regulator (GntR family), OAD membrane oxaloacetate decarboxylase complex (Na(+)-transport decarboxylase enzyme family) and CitH citrate transporter (CitMHS family). We isolated and identified 17 E. faecium strains from regional cheeses. PCR analyses allowed us to classify them as cit(-) or cit(+). Within the latter classification we could differentiate type I but no type II organization. Remarkably, we came upon E. faecium GM75 strain which carries the insertion sequence IS256, involved in adaptative and evolution processes of bacteria related to Staphylococcus and Enterococcus genera. In this work we describe the differential behavior in citrate transport, metabolism and aroma generation of three strains and we present results that link citrate metabolism and genetic organizations in E. faecium for the first time

  3. Growth and energy generation by Enterococcus faecium FAIR-E 198 during citrate metabolism.

    PubMed

    Sarantinopoulos, Panagiotis; Makras, Lefteris; Vaningelgem, Frederik; Kalantzopoulos, George; De Vuyst, Luc; Tsakalidou, Effie

    2003-07-25

    Citrate metabolism by Enterococcus faecium FAIR-E 198, isolated from Greek Feta cheese, was studied in various growth media containing citrate either in the presence of glucose, or as the sole carbon source, both under aerobic and anaerobic conditions. In de Man-Rogosa-Sharpe (MRS) broth with increasing citrate concentrations, cometabolism of citrate and glucose took place. Glucose was stoichiometrically converted into lactate, while citrate into acetate. Glucose consumption and biomass yield were enhanced with increasing initial citrate concentrations, even though maximum specific growth rate was not. When citrate was used as the sole carbon source in increasing initial concentrations, the main end product was acetate. Small amounts of lactate, formate, ethanol, and acetoin were also produced. In all cases, no significant differences were observed between aerobic and anaerobic conditions. However, when citrate was used as sole carbon source, formate production was favored in the absence of oxygen. The present work shows that E. faecium is able to utilize citrate in synthetic media, either in the presence of glucose or as the sole carbon source, resulting in energy production and the formation of aroma compounds.

  4. Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice.

    PubMed

    Leandro, João G B; Espindola-Netto, Jair M; Vianna, Maria Carolina F; Gomez, Lilian S; DeMaria, Thaina M; Marinho-Carvalho, Monica M; Zancan, Patricia; Paula Neto, Heitor A; Sola-Penna, Mauro

    2016-03-28

    Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed. Extracellular citrate can freely enter the cells via the constitutively expressed plasma membrane citrate transporter. Within the cytosol, citrate is readily metabolised by ATP-citrate lyase into acetyl-CoA - the metabolic precursor of endogenously produced lipids and cholesterol. We therefore hypothesised that the citrate ingested from processed foods and drinks could contribute to increased postprandial fat production and weight gain. To test our hypothesis, we administered citrate to mice through their drinking water with or without sucrose and monitored their weight gain and other metabolic parameters. Our results showed that mice receiving citrate or citrate+sucrose did not show increased weight gain or an increase in the weight of the liver, skeletal muscles or adipose tissues (AT). Moreover, the plasma lipid profiles (TAG, total cholesterol, LDL and HDL) were similar across all groups. However, the group receiving citrate+sucrose showed augmented fasting glycaemia, glucose intolerance and the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) in their AT. Therefore, our results suggest that citrate consumption contributes to increased AT inflammation and altered glucose metabolism, which is indicative of initial insulin resistance. Thus, citrate consumption could be a previously unknown causative agent for the complications associated with obesity.

  5. High bovine blastocyst development in a static in vitro production system using SOFaa medium supplemented with sodium citrate and myo-inositol with or without serum-proteins.

    PubMed

    Holm, P; Booth, P J; Schmidt, M H; Greve, T; Callesen, H

    1999-09-01

    We describe a bovine embryo culture system that supports repeatable high development in the presence of serum or BSA as well as under defined conditions in the absence of those components. In the first experiment, embryo development in SOF with amino acids (SOFaa), sodium citrate (SOFaac) and myo-inositol (SOFaaci) and with BSA or polyvinyl alcohol (PVA) was compared with that in a M199 granulosa cell co-culture (M199 co-culture). Subsequently, development and cell numbers of blastocysts cultured under defined conditions in SOFaaci with PVA (SOFaaci-PVA), or under undefined conditions in SOFaaci with 5% cow serum (SOFaaci-CS) or M199 co-culture were compared. The repeatability of culture results in SOFaaci-CS was checked by weekly replicates (n = 30) spread over 11 months. The viability of embryos developed in SOFaaci-PVA was estimated by transfer of morphologically good blastocysts (n = 10) to synchronized recipients. In the second experiment, the effect of omitting CS or BSA from IVM and IVM-IVF on subsequent embryo development in SOFaaci-PVA or in SOFaaci-CS was investigated. Blastocyst development in SOFaa-PVA, SOFaac-PVA, SOFaa-BSA and M199 was 16 +/- 3b, 23 +/- 2ab, 30 +/- 8a and 36 +/- 7a%, respectively (Pab < 0.05). Additional inclusion of myoinositol resulted in 42 +/- 1a% blastocysts in SOFaaci-PVA vs 19 +/- 3b% in SOFaac-PVA, 47 +/- 7a% in SOFaac-BSA, and 36 +/- 7a% in M199 co-culture, respectively (Pab < 0.01). In 30 replicates, the average cleavage and blastocyst rates of oocytes in SOFaaci-CS were 87 +/- 4 and 49 +/- 5%, respectively. Five normal calves were produced after transfer of 10 blastocysts developed in defined culture medium (i.e., SOFaaci-PVA). Defined IVM or IVM-IVF (i.e., in absence of CS and BSA) reduced cleavage rates (83 +/- 3 and 55 +/- 3% vs 90 +/- 1% in presence of CS; P < 0.01). Subsequent embryo development in SOFaaci-CS was not affected in either of these defined conditions. However, cleavage and blastocyst rates under completely

  6. SbnG, a citrate synthase in Staphylococcus aureus: a new fold on an old enzyme.

    PubMed

    Kobylarz, Marek J; Grigg, Jason C; Sheldon, Jessica R; Heinrichs, David E; Murphy, Michael E P

    2014-12-05

    In response to iron deprivation, Staphylococcus aureus produces staphyloferrin B, a citrate-containing siderophore that delivers iron back to the cell. This bacterium also possesses a second citrate synthase, SbnG, that is necessary for supplying citrate to the staphyloferrin B biosynthetic pathway. We present the structure of SbnG bound to the inhibitor calcium and an active site variant in complex with oxaloacetate. The overall fold of SbnG is structurally distinct from TCA cycle citrate synthases yet similar to metal-dependent class II aldolases. Phylogenetic analyses revealed that SbnG forms a separate clade with homologs from other siderophore biosynthetic gene clusters and is representative of a metal-independent subgroup in the phosphoenolpyruvate/pyruvate domain superfamily. A structural superposition of the SbnG active site to TCA cycle citrate synthases and site-directed mutagenesis suggests a case for convergent evolution toward a conserved catalytic mechanism for citrate production.

  7. Regulation of anaerobic citrate metabolism in Klebsiella pneumoniae.

    PubMed

    Bott, M; Meyer, M; Dimroth, P

    1995-11-01

    Three enzymes are specifically required for uptake and catabolism of citrate by Klebsiella pneumoniae under anaerobic conditions: a Na+ -dependent citrate carrier (CitS), citrate lyase (CitDEF), and the Na+ pump oxaloacetate decarboxylase (OadGAB). The corresponding genes are clustered on the chromosome, with the citCDEFG genes located upstream and divergent to the citS-oadGAB genes. We found that expression of citS from its native promoter in Escherichia coli requires the DNA region downstream of oadB. Nucleotide sequence analysis of this region revealed the presence of two adjacent genes, citA and citB. By sequence similarity, the predicted CitA and CitB proteins were identified as members of the two-component regulatory systems. The sensor kinase CitA contained, in the N-terminal half, two putative transmembrane helices which enclosed a presumably periplasmic domain of about 130 amino acids. The C-terminal half of the response regulator CitB harboured a helix-turn-helix motif typical of DNA-binding proteins. K. pneumoniae citB null mutants were unable to grow anaerobically with citrate as the sole carbon and energy source (Cit- phenotype). When cultivated anaerobically with citrate plus glycerol, all of the citrate-specific fermentation enzymes were synthesized in the wild type, but not in the citB mutants. This showed that citS, oadGAB and citDEF required the CitB protein for expression and therefore are part of a regulon. In the wild type, synthesis of CitS, oxaloacetate decarboxylase and citrate lyase was dependent on the presence of citrate, sodium ions and a low oxygen tension. In a citA null mutant which expressed citB constitutively at high levels, none of these signals was required for the formation of the citrate fermentation enzymes. This result suggested that citrate, Na+, and oxygen exerted their regulatory effects via the CitA/CitB system. In the presence of these signals, the citAB gene products induced their own synthesis. The positive

  8. Citrate and Sugar Cofermentation in Leuconostoc oenos, a (sup13)C Nuclear Magnetic Resonance Study

    PubMed Central

    Ramos, A.; Santos, H.

    1996-01-01

    (sup13)C nuclear magnetic resonance spectroscopy was used to investigate citrate-glucose cometabolism in nongrowing cell suspensions of the wine lactic acid bacterium Leuconostoc oenos. The use of isotopically enriched substrates allowed us to identify and quantify in the end products the carbon atoms derived from each of the substrates supplied; furthermore, it was possible to differentiate between products derived from the metabolism of endogenous carbon reserves and those derived from external substrates. Citrate-sugar cometabolism was also monitored in dilute cell suspensions for comparison with the nuclear magnetic resonance results. A clear metabolic shift of the end products from glucose metabolism was observed when citrate was provided along with glucose: ethanol was replaced by acetate, and 2,3-butanediol was produced. Reciprocally, the production of lactate and 2,3-butanediol from citrate was increased in the presence of glucose. When citrate was cometabolized with glucose, a 10-fold reduction in the intracellular concentration of glucose-6-phosphate was observed, a result in line with the observed citrate-induced stimulation of glucose consumption. The presence of citrate provided additional pathways for NADP(sup+) regeneration and allowed the diversion of sugar carbon to reactions in which ATP was synthesized. The increased growth rates and maximal biomass yields of L. oenos growing on citrate-glucose mixtures resulted from increased ATP synthesis both by substrate-level phosphorylation and by a chemiosmotic mechanism. PMID:16535363

  9. 21 CFR 184.1449 - Manganese citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Manganese citrate. 184.1449 Section 184.1449 Food... Specific Substances Affirmed as GRAS § 184.1449 Manganese citrate. (a) Manganese citrate (Mn3(C6H5O7)2, CAS... manganese carbonate from manganese sulfate and sodium carbonate solutions. The filtered and washed...

  10. 21 CFR 184.1449 - Manganese citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Manganese citrate. 184.1449 Section 184.1449 Food... Specific Substances Affirmed as GRAS § 184.1449 Manganese citrate. (a) Manganese citrate (Mn3(C6H5O7)2, CAS... manganese carbonate from manganese sulfate and sodium carbonate solutions. The filtered and washed...

  11. 21 CFR 184.1449 - Manganese citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Manganese citrate. 184.1449 Section 184.1449 Food... Specific Substances Affirmed as GRAS § 184.1449 Manganese citrate. (a) Manganese citrate (Mn3(C6H5O7)2, CAS... manganese carbonate from manganese sulfate and sodium carbonate solutions. The filtered and...

  12. 21 CFR 573.560 - Iron ammonium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Iron ammonium citrate. 573.560 Section 573.560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food...

  13. 21 CFR 573.560 - Iron ammonium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Iron ammonium citrate. 573.560 Section 573.560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food...

  14. 21 CFR 573.560 - Iron ammonium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Iron ammonium citrate. 573.560 Section 573.560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food...

  15. 21 CFR 573.560 - Iron ammonium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Iron ammonium citrate. 573.560 Section 573.560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food...

  16. 21 CFR 520.1803 - Piperazine citrate capsules.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1803 Piperazine citrate.... (c) Conditions of use. (1) It is used in dogs and cats for the removal of large roundworms (Toxocara... for each 5 pounds, or fraction thereof of body weight, except dogs weighing over 25 pounds should be...

  17. 21 CFR 520.1803 - Piperazine citrate capsules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1803 Piperazine citrate.... (c) Conditions of use. (1) It is used in dogs and cats for the removal of large roundworms (Toxocara... for each 5 pounds, or fraction thereof of body weight, except dogs weighing over 25 pounds should be...

  18. 21 CFR 520.1803 - Piperazine citrate capsules.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1803 Piperazine citrate.... (c) Conditions of use. (1) It is used in dogs and cats for the removal of large roundworms (Toxocara... for each 5 pounds, or fraction thereof of body weight, except dogs weighing over 25 pounds should be...

  19. 21 CFR 520.1803 - Piperazine citrate capsules.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1803 Piperazine citrate.... (c) Conditions of use. (1) It is used in dogs and cats for the removal of large roundworms (Toxocara... for each 5 pounds, or fraction thereof of body weight, except dogs weighing over 25 pounds should be...

  20. 21 CFR 520.1803 - Piperazine citrate capsules.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1803 Piperazine citrate.... (c) Conditions of use. (1) It is used in dogs and cats for the removal of large roundworms (Toxocara... for each 5 pounds, or fraction thereof of body weight, except dogs weighing over 25 pounds should be...

  1. 21 CFR 573.560 - Iron ammonium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iron ammonium citrate. 573.560 Section 573.560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food...

  2. 21 CFR 573.580 - Iron-choline citrate complex.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iron-choline citrate complex. 573.580 Section 573.580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS...

  3. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  4. 21 CFR 522.300 - Carfentanil citrate injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Carfentanil citrate injection. 522.300 Section 522.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  5. 21 CFR 522.300 - Carfentanil citrate injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Carfentanil citrate injection. 522.300 Section 522.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  6. 21 CFR 522.300 - Carfentanil citrate injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Carfentanil citrate injection. 522.300 Section 522.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  7. 21 CFR 522.300 - Carfentanil citrate injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Carfentanil citrate injection. 522.300 Section 522.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  8. Citrate metabolism by Enterococcus faecium and Enterococcus durans isolated from goat's and ewe's milk: influence of glucose and lactose.

    PubMed

    Cabral, María E; Abeijón Mukdsi, María C; Medina de Figueroa, Roxana B; González, Silvia N

    2007-05-01

    Citrate metabolism by Enterococcus faecium ET C9 and Enterococcus durans Ov 421 was studied as sole energy source and in presence of glucose or lactose. Both strains utilized citrate as the sole energy source. Enterococcus faecium ET C9 showed diauxic growth in the presence of a limiting concentration of glucose. Neither strain used citrate until glucose was fully metabolized. The strains showed co-metabolism of citrate and lactose. Lactate, acetate, formate, and flavour compounds (diacetyl, acetoin, and 2,3-butanediol) were detected in both strains. The highest production of flavour compounds was detected during growth of E. durans Ov 421 in media supplemented with citrate-glucose and citrate-lactose. Citrate lyase was inducible in both strains. Acetate kinase activities presented the highest values in LAPTc medium, with E. faecium ET C9 displaying a specific activity 2.4-fold higher than E. durans. The highest levels of alpha-acetolactate synthase specific activity were detected in E. durans grown in LAPTc+g, in accordance with the maximum production of flavour compounds detected in this medium. Diacetyl and acetoinreductases displayed lower specific activity values in the presence of citrate. Enterococcus faecium and E. durans displayed citrate lyase, acetate kinase, alpha-acetolactate synthase, and diacetyl and acetoin reductase activities. These enzymes are necessary for conversion of citrate to flavour compounds that are important in fermented dairy products.

  9. Citrate-Stabilized Gold Nanorods

    PubMed Central

    2015-01-01

    Stable aqueous dispersions of citrate-stabilized gold nanorods (cit-GNRs) have been prepared in scalable fashion by surfactant exchange from cetyltrimethylammonium bromide (CTAB)-stabilized GNRs, using polystyrenesulfonate (PSS) as a detergent. The surfactant exchange process was monitored by infrared spectroscopy, surface-enhanced Raman scattering (SERS), and X-ray photoelectron spectroscopy (XPS). The latter established the quantitative displacement of CTAB (by PSS) and of PSS (by citrate). The Cit-GNRs are indefinitely stable at low ionic strength, and are conducive to further ligand exchange without loss of dispersion stability. The reliability of the surface exchange process supports the systematic analysis of ligand structure on the hydrodynamic size of GNRs, as described in a companion paper. PMID:25254292

  10. Citrate anticoagulation and adverse events.

    PubMed

    De Vos, J; Hombrouckx, R

    2003-01-01

    Several patients with heparin intolerance were dialysed with tri-sodium citrate as anticoagulant without acute clinical problems (good tolerance). After some weeks however problems arose. In all patients an alkalosis developed: the pre dialysis bicarbonate level rose progressively from 27 mmol/l to 40 mmol/l. This could be tempered by lowering the dialysis fluid bicarbonate concentration from 37 mmol/l to 25 mmol/l. A second problem was a progressive rise in pre dialysis sodium level from a mean of 136 mmol/l to 150 mmol/l. Adapting the dialysis fluid sodium concentration from 140 mmol/l towards 132 mmol/l could solve this. The third problem was a progressive rise in serum aluminium level in patients from 3 microg/l to 38 microg/l. After excluding water, concentrate, dialysis fluid, drug intake, etc... as possible sources, we controlled the aluminium level in the glass bottle containing tri-sodium citrate. We noted the very high value of 35,300 microg/l. After replacing the glass bottles with polyvinylchloride bags with a negligible aluminium content, the serum aluminium levels returned back to normal. It is known that citrate chelates the aluminium present in the glass of bottles or vials.

  11. Photochemical degradation of citrate buffers leads to covalent acetonation of recombinant protein therapeutics

    PubMed Central

    Valliere-Douglass, John F; Connell-Crowley, Lisa; Jensen, Randy; Schnier, Paul D; Trilisky, Egor; Leith, Matt; Follstad, Brian D; Kerr, Jennifer; Lewis, Nathan; Vunnum, Suresh; Treuheit, Michael J; Balland, Alain; Wallace, Alison

    2010-01-01

    Novel acetone and aldimine covalent adducts were identified on the N-termini and lysine side chains of recombinant monoclonal antibodies. Photochemical degradation of citrate buffers, in the presence of trace levels of iron, is demonstrated as the source of these modifications. The link between degradation of citrate and the observed protein modifications was conclusively established by tracking the citrate decomposition products and protein adducts resulting from photochemical degradation of isotope labeled 13C citrate by mass spectrometry. The structure of the acetone modification was determined by nuclear magnetic resonance (NMR) spectroscopy on modified–free glycine and found to correspond to acetone linked to the N-terminus of the amino acid through a methyl carbon. Results from mass spectrometric fragmentation of glycine modified with an acetone adduct derived from 13C labeled citrate indicated that the three central carbons of citrate are incorporated onto protein amines in the presence of iron and light. While citrate is known to stoichiometrically decompose to acetone and CO2 through various intermediates in photochemical systems, it has never been shown to be a causative agent in protein carbonylation. Our results point to a previously unknown source for the generation of reactive carbonyl species. This work also highlights the potential deleterious impact of trace metals on recombinant protein therapeutics formulated in citrate buffers. PMID:20836085

  12. Effects of citrate on hexavalent chromium reduction by structural Fe(II) in nontronite

    DOE PAGES

    Liu, Xiaolei; Dong, Hailiang; Yang, Xuewei; ...

    2017-09-23

    Previous studies have shown that organic ligands could influence Cr(VI) reduction by aqueous Fe2+ and pyrite. In this study, the effects of citrate on Cr(VI) reduction by structural Fe(II) in nontronite (NAu-2) were investigated at pH 6. Our results showed that the presence of citrate decreased the rate but increased the amount of Cr(VI) reduction. The decreased rate was likely due to competitive sorption of citrate and anionic dichromate (Cr2O7–) to NAu-2 surface sites, because sorption of dichromate appeared to be the first step for subsequent Cr(VI) reduction. The increased amount of Cr(VI) reduction was likely because citrate served asmore » an additional electron donor to reduce Cr(VI) through ligand-metal electron transfer in the presence of soluble Fe3+, which was possibly derived from dissolution of reduced NAu-2. Soluble Cr(III)-citrate complex was a possible form of reduced Cr(VI) when citrate was present. Without citrate, nanometer-sized Cr2O3 particles were the product of Cr(VI) reduction. In conclusion, our study highlights the importance of citrate on Cr(VI) reduction and immobilization when iron-rich smectite is applied to treat Cr(VI) contaminant in organic carbon rich environments.« less

  13. Divalent cation chelators citrate and EDTA unmask an intrinsic uncoupling pathway in isolated mitochondria.

    PubMed

    Starkov, Anatoly A; Chinopoulos, Christos; Starkova, Natalia N; Konrad, Csaba; Kiss, Gergely; Stepanova, Anna; Popov, Vasily N

    2017-02-01

    We demonstrate a suppression of ROS production and uncoupling of mitochondria by exogenous citrate in Mg(2+) free medium. Exogenous citrate suppressed H2O2 emission and depolarized mitochondria. The depolarization was paralleled by the stimulation of respiration of mitochondria. The uncoupling action of citrate was independent of the presence of sodium, potassium, or chlorine ions, and it was not mediated by the changes in permeability of the inner mitochondrial membrane to solutes. The citrate transporter was not involved in the citrate effect. Inhibitory analysis data indicated that several well described mitochondria carriers and channels (ATPase, IMAC, ADP/ATP translocase, mPTP, mKATP) were not involved in citrate's effect. Exogenous MgCl2 strongly inhibited citrate-induced depolarization. The uncoupling effect of citrate was demonstrated in rat brain, mouse brain, mouse liver, and human melanoma cells mitochondria. We interpreted the data as an evidence to the existence of a hitherto undescribed putative inner mitochondrial membrane channel that is regulated by extramitochondrial Mg(2+) or other divalent cations.

  14. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium citrate. 184.1625 Section 184.1625 Food... GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric acid with potassium...

  15. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric...

  16. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric...

  17. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric...

  18. 21 CFR 184.1625 - Potassium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS Reg. No. 006100-0905-096) is the potassium salt of citric acid. It is prepared by neutralizing citric...

  19. 21 CFR 184.1449 - Manganese citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Manganese citrate. 184.1449 Section 184.1449 Food... GRAS § 184.1449 Manganese citrate. (a) Manganese citrate (Mn3(C6H5O7)2, CAS Reg. No. 10024-66-5) is a pale orange or pinkish white powder. It is obtained by precipitating manganese carbonate from manganese...

  20. 21 CFR 184.1195 - Calcium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... acid with calcium hydroxide or calcium carbonate. It occurs as a fine white, odorless powder and... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium citrate. 184.1195 Section 184.1195 Food... Specific Substances Affirmed as GRAS § 184.1195 Calcium citrate. (a) Calcium citrate (Ca3(C6H5O7)2·4H2O...

  1. 21 CFR 184.1195 - Calcium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... acid with calcium hydroxide or calcium carbonate. It occurs as a fine white, odorless powder and... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium citrate. 184.1195 Section 184.1195 Food... Specific Substances Affirmed as GRAS § 184.1195 Calcium citrate. (a) Calcium citrate (Ca3(C6H5O7)2·4H2O...

  2. 21 CFR 184.1195 - Calcium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... calcium hydroxide or calcium carbonate. It occurs as a fine white, odorless powder and usually contains... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium citrate. 184.1195 Section 184.1195 Food and... Substances Affirmed as GRAS § 184.1195 Calcium citrate. (a) Calcium citrate (Ca3(C6H5O7)2·4H2O, CAS Reg. No...

  3. 21 CFR 184.1195 - Calcium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... acid with calcium hydroxide or calcium carbonate. It occurs as a fine white, odorless powder and... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium citrate. 184.1195 Section 184.1195 Food... Specific Substances Affirmed as GRAS § 184.1195 Calcium citrate. (a) Calcium citrate (Ca3(C6H5O7)2·4H2O...

  4. Molecular characterization of microbial population dynamics during sildenafil citrate degradation.

    PubMed

    De Felice, Bruna; Argenziano, Carolina; Guida, Marco; Trifuoggi, Marco; Russo, Francesca; Condorelli, Valerio; Inglese, Mafalda

    2009-02-01

    Little is known about pharmaceutical and personal care products pollutants (PPCPs), but there is a growing interest in how they might impact the environment and microbial communities. The widespread use of Viagra (sildenafil citrate) has attracted great attention because of the high usage rate, the unpredictable disposal and the unknown potential effects on wildlife and the environment. Until now information regarding the impact of Viagra on microbial community in water environment has not been reported. In this research, for the first time, the genetic profile of the microbial community, developing in a Viagra polluted water environment, was evaluated by means of the 16S and 18S rRNA genes, for bacteria and fungi, respectively, amplified by polymerase chain reaction (PCR) and separated using the denaturing gradient gel electrophoresis (DGGE) technique. The DGGE results revealed a complex microbial community structure with most of the population persisting throughout the experimental period. DNA sequences from bands observed in the different denaturing gradient gel electrophoresis profiles exhibited the highest degree of identity to uncultured bacteria and fungi found previously mainly in polluted environmental and treating bioreactors. Biotransformation ability of sildenafil citrate by the microbial pool was studied and the capability of these microorganisms to detoxify a polluted water ecosystem was assessed. The bacterial and fungal population was able to degrade sildenafil citrate entirely. Additionally, assays conducted on Daphnia magna, algal growth inhibition assay and cell viability determination on HepG2 human cells showed that biotransformation products obtained from the bacterial growth was not toxic. The higher removal efficiency for sildenafil citrate and the lack of toxicity by the biotransformation products obtained showed that the microbial community identified here represented a composite population that might have biotechnological relevance to

  5. 21 CFR 184.1307c - Ferrous citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ferrous citrate. 184.1307c Section 184.1307c Food... Specific Substances Affirmed as GRAS § 184.1307c Ferrous citrate. (a) Ferrous citrate (iron (II) citrate... the reaction of sodium citrate with ferrous sulfate or by direct action of citric acid on iron filings...

  6. Synthesis of Stable Citrate-Capped Silver Nanoprisms.

    PubMed

    Haber, Jason M; Sokolov, Konstantin

    2017-09-12

    Citrate-stabilized silver nanoprisms (AgNPrs) can be easily functionalized using well-developed thiol based surface chemistry that is an important requirement for biosensor applications utilizing localized surface plasmon resonance (LSPR) and surface-enhanced Raman Scattering (SERS). Unfortunately, currently available protocols for synthesis of citrate-coated AgNPrs do not produce stable nanoparticles thus limiting their usefulness in biosensing applications. Here we address this problem by carrying out a systematic study of citrate-stabilized, peroxide-based synthesis of AgNPrs to optimize reaction conditions for production of stable and reproducible nanoprisms. Our analysis showed that concentration of secondary reducing agent, L-ascorbic acid, is critical to AgNPr stability. Furthermore, we demonstrated that optimization of other synthesis conditions such as stabilizer concentration, rate of silver nitrate addition and seed dilution result in highly stable nanoprisms with narrow absorption peaks ranging from 450nm into near-IR. In addition, the optimized reaction conditions can be used to produce AgNPrs in a one-pot synthesis instead of a previously described two-step reaction. The resulting nanoprisms can readily interact with thiols for easy surface functionalization. These studies provide an optimized set of parameters for precise control of citrate stabilized AgNPr synthesis for biomedical applications.

  7. Renal tissue citrate: independence from citrate utilization, reabsorption, and pH.

    PubMed

    Anaizi, N H; Cohen, J J; Black, A J; Wertheim, S J

    1986-09-01

    During alkalosis in vivo, renal tissue [citrate] [( citrate]t) increases and citrate reabsorption (Tcit) and utilization (Qcit) simultaneously decrease. The decrease in Qcit is interpreted to cause the increased [citrate]t, which in turn decreases Tcit X Renal citrate handling and [citrate]t could be regulated by other mechanisms, since alkalosis changes [substrate] and [H+] in extracellular (ECF) and intracellular (ICF) fluid. Also, since high plasma [citrate] decreases ionized [Ca2+] (Cai), it is not possible to determine in vivo whether there is a maximum for Tcit or Qcit and whether change in extracellular fluid (delta ECF) pH affects these maxima. We perfused the substrate-limited isolated rat kidney for either 110 (n = 36) or 50 min (n = 44) at pH 7.2, 7.4, or 7.6; pH was changed by varying [HCO3-]; Cai was held constant at approximately 2.5 meq/liter. When citrate was the only substrate available in a Krebs-Ringer-HCO3 perfusate containing 6% substrate-free albumin, both Qcit and Tcit had maximal rates: Qcit much greater than Tcit; at pH 7.6, Qcit and Tcit were significantly reduced below their values at pH 7.2 or 7.4. In contrast to in vivo observations, [citrate]t was not significantly increased at high ECF pH. To test whether [citrate]t in the perfused kidney can increase in alkalosis, 11 additional perfusions were done in the presence of glucose plus lactate plus malate but without added citrate: [citrate]t = 0.6 mumol X g-1 at pH 7.6 and 0.3 mumol X g-1 at pH 7.2 (P less than 0.01); no citrate was detectable in the perfusate, and urinary citrate excretion was negligible. Thus, in the isolated rat kidney, an increase in [citrate]t occurred in alkalosis and was derived from precursors and not from citrate in the ECF. Overall, when only citrate was available to the isolated kidney during alkalosis, a significant rise in [citrate]t did not occur, although Vmax for Tcit and Qcit decreased. These effects of alkalosis on Tcit are consistent with observations

  8. 21 CFR 184.1386 - Isopropyl citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Specific Substances Affirmed as GRAS § 184.1386 Isopropyl citrate. (a) Isopropyl citrate is a mixture of the mono-, di-, and triisopropyl esters of citric acid. It is prepared by esterifying citric acid with... practice. The affirmation of this ingredient as generally recognized as safe (GRAS) as a direct human...

  9. 21 CFR 184.1851 - Stearyl citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Specific Substances Affirmed as GRAS § 184.1851 Stearyl citrate. (a) Stearyl citrate is a mixture of the mono-, di-, and tristearyl esters of citric acid. It is prepared by esterifying citric acid with... manufacturing practice. The affirmation of this ingredient as generally recognized as safe (GRAS) as a...

  10. [Development of identification method for isopropyl citrate].

    PubMed

    Furusho, Noriko; Ohtsuki, Takashi; Tatebe-Sasaki, Chiye; Kubota, Hiroki; Sato, Kyoko; Akiyama, Hiroshi

    2014-01-01

    In Japan's Specification and Standards for Food Additive, 8th edition, two identification tests involving isopropyl citrate for detecting isopropyl alcohol and citrate are stipulated. However, these identification tests use mercury compound, which is toxic, or require a time-consuming pretreatment process. To solve these problems, an identification test method using GC-FID for detecting isopropyl alcohol was developed. In this test, a good linearity was observed in the range of 0.1-40 mg/mL of isopropyl alcohol. While investigating the pretreatment process, we found that isopropyl alcohol could be detected using GC-FID in the distillation step only, without involving any reflux step. The study also showed that the citrate moiety of isopropyl citrate was identified using the solution remaining after conducting the distillation of isopropyl alcohol. The developed identification tests for isopropyl citrate are simple and use no toxic materials.

  11. Incompatibility of Contrast Medium and Trisodium Citrate

    SciTech Connect

    Delcour, Christian Bruninx, Guy

    2013-02-15

    To test the compatibility of trisodium citrate, a catheter lock solution, with iodinated contrast medium. Iohexol, iobitridol, iodixanol, ioxaglate, ioxithalamate, iomeprol, and iopromide were tested. In all tests, 2 ml of contrast medium were mixed with 2 ml of trisodium citrate solution. Iodixanol and ioxaglate provoked a highly viscous gluelike precipitation when mixed with trisodium citrate. A brief transient precipitate was observed with iohexol, iomeprol, and ioxithalamate. Permanent precipitation occurred with iobitridol and iopromide. One must be aware of the potential for precipitation when contrast medium is mixed with trisodium citrate solution. Before trisodium citrate solution is injected, the catheter should be thoroughly flushed with saline if a contrast medium has previously been injected through it.

  12. Effect of volume expansion on renal citrate and ammonia metabolism in KCl-deficient rats.

    PubMed Central

    Adler, S; Zett, B; Anderson, B; Fraley, D S

    1975-01-01

    When rats with desoxycorticosterone acetate (DOCA)-induced potassium chloride deficiency are given sodium chloride there is simultaneously a partial correction of metabolic alkalosis and a marked reduction in urinary citrate excretion and renal citrate content. To examine DOCA's role in this phenomenon and to determine how sodium chloride alters renal metabolism, rats were made KC1 deficient using furosemide and a KC1-deficient diet. Renal citrate and ammonia metabolism were then studied after chronic oral sodium chloride administration or acute volume expansion with isotonic mannitol. Although both maneuvers partially corrected metabolic alkalosis, sodium chloride raised serum chloride concentration while mannitol significantly decreased it. Urinary citrate excretion decreased to 10% of control in rats given NaCl and to 50% of control in rats infused with mannitol. The filtered load of citrate was constant or increased indicating increased tubular citrate reabsorption. Renal cortical citrate content also decreased approximately 50%. Renal cortical slices from KCl-deficient rats incubated in low or normal chloride media produced equal amounts of 14CO2 from (1, 5-14C) citrate. In addition, urinary ammonia excretion increased by over 300% in both groups. This occurred in the mannitol group despite increased urinary pH and flow rate indicating a rise in renal ammonia production. It seems that neither DOCA nor an increase in serum chloride concentration explains the experimental results. Rather, it appears that volume expansion is responsible for increased renal tubular citrate reabsorption and renal ammonia production. As these renal metabolic responses ordinarily occur in response to acidosis, the data are consistent with the hypothesis that volume expansion reduces renal cell pH in 3KCl-deficient rats. PMID:239022

  13. [Butamyrate citrate in cough controlling].

    PubMed

    Płusa, Tadeusz

    2013-12-01

    The cough as one of the main symptoms of respiratory infections in the most cases is carried out in children and adults using preparations without a prescription (OTC--over-the-counter) and cold medications (CCMs). Their efficacy and safety have not been fully confirmed. In turn, the administration of drugs that inhibit cough by acting on the central nervous system requires adherence to dosage. Codeine as the main standard of the cough suppressants is not always effective. Used for many years butamyrate citrate is highly effective and complete safety. The number and quality of the side effects after application of this preparation is small and is not limited especially in pediatrics. Conducted research on new drugs that inhibit cough are very promising.

  14. 13C Nuclear Magnetic Resonance Studies of Citrate and Glucose Cometabolism by Lactococcus lactis

    PubMed Central

    Ramos, Ana; Jordan, Kieran N.; Cogan, Timothy M.; Santos, Helena

    1994-01-01

    13C nuclear magnetic resonance (13C-NMR) was used to investigate the metabolism of citrate plus glucose and pyruvate plus glucose by nongrowing cells of Lactococcus lactis subsp. lactis 19B under anaerobic conditions. The metabolism of citrate plus glucose during growth was also monitored directly by in vivo NMR. Although pyruvate is a common intermediate metabolite in the metabolic pathways of both citrate and glucose, the origin of the carbon atoms in the fermentation products was determined by using selectively labeled substrates, e.g., [2,4-13C]citrate, [3-13C]pyruvate, and [2-13C]glucose. The presence of an additional substrate caused a considerable stimulation in the rates of substrate utilization, and the pattern of end products was changed. Acetate plus acetoin and butanediol represented more than 80% (molar basis) of the end products of the metabolism of citrate (or pyruvate) alone, but when glucose was also added, 80% of the citrate (or pyruvate) was converted to lactate. This result can be explained by the activation of lactate dehydrogenase by fructose 1,6-bisphosphate, an intermediate in glucose metabolism. The effect of different concentrations of glucose on the metabolism of citrate by dilute cell suspensions was also probed by using analytical methods other than NMR. Pyruvate dehydrogenase (but not pyruvate formate-lyase) was active in the conversion of pyruvate to acetyl coenzyme A. α-Acetolactate was detected as an intermediate metabolite of citrate or pyruvate metabolism, and the labeling pattern of the end products agrees with the α-acetolactate pathway. It was demonstrated that the contribution of the acetyl coenzyme A pathway for the synthesis of diacetyl, should it exist, is lower than 10%. Evidence for the presence of internal carbon reserves in L. lactis is presented. PMID:16349269

  15. Citrate bridges between mineral platelets in bone.

    PubMed

    Davies, Erika; Müller, Karin H; Wong, Wai Ching; Pickard, Chris J; Reid, David G; Skepper, Jeremy N; Duer, Melinda J

    2014-04-08

    We provide evidence that citrate anions bridge between mineral platelets in bone and hypothesize that their presence acts to maintain separate platelets with disordered regions between them rather than gradual transformations into larger, more ordered blocks of mineral. To assess this hypothesis, we take as a model for a citrate bridging between layers of calcium phosphate mineral a double salt octacalcium phosphate citrate (OCP-citrate). We use a combination of multinuclear solid-state NMR spectroscopy, powder X-ray diffraction, and first principles electronic structure calculations to propose a quantitative structure for this material, in which citrate anions reside in a hydrated layer, bridging between apatitic layers. To assess the relevance of such a structure in native bone mineral, we present for the first time, to our knowledge, (17)O NMR data on bone and compare them with (17)O NMR data for OCP-citrate and other calcium phosphate minerals relevant to bone. The proposed structural model that we deduce from this work for bone mineral is a layered structure with thin apatitic platelets sandwiched between OCP-citrate-like hydrated layers. Such a structure can explain a number of known structural features of bone mineral: the thin, plate-like morphology of mature bone mineral crystals, the presence of significant quantities of strongly bound water molecules, and the relatively high concentration of hydrogen phosphate as well as the maintenance of a disordered region between mineral platelets.

  16. A citrate-binding site in calmodulin.

    PubMed

    Neufeld, T; Eisenstein, M; Muszkat, K A; Fleminger, G

    1998-01-01

    Calmodulin (CaM) is a major Ca2+ messenger which, upon Ca2+ activation, binds and activates a number of target enzymes involved in crucial cellular processes. The dependence on Ca2+ ion concentration suggests that CaM activation may be modulated by low-affinity Ca2+ chelators. The effect on CaM structure and function of citrate ion, a Ca2+ chelator commonly found in the cytosol and the mitochondria, was therefore investigated. A series of structural and biochemical methods, including tryptic mapping, immunological recognition by specific monoclonal antibodies, CIDNP-NMR, binding to specific ligands and association with radiolabeled citrate, showed that citrate induces conformational modifications in CaM which affect the shape and activity of the protein. These changes were shown to be associated with the C-terminal lobe of the molecule and involve actual binding of citrate to CaM. Analyzing X-ray structures of several citrate-binding proteins by computerized molecular graphics enabled us to identify a putative citrate-binding site (CBS) on the CaM molecule around residues Arg106-His107. Owing to the tight proximity of this site to the third Ca(2+)-binding loop of CaM, binding of citrate is presumably translated into changes in Ca2+ binding to site III (and indirectly to site IV). These changes apparently affect the structural and biochemical properties of the conformation-sensitive protein.

  17. Myocardial citrate metabolism in control subjects and patients with coronary artery disease.

    PubMed

    Nielsen, T T; Henningsen, P; Bagger, J P; Thomsen, P E; Eyjolfsson, K

    1980-10-01

    A significant release of citrate across the myocardium was demonstrated in twenty-two patients with coronary artery disease (CAD) and in ten control subjects in fasting resting state. In both groups, increasingly negative arterio-coronary sinus (A-Cs) plasma citrate differences correlated positively to arterial plasma free fatty acid (FFA)concentrations and negatively to (A-Cs) differences of plasma glucose. This supports the hypothesis that a citrate inhibition of glycolysis at the site of phosphofructokinase is of regulatory importance for myocardial glucose metabolism, and suggests that FFA supress glucose utilization by the heart in many by this mechanism. The capacity of plasma FFA to increase myocardial citrate release was significantly higher in controls than in patients with CAD, and was found to be positively related to myocardial capacity of oxygen consumption as estimated from the product of heart rate and systolic blood pressure during an exercise tolerance test.

  18. 21 CFR 172.430 - Iron ammonium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Iron ammonium citrate. 172.430 Section 172.430... CONSUMPTION Anticaking Agents § 172.430 Iron ammonium citrate. Iron ammonium citrate may be safely used in... human consumption so that the level of iron ammonium citrate does not exceed 25 parts per million (0...

  19. 21 CFR 172.430 - Iron ammonium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Iron ammonium citrate. 172.430 Section 172.430 Food... Anticaking Agents § 172.430 Iron ammonium citrate. Iron ammonium citrate may be safely used in food in... consumption so that the level of iron ammonium citrate does not exceed 25 parts per million (0.0025 percent...

  20. 21 CFR 172.430 - Iron ammonium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Iron ammonium citrate. 172.430 Section 172.430... CONSUMPTION Anticaking Agents § 172.430 Iron ammonium citrate. Iron ammonium citrate may be safely used in... human consumption so that the level of iron ammonium citrate does not exceed 25 parts per million (0...

  1. 21 CFR 172.430 - Iron ammonium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Iron ammonium citrate. 172.430 Section 172.430... CONSUMPTION Anticaking Agents § 172.430 Iron ammonium citrate. Iron ammonium citrate may be safely used in... human consumption so that the level of iron ammonium citrate does not exceed 25 parts per million (0...

  2. Citrate bridges between mineral platelets in bone

    PubMed Central

    Davies, Erika; Müller, Karin H.; Wong, Wai Ching; Pickard, Chris J.; Reid, David G.; Skepper, Jeremy N.; Duer, Melinda J.

    2014-01-01

    We provide evidence that citrate anions bridge between mineral platelets in bone and hypothesize that their presence acts to maintain separate platelets with disordered regions between them rather than gradual transformations into larger, more ordered blocks of mineral. To assess this hypothesis, we take as a model for a citrate bridging between layers of calcium phosphate mineral a double salt octacalcium phosphate citrate (OCP-citrate). We use a combination of multinuclear solid-state NMR spectroscopy, powder X-ray diffraction, and first principles electronic structure calculations to propose a quantitative structure for this material, in which citrate anions reside in a hydrated layer, bridging between apatitic layers. To assess the relevance of such a structure in native bone mineral, we present for the first time, to our knowledge, 17O NMR data on bone and compare them with 17O NMR data for OCP-citrate and other calcium phosphate minerals relevant to bone. The proposed structural model that we deduce from this work for bone mineral is a layered structure with thin apatitic platelets sandwiched between OCP-citrate–like hydrated layers. Such a structure can explain a number of known structural features of bone mineral: the thin, plate-like morphology of mature bone mineral crystals, the presence of significant quantities of strongly bound water molecules, and the relatively high concentration of hydrogen phosphate as well as the maintenance of a disordered region between mineral platelets. PMID:24706850

  3. Cardiovascular effects of diethylcarbamazine citrate.

    PubMed Central

    Abaitey, A K; Parratt, J R

    1976-01-01

    1 The cardiovascular effects of the anthelmintic drug diethylcarbamazine citrate (DECC) were examined in cats anaesthetized with pentobarbitone. There were two quite distinct haemodynamic responses, an initial transient hypotension (occurring within 10 s of an intravenous injection) and a pronounced secondary hypertension which reached a peak 30-60 s after the injection. 2 Within 10 s of an intravenous injection of DECC (2.5 to 10 mg/kg) there was hypotension, bradycardia and there were reductions in left ventricular and carotid artery dP/dt max. These effects were most pronounced following injections into the pulmonary artery; they were not observed after bilateral vagotomy or after injections into the lumen of the left ventricle. It is suggested that DECC, like nicotine, stimulates vagal receptors in the pulmonary vascular bed. 3 The secondary phase was characterized by marked systemic and pulmonary hypertension, by contractions of the nictitating membrane and by increases in left ventricular dP/dt (at fixed isovolumic pressures), in cardiac output and in myocardial blood flow. All these effects were prevented, or markedly reduced, following the administration of hexamethonium or bethanidine and the pressor response was prevented by phentolamine. It is concluded that, in doses similar to those used in therapeutics, DECC stimulates sympathetic ganglia and releases noradrenaline. The relevance of this finding to the reported side effects of the drug are discussed. 4 DECC (5 or 10 mg/kg) significantly inhibited prostaglandin F2alpha-induced increases in peak inspiratory intra-tracheal pressure without modifying its pulmonary hypertensive effect. The possible relevance of this finding to the use of DECC in asthma is discussed. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:1252670

  4. Photodegradation of propranolol by Fe(III)-citrate complexes: kinetics, mechanism and effect of environmental media.

    PubMed

    Chen, Yong; Liu, Zizheng; Wang, Zongping; Xue, Miaomiao; Zhu, Xianchen; Tao, Tao

    2011-10-30

    Photogeneration of HO was optimized in Fe(III)-citrate solution within the pH range of 3.0-9.0 to investigate its photoreactivity at neutral pH without the addition of H(2)O(2) under simulated sunlight. The generation of HO decreased with increasing pH within the range of 6.0-9.0 at the Fe(III)-to-citrate ratio of 10:50 (10(-6)M). However, when the concentration of citrate increased to 1.5 × 10(-4)M, the formation rate of HO increased in the order of pH 9.0<3.0<7.0<4.0<5.0. The pH-dependent HO production was governed by the stability of Fe(II)/Fe(II)-citrate and the amount of O(2)(-) in the solution. Propranolol can be efficiently photodegraded in Fe(III)-citrate system at pH 7.0 with pseudo-first-order constant 3.1 × 10(-4)s(-1). HO was verified to be the main reactive oxygen species (ROS) responsible for the photodegradation of propranolol. The presence of metal ions inhibited the Fe(III)-cit-induced photodegradation in the order of Mn(2+)>Cu(2+)>Ca(2+)>Mg(2+). Both humic acid (HA) and fulvic acid (FA) markedly suppressed the degradation of propranolol. Moreover, the iron in Fe(III)-citrate system was reused by a simple addition of citrate to the reaction solution. By GC-MS analysis, the photoproducts of the propranolol were identified and the degradation pathway was proposed. This work suggests that Fe(III)-citrate complexes are good alternative for the advanced treatment of organic pollutants at neutral pH in aqueous solution. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. SbnG, a citrate synthase in Staphylococcus aureus: A new fold on an old enzyme

    DOE PAGES

    Kobylarz, Marek J.; Grigg, Jason C.; Sheldon, Jessica R.; ...

    2014-10-21

    In response to iron deprivation, Staphylococcus aureus produces staphyloferrin B, a citrate-containing siderophore that delivers iron back to the cell. This bacterium also possesses a second citrate synthase, SbnG, that is necessary for supplying citrate to the staphyloferrin B biosynthetic pathway. In this paper, we present the structure of SbnG bound to the inhibitor calcium and an active site variant in complex with oxaloacetate. The overall fold of SbnG is structurally distinct from TCA cycle citrate synthases yet similar to metal-dependent class II aldolases. Phylogenetic analyses revealed that SbnG forms a separate clade with homologs from other siderophore biosynthetic genemore » clusters and is representative of a metal-independent subgroup in the phosphoenolpyruvate/pyruvate domain superfamily. Finally, a structural superposition of the SbnG active site to TCA cycle citrate synthases and site-directed mutagenesis suggests a case for convergent evolution toward a conserved catalytic mechanism for citrate production.« less

  6. Citrate synthase encoded by the CIT2 gene of Saccharomyces cerevisiae is peroxisomal.

    PubMed Central

    Lewin, A S; Hines, V; Small, G M

    1990-01-01

    The product of the CIT2 gene has the tripeptide SKL at its carboxyl terminus. This amino acid sequence has been shown to act as a peroxisomal targeting signal in mammalian cells. We examined the subcellular site of this extramitochondrial citrate synthase. Cells of Saccharomyces cerevisiae were grown on oleate medium to induce peroxisome proliferation. A fraction containing membrane-enclosed vesicles and organelles was analyzed by sedimentation on density gradients. In wild-type cells, the major peak of citrate synthase activity was recovered in the mitochondrial fraction, but a second peak of activity cosedimented with peroxisomes. The peroxisomal activity, but not the mitochondrial activity, was inhibited by incubation at pH 8.1, a characteristic of the extramitochondrial citrate synthase encoded by the CIT2 gene. In a strain in which the CIT1 gene encoding mitochondrial citrate synthase had been disrupted, the major peak of citrate synthase activity was peroxisomal, and all of the activity was sensitive to incubation at pH 8.1. Yeast cells bearing a cit2 disruption were unable to mobilize stored lipids and did not form stable peroxisomes in oleate. We conclude that citrate synthase encoded by CIT2 is peroxisomal and participates in the glyoxylate cycle. Images PMID:2181273

  7. Platinum states in citrate sols by EXAFS.

    PubMed

    Lin, Chia-Shiang; Khan, Maksudur R; Lin, Shawn D

    2005-07-01

    Platinum sols have been prepared by citrate reduction in the temperature range of 343-363 K. The Pt state in the solution was examined by EXAFS (extended X-ray absorption fine-structure spectroscopy). It did not show any PtPt bonding, a characteristic for reduced Pt sols. EXAFS model fitting further proved the presence of PtO with 4 oxygen neighbors, which suggests a tetraplanar coordination configuration. The possibility of neighboring Pt sharing oxygen ligand or the formation of PtO(x) is rejected by EXAFS model fitting. Citrate was found to be the most likely ligand to orient its oxygen end toward a charged Pt center. Thus we have revealed that the citrate treatment at this temperature range was clearly insufficient to reduce H2PtCl(6(aq)). Neither an extended period of reaction time nor an excess citrate reduced the Pt precursor. It is therefore highly recommended that the citrate sols should be carefully prepared and used.

  8. Citrate, a specific substrate for the isolation of Clostridium sphenoides.

    PubMed Central

    Walther, R; Hippe, H; Gottschalk, G

    1977-01-01

    With a medium containing citrate as the carbon and energy source, 10 clostridial strains were isolated from various mud samples. Characterization of these strains revealed that they all belonged to the same species, Clostridium sphenoides. Strains of this organism obtained from culture collections were also able to grow citrate, whereas 15 other clostridial species tested were not. Citrate was fermented by C. sphenoides to acetate, ethanol, carbon dioxide, and hydrogen. Experiments with stereospecifically 14C-labeled citrate indicated that citrate lyase was involved in citrate degradation. Images PMID:869540

  9. Enhanced citric acid biosynthesis in Pseudomonas fluorescens ATCC 13525 by overexpression of the Escherichia coli citrate synthase gene.

    PubMed

    Buch, Aditi D; Archana, G; Kumar, G Naresh

    2009-08-01

    Citric acid secretion by fluorescent pseudomonads has a distinct significance in microbial phosphate solubilization. The role of citrate synthase in citric acid biosynthesis and glucose catabolism in pseudomonads was investigated by overexpressing the Escherichia coli citrate synthase (gltA) gene in Pseudomonas fluorescens ATCC 13525. The resultant approximately 2-fold increase in citrate synthase activity in the gltA-overexpressing strain Pf(pAB7) enhanced the intracellular and extracellular citric acid yields during the stationary phase, by about 2- and 26-fold, respectively, as compared to the control, without affecting the growth rate, glucose depletion rate or biomass yield. Decreased glucose consumption was paralleled by increased gluconic acid production due to an increase in glucose dehydrogenase activity. While the extracellular acetic acid yield increased in Pf(pAB7), pyruvic acid secretion decreased, correlating with an increase in pyruvate carboxylase activity and suggesting an increased demand for the anabolic precursor oxaloacetate. Activities of two other key enzymes, glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase, remained unaltered, and the contribution of phosphoenolpyruvate carboxylase and isocitrate lyase to glucose catabolism was negligible. Strain Pf(pAB7) demonstrated an enhanced phosphate-solubilizing ability compared to the control. Co-expression of the Synechococcus elongatus PCC 6301 phosphoenolpyruvate carboxylase and E. coli gltA genes in P. fluorescens ATCC 13525, so as to supplement oxaloacetate for citrate biosynthesis, neither significantly affected citrate biosynthesis nor caused any change in the other physiological and biochemical parameters measured, despite approximately 1.3- and 5-fold increases in citrate synthase and phosphoenolpyruvate carboxylase activities, respectively. Thus, our results demonstrate that citrate synthase is rate-limiting in enhancing citrate biosynthesis in P. fluorescens ATCC 13525

  10. Vibrational study of tamoxifen citrate polymorphism

    NASA Astrophysics Data System (ADS)

    Gamberini, M. C.; Baraldi, C.; Tinti, A.; Palazzoli, F.; Ferioli, V.

    2007-09-01

    The trans isomer of ( Z)-2-[ p-(1,2-diphenyl-butenyl)phenoxy]- N, N-dimethyletylamine (tamoxifen) is well known for its endocrine activity as an antiestrogenic agent. Its citrate salt, a widely used pharmaceutical agent, appears in three main polymorphic forms, two of which are well known (I and II) and another form not yet well evidenced. A vibrational study has been conducted for identifying the two known polymorphic forms of tamoxifen citrate (I and II) and for characterising the other form (form III) examined in this study. Other techniques for the characterization of the different polymorphs, such as XRDP, have been used.

  11. Nickel sorption to goethite and montmorillonite in presence of citrate.

    PubMed

    Marcussen, Helle; Holm, Peter E; Strobel, Bjarne W; Hansen, Hans Chr B

    2009-02-15

    Mobility and bioavailability of nickel (Ni) in soil strongly depends on the interaction between Ni(II), ligands, and sorbents like organic matter and minerals. Sorption of Ni(II) and Ni(II)-citrate complexes to goethite and montmorillonite was examined in batch experiments with and without citrate as ligand in the pH range pH 4-7.5. Without citrate, montmorillonite shows higher Ni sorption than goethite. Citrate strongly decreases Ni sorption to montmorillonite; in presence of 100 microM citrate goethite becomes a stronger Ni sorbent than montmorillonite. Ni and citrate sorption was modeled successfully using the diffuse double layer model with the following reactions: Goethite: 3 [triple bond]FeOH + Citrate(3-) + 3H+ <=> [triple bond] Fe3Citrate + 3H2O, [triple bond]FeOH + Ni2+ <=> [triple bond] FeONi + H+ and 2 [triple bond] FeOH + Citrate(3)- + Ni2+ <=> [triple bond] FeONiCitrate(2-) + H+. Montmorillonite: 2X- + Ni2+ <=> X2Ni and [triple bond] AIOH + Ni2+ <=> AIONi+ + H+. Sorption of Ni to a mixture of goethite and montmorillonite could be calculated by use of reactions and constants for the monomineral systems. Without citrate, the sorbed amount of Ni per mass unit in the mixture can be found as a simple average of sorption to the two single sorbents, while in presence of citrate Ni sorption to montmorillonite is strongly influenced by citrate sorption to goethite.

  12. Flipping a citrate switch on liver cancer cells.

    PubMed

    Peters, Jeffrey M

    2017-08-18

    Energy homeostasis and oncogenic signaling are critical determinants of the growth of human liver cancer cells, providing a strong rationale to elucidate the regulatory mechanisms for these systems. A new study reports that loss of solute carrier family 13 member 5, which transports citrate across cell membranes, halts liver cancer cell growth by altering both energy production and mammalian target of rapamycin signaling in human liver cancer cell lines and in both an in vitro and in vivo model of liver tumors, suggesting a new target for liver cancer chemoprevention and/or chemotherapy. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Effect of two anti-estrogens, clomiphene citrate and tamoxifen, on cervical mucus and sperm-cervical mucus interaction.

    PubMed

    Annapurna, V; Dhaliwal, L K; Gopalan, S

    1997-01-01

    To compare the effect of two ovulation-inducing agents, clomiphene citrate and tamoxifen, on cervical mucus and sperm-cervical mucus interaction. Forty couples with unexplained infertility attending infertility clinic. Cervical mucus scoring and postcoital test done using the Moghissi system in a spontaneous cycle (control cycle) and with clomiphene citrate or tamoxifen (study cycles). Clomiphene citrate significantly decreased cervical mucus production, whereas tamoxifen significantly improved the total score. Tamoxifen is a better drug than clomiphene for ovulation induction in women with poor cervical mucus quality.

  14. 21 CFR 184.1296 - Ferric ammonium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... granules or as a brownish-yellowish powder. (2) Ferric ammonium citrate (iron (III) ammonium citrate, CAS... granules, as a powder, or as transparent green crystals. (b) The ingredients meet the specifications of the...

  15. Photochemistry of iron citrates initiated by UV-VIS light

    NASA Astrophysics Data System (ADS)

    Corral Arroyo, Pablo; Dou, Jing; Alpert, Peter; Krieger, Ulrich; Ammann, Markus

    2017-04-01

    Aerosol aging refers to the multitude of physical and chemical transformation atmospheric particles undergo, which play an important role in the impact of aerosols on climate, air quality and health. Aging processes may be started by chromophores, which act as photocatalysts that induce the oxidation of non-absorbing molecules [1]. Iron (Fe(III)) carboxylate complexes absorb light below about 500 nm, which is followed by ligand to metal charge transfer (LMCT) resulting in the reduction of iron to Fe(II) and oxidation of the carboxylate ligands, a process that represents an important sink of organic acids in the troposphere [2]. Our goal is to investigate how these photochemical processes contribute to the change of chemical and physical properties of the aerosol particles. To achieve this scope, we carry out coated wall flow tube experiments, exposing films with iron citrate to UV light, which will give information about the radical and LVOC production (connecting the CWFT to a Chemiluminescent Detector or PTR-TOF-MS respectively). From extracting and analyzing the films after irradiation with UV light, we obtain a profile of low-volatility products evolving from the photochemistry of iron citrates. By Scanning Transmission X-Ray Microspectroscopy (STXM) we analyze changes in the C K-edge and Fe L-edge in particles loaded with iron citrate upon exposure to light and follow their chemical and structural evolution upon photochemical oxidation in situ to investigate the degradation kinetics under varying environmental conditions. [1] George G., Ammann M., D'Anna B., Donaldson D. J., Nizkorodov S. A., Heterogeneous photochemistry in the Atmosphere, Chem. Rev., 2015, 115 (10), pp 4218-4258 [2] Weller, C., Horn, S., and Herrmann, H.: Photolysis of Fe(III) carboxylate complexes: Fe(II) quantum yields and reaction mechanisms, Photochemistry and Photobiology A: Chemistry, 268, 24-36, 2013.

  16. 21 CFR 73.2110 - Bismuth citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... restrictions. The color additive bismuth citrate may be safely used in cosmetics intended for coloring hair on..., eyebrows, or hair on parts of the body other than the scalp. (d) Labeling. (1) The label of the color... abraded scalp. Do not use to color eyelashes, eyebrows, or hair on parts of the body other than the scalp...

  17. 21 CFR 73.2110 - Bismuth citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... restrictions. The color additive bismuth citrate may be safely used in cosmetics intended for coloring hair on..., eyebrows, or hair on parts of the body other than the scalp. (d) Labeling. (1) The label of the color... abraded scalp. Do not use to color eyelashes, eyebrows, or hair on parts of the body other than the scalp...

  18. 21 CFR 73.2110 - Bismuth citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... restrictions. The color additive bismuth citrate may be safely used in cosmetics intended for coloring hair on..., eyebrows, or hair on parts of the body other than the scalp. (d) Labeling. (1) The label of the color... abraded scalp. Do not use to color eyelashes, eyebrows, or hair on parts of the body other than the scalp...

  19. 21 CFR 73.2110 - Bismuth citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... restrictions. The color additive bismuth citrate may be safely used in cosmetics intended for coloring hair on..., eyebrows, or hair on parts of the body other than the scalp. (d) Labeling. (1) The label of the color... abraded scalp. Do not use to color eyelashes, eyebrows, or hair on parts of the body other than the scalp...

  20. 21 CFR 73.2110 - Bismuth citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... restrictions. The color additive bismuth citrate may be safely used in cosmetics intended for coloring hair on..., eyebrows, or hair on parts of the body other than the scalp. (d) Labeling. (1) The label of the color... abraded scalp. Do not use to color eyelashes, eyebrows, or hair on parts of the body other than the scalp...

  1. 14 N NQR spectrum of sildenafil citrate

    NASA Astrophysics Data System (ADS)

    Stephenson, David; Singh, Nadia

    2015-04-01

    The 14N nuclear quadrupole resonance (NQR) spectrum of sildenafil citrate tablets has been recorded allowing the quadrupole coupling constants and asymmetry parameters of all six unique nitrogen atoms in its structure to be determined. A density function calculation gives results that are largely in agreement with the experimental values.

  2. 21 CFR 184.1195 - Calcium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium citrate. 184.1195 Section 184.1195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as...

  3. 21 CFR 184.1386 - Isopropyl citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Isopropyl citrate. 184.1386 Section 184.1386 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of...

  4. 21 CFR 184.1449 - Manganese citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Manganese citrate. 184.1449 Section 184.1449 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of...

  5. 21 CFR 172.430 - Iron ammonium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Iron ammonium citrate. 172.430 Section 172.430... ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Anticaking Agents § 172.430 Iron ammonium citrate. Iron ammonium citrate may be safely used in food in accordance with the following...

  6. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Iron-choline citrate complex. 172.370 Section 172... Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline citrate complex made by reacting... source of iron in foods for special dietary use. ...

  7. 21 CFR 520.622b - Diethylcarbamazine citrate syrup.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate syrup. 520.622b Section... Diethylcarbamazine citrate syrup. (a)(1) Specifications. Each milliliter of syrup contains 60 milligrams of diethylcarbamazine citrate. (2) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (3) Conditions of use....

  8. 21 CFR 520.622b - Diethylcarbamazine citrate syrup.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine citrate syrup. 520.622b Section... Diethylcarbamazine citrate syrup. (a)(1) Specifications. Each milliliter of syrup contains 60 milligrams of diethylcarbamazine citrate. (2) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (3) Conditions of use....

  9. 21 CFR 520.622b - Diethylcarbamazine citrate syrup.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate syrup. 520.622b Section... Diethylcarbamazine citrate syrup. (a)(1) Specifications. Each milliliter of syrup contains 60 milligrams of diethylcarbamazine citrate. (2) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (3) Conditions of use....

  10. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate, oxibendazole chewable... § 520.623 Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet contains either 60, 120, or 180 milligrams of diethylcarbamazine citrate with 45, 91, or 136 milligrams...

  11. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate, oxibendazole chewable... § 520.623 Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet contains either 60, 120, or 180 milligrams of diethylcarbamazine citrate with 45, 91, or 136 milligrams...

  12. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine citrate, oxibendazole chewable... § 520.623 Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet contains either 60, 120, or 180 milligrams of diethylcarbamazine citrate with 45, 91, or 136 milligrams...

  13. 21 CFR 520.622d - Diethylcarbamazine citrate capsules.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate capsules. 520.622d... Diethylcarbamazine citrate capsules. (a) Specifications. Each capsule contains 12.5, 50, 200, or 400 milligrams (mg) diethylcarbamazine citrate. (b) Sponsor. See No. 011014 in § 510.600(c) of this chapter. (c) Conditions of use...

  14. Enhanced localized surface plasmon resonance dependence of silver nanoparticles on the stoichiometric ratio of citrate stabilizers

    NASA Astrophysics Data System (ADS)

    McClary, Felicia A.; Gaye-Campbell, Shauna; Hai Ting, Andy Yuen; Mitchell, James W.

    2013-02-01

    A stoichiometric approach to the synthesis of silver nanoparticles (AgNPs) with appreciable enhancements in the localized surface plasmon resonance is presented. Microwave irradiation afforded AgNPs, optimized to a thermodynamic equilibrium by varying the silver to trisodium citrate (Ag0/citrate3-) stoichiometric ratio from 1:1 to 1:10, and ranging in size from 32 to 65 nm (±1-9 nm, hydrodynamic diameter). The concentration-dependent plasmonic enhancements were monitored by UV-Vis absorption spectrophotometry, showing absorption maxima typical of AgNPs, at 440-450 nm. A linear accession in plasmon absorbance intensity, approaching 1:5 (Ag0/citrate3-), followed by a linear depletion, at larger stoichiometries (1:6-1:10), was observed. Size distribution measurements, using dynamic light scattering, showed the highest polydispersity index, 0.547, for 1:10 suspensions and the lowest, 0.305, for the thermodynamic maximum, determined to occur at 1:5. Surface charge measurements approaching 0 mV confirm the destabilizing effect of high concentrations of citrate, leading to greater instances of aggregation and large hydrodynamic diameters. Reaction kinetics data suggests an increased preference for Ag n + -citrate, metal/ligand complexation, at 1:10, diminishing nanoparticle production.

  15. Study on the Antimicrobial Properties of Citrate-Based Biodegradable Polymers

    PubMed Central

    Su, Lee-Chun; Xie, Zhiwei; Zhang, Yi; Nguyen, Kytai Truong; Yang, Jian

    2014-01-01

    Citrate-based polymers possess unique advantages for various biomedical applications since citric acid is a natural metabolism product, which is biocompatible and antimicrobial. In polymer synthesis, citric acid also provides multiple functional groups to control the crosslinking of polymers and active binding sites for further conjugation of biomolecules. Our group recently developed a number of citrate-based polymers for various biomedical applications by taking advantage of their controllable chemical, mechanical, and biological characteristics. In this study, various citric acid derived biodegradable polymers were synthesized and investigated for their physicochemical and antimicrobial properties. Results indicate that citric acid derived polymers reduced bacterial proliferation to different degrees based on their chemical composition. Among the studied polymers, poly(octamethylene citrate) showed ~70–80% suppression to microbe proliferation, owing to its relatively higher ratio of citric acid contents. Crosslinked urethane-doped polyester elastomers and biodegradable photoluminescent polymers also exhibited significant bacteria reduction of ~20 and ~50% for Staphylococcus aureus and Escherichia coli, respectively. Thus, the intrinsic antibacterial properties in citrate-based polymers enable them to inhibit bacteria growth without incorporation of antibiotics, silver nanoparticles, and other traditional bacteria-killing agents suggesting that the citrate-based polymers are unique beneficial materials for wound dressing, tissue engineering, and other potential medical applications where antimicrobial property is desired. PMID:25023605

  16. Analytical chemistry of the citrate process for flue gas desulfurization

    SciTech Connect

    Marchant, W.N.; May, S.L.; Simpson, W.W.; Winter, J.K.; Beard, H.R.

    1980-01-01

    The citrate process for flue gas desulfurization (FGD) is a product of continuing research by the US Bureau of Mines to meet the goal of minimizing the objectionable effects of minerals industry operations upon the environment. The reduction of SO/sub 2/ in solution by H/sub 2/S to produce elemental sulfur by the citrate process is extremely complex and results in solutions that contain at least nine different sulfur species. Process solution analysis is essential to a clear understanding of process chemistry and its safe, efficient operation. The various chemical species, the approximate ranges of their concentrations in citrate process solutions, and the analytical methods evolved to determine them are hydrogen sulfide (approx. 0M to 0.06M) by specific ion electrode, polysulfides (unknown) by ultraviolet (uv) spectrophotometry, elemental sulfur (approx. 0M to approx. 0.001M dissolved, approx. 0M to approx. 0.1M suspended) by uv spectrophotometry, thiosulfate (approx. 0M to approx. 0.25M) by iodometry or high performance liquid chromatography (HPLC), polythionates (approx. 0M to approx. 0.01M) by thin layer chromatography (TLC), dithionite (searched for but not detected in process solutions) by polarography or TLC, bisulfite (approx. 0M to 0.2M) by iodometry, sulfate (approx. 0M to 1M) by a Bureau-developed gravimetric procedure, citric acid (approx. 0M to 0.5M) by titration or visible colorimetry, glycolic acid (approx. 0M to 1M) by HPLC, sodium (approx. 1.5M) by flame photometry, and chloride by argentometric titration.

  17. Forsterite Carbonation in Wet Supercritical CO2 and Sodium Citrate

    NASA Astrophysics Data System (ADS)

    Qiu, L.; Schaef, T.; Wang, Z.; Miller, Q.; McGrail, P.

    2013-12-01

    Lin Qiu1*, Herbert T. Schaef2, Zhengrong Wang1, Quin R.S. Miller3, BP McGrail2 1. Yale University, New Haven, CT, USA 2. Pacific Northwest National Laboratory, Richland, WA, USA 3. University of Wyoming, Laramie, WY, USA Geologic reservoirs for managing carbon emissions (mostly CO2) have expanded over the last 5 years to include unconventional formations including basalts and fractured shales. Recently, ~1000 metric tons of CO2 was injected into the Columbia River Basalt (CRB) in Eastern Washington as part of the Wallula Pilot Project, Big Sky Regional Carbon Partnership. Based on reservoir conditions, the injected CO2 is present as a supercritical fluid that dissolves into the formation water over time, and reacts with basalt components to form carbonate minerals. In this paper, we discuss mineral transformation reactions occurring when the forsterite (Mg2SiO4) is exposed to wet scCO2 in equilibrium with pure water and sodium citrate solutions. Forsterite was selected as it is an important olivine group mineral present in igneous and mafic rocks. Citrate was selected as it has been shown to enhance mineral dissolution and organic ligands are possible degradation products of the microbial communities present in the formational waters of the CRB. For the supercritical phase, transformation reactions were examined by in situ high pressure x-ray diffraction (HXRD) in the presence of supercritical carbon dioxide (scCO2) in contact with water and sodium citrate solutions at conditions relevant to carbon sequestration. Experimental results show close-to-complete dissolution of forsterite in contact with scCO2 equilibrated with pure water for 90 hours (90 bar and 50°C). Under these conditions, thin films of water coated the mineral surface, providing a mechanism for silicate dissolution and transport of cations necessary for carbonate formation. The primary crystalline component initially detected with in situ HXRD was the hydrated magnesium carbonate, nesquehonite [Mg

  18. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dithiazanine iodide and piperazine citrate suspension. 520.763c Section 520.763c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL...

  19. Methodology of citrate-based biomaterial development and application

    NASA Astrophysics Data System (ADS)

    Tran, M. Richard

    Biomaterials play central roles in modern strategies of regenerative medicine and tissue engineering. Attempts to find tissue-engineered solutions to cure various injuries or diseases have led to an enormous increase in the number of polymeric biomaterials over the past decade. The breadth of new materials arises from the multiplicity of anatomical locations, cell types, and mode of application, which all place application-specific requirements on the biomaterial. Unfortunately, many of the currently available biodegradable polymers are limited in their versatility to meet the wide range of requirements for tissue engineering. Therefore, a methodology of biomaterial development, which is able to address a broad spectrum of requirements, would be beneficial to the biomaterial field. This work presents a methodology of citrate-based biomaterial design and application to meet the multifaceted needs of tissue engineering. We hypothesize that (1) citric acid, a non-toxic metabolic product of the body (Krebs Cycle), can be exploited as a universal multifunctional monomer and reacted with various diols to produce a new class of soft biodegradable elastomers with the flexibility to tune the material properties of the resulting material to meet a wide range of requirements; (2) the newly developed citrate-based polymers can be used as platform biomaterials for the design of novel tissue engineering scaffolding; and (3) microengineering approaches in the form thin scaffold sheets, microchannels, and a new porogen design can be used to generate complex cell-cell and cell-microenvironment interactions to mimic tissue complexity and architecture. To test these hypotheses, we first developed a methodology of citrate-based biomaterial development through the synthesis and characterization of a family of in situ crosslinkable and urethane-doped elastomers, which are synthesized using simple, cost-effective strategies and offer a variety methods to tailor the material properties to

  20. Endometrial Receptivity Markers in Mice Stimulated With Raloxifene Versus Clomiphene Citrate and Natural Cycles.

    PubMed

    Chen, Cairong; Yan, Qiuxia; Liu, Kunping; Zhou, Xiuqin; Xian, Yingjie; Liang, Dali; Zhao, Xiaoying; Guo, Xiaoyan; Quan, Song

    2016-06-01

    Ovulation induction therapy with clomiphene citrate can suppress endometrial receptivity. Raloxifene may be an alternative therapeutic for women with ovulatory disorders. This study aimed to compare the expression of endometrial receptivity markers, including homeobox gene 10 (HOXA10), integrin β3, and leukemia inhibitory factor (LIF), as well as pinopode production during the implantation window in mice stimulated with raloxifene and clomiphene citrate and natural cycles. Thirty-six 8-week-old female Kunming mice were randomly divided into 3 groups (n = 12) and administered daily raloxifene (22 mg/kg), clomiphene citrate (18 mg/kg), and normal saline (1 mL), respectively, by gavage. Two days later, mice were injected with 5 IU human chorionic gonadotropin and mated. Successfully mated female animals were identified with vaginal plugs designated gestation day 1. At day 4.5, pregnant donor mice were euthanized, and uterus samples were collected for immunohistochemistry, quantitative polymerase chain reaction, Western blot, and scanning electron microscopy analyses. Homeobox gene 10, integrin β3, and LIF messenger RNA (mRNA) and protein levels were significantly higher in the raloxifene-treated animals compared with the clomiphene citrate group (all P < .05) but not significantly different from saline group values, except for LIF and integrin β3 mRNA levels (P < .05). Pinopodes were abundant and well developed in the raloxifene and saline groups; however, in the clomiphene citrate-treated mice, fewer and poorly developed pinopodes were obtained. In mice, raloxifene had no effect on HOXA10, integrin β3, and LIF expression as well as pinopode production, suggesting it has no adverse effects on endometrial receptivity. Raloxifene may provide a viable alternative oral ovulation induction agent to clomiphene citrate.

  1. Reduced peroxisomal citrate synthase activity increases substrate availability for polyhydroxyalkanoate biosynthesis in plant peroxisomes.

    PubMed

    Tilbrook, Kimberley; Poirier, Yves; Gebbie, Leigh; Schenk, Peer M; McQualter, Richard B; Brumbley, Stevens M

    2014-10-01

    Polyhydroxyalkanoates (PHAs) are bacterial carbon storage polymers used as renewable, biodegradable plastics. PHA production in plants may be a way to reduce industrial PHA production costs. We recently demonstrated a promising level of peroxisomal PHA production in the high biomass crop species sugarcane. However, further production strategies are needed to boost PHA accumulation closer to commercial targets. Through exogenous fatty acid feeding of Arabidopsis thaliana plants that contain peroxisome-targeted PhaA, PhaB and PhaC enzymes from Cupriavidus necator, we show here that the availability of substrates derived from the β-oxidation cycle limits peroxisomal polyhydroxybutyrate (PHB) biosynthesis. Knockdown of peroxisomal citrate synthase activity using artificial microRNA increased PHB production levels approximately threefold. This work demonstrates that reduction of peroxisomal citrate synthase activity may be a valid metabolic engineering strategy for increasing PHA production in other plant species.

  2. Green synthesis of multi metal- citrate complexes and their characterization

    NASA Astrophysics Data System (ADS)

    Raju, Usha; Warkar, Sudhir G.; Kumar, Anil

    2017-04-01

    Four new multi metal-citrate complexes have been synthesized through green synthetic pathways. Their synthesis by hydrothermal route in the present research is decorated with features such as, a simple one pot synthesis, cost effectiveness, easy to scale up for commercial production, efficient synthesis conditions like mild temperature and shorter duration which further rules out the possibility of forming byproducts which may cause damage to the environment and being environmental benign as it eliminates the use and recovery of harmful organic solvents such as N, N- dimethyl formamide and N, N- diethyl formamide, used by the researchers in the past during the synthesis of similar metal- organic framework complexes. All four complexes are well defined crystalline materials with polynuclear multi metal-citrate framework having cubic crystal structure as indicated by their Powder X-ray Diffraction patterns. These complexes have been characterized by Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy, Thermogravimetric analysis and Powder XRD techniques.

  3. Photodegradation of uranium-citrate complex with uranium recovery

    SciTech Connect

    Dodge, C.J.; Francis, A.J. )

    1994-07-01

    Upon exposure to visible light, uranyl citrate complex showed photodegradation of citric acid to acetic acid and carbon dioxide, with the precipitation of uranium as uranium trioxide (UO[sub 3][center dot]2H[sub 2]O). The initial pH and presence of oxygen affected the rate and extent of photochemical degradation of the complex, the formation of intermediate organic degradation products, and uranium speciation. Under aerobic conditions at pH 3.5, acetic, acetoacetic, 3-oxoglutaric, and malonic acids and acetone were detected; at pH 6.0, 3-oxoglutaric and acetic acids were present. The uranyl U(VI) ion was reduced to uranous U(IV) ion and was subsequently reoxidized to the hexavalent form and precipitated out of solution as uranium trioxide. Uranium trioxide precipitate was insoluble at near-neutral pH and was soluble in acidic pH (<4.1). Under anaerobic conditions, the uranyl citrate complex showed only partial (57%) degradation, and uranium was present in the reduced form as U(IV). Excess citric acid retarded the precipitation of uranium. 26 refs., 9 figs., 1 tab.

  4. The Role of Lithium Carbonate and Lithium Citrate in Regulating Urinary Citrate Level and Preventing Nephrolithiasis

    PubMed Central

    Zhang, Xiaobo; Aggarwal, Piyush; Li, Xiaoming; Oakman, Crystale; Wang, Zhiping; Rodriguez, Ronald

    2009-01-01

    Background and purpose: Urinary Citrate is an inhibitor of Calcium oxalate stone formation. It is reabsorbed in the proximal kidney through sodium dicarboxylate co-transporters (NaDC-1, NaDC-3) present in the renal tubular epithelium. Lithium (Li) is a known potent inhibitor of these transporters. We investigated the effect of lithium carbonate (LiC) and lithium citrate (LiCit) in regulating urinary citrate levels and preventing nephrolithiasis (NL) in the rat model. Experimental approach: We took 220 Wistar rats and induced nephrolithiasis in 130 of them by administering high doses of 5% ammonium oxalate (AmOx) for seven days and labeled them as Group B. Rest were labeled as Group A. Each group was then divided into 3 subgroups. First sub-group acted as control while other two were treated with either lithium carbonate (LiC) or lithium citrate (LiCit) for 21 days. Ten rats from each of the six sub-groups were randomly selected for sacrifice on 3rd, 7th and 14th day and additional 10th and 21st day from Li treated groups. Blood and urine samples were collected and analyzed on these days. The kidneys of the sacrificed rats were dissected and studied under light microscopy for crystal deposition (left kidney) and histological changes (right kidney). Key results: Urinary citrate levels were significantly increased in response to either LiC (p<0.001) or LiCit (p<0.001). Increased urinary citrate levels resulted in the reduction of calcium oxalate (CaOx) crystal deposition, kidney tubular dilatation and infiltration of inflammatory cell in the tubulo-interstitium. Conclusions and implications: Use of lithium salts might be a potentially useful approach in the prevention of recurrent NL. PMID:23675140

  5. Probing the origin of acetyl-CoA and oxaloacetate entering the citric acid cycle from the 13C labeling of citrate released by perfused rat hearts.

    PubMed

    Comte, B; Vincent, G; Bouchard, B; Des Rosiers, C

    1997-10-17

    We present a strategy for simultaneous assessment of the relative contributions of anaplerotic pyruvate carboxylation, pyruvate decarboxylation, and fatty acid oxidation to citrate formation in the perfused rat heart. This requires perfusing with a mix of 13C-substrates and determining the 13C labeling pattern of a single metabolite, citrate, by gas chromatography-mass spectrometry. The mass isotopomer distributions of the oxaloacetate and acetyl moieties of citrate allow calculation of the flux ratios: (pyruvate carboxylation)/(pyruvate decarboxylation), (pyruvate carboxylation)/(citrate synthesis), (pyruvate decarboxylation)/(citrate synthesis) (pyruvate carboxylation)/(fatty acid oxidation), and (pyruvate decarboxylation)/(fatty acid oxidation). Calculations, based on precursor-product relationship, are independent of pool size. The utility of our method was demonstrated for hearts perfused under normoxia with [U-13C3](lactate + pyruvate) and [1-13C]octanoate under steady-state conditions. Under these conditions, effluent and tissue citrate were similarly enriched in all 13C mass isotopomers. The use of effluent citrate instead of tissue citrate allows probing substrate fluxes through the various reactions non-invasively in the intact heart. The methodology should also be applicable to hearts perfused with other 13C-substrates, such as 1-13C-labeled long chain fatty acid, and under various conditions, provided that assumptions on which equations are developed are valid.

  6. Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis

    PubMed Central

    Li, Kai; Xu, Yuan

    2015-01-01

    Metabolic alkalosis commonly results from excessive hydrochloric acid (HCl), potassium (K+) and water (H2O) loss from the stomach or through the urine. The plasma anion gap increases in non-hypoproteinemic metabolic alkalosis due to an increased negative charge equivalent on albumin and the free ionized calcium (Ca++) content of plasma decreases. The mean citrate load in all patients was 8740±7027 mg from 6937±6603 mL of transfused blood products. The citrate load was significantly higher in patients with alkalosis (9164±4870 vs. 7809±3967, P < 0.05). The estimated mean total citrate administered via blood and blood products was calculated as 43.2±34.19 mg/kilogram/day. In non-massive and frequent blood transfusions, the elevated carbon dioxide output has been shown to occur. Due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis + respiratory acidosis and electrolyte imbalance may develop, blood transfusions may result in certain complications. PMID:26131288

  7. Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis.

    PubMed

    Li, Kai; Xu, Yuan

    2015-01-01

    Metabolic alkalosis commonly results from excessive hydrochloric acid (HCl), potassium (K(+)) and water (H2O) loss from the stomach or through the urine. The plasma anion gap increases in non-hypoproteinemic metabolic alkalosis due to an increased negative charge equivalent on albumin and the free ionized calcium (Ca(++)) content of plasma decreases. The mean citrate load in all patients was 8740±7027 mg from 6937±6603 mL of transfused blood products. The citrate load was significantly higher in patients with alkalosis (9164±4870 vs. 7809±3967, P < 0.05). The estimated mean total citrate administered via blood and blood products was calculated as 43.2±34.19 mg/kilogram/day. In non-massive and frequent blood transfusions, the elevated carbon dioxide output has been shown to occur. Due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis + respiratory acidosis and electrolyte imbalance may develop, blood transfusions may result in certain complications.

  8. SbnG, a citrate synthase in Staphylococcus aureus: A new fold on an old enzyme

    SciTech Connect

    Kobylarz, Marek J.; Grigg, Jason C.; Sheldon, Jessica R.; Heinrichs, David E.; Murphy, Michael E. P.

    2014-10-21

    In response to iron deprivation, Staphylococcus aureus produces staphyloferrin B, a citrate-containing siderophore that delivers iron back to the cell. This bacterium also possesses a second citrate synthase, SbnG, that is necessary for supplying citrate to the staphyloferrin B biosynthetic pathway. In this paper, we present the structure of SbnG bound to the inhibitor calcium and an active site variant in complex with oxaloacetate. The overall fold of SbnG is structurally distinct from TCA cycle citrate synthases yet similar to metal-dependent class II aldolases. Phylogenetic analyses revealed that SbnG forms a separate clade with homologs from other siderophore biosynthetic gene clusters and is representative of a metal-independent subgroup in the phosphoenolpyruvate/pyruvate domain superfamily. Finally, a structural superposition of the SbnG active site to TCA cycle citrate synthases and site-directed mutagenesis suggests a case for convergent evolution toward a conserved catalytic mechanism for citrate production.

  9. Citrate in plasma and urine during total fasting.

    PubMed

    Nielsen, T T; Sørensen, N S

    1979-01-01

    Plasma citrate was determined in 12 obese subjects who underwent total fasting for 10 days. Mean plasma citrate concentration rose significantly from 128 before to 205 micro mol/1 on the 10th day of fasting. Plasma citrate rose continuously during fasting in seven subjects in whom daily determinations were carried out. The 24-hour urinary citrate excretion was followed in six subjects. A significant decrease was found from 2.91 mmol/24 h in the prefasting state to 0.25 mmol/24 h at the end of the fast. Intravenous glucose tolerance test were performed before and on the 10th day of fasting. Kivgtt decreased significantly and was inversely related to plasma citrate concentration on the 10th day of fasting. The results agree well with the concept that an increased citrate level of tissues is of regulatory importance for the decreased glucose utilization during fasting in man.

  10. Sildenafil citrate for female sexual arousal disorder: a future possibility?

    PubMed

    Schoen, Corina; Bachmann, Gloria

    2009-04-01

    Female sexual arousal disorder (FSAD) is a common disorder encountered in clinical practice, with self-reported arousal difficulties reported in up to 26% of American women. Various oral therapies for FSAD have been studied, including sildenafil citrate, a phosphodiesterase inhibitor that is currently used to treat male erectile dysfunction. In vitro studies of sildenafil citrate have demonstrated smooth-muscle relaxation in clitoral tissue, and phosphodiesterase type-5 has been shown to be present in vaginal, clitoral and labial smooth muscle; these findings have led to theories that sildenafil citrate might be successful for treating FSAD. This Review discusses the data from clinical trials that have assessed sildenafil citrate for the treatment of FSAD; the trials show that sildenafil citrate is moderately effective. Sildenafil citrate may also be effective in women with FSAD secondary to multiple sclerosis, diabetes or antidepressant use; however, more trials in these patient populations are required to confirm these findings.

  11. The mechanisms of citrate on regulating the distribution of carbon flux in the biosynthesis of uridine 5'-monophosphate by Saccharomyces cerevisiae.

    PubMed

    Chen, Yong; Li, Shuya; Xiong, Jian; Li, Zhenjiang; Bai, Jianxin; Zhang, Lei; Ye, Qi; Ouyang, Pingkai; Ying, Hanjie

    2010-03-01

    A whole cell biocatalytic process for uridine 5'-monophosphate (UMP) production from orotic acid by Saccharomyces cerevisiae was developed. The concentration of UMP was increased by 23% when 1 g l(-1) sodium citrate was fed into the broth. Effects of citrate addition on UMP production were investigated. Glucose-6-phosphate pool was elevated by onefold, while FBP and pyruvate were decreased by 42% and 40%, respectively. Organic acid pools such as acetate and succinate were averagely decreased by 30% and 49%. The results demonstrated that manipulation of citrate levels could be used as a novel tool to regulate the metabolic fluxes distribution among glycolysis, pentose phosphate pathway, and TCA cycle.

  12. Kinetics of Ga(NOTA) formation from weak Ga-citrate complexes.

    PubMed

    Morfin, Jean-François; Tóth, Éva

    2011-10-17

    Gallium complexes are gaining increasing importance in biomedical imaging thanks to the practical advantages of the (68)Ga isotope in Positron Emission Tomography (PET) applications. (68)Ga has a short half-time (t(1/2) = 68 min); thus the (68)Ga complexes have to be prepared in a limited time frame. The acceleration of the formation reaction of gallium complexes with macrocyclic ligands for application in PET imaging represents a significant coordination chemistry challenge. Here we report a detailed kinetic study of the formation reaction of the highly stable Ga(NOTA) from the weak citrate complex (H(3)NOTA = 1,4,7-triazacyclononane-1,4,7- triacetic acid). The transmetalation has been studied using (71)Ga NMR over a large pH range (pH = 2.01-6.00). The formation of Ga(NOTA) is a two-step process. First, a monoprotonated intermediate containing coordinated citrate, GaHNOTA(citrate)*, forms in a rapid equilibrium step. The rate-determining step of the reaction is the deprotonation and slow rearrangement of the intermediate accompanied by the citrate release. The observed reaction rate shows an unusual pH dependency with a minimum at pH 5.17. In contrast to the typical formation reactions of poly(amino carboxylate) complexes, the Ga(NOTA) formation from the weak citrate complex becomes considerably faster with increasing proton concentration below pH 5.17. We explain this unexpected tendency by the role of protons in the decomposition of the GaHNOTA(citrate)* intermediate which proceeds via the protonation of the coordinated citrate ion and its subsequent decoordination to yield the final product Ga(NOTA). The stability constant of this intermediate, log K(GaHNOTA(citrate)*) = 15.6, is remarkably high compared to the corresponding values reported for the formation of macrocyclic lanthanide(III)-poly(amino carboxylates). These kinetic data do not only give mechanistic insight into the formation reaction of Ga(NOTA), but might also contribute to establish optimal

  13. TRANSFUSIONS—Hazardous Acid-Base Changes with Citrated Blood

    PubMed Central

    Pedro, Jovita M. San; Iwai, Seizo; Hattori, Mitsuo; Leigh, M. Digby

    1962-01-01

    In a study of the acid-base changes in the blood of rabbits during and following transfusions of citrated blood and of heparinized blood, it was observed that, with citrated blood, pH decreased and carbon dioxide tensions rose. With heparinized blood, the acid-base balance was maintained within normal limits following transfusions. The potential hazards of rapid massive citrated blood transfusions in the anesthetized patient during operation must be kept in mind. PMID:14496706

  14. Sildenafil citrate ingestion in a pediatric patient.

    PubMed

    Cantrell, F Lee

    2004-05-01

    Sildenafil citrate is the first FDA-approved oral agent for male erectile dysfunction. Common adverse effects include flushing, headache, and dyspepsia, although more serious side effects have been reported. Because of its specific therapeutic indication, sildenafil toxicity has been limited almost exclusively to adults. We report a symptomatic case of pediatric sildenafil ingestion. A 2-year-old male ingested 75 mg of sildenafil citrate (Viagra) 2 hours prior to arrival at an emergency room. Ipecac syrup had been given at home with one episode of vomiting. Activated charcoal was considered but withheld due to the delayed presentation to the hospital. The patient was observed in the hospital for 17.5 hours. Observed clinical effects included facial flushing, transient penile engorgement, bilateral rhonchi, and diarrhea. No significant cardiovascular effects were seen. A bronchodilator was given with resolution of rhonchi. No other specific interventions were required. One day after discharge, the patient had one additional bout of diarrhea and complained of pain in the penile region for one day. Two weeks after the exposure, the patient's mother denied any unusual symptoms. Pediatric ingestion of sildenafil may result in mild symptoms including persistent flushing and penile engorgement with associated pain. Penile pain may persist even after resolution of the erection. It is questionable whether the respiratory symptoms and diarrhea were related since neither has been described following sildenafil exposure. Significant cardiovascular symptoms were not seen. Early administration of ipecac syrup did not prevent symptoms from developing.

  15. 40 CFR 721.10357 - Iron, citrate phosphate potassium complexes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Iron, citrate phosphate potassium... Specific Chemical Substances § 721.10357 Iron, citrate phosphate potassium complexes. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as iron...

  16. 40 CFR 721.10357 - Iron, citrate phosphate potassium complexes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Iron, citrate phosphate potassium... Specific Chemical Substances § 721.10357 Iron, citrate phosphate potassium complexes. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as iron...

  17. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Iron-choline citrate complex. 172.370 Section 172... CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline... citric acid may be safely used as a source of iron in foods for special dietary use. ...

  18. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Iron-choline citrate complex. 172.370 Section 172... CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline... citric acid may be safely used as a source of iron in foods for special dietary use. ...

  19. 40 CFR 721.10357 - Iron, citrate phosphate potassium complexes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Iron, citrate phosphate potassium... Specific Chemical Substances § 721.10357 Iron, citrate phosphate potassium complexes. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as iron...

  20. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Iron-choline citrate complex. 172.370 Section 172... CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline... citric acid may be safely used as a source of iron in foods for special dietary use. ...

  1. 21 CFR 172.370 - Iron-choline citrate complex.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Iron-choline citrate complex. 172.370 Section 172... CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline... citric acid may be safely used as a source of iron in foods for special dietary use. ...

  2. Enhanced dissolution of sildenafil citrate as dry foam tablets.

    PubMed

    Sawatdee, Somchai; Atipairin, Apichart; Sae Yoon, Attawadee; Srichana, Teerapol; Changsan, Narumon

    2017-01-30

    Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5 kg, friability test <1% with a disintegration time <5 min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.

  3. 21 CFR 73.1025 - Ferric ammonium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1025 Ferric ammonium citrate. (a) Identity. The color additive ferric ammonium citrate consists of complex chelates prepared by the interaction of... general and ophthalmic surgery subject to the following conditions: (1) The dyed suture shall conform in...

  4. Aluminum Citrate Prevents Renal Injury from Calcium Oxalate Crystal Deposition

    PubMed Central

    Besenhofer, Lauren M.; Cain, Marie C.; Dunning, Cody

    2012-01-01

    Calcium oxalate monohydrate crystals are responsible for the kidney injury associated with exposure to ethylene glycol or severe hyperoxaluria. Current treatment strategies target the formation of calcium oxalate but not its interaction with kidney tissue. Because aluminum citrate blocks calcium oxalate binding and toxicity in human kidney cells, it may provide a different therapeutic approach to calcium oxalate-induced injury. Here, we tested the effects of aluminum citrate and sodium citrate in a Wistar rat model of acute high-dose ethylene glycol exposure. Aluminum citrate, but not sodium citrate, attenuated increases in urea nitrogen, creatinine, and the ratio of kidney to body weight in ethylene glycol–treated rats. Compared with ethylene glycol alone, the addition of aluminum citrate significantly increased the urinary excretion of both crystalline calcium and crystalline oxalate and decreased the deposition of crystals in renal tissue. In vitro, aluminum citrate interacted directly with oxalate crystals to inhibit their uptake by proximal tubule cells. These results suggest that treating with aluminum citrate attenuates renal injury in rats with severe ethylene glycol toxicity, apparently by inhibiting calcium oxalate’s interaction with, and retention by, the kidney epithelium. PMID:23138489

  5. Diffuse abdominal gallium-67 citrate uptake in salmonella infections

    SciTech Connect

    Garty, I.; Koren, A.

    1987-11-01

    Two pediatric patients with salmonella infections (one with typhoid fever and the second with salmonella C2 gastroenteritis), had a diffuse abdominal uptake of Ga-67 citrate. The possible explanation for this finding is discussed. Salmonella infection should be included as a cause in the differential diagnosis of diffuse accumulation of Ga-67 citrate.

  6. Structural Basis for Norovirus Inhibition and Fucose Mimicry by Citrate

    SciTech Connect

    Hansman, Grant S.; Shahzad-ul-Hussan, Syed; McLellan, Jason S.; Chuang, Gwo-Yu; Georgiev, Ivelin; Shimoike, Takashi; Katayama, Kazuhiko; Bewley, Carole A.; Kwong, Peter D.

    2012-01-20

    Human noroviruses bind with their capsid-protruding domains to histo-blood-group antigens (HBGAs), an interaction thought to direct their entry into cells. Although human noroviruses are the major cause of gastroenteritis outbreaks, development of antivirals has been lacking, mainly because human noroviruses cannot be cultivated. Here we use X-ray crystallography and saturation transfer difference nuclear magnetic resonance (STD NMR) to analyze the interaction of citrate with genogroup II (GII) noroviruses. Crystals of citrate in complex with the protruding domain from norovirus GII.10 Vietnam026 diffracted to 1.4 {angstrom} and showed a single citrate bound at the site of HBGA interaction. The citrate interaction was coordinated with a set of capsid interactions almost identical to that involved in recognizing the terminal HBGA fucose, the saccharide which forms the primary conserved interaction between HBGAs and GII noroviruses. Citrate and a water molecule formed a ring-like structure that mimicked the pyranoside ring of fucose. STD NMR showed the protruding domain to have weak affinity for citrate (460 {mu}M). This affinity, however, was similar to the affinities of the protruding domain for fucose (460 {mu}M) and H type 2 trisaccharide (390 {mu}M), an HBGA shown previously to be specifically recognized by human noroviruses. Importantly, competition STD NMR showed that citrate could compete with HBGA for norovirus binding. Together, the results suggest that citrate and other glycomimetics have the potential to block human noroviruses from binding to HBGAs.

  7. Structural basis for norovirus inhibition and fucose mimicry by citrate.

    PubMed

    Hansman, Grant S; Shahzad-Ul-Hussan, Syed; McLellan, Jason S; Chuang, Gwo-Yu; Georgiev, Ivelin; Shimoike, Takashi; Katayama, Kazuhiko; Bewley, Carole A; Kwong, Peter D

    2012-01-01

    Human noroviruses bind with their capsid-protruding domains to histo-blood-group antigens (HBGAs), an interaction thought to direct their entry into cells. Although human noroviruses are the major cause of gastroenteritis outbreaks, development of antivirals has been lacking, mainly because human noroviruses cannot be cultivated. Here we use X-ray crystallography and saturation transfer difference nuclear magnetic resonance (STD NMR) to analyze the interaction of citrate with genogroup II (GII) noroviruses. Crystals of citrate in complex with the protruding domain from norovirus GII.10 Vietnam026 diffracted to 1.4 Å and showed a single citrate bound at the site of HBGA interaction. The citrate interaction was coordinated with a set of capsid interactions almost identical to that involved in recognizing the terminal HBGA fucose, the saccharide which forms the primary conserved interaction between HBGAs and GII noroviruses. Citrate and a water molecule formed a ring-like structure that mimicked the pyranoside ring of fucose. STD NMR showed the protruding domain to have weak affinity for citrate (460 μM). This affinity, however, was similar to the affinities of the protruding domain for fucose (460 μM) and H type 2 trisaccharide (390 μM), an HBGA shown previously to be specifically recognized by human noroviruses. Importantly, competition STD NMR showed that citrate could compete with HBGA for norovirus binding. Together, the results suggest that citrate and other glycomimetics have the potential to block human noroviruses from binding to HBGAs.

  8. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Diethylcarbamazine citrate oral dosage forms....

  9. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Diethylcarbamazine citrate oral dosage forms....

  10. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Diethylcarbamazine citrate oral dosage forms....

  11. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Diethylcarbamazine citrate oral dosage forms....

  12. Internet-ordered viagra (sildenafil citrate) is rarely genuine.

    PubMed

    Campbell, Neil; Clark, John P; Stecher, Vera J; Goldstein, Irwin

    2012-11-01

    Counterfeit medication is a growing problem. This study assessed the requirement for prescription, cost, origin, and content of medications sold via the Internet and purporting to be the phosphodiesterase type 5 inhibitor Viagra (sildenafil citrate). Pfizer monitored top search results for the query "buy Viagra" on the two leading Internet search engines in March 2011. Orders were placed from 22 unique Web sites claiming to sell Viagra manufactured by Pfizer. Tablets received were assessed for chemical composition. No Web site examined required a prescription for purchase or a health screening survey; 90% offered illegal "generic Viagra." Cost per tablet ranged from $3.28-$33.00. Shipment origins of purchases were Hong Kong (N = 11), the United States (N = 6), and the United Kingdom (N = 2) as well as Canada, China, and India (N = 1 each). Notably, the four Internet pharmacies claiming to be Canadian did not ship medication from a Canadian address. Of 22 sample tablets examined, 17 (77%) were counterfeit, 4 (18%) were authentic, and 1 (5%) was an illegal generic. Counterfeit tablets were analyzed for sildenafil citrate, the active pharmaceutical ingredient (API) of Viagra, and contents varied between 30% and 50% of the label claim. Counterfeits lacked product information leaflets, including appropriate safety warnings, and genuine Viagra formulations. Internet sites claiming to sell authentic Viagra shipped counterfeit medication 77% of the time; counterfeits usually came from non-U.S. addresses and had 30% to 50% of the labeled API claim. Caution is warranted when purchasing Viagra via the Internet. © 2012 International Society for Sexual Medicine.

  13. Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy.

    PubMed

    Abouzeid, Sameh Mohamed; ElHossary, Hossam E

    2016-05-01

    Contrast-induced nephropathy (CIN) is one of the important complications of radiographic procedures, especially in patients with chronic kidney disease. It is also one of the common causes of acute kidney injury. The pathogenesis is postulated to be the effect of oxygen- free radicals and hyperosmolar stress on the renal medulla. It is reported that the production of superoxide is most active at acid environment. K/Na citrate is well known as a urine alkalinization medium, and this has been evaluated earlier with standard hydration for reduction of CIN and was stated to be efficient. We aimed to determine the efficacy of Na/K citrate in reducing the frequency of CIN in comparison to sodium bicarbonate in patients after coronary angiography. Two hundred and ten patients with renal dysfunction [estimated glomerular filtration rate (eGFR), 60 mL/min/1.73 m(2) or less] who underwent elective or emergency coronary angiography (CAG) with/without percutaneous coronary intervention (PCI) at our institution were enrolled into the study. The patients were randomized into two groups, Group 1-Taking Na/K citrate and Group 2-Taking sodium bicarbonate. Radiographic contrast agent iohexol was used. Change in creatinine, percent change in creatinine, percent change in eGFR, change in serum potassium, and urine pH were all compared between the two groups. There was no significant difference for prevention of CIN when comparing the Na/K citrate with sodium bicarbonate solution in patients exposed to CAG with or without PCI. Mean absolute change in eGFR after 48 h after administration of contrast between sodium bicarbonate group and Na/K citrate group was -0.60 ± 1.58 versus -0.71 ± 1.38. Serum potassium decreased postprocedure in the sodium bicarbonate group than in the citrate group (3.90 ± 0.33 vs. 4.14 ± 0.39). Both agents are equally effective in reducing the incidence of CIN, but the citrate would possibly be a safer option for patients at risk of hypokalemia.

  14. Synthesis and Characterization of Biomimetic Citrate-Based Biodegradable Composites

    PubMed Central

    Tran, Richard T.; Wang, Liang; Zhang, Chang; Huang, Minjun; Tang, Wanjin; Zhang, Chi; Zhang, Zhongmin; Jin, Dadi; Banik, Brittany; Brown, Justin L.; Xie, Zhiwei; Bai, Xiaochun; Yang, Jian

    2013-01-01

    Natural bone apatite crystals, which mediate the development and regulate the load-bearing function of bone, have recently been associated with strongly bound citrate molecules. However, such understanding has not been translated into bone biomaterial design and osteoblast cell culture. In this work, we have developed a new class of biodegradable, mechanically strong, and biocompatible citrate-based polymer blends (CBPBs), which offer enhanced hydroxyapatite binding to produce more biomimetic composites (CBPBHAs) for orthopedic applications. CBPBHAs consist of the newly developed osteoconductive citrate-presenting biodegradable polymers, crosslinked urethane-doped polyester (CUPE) and poly (octanediol citrate) (POC), which can be composited with up to 65 wt.-% hydroxyapatite (HA). CBPBHA networks produced materials with a compressive strength of 116.23 ± 5.37 MPa comparable to human cortical bone (100 – 230 MPa), and increased C2C12 osterix (OSX) gene and alkaline phosphatase (ALP) gene expression in vitro. The promising results above prompted an investigation on the role of citrate supplementation in culture medium for osteoblast culture, which showed that exogenous citrate supplemented into media accelerated the in vitro phenotype progression of MG-63 osteoblasts. After 6-weeks of implantation in a rabbit lateral femoral condyle defect model, CBPBHA composites elicited minimal fibrous tissue encapsulation and were well integrated with the surrounding bone tissues. The development of citrate-presenting CBPBHA biomaterials and preliminary studies revealing the effects of free exogenous citrate on osteoblast culture shows the potential of citrate biomaterials to bridge the gap in orthopedic biomaterial design and osteoblast cell culture in that the role of citrate molecules has previously been overlooked. PMID:23996976

  15. Synthesis and characterization of biomimetic citrate-based biodegradable composites.

    PubMed

    Tran, Richard T; Wang, Liang; Zhang, Chang; Huang, Minjun; Tang, Wanjin; Zhang, Chi; Zhang, Zhongmin; Jin, Dadi; Banik, Brittany; Brown, Justin L; Xie, Zhiwei; Bai, Xiaochun; Yang, Jian

    2014-08-01

    Natural bone apatite crystals, which mediate the development and regulate the load-bearing function of bone, have recently been associated with strongly bound citrate molecules. However, such understanding has not been translated into bone biomaterial design and osteoblast cell culture. In this work, we have developed a new class of biodegradable, mechanically strong, and biocompatible citrate-based polymer blends (CBPBs), which offer enhanced hydroxyapatite binding to produce more biomimetic composites (CBPBHAs) for orthopedic applications. CBPBHAs consist of the newly developed osteoconductive citrate-presenting biodegradable polymers, crosslinked urethane-doped polyester and poly (octanediol citrate), which can be composited with up to 65 wt % hydroxyapatite. CBPBHA networks produced materials with a compressive strength of 116.23 ± 5.37 MPa comparable to human cortical bone (100-230 MPa), and increased C2C12 osterix gene and alkaline phosphatase gene expression in vitro. The promising results above prompted an investigation on the role of citrate supplementation in culture medium for osteoblast culture, which showed that exogenous citrate supplemented into media accelerated the in vitro phenotype progression of MG-63 osteoblasts. After 6 weeks of implantation in a rabbit lateral femoral condyle defect model, CBPBHA composites elicited minimal fibrous tissue encapsulation and were well integrated with the surrounding bone tissues. The development of citrate-presenting CBPBHA biomaterials and preliminary studies revealing the effects of free exogenous citrate on osteoblast culture shows the potential of citrate biomaterials to bridge the gap in orthopedic biomaterial design and osteoblast cell culture in that the role of citrate molecules has previously been overlooked.

  16. Bioavailability of iron from ferric choline citrate and a ferric copper cobalt choline citrate complex for young pigs.

    PubMed

    Miller, E R; Parsons, M J; Ullrey, D E; Ku, P K

    1981-04-01

    Two experiments were conducted to determine the bioavailability for young pigs of Fe from ferric choline citrate or from a commercial mixture of Fe, Cu and Co choline citrate salts. Relative biological value of Fe from either source with a standard of 100 for FeSO4 x 7H20 was about 140 by both hemoglobin regeneration and Fe retention methods.

  17. Acquired immunodeficiency syndrome: Ga-67 citrate imaging

    SciTech Connect

    Woolfenden, J.M.; Carrasquillo, J.A.; Larson, S.M.; Simmons, J.T.; Masur, H.; Smith, P.D.; Shelhamer, J.H.; Ognibene, F.P.

    1987-02-01

    All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

  18. Citrate-stabilized Q-CdSe seed-mediated synthesis of silver nanoparticles: The role of citrate moieties anchored to the Q-CdSe surface

    NASA Astrophysics Data System (ADS)

    Ingole, Pravin P.; Bhat, Mohsin A.

    2016-03-01

    Here, we try to explore a new dimension/role for citrate molecules in the bound state, i.e. anchored to the surface of cadmium selenide quantum dots (Q-CdSe), in the synthesis of metal nanoparticles (MNPs). Being labile, the citrate molecule is considered a good candidate for the stabilization of semiconductor quantum dots (QDs) such as Q-CdSe that can be used for further functionalization/modification of the surface properties of the QDs. In its free/ionic form (i.e. not bound to the surface), it is well known for its role as a reducing as well as a capping agent in the synthesis of silver and gold MNPs. A simple strategy for the preparation of silver MNPs following the chemical reduction of silver ions that is mediated by citrate-stabilized Q-CdSe seeds without addition of an external reducing agent is presented. The citrate moieties anchored to the surface of Q-CdSe are found to play an important role in the chemical reduction of silver ions. The obtained product was analysed by spectroscopic, microscopic and structural characterization techniques such as surface plasmon resonance (SPR), transmission electron microscopy (TEM) and cyclic voltammetry. The characteristic redox behaviour observed in cyclic voltammograms (CVs) also supports the formation of Ag MNPs in the samples. Further, the impact of the reaction solution pH on the feasibility of silver ion reduction by Q-CdSe seeds resulting into the formation of Ag MNPs is also briefly discussed.

  19. Quantification of active pharmaceutical ingredient and impurities in sildenafil citrate obtained from the Internet

    PubMed Central

    Nutan, Mohammad T.; Dodla, Uday Krishna Reddy

    2014-01-01

    Background: The accessibility of prescription drugs produced outside of the United States, most notably sildenafil citrate (innovator product, Viagra®), has been made much easier by the Internet. Of greatest concern to clinicians and policymakers is product quality and patient safety. The US Food and Drug Administration (FDA) has issued warnings to potential buyers that the safety of drugs purchased from the Internet cannot be guaranteed, and may present a health risk to consumers from substandard products. Objective: The objective of this study was to determine whether generic sildenafil citrate tablets from international markets obtained via the Internet are equivalent to the US innovator product regarding major aspects of pharmaceutical quality: potency, accuracy of labeling, and presence and level of impurities. This will help identify aspects of drug quality that may impact public health risks. Methods: A total of 15 sildenafil citrate tablets were obtained for pharmaceutical analysis: 14 generic samples from international Internet pharmacy websites and the US innovator product. According to US Pharmacopeial guidelines, tablet samples were tested using high-performance liquid chromatography for potency of active pharmaceutical ingredient (API) and levels of impurities (impurities A, B, C, and D). Impurity levels were compared with International Conference on Harmonisation (ICH) limits. Results: Among the 15 samples, 4 samples possessed higher impurity B levels than the ICH qualification threshold, 8 samples possessed higher impurity C levels than the ICH qualification threshold, and 4 samples possessed more than 1% impurity quantity of maximum daily dose (MDD). For API, 6 of the samples failed to fall within the 5% assay limit. Conclusions: Quality assurance tests are often used to detect formulation defects of drug products during the manufacturing and/or storage process. Results suggest that manufacturing standards for sildenafil citrate generic drug

  20. Quantification of active pharmaceutical ingredient and impurities in sildenafil citrate obtained from the Internet.

    PubMed

    Veronin, Michael A; Nutan, Mohammad T; Dodla, Uday Krishna Reddy

    2014-10-01

    The accessibility of prescription drugs produced outside of the United States, most notably sildenafil citrate (innovator product, Viagra®), has been made much easier by the Internet. Of greatest concern to clinicians and policymakers is product quality and patient safety. The US Food and Drug Administration (FDA) has issued warnings to potential buyers that the safety of drugs purchased from the Internet cannot be guaranteed, and may present a health risk to consumers from substandard products. The objective of this study was to determine whether generic sildenafil citrate tablets from international markets obtained via the Internet are equivalent to the US innovator product regarding major aspects of pharmaceutical quality: potency, accuracy of labeling, and presence and level of impurities. This will help identify aspects of drug quality that may impact public health risks. A total of 15 sildenafil citrate tablets were obtained for pharmaceutical analysis: 14 generic samples from international Internet pharmacy websites and the US innovator product. According to US Pharmacopeial guidelines, tablet samples were tested using high-performance liquid chromatography for potency of active pharmaceutical ingredient (API) and levels of impurities (impurities A, B, C, and D). Impurity levels were compared with International Conference on Harmonisation (ICH) limits. Among the 15 samples, 4 samples possessed higher impurity B levels than the ICH qualification threshold, 8 samples possessed higher impurity C levels than the ICH qualification threshold, and 4 samples possessed more than 1% impurity quantity of maximum daily dose (MDD). For API, 6 of the samples failed to fall within the 5% assay limit. Quality assurance tests are often used to detect formulation defects of drug products during the manufacturing and/or storage process. Results suggest that manufacturing standards for sildenafil citrate generic drug products compared with the US innovator product are not

  1. Citrate attenuates vascular calcification in chronic renal failure rats.

    PubMed

    Ou, Yan; Liu, Zengying; Li, Shuiqin; Zhu, Xiaojing; Lin, Yan; Han, Jin; Duan, Zhaoyang; Jia, Lining; Gui, Baosong

    2017-05-01

    Vascular calcification (VC) is a major contributor of cardiovascular dysfunction in chronic renal failure (CRF). Citrate binds calcium and inhibits the growth of calcium crystals. This present study intends to evaluate the effect of citrate on VC in adenine-induced CRF rats. The rats were randomly divided into five groups: the control group, the citrate control group, model group, model rats with low-dose treatment of citrate (216 mg/kg) and model rats with high-dose treatment of citrate (746 mg/kg). The rats were euthanized at 5 weeks with their blood and aorta in detection. The results showed that serum level of blood urea nitrogen, serum creatinine, phosphorus, calcium, and related renal failure function marker were elevated in the model group. Furthermore, the aortic calcium accumulation and alkaline phosphatase activity were significantly increased in the model group compared with control groups. Additionally, hematoxylin-eosin staining results demonstrated that the vascular calcification in aorta is significantly increased in the model group. Finally, the expression of VC-related proteins including bone morphogenetic protein and osteocalcin were increased in the model group, whereas alpha-smooth muscle actin was decreased in the model group compared with the control group. However, treatment with citrate caused a reversal effect of all the above events in a dose-dependent manner. In conclusion, citrate may attenuate vascular calcification in adenine-induced CRF rats. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  2. Allatostatin-C reversibly blocks the transport of citrate out of the mitochondria and inhibits juvenile hormone synthesis in mosquitoes.

    PubMed

    Nouzova, Marcela; Rivera-Perez, Crisalejandra; Noriega, Fernando G

    2015-02-01

    Aedes aegypti allatostatin-C (AeaAST-C or PISCF-AST) is a strong and fast reversible inhibitor of juvenile hormone III (JH III) synthesis by the corpora allata (CA) of mosquitoes; however, its mechanism of action remains poorly understood. AeaAST-C showed no inhibitory activity in the presence of any of the intermediate precursors of JH III indicating that the AeaAST-C target is located before the entry of acetyl-CoA in the pathway. Stimulation experiments using different sources of carbon (glucose, pyruvate, acetate and citrate) suggest that AST-C acts after pyruvate is transformed to citrate in the mitochondria. In vitro inhibition of the citrate mitochondrial carrier (CIC) mimicked the effect of AeaAST-C, and was overridden by addition of citrate or acetate. Our results provide compelling evidence that AeaAST-C inhibits JH III synthesis by blocking the CIC carrier that transports citrate from the mitochondria to the cytosol, obstructing the production of cytoplasmic acetyl-CoA that sustains JH III synthesis in the CA of mosquitoes.

  3. Adaptive responses of GLUT-4 and citrate synthase in fast-twitch muscle of voluntary running rats

    NASA Technical Reports Server (NTRS)

    Henriksen, E. J.; Halseth, A. E.

    1995-01-01

    Glucose transporter (GLUT-4) protein, hexokinase, and citrate synthase (proteins involved in oxidative energy production from blood glucose catabolism) increase in response to chronically elevated neuromuscular activity. It is currently unclear whether these proteins increase in a coordinated manner in response to this stimulus. Therefore, voluntary wheel running (WR) was used to chronically overload the fast-twitch rat plantaris muscle and the myocardium, and the early time courses of adaptative responses of GLUT-4 protein and the activities of hexokinase and citrate synthase were characterized and compared. Plantaris hexokinase activity increased 51% after just 1 wk of WR, whereas GLUT-4 and citrate synthase were increased by 51 and 40%, respectively, only after 2 wk of WR. All three variables remained comparably elevated (+50-64%) through 4 wk of WR. Despite the overload of the myocardium with this protocol, no substantial elevations in these variables were observed. These findings are consistent with a coordinated upregulation of GLUT-4 and citrate synthase in the fast-twitch plantaris, but not in the myocardium, in response to this increased neuromuscular activity. Regulation of hexokinase in fast-twitch muscle appears to be uncoupled from regulation of GLUT-4 and citrate synthase, as increases in the former are detectable well before increases in the latter.

  4. Substrate Specificity of the Citrate Transporter CitP of Lactococcus lactis

    PubMed Central

    Pudlik, Agata M.

    2012-01-01

    The citrate transporter CitP of lactic acid bacteria catalyzes electrogenic precursor-product exchange of citrate versus l-lactate during citrate-glucose cometabolism. In the absence of sugar, l-lactate is replaced by the metabolic intermediates/end products pyruvate, α-acetolactate, and acetate. In this study, the binding and translocation properties of CitP were analyzed systematically for a wide variety of mono- and dicarboxylates of the form X-CR2-COO−, where X represents OH (2-hydroxy acid), O (2-keto acid), or H (acid) and R groups differ in size, hydrophobicity, and composition. It follows that CitP is a very promiscuous carboxylate transporter. A carboxylate group is both essential and sufficient for recognition by the transporter. A C-2 atom is not essential, formate is a substrate, and C-2 may be part of a ring structure, as in benzoate. The R group may be as bulky as an indole ring structure. For all monocarboxylates of the form X-CHR-COO−, the hydroxy (X = OH) analogs were the preferred substrates. The preference for keto (X = O) or acid (X = H) analogs was dependent on the bulkiness of the R group, such that the acid was preferred for small R groups and the 2-ketoacid was preferred for more bulky R groups. The C4 to C6 dicarboxylates succinate, glutarate, and adipate were also substrates of CitP. The broad substrate specificity is discussed in the context of a model of the binding site of CitP. Many of the substrates of CitP are intermediates or products of amino acid metabolism, suggesting that CitP may have a broader physiological function than its role in citrate fermentation alone. PMID:22563050

  5. Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women.

    PubMed

    Karp, Heini J; Ketola, Maarit E; Lamberg-Allardt, Christel J E

    2009-11-01

    Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.

  6. Exogenous γ-aminobutyric acid treatment affects citrate and amino acid accumulation to improve fruit quality and storage performance of postharvest citrus fruit.

    PubMed

    Sheng, Ling; Shen, Dandan; Luo, Yi; Sun, Xiaohua; Wang, Jinqiu; Luo, Tao; Zeng, Yunliu; Xu, Juan; Deng, Xiuxin; Cheng, Yunjiang

    2017-02-01

    The loss of organic acids during postharvest storage is one of the major factors that reduces the fruit quality and economic value of citrus. Citrate is the most important organic acid in citrus fruits. Molecular evidence has proved that γ-aminobutyric acid (GABA) shunt plays a key role in citrate metabolism. Here, we investigated the effects of exogenous GABA treatment on citrate metabolism and storage quality of postharvest citrus fruit. The content of citrate was significantly increased, which was primarily attributed to the inhibition of the expression of glutamate decarboxylase (GAD). Amino acids, including glutamate, alanine, serine, aspartate and proline, were also increased. Moreover, GABA treatment decreased the fruit rot rate. The activities of antioxidant enzymes and the content of energy source ATP were affected by the treatment. Our results indicate that GABA treatment is a very effective approach for postharvest quality maintenance and improvement of storage performance in citrus production.

  7. 21 CFR 184.1296 - Ferric ammonium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... brown or garnet red scales or granules or as a brownish-yellowish powder. (2) Ferric ammonium citrate... occurs as thin transparent green scales, as granules, as a powder, or as transparent green crystals. (b...

  8. 21 CFR 184.1296 - Ferric ammonium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... brown or garnet red scales or granules or as a brownish-yellowish powder. (2) Ferric ammonium citrate... occurs as thin transparent green scales, as granules, as a powder, or as transparent green crystals. (b...

  9. Properties of peroxisomal and mitochondrial citrate synthase from Agave americana.

    PubMed

    Segovia, J L; Zafra, M F; Alejandre, M J; García-Peregrín, E

    1982-09-01

    Adenine nucleotides were tested as effectors of peroxisomal and mitochondrial citrate synthase from Agave americana leaves in the presence of different concentrations of acetyl-CoA and oxalacetate substrates. ATP inhibited both enzyme activities but with a different inhibition profile. 1.0-7.5 mM ADP did not inhibit the peroxisomal citrate synthase in the presence of high substrate concentrations, while the mitochondrial enzyme was strongly inhibited by 1.0 mM ADP in the same conditions. Likewise, a different pattern was obtained with AMP on both peroxisomal and mitochondrial activities. The rate of citrate formation as function of acetyl-CoA and oxalacetate concentration was also studied in both fractions. Maximal velocity was highest in the peroxisomal fraction, whether acetyl-CoA or oxalacetate were the variable substrates. These differences indicate that peroxisomal and mitochondrial citrate synthases seem to be two different isoenzymes.

  10. Ferric citrate decreases ruminal hydrogen sulphide concentrations in feedlot cattle fed diets high in sulphate.

    PubMed

    Drewnoski, Mary E; Doane, Perry; Hansen, Stephanie L

    2014-01-28

    Dissimilatory reduction of sulphate by sulphate-reducing bacteria in the rumen produces sulphide, which can lead to a build-up of the toxic gas hydrogen sulphide (H2S) in the rumen when increased concentrations of sulphate are consumed by ruminants. We hypothesised that adding ferric Fe would competitively inhibit ruminal sulphate reduction. The effects of five concentrations and two sources (ferric citrate or ferric ammonium citrate) of ferric Fe were examined in vitro (n 6 per treatment). Rumen fluid was collected from a steer that was adapted to a high-concentrate, high-sulphate diet (0·51 % S). The addition of either source of ferric Fe decreased (P< 0·01) H2S concentrations without affecting gas production (P= 0·38), fluid pH (P= 0·80) or in vitro DM digestibility (P= 0·38) after a 24 h incubation. An in vivo experiment was conducted using eight ruminally fistulated steers (543 (sem 12) kg) in a replicated Latin square with four periods and four treatments. The treatments included a high-concentrate, high-sulphate control diet (0·46 % S) or the control diet plus ferric ammonium citrate at concentrations of 200, 300 or 400 mg Fe/kg diet DM. The inclusion of ferric Fe did not affect DM intake (P= 0·21). There was a linear (P< 0·01) decrease in the concentration of ruminal H2S as the addition of ferric Fe concentrations increased. Ferric citrate appears to be an effective way to decrease ruminal H2S concentrations, which could allow producers to safely increase the inclusion of ethanol co-products.

  11. Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.

    PubMed

    Chen, Meiling; Xu, Shuhong; Zhou, Peipei; He, Guangwei; Jie, Qiong; Wu, Yulin

    2015-11-15

    Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway.

  12. Citrate-Based Biomaterials and Their Applications in Regenerative Engineering

    PubMed Central

    Tran, Richard T.; Yang, Jian; Ameer, Guillermo A.

    2015-01-01

    Advances in biomaterials science and engineering are crucial to translating regenerative engineering, an emerging field that aims to recreate complex tissues, into clinical practice. In this regard, citrate-based biomaterials have become an important tool owing to their versatile material and biological characteristics including unique antioxidant, antimicrobial, adhesive, and fluorescent properties. This review discusses fundamental design considerations, strategies to incorporate unique functionality, and examples of how citrate-based biomaterials can be an enabling technology for regenerative engineering. PMID:27004046

  13. Injectable citrate-modified Portland cement for use in vertebroplasty

    PubMed Central

    Wynn-Jones, Gareth; Shelton, Richard M; Hofmann, Michael P

    2014-01-01

    The injectability of Portland cement (PC) with several citrate additives was investigated for use in clinical applications such as vertebroplasty (stabilization of a fractured vertebra with bone cement) using a syringe. A 2-wt % addition of sodium or potassium citrate with PC significantly improved cement injectability, decreased cement setting times from over 2 h to below 25 min, while increasing the compressive strength to a maximum of 125 MPa. Zeta-potential measurements indicated that the citrate anion was binding to one or more of the positively charged species causing charged repulsion between cement particles which dispersed aggregates and caused the liquefying effect of the anion. Analysis of the hydrating phases of PC indicated that the early strength producing PC phase (ettringite) developed within the first 2 h of setting following addition of the citrate anion, while this did not occur in the control cement (PC only). Within 24 h ettringite developed in PC as well as calcium–silicate–hydrate (C–S–H), the major setting phase of PC, whereas cements containing citrate did not develop this phase. The evidence suggested that in the presence of citrate the cements limited water supply appeared to be utilized for ettringite formation, producing the early strength of the citrate cements. The present study has demonstrated that it is possible to modify PC with citrate to both improve the injectability and crucially reduce the setting times of PC while improving the strength of the cement. © 2014 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1799–1808, 2014. PMID:24711245

  14. Citrate-Based Biomaterials and Their Applications in Regenerative Engineering

    NASA Astrophysics Data System (ADS)

    Tran, Richard T.; Yang, Jian; Ameer, Guillermo A.

    2015-07-01

    Advances in biomaterials science and engineering are crucial to translating regenerative engineering, an emerging field that aims to recreate complex tissues, into clinical practice. In this regard, citrate-based biomaterials have become an important tool owing to their versatile material and biological characteristics including unique antioxidant, antimicrobial, adhesive, and fluorescent properties. This review discusses fundamental design considerations, strategies to incorporate unique functionality, and examples of how citrate-based biomaterials can be an enabling technology for regenerative engineering.

  15. Citric/citrate buffer: an effective antiglycolytic agent.

    PubMed

    del Pino, Isabel García; Constanso, Ignacio; Mourín, Luis Vázquez; Safont, Carmela Barbuzano; Vázquez, Pastora Rodríguez

    2013-10-01

    In order to minimize the influence of glycolysis on diabetes mellitus (DM) diagnostic tests, we have compared the behavior of citric/citrate, fluoride additives and gel-serum with plasma-heparin under careful preanalytical conditions. Subsequently, we compared the effectiveness of both fluoride and citric additives at different pre-centrifugation times. Finally, the influence of citric/citrate collection tube on diagnostic tests results was evaluated. The first study of 80 voluntary patients assessed the glucose bias of citric/citrate, fluoride additive tubes and gel-serum tubes versus plasma-heparin tubes at several medical decision cut-offs (MDC). The second study performed with 72 volunteers evaluated additives, simulating transport times to the laboratory and centrifugation delay periods. Final evaluation compares the proportion of positive tests in total tests carried out in two different periods. When citric/citrate (n=79) and fluoride tubes (n=60) were compared with plasma-heparin under controlled preanalytical conditions, both met the bias specification for plasma glucose (±1.8%) at seven MDC. On the contrary, serum samples (n=15) did not meet it at five MDC. In the second study, differences in glucose values at distinct pre-centrifugation times were not statistically significant for citric/citrate tubes, but significant for fluoride tubes and also for comparison of fluoride and citric/citrate tubes. Hemolysis in fluoride tubes was higher. Citric/citrate tube implementation in our laboratory caused an increase in positive diagnostic tests that were only statistically significant for gestational diabetes mellitus (GDM) screening. Citric/citrate additive tube is equivalent to plasma-heparin avoiding glycolysis completely and immediately under careful preanalytical conditions even with a 3-h delay in plasma separation. According to used MDC we have not statistically significantly increased the diagnoses of DM cases.

  16. Citrate uptake into Pectobacterium atrosepticum is critical for bacterial virulence.

    PubMed

    Urbany, Claude; Neuhaus, H Ekkehard

    2008-05-01

    To analyze whether metabolite import into Pectobacterium atrosepticum cells affects bacterial virulence, we investigated the function of a carrier which exhibits significant structural homology to characterized carboxylic-acid transport proteins. The corresponding gene, ECA3984, previously annotated as coding for a Na(+)/sulphate carrier, in fact encodes a highly specific citrate transporter (Cit1) which is energized by the proton-motive force. Expression of the cit1 gene is stimulated by the presence of citrate in the growth medium and is substantial during growth of P. atrosepticum on potato tuber tissue. Infection of tuber tissue with P. atrosepticum leads to reduced citrate levels. P. atrosepticum insertion mutants, lacking the functional Cit1 protein, did not grow in medium containing citrate as the sole carbon source, showed a substantially reduced ability to macerate potato tuber tissue, and did not provoke reduced citrate levels in the plant tissue upon infection. We propose that citrate uptake into P. atrosepticum is critical for full bacterial virulence.

  17. Tamoxifen citrate: a glimmer of hope for silicosis.

    PubMed

    Yoldas, Omer; Karaca, Turgut; Bilgin, Bulent Caglar; Yilmaz, Omer Hinc; Simsek, Gulcin Guler; Alici, Ibrahim Onur; Uzdogan, Andaç; Karaca, Nihal; Akin, Tezcan; Yoldas, Suna; Akbiyik, Filiz

    2015-01-01

    Inhalation of crystalline silica nanoparticles causes pulmonary damage resulting in progressive lung fibrosis. Currently, there is no effective treatment for silicosis. Tamoxifen citrate is a selective estrogen receptor modulator, which is one of the adjuvant treatment choices for breast cancer. It is also known with its inhibitory effect on the production of transforming growth factor-beta (TGF-β) and studied for the anti-fibrotic effect in some fibrotic diseases. The aim of the study was to determine the effect of tamoxifen citrate on the prevention of pulmonary fibrosis and the treatment of silicosis. A total of 100 adult female Wistar Albino rats (200-250 g) were used in this study. The rats were divided into five groups including 20 rats in each. Rats were exposed to silica for 84 d in all groups. In group 1, rats were sacrificed on the day 84 without receiving treatment. In group 2, rats received 1 mg/kg tamoxifen (tmx1 + 1), from the first day of the study for the whole 114 d of the study. In group 3, (tmx10 + 10) rats were given 10 mg/kg tamoxifen from the first day of the study for the whole 114 d of the study. In group 4 (tmx1), rats were started 1 mg/kg of tamoxifen on day 84 and were given until day 114. In group 5 (tmx10), rats were fed with 10 mg/kg tamoxifen starting from day 84 to day 114. All rats except group 1 were sacrificed on 114 day of the study. Lung inflammation and fibrosis scores, serum TGF β levels, lung smooth muscle antigen and tissue transforming growth factor β (t-TGF-β) antibody staining levels, and number of silicotic rats were compared between groups. Silicosis was caused successfully in all rats in group 1. There were six silicotic rats in group 3 and it was the lowest number of all groups. Plasma TGF-ß levels and fibrosis score were significantly lower in all groups when compared with the control group. Tamoxifen could have preventive or treating effects in silicosis and found that lung fibrosis score was

  18. Low Temperature Induced Changes in Citrate Metabolism in Ponkan (Citrus reticulata Blanco cv. Ponkan) Fruit during Maturation.

    PubMed

    Lin, Qiong; Qian, Jing; Zhao, Chenning; Wang, Dengliang; Liu, Chunrong; Wang, Zhidong; Sun, Chongde; Chen, Kunsong

    2016-01-01

    Citrate is the most important organic acid in citrus fruit, and its concentration in fruit cells is regulated mainly by the balance between synthesis and degradation. Ponkan (Citrus reticulate Blanco cv. Ponkan) is one of the major citrus cultivars grew in China, and the fruit are picked before fully mature to avoid bad weather. Greenhouse production is widely used to prolong the maturation period and improve the quality of Ponkan fruit by maintaining adequate temperature and providing protection from adverse weather. In this research, Ponkan fruit cultivated in either a greenhouse or open field were used to investigate differences in the expression of genes related to citrate metabolism during maturation in the two environments. The citrate contents were higher in open field fruit, and were mainly correlated with expressions of CitPEPCs, CitCSs, CitAco3 and CitGAD4, which were significantly increased. In addition, the impacts of low temperature (LT) and water stress (WS) on citrate metabolism in Ponkan were investigated during fruit maturation. The citrate contents in LT fruit were significantly increased, by between 1.4-1.9 fold, compared to the control; it showed no significant difference in fruit with water stress treatment compared to the control fruit. Furthermore, the expressions of CitPEPCs, CitCSs, CitAco3 and CitGAD4 were significantly increased in response to LT treatment, but showed no significant difference in WS compared to the control fruit. Thus, it can be concluded that low temperature may be the main factor influencing citrate metabolism during maturation in Ponkan fruit.

  19. Low Temperature Induced Changes in Citrate Metabolism in Ponkan (Citrus reticulata Blanco cv. Ponkan) Fruit during Maturation

    PubMed Central

    Lin, Qiong; Qian, Jing; Zhao, Chenning; Wang, Dengliang; Liu, Chunrong; Wang, Zhidong; Sun, Chongde; Chen, Kunsong

    2016-01-01

    Citrate is the most important organic acid in citrus fruit, and its concentration in fruit cells is regulated mainly by the balance between synthesis and degradation. Ponkan (Citrus reticulate Blanco cv. Ponkan) is one of the major citrus cultivars grew in China, and the fruit are picked before fully mature to avoid bad weather. Greenhouse production is widely used to prolong the maturation period and improve the quality of Ponkan fruit by maintaining adequate temperature and providing protection from adverse weather. In this research, Ponkan fruit cultivated in either a greenhouse or open field were used to investigate differences in the expression of genes related to citrate metabolism during maturation in the two environments. The citrate contents were higher in open field fruit, and were mainly correlated with expressions of CitPEPCs, CitCSs, CitAco3 and CitGAD4, which were significantly increased. In addition, the impacts of low temperature (LT) and water stress (WS) on citrate metabolism in Ponkan were investigated during fruit maturation. The citrate contents in LT fruit were significantly increased, by between 1.4–1.9 fold, compared to the control; it showed no significant difference in fruit with water stress treatment compared to the control fruit. Furthermore, the expressions of CitPEPCs, CitCSs, CitAco3 and CitGAD4 were significantly increased in response to LT treatment, but showed no significant difference in WS compared to the control fruit. Thus, it can be concluded that low temperature may be the main factor influencing citrate metabolism during maturation in Ponkan fruit. PMID:27249065

  20. Effectiveness and Safety Assessment of Citrate Anticoagulation During Albumin Dialysis in Comparison to Other Methods of Anticoagulation.

    PubMed

    Dyla, Agnieszka; Mielnicki, Wojciech; Bartczak, Joanna; Zawada, Tomasz; Garba, Piotr

    2017-03-23

    Liver failure is a serious and often deadly disease often requiring MARS (Molecular Adsorbent Recirculating System) therapy. Choosing the safe and effective method of anticoagulation during artificial liver support systems seems to be very difficult and extremely important. The aim of this study was to assess effectiveness and safety of regional anticoagulation with citrate in liver failure patients during MARS. We used a single center observational study. We analyzed 158 MARS sessions performed in 65 patients: 105 (66.5%) sessions in 41 patients with heparin anticoagulation, 40 (25.3%) sessions in 19 patients with citrate, and 13 (8%) sessions in only five patients without anticoagulation, that were excluded from part of the analysis. To determine the effectiveness of regional anticoagulation with citrate, probability of filter survival and changes in laboratory parameters were analyzed according to the applied method of anticoagulation. The safety of citrate was determined by Ca/Ca(2+) ratio, acid-base balance, bleeding complications, and the need for blood product transfusions. The probability of filter survival in the citrate group was 94% and in the heparin group 82% (P = 0.204). There was no relationship between the method of anticoagulation and effectiveness of MARS therapy in lowering the levels of the analyzed parameters. Only one patient had a Ca/Ca(2+) ratio higher than he safety margin. There were no statistically significant changes in pH and lactate level irrespective of anticoagulation; bicarbonate dropped significantly only in the heparin group (P = 0.03). The frequency of bleeding complications and the need for transfusions did not differ significantly between groups. Regional anticoagulation with citrate can be an effective and safe method of anticoagulation during MARS therapy, but requires attentive monitoring and further studies in liver failure patients.

  1. Ionized hypomagnesemia in patients undergoing orthotopic liver transplantation: a complication of citrate intoxication.

    PubMed

    Scott, V L; De Wolf, A M; Kang, Y; Altura, B T; Virji, M A; Cook, D R; Altura, B M

    1996-09-01

    Using a new ion-selective electrode, plasma concentration of ionized magnesium was measured in nine adult patients undergoing orthotopic liver transplantation. Baseline plasma ionized magnesium (IMg2+) concentration (0.49 +/- 0.07 mmol/L) was slightly below normal values (0.55-0.66 mmol/L, 95% CI): Six patients had ionized hypomagnesemia and two of these had total hypomagnesemia. Ionized IMg2+ concentration progressively decreased during the dissection (0.45 +/- 0.07 mmol/L, p < 0.05) and anhepatic stage (0.38 +/- 0.07 mmol/L, p < 0.05) and returned toward baseline values by 2 hours after graft reperfusion. Plasma ionized calcium levels and acid-base status were maintained within normal limits during surgery. Serum citrate concentration increased during the dissection (0.58 +/- 0.60 mmol/L) and anhepatic stages (1.18 +/- 0.78 mmol/L), the result of transfusion of citrate-rich blood products in the absence of adequate hepatic function, and gradually returned toward baseline values after graft reperfusion. IMg2+ concentration inversely correlated with the plasma citrate concentration (r2 = 0.54). The results of this study demonstrate that ionized hypomagnesemia invariably occurs during liver transplantation and suggest that this derangement may be a clinical concern, because magnesium is an important cofactor for the maintenance of cardiovascular homeostasis. The data further suggest the clinical importance of supplementation with magnesium based on the monitoring of plasma IMg2+ concentration.

  2. A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation

    PubMed Central

    Infantino, Vittoria; Iacobazzi, Vito; Menga, Alessio

    2014-01-01

    The chronic induction of inflammation underlies multiple pathological conditions, including metabolic, autoimmune disorders and cancer. The mitochondrial citrate carrier (CIC), encoded by the SLC25A1 gene, promotes the export of citrate from the mitochondria to the cytoplasm, a process that profoundly influences energy balance in the cells. We have previously shown that SLC25A1 is a target gene for lipopolysaccharide signaling and promotes the production of inflammatory mediators. We now demonstrate that SLC25A1 is induced at the transcriptional level by two key pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ), and such induction involves the activity of the nuclear factor kappa B and STAT1 transcription factors. By studying the down-stream events following SLC25A1 activation during signals that mimic inflammation, we demonstrate that CIC is required for regulating the levels of nitric oxide and of prostaglandins by TNFα or IFNγ. Importantly, we show that the citrate exported from mitochondria via CIC and its downstream metabolic intermediate, acetyl-coenzyme A, are necessary for TNFα or IFNγ to induce nitric oxide and prostaglandin production. These findings provide the first line of evidence that the citrate export pathway, via CIC, is central for cytokine-induced inflammatory signals and shed new light on the relationship between energy metabolism and inflammation. PMID:25072865

  3. A study of the effects of citrate-coated silver nanoparticles on RAW 264.7 cells using a toolbox of cytotoxic endpoints

    NASA Astrophysics Data System (ADS)

    Bastos, V.; Duarte, I. F.; Santos, C.; Oliveira, H.

    2017-05-01

    Citrate-coated silver nanoparticles (citrate-AgNPs) are among the most commonly used nanomaterials, widely present in industrial and biomedical products. In this study, the cytotoxicity of 30-nm citrate-AgNPs on the macrophage cell line RAW 264.7 was evaluated, using a battery of cytotoxicity endpoints (viability, oxidative stress, and cytostaticity/clastogenicity), at 24 and 48 h of exposure. Citrate-AgNPs decreased cell proliferation and viability only at 75 μg/mL, suggesting a low sensitivity of RAW cells to lower doses of these AgNPs. After 24 h of exposure, ROS content decreased in cells exposed to 60 μg/mL AgNPs (IC20 value), corroborating the high tolerance of these cells to citrate-AgNPs. However, these cells suffered an impairment of the cell cycle, shown by an increase at the sub-G1 phase. This increase of the sub-G1 population was correlated with an increase of DNA fragmentation, suggesting an increase of apoptosis. Thus, our data are important to understand the effects of low concentrations (IC20) of citrate-AgNPs on in vitro vital macrophage functions.

  4. Alkali absorption and citrate excretion in calcium nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Sakhaee, K.; Williams, R. H.; Oh, M. S.; Padalino, P.; Adams-Huet, B.; Whitson, P.; Pak, C. Y.

    1993-01-01

    The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

  5. Alkali absorption and citrate excretion in calcium nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Sakhaee, K.; Williams, R. H.; Oh, M. S.; Padalino, P.; Adams-Huet, B.; Whitson, P.; Pak, C. Y.

    1993-01-01

    The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

  6. Simplified citrate anticoagulation for high-flux hemodialysis.

    PubMed

    Apsner, R; Buchmayer, H; Lang, T; Unver, B; Speiser, W; Sunder-Plassmann, G; Hörl, W H

    2001-11-01

    In a randomized crossover trial, we compared a simple citrate anticoagulation protocol for high-flux hemodialysis with standard anticoagulation by low-molecular-weight heparin (dalteparin). Primary end points were urea reduction rate (URR), Kt/V, and control of electrolyte and acid-base homeostasis. Secondary end points were bleeding time at vascular puncture sites and markers of activation of platelets, coagulation, and fibrinolysis. Solute removal during citrate dialysis was excellent (URR, 0.71 +/- 0.06; Kt/V, 1.55 +/- 0.3) and similar to results of conventional bicarbonate hemodialysis anticoagulation with dalteparin (URR, 0.72 +/- 0.04; Kt/V, 1.56 +/- 0.2). Electrolyte control was effective with both anticoagulation regimens, and total and ionized calcium, sodium, potassium, and phosphate concentrations at the end of dialysis did not differ. Alkalemia was less frequent after citrate than conventional dialysis (pH 7.5 in 25% versus 62% of patients; mean pH at end of dialysis, 7.46 +/- 0.06 versus 7.51 +/- 0.07; P < 0.01). Bleeding time at puncture sites was shorter by 30% after citrate compared with dalteparin anticoagulation (5.43 +/- 2.80 versus 7.86 +/- 2.93 minutes; P < 0.001). Activation of platelets, coagulation, and fibrinolysis was modest for both treatments and occurred mainly within the dialyzer during dalteparin treatment and in the vascular-access region during citrate anticoagulation. Citrate-related adverse events were not observed. We conclude that citrate anticoagulation for high-flux hemodialysis is feasible and safe using a simple infusion protocol.

  7. Treatment Efficacy and Safety During Plasma Exchange With Citrate Anticoagulation: A Randomized Study of 4 Versus 15% Citrate.

    PubMed

    Antonic, Manja; Gubensek, Jakob; Buturovic-Ponikvar, Jadranka; Ponikvar, Rafael

    2016-04-01

    In plasma exchange (PE), contrary to dialysis, there is no ultrafiltration, and the volume of anticoagulant contributes to volume overload of the patient and might also reduce PE efficiency through dilution. To reduce the volume of citrate, we compared 4 and 15% citrate anticoagulation protocols in PE in a randomized study, aiming to evaluate PE efficacy, anticoagulation efficiency, and overall safety. In addition to standard biochemical analyses during PE treatments, the elimination rate (ER) of immunoglobulins was calculated to evaluate PE efficacy. Anticoagulation was evaluated by postfilter ionized calcium, visual evaluation of the extracorporeal system, and change in the sieving coefficient (SC) during PE. Accumulation of citrate was determined by calculating the total-to-ionized calcium ratio and measuring the citrate concentration after PE. One hundred forty procedures (70 in each group) were performed in 37 patients. The mean citrate infusion rate was 197 ± 10 mL/h in the 4% and 59 ± 5.5 mL/h in the 15% groups, respectively; the total volume of infused citrate was 502 ± 77 mL versus 164 ± 52 mL (P < 0.001). ER for immunoglobulin G (0.57 ± 0.06 vs. 0.55 ± 0.1, P = 0.18), M, and A were comparable. Ionized calcium was stable during the procedures, and there were no significant side effects. Although postfilter ionized calcium was on the upper limit of the target range (0.41 ± 0.16 vs. 0.37 ± 0.14 mmol/L, P = 0.38), the visual assessment score was excellent, and even a rise in SC was observed during the procedures in both groups. The total-to-ionized calcium ratio was increased in 20 versus 22% of procedures, and citrate concentrations after PE were also similar (1306 ± 441 vs. 1263 ± 405 μmol/L). To conclude, we were unable to show superior PE efficacy in the 15% citrate group, but we significantly reduced the infused volume, which is important in patients with fluid overload. Both

  8. A Feasibility Study Showing [(68)Ga]Citrate PET Detects Prostate Cancer.

    PubMed

    Behr, Spencer C; Aggarwal, Rahul; Seo, Youngho; Aparici, Carina M; Chang, Emily; Gao, Kenneth T; Tao, Dora H; Small, Eric J; Evans, Michael J

    2016-12-01

    The management of advanced or recurrent prostate cancer is limited in part by the lack of effective imaging agents. Metabolic changes in prostate cancer have previously been exploited for imaging, culminating in the recent US FDA approval of [(11)C]choline for the detection of subclinical recurrent disease after definitive local therapy. Despite this milestone, production of [(11)C]choline requires an on-site cyclotron, limiting the scope of medical centers at which this scan can be offered. In this pilot study, we tested whether prostate cancer could be imaged with positron emission tomography (PET) using [(68)Ga]citrate, a radiotracer that targets iron metabolism but is produced without a cyclotron. Eight patients with castrate-resistant prostate cancer were enrolled in this single-center feasibility study. All patients had evidence of metastatic disease by standard of care imaging [X-ray computed tomography (CT), bone scan, or magnetic resonance imaging (MRI)] prior to PET with [(68)Ga]citrate. Patients were intravenously injected with increasing doses of [(68)Ga]citrate (136.9 to a maximum of 259 MBq). Uptake time was steadily increased from 1 h to approximately 3.5 h for the final 4 patients, and all patients were imaged with a PET/MRI. Qualitative and semi-quantitative (maximum standardized uptake value (SUVmax)) assessment of the metastatic lesions was performed and compared to the standard of care imaging. At 1- and 2-h imaging times post injection, there were no detectable lesions with [(68)Ga]citrate PET. At 3- to 4-h uptake time, there were a total of 71 [(68)Ga]citrate-positive lesions (67 osseous, 1 liver, and 3 lymph node). Of these, 65 lesions were visible on the standard of care imaging (CT and/or bone scan). One PET-avid osseous vertebral body metastasis was not apparent on either CT or bone scan. Twenty-five lesions were not PET-avid but seen on CT and bone scan (17 bone, 6 lymph node, 1 pleural, and 1 liver). The average of the maximum SUVs

  9. Nanoscale observations of the effect of citrate on calcium oxalate precipitation on calcite surfaces.

    NASA Astrophysics Data System (ADS)

    Burgos-Cara, Alejandro; Ruiz-Agudo, Encarnacion; Putnis, Christine V.

    2016-04-01

    Calcium oxalate (CaC2O4ṡxH2O) minerals are naturally occurring minerals found in fossils, plants, kidney stones and is a by-product in some processes such as paper, food and beverage production [1,2]. In particular, calcium oxalate monohydrate phase (COM) also known as whewellite (CaC2O4ṡH2O), is the most frequently reported mineral phase found in urinary and kidney stones together with phosphates. Organic additives are well known to play a key role in the formation of minerals in both biotic and abiotic systems, either facilitating their precipitation or hindering it. In this regard, recent studies have provided direct evidence demonstrating that citrate species could enhance dissolution of COM and inhibit their precipitation. [3,4] The present work aims at evauate the influence of pH, citrate and oxalic acid concentrations in calcium oxalate precipitation on calcite surfaces (Island Spar, Chihuahua, Mexico) through in-situ nanoscale observation using in situ atomic force microscopy (AFM, Multimode, Bruker) in flow-through experiments. Changes in calcium oxalate morphologies and precipitated phases were observed, as well as the inhibitory effect of citrate on calcium oxalate precipitation, which also lead to stabilization an the amorphous calcium oxalate phase. [1] K.D. Demadis, M. Öner, Inhibitory effects of "green"additives on the crystal growth of sparingly soluble salts, in: J.T. Pearlman (Ed.), Green Chemistry Research Trends, Nova Science Publishers Inc., New York, 2009, pp. 265-287. [2] M. Masár, M. Zuborová, D. Kaniansky, B. Stanislawski, Determination of oxalate in beer by zone electrophoresis on a chip with conductivity detection, J. Sep. Sci. 26 (2003) 647-652. [3] Chutipongtanate S, Chaiyarit S, Thongboonkerd V. Citrate, not phosphate, can dissolve calcium oxalate monohydrate crystals and detach these crystals from renal tubular cells. Eur J Pharmacol 2012;689:219-25. [4] Weaver ML, Qiu SR, Hoyer JR, Casey WH, Nancollas GH, De Yoreo JJ

  10. Citrate metabolism and its complications in non-massive blood transfusions: association with decompensated metabolic alkalosis+respiratory acidosis and serum electrolyte levels.

    PubMed

    Bıçakçı, Zafer; Olcay, Lale

    2014-06-01

    Metabolic alkalosis, which is a non-massive blood transfusion complication, is not reported in the literature although metabolic alkalosis dependent on citrate metabolism is reported to be a massive blood transfusion complication. The aim of this study was to investigate the effect of elevated carbon dioxide production due to citrate metabolism and serum electrolyte imbalance in patients who received frequent non-massive blood transfusions. Fifteen inpatients who were diagnosed with different conditions and who received frequent blood transfusions (10-30 ml/kg/day) were prospectively evaluated. Patients who had initial metabolic alkalosis (bicarbonate>26 mmol/l), who needed at least one intensive blood transfusion in one-to-three days for a period of at least 15 days, and whose total transfusion amount did not fit the massive blood transfusion definition (<80 ml/kg) were included in the study. The estimated mean total citrate administered via blood and blood products was calculated as 43.2 ± 34.19 mg/kg/day (a total of 647.70 mg/kg in 15 days). Decompensated metabolic alkalosis+respiratory acidosis developed as a result of citrate metabolism. There was a positive correlation between cumulative amount of citrate and the use of fresh frozen plasma, venous blood pH, ionized calcium, serum-blood gas sodium and mortality, whereas there was a negative correlation between cumulative amount of citrate and serum calcium levels, serum phosphorus levels and amount of urine chloride. In non-massive, but frequent blood transfusions, elevated carbon dioxide production due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis+respiratory acidosis and electrolyte imbalance may develop. This situation may contribute to the increase in mortality. In conclusion, it should be noted that non-massive, but frequent blood transfusions may result in certain complications. Copyright © 2014 Elsevier Ltd

  11. Saccharomyces cerevisiae contains two functional citrate synthase genes.

    PubMed Central

    Kim, K S; Rosenkrantz, M S; Guarente, L

    1986-01-01

    The tricarboxylic acid cycle occurs within the mitochondria of the yeast Saccharomyces cerevisiae. A nuclear gene encoding the tricarboxylic acid cycle enzyme citrate synthase has previously been isolated (M. Suissa, K. Suda, and G. Schatz, EMBO J. 3:1773-1781, 1984) and is referred to here as CIT1. We report here the isolation, by an immunological method, of a second nuclear gene encoding citrate synthase (CIT2). Disruption of both genes in the yeast genome was necessary to produce classical citrate synthase-deficient phenotypes: glutamate auxotrophy and poor growth on rich medium containing lactate, a nonfermentable carbon source. Therefore, the citrate synthase produced from either gene was sufficient for these metabolic roles. Transcription of both genes was maximally repressed in medium containing both glucose and glutamate. However, transcription of CIT1 but not of CIT2 was derepressed in medium containing a nonfermentable carbon source. The significance of the presence of two genes encoding citrate synthase in S. cerevisiae is discussed. Images PMID:3023912

  12. Simplified Citrate Anticoagulation for CRRT Without Calcium Replacement.

    PubMed

    Broman, Marcus; Klarin, Bengt; Sandin, Karin; Carlsson, Ola; Wieslander, Anders; Sternby, Jan; Godaly, Gabriela

    2015-01-01

    Since 2012, citrate anticoagulation is the recommended anticoagulation strategy for continuous renal replacement therapy (CRRT). The main drawback using citrate as anticoagulant compared with heparin is the need for calcium replacement and the rigorous control of calcium levels. This study investigated the possibility to achieve anticoagulation while eliminating the need for calcium replacement. This was successfully achieved by including citrate and calcium in all CRRT solutions. Thereby the total calcium concentration was kept constant throughout the extracorporeal circuit, whereas the ionized calcium was kept at low levels enough to avoid clotting. Being a completely new concept, only five patients with acute renal failure were included in a short, prospective, intensely supervised nonrandomized pilot study. Systemic electrolyte levels and acid-base parameters were stable and remained within physiologic levels. Ionized calcium levels declined slightly initially but stabilized at 1.1 mmol/L. Plasma citrate concentrations stabilized at approximately 0.6 mmol/L. All postfilter ionized calcium levels were <0.5 mmol/L, that is, an anticoagulation effect was reached. All filter pressures were normal indicating no clotting problems, and no visible clotting was observed. No calcium replacement was needed. This pilot study suggests that it is possible to perform regional citrate anticoagulation without the need for separate calcium infusion during CRRT.

  13. Phospho-oligosaccharide dependent phosphorylation of ATP citrate lyase.

    PubMed

    Puerta, J; Mato, J M; Alemany, S

    1990-01-01

    The effect of insulin on ATP citrate lyase phosphorylation has been shown to be mimicked by a phospho-oligosaccharide in intact adipocytes. We demonstrate that the addition of phospho-oligosaccharide to intact adipocytes enhances the phosphorylation of ATP citrate lyase in the same tryptic peptide as insulin does. The addition of phospho-oligosaccharide to an adipocyte extract also results in an increase in ATP citrate lyase phosphorylation but in a different site than that observed in intact cells. The phospho-oligosaccharide-dependent incorporation of phosphate into ATP citrate lyase in intact cells is resistant to isopropanol and acetic acid, but the phosphoenzyme phosphorylated in cell extracts is acid labile. In cell extracts, the addition of phospho-oligosaccharide markedly inhibits ATP hydrolysis, which may explain the effect of this molecule on ATP citrate lyase phosphorylation in broken cells. These results support the hypothesis that this phospho-oligosaccharide mediates some of the effects of insulin on protein phosphorylation. They also indicate that caution should be exercised in interpreting the results obtained by adding phospho-oligosaccharide to broken cell preparations.

  14. Colloid mobilization in the field using citrate to remediate chromium.

    PubMed

    Johnson, C R; Hellerich, L A; Nikolaidis, N P; Gschwend, P M

    2001-01-01

    We investigated the feasibility of cleaning aquifer sediments, long contaminated with chromium (Cr) from a metal plating facility, by detaching colloid-sized sorbents from the immobile aquifer solids and then pumping those colloids to the surface for treatment. In laboratory experiments using aquifer solids from the site, several solutions (water at various pHs, phosphate, oxalate, ascorbate, citrate) were examined for their ability to disperse colloids and Cr. Based on these tests, a 5 mM citrate solution at pH 7 was selected. Subsequently, such a citrate solution was used in the field in two single-well injection-withdrawal experiments. Large quantities of colloids were released immediately after injection. The colloidal particles mobilized by citrate in the field had more than 20 times higher Cr concentrations than did the average aquifer sediments, implying success in mobilizing Cr-associated phases. Further, laboratory and field tests showed that anion exchange of citrate for chromate caused some additional release of Cr from these aquifer solids.

  15. Identification of two distinct Bacillus subtilis citrate synthase genes.

    PubMed

    Jin, S; Sonenshein, A L

    1994-08-01

    Two distinct Bacillus subtilis genes (citA and citZ) were found to encode citrate synthase isozymes that catalyze the first step of the Krebs cycle. The citA gene was cloned by genetic complementation of an Escherichia coli citrate synthase mutant strain (W620) and was in a monocistronic transcriptional unit. A divergently transcribed gene, citR, could encode a protein with strong similarity to the bacterial LysR family of regulatory proteins. A null mutation in citA had little effect on citrate synthase enzyme activity or sporulation. The residual citrate synthase activity was purified from a citA null mutant strain, and the partial amino acid sequence for the purified protein (CitZ) was determined. The citZ gene was cloned from B. subtilis chromosomal DNA by using a PCR-generated probe synthesized with oligonucleotide primers derived from the partial amino acid sequence of purified CitZ. The citZ gene proved to be the first gene in a tricistronic cluster that also included citC (coding for isocitrate dehydrogenase) and citH (coding for malate dehydrogenase). A mutation in citZ caused a substantial loss of citrate synthase enzyme activity, glutamate auxotrophy, and a defect in sporulation.

  16. Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

    PubMed Central

    2014-01-01

    Background During continuous venovenous haemofiltration (CVVH), regional anticoagulation with citrate may be superior to heparin in terms of biocompatibility, since heparin as opposed to citrate may activate complement (reflected by circulating C5a) and induce neutrophil degranulation in the filter and myeloperoxidase (MPO) release from endothelium. Methods No anticoagulation (n = 13), unfractionated heparin (n = 8) and trisodium citrate (n = 17) regimens during CVVH were compared. Blood samples were collected pre- and postfilter; C5a, elastase and MPO were determined by ELISA. Additionally, C5a was also measured in the ultrafiltrate. Results In the heparin group, there was C5a production across the filter which most decreased over time as compared to other groups (P = 0.007). There was also net production of elastase and MPO across the filter during heparin anticoagulation (P = 0.049 or lower), while production was minimal and absent in the no anticoagulation and citrate group, respectively. During heparin anticoagulation, plasma concentrations of MPO at the inlet increased in the first 10 minutes of CVVH (P = 0.024). Conclusion Citrate confers less filter-induced, potentially harmful complement activation and neutrophil degranulation and less endothelial activation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients. PMID:24438360

  17. Effect of citrate ions on the softening of root crops prepared with freeze-thaw impregnation of macerating enzymes.

    PubMed

    Nakatsu, Sayaka; Shimoda, Mitsuya; Shibata, Kenya; Kajihara, Ryo; Ishihara, Masako; Sakamoto, Koji

    2014-03-01

    Freeze-thaw impregnation is a technique used for the rapid impregnation of substances into foodstuffs. Freeze-thaw impregnation with macerating enzymes has been applied to soften foodstuffs, while retaining their original shapes and flavors. In this study, we found that co-impregnation with citrate ions and macerating enzymes significantly facilitated the softening of root crops. When burdock roots were processed by the impregnating solution at pH 4.0-5.0, co-impregnated burdock roots exhibited 1/6-1/3 firmness values compared with burdock roots impregnated with only enzymes. The impregnation with citrate ions alone at pH 4.0 to 5.0 did not soften burdock roots. The firmness of burdock roots was positively correlated with the amount of water-insoluble calcium in the samples. The results suggested that the degradation of pectins by pectinolytic activities could promote contact with citrate to bridging-calcium ions interacting with the pectin chains. Therefore, the softening by the synergistic effect of citrate ions and macerating enzymes was related to the amount of pectins contained in root crops. That is, the synergistic effect was significant with burdock roots and carrots (from which 50% of polysaccharides are pectins) unlike with lotus rhizomes and bamboo shoots (from which 30% and 10% of polysaccharides are pectins, respectively). Freeze-thaw impregnation with macerating enzymes and citrate ions can be applied for the production of care foods which can be eaten without chewing. The softened products induce the pleasure of eating for consumers because their original shapes and flavors are retained. © 2014 Institute of Food Technologists®

  18. Magnetic nanoparticles coated with cyclodextrins and citrate for irinotecan delivery.

    PubMed

    Monteiro, Ana P F; Caminhas, Larissa D; Ardisson, José D; Paniago, Roberto; Cortés, Maria E; Sinisterra, Rubén D

    2017-05-01

    In the present work, we study the role of different components in the formation of more stable iron oxide magnetic nanoparticles (MNPs): β-cyclodextrin (BCD), 2-hydroxypropyl-β-cyclodextrin (HP) and citrate anion. MNPs formulations were characterized by FTIR, particles size measurements, zeta potential based on dynamic light scattering principle technique, X-ray powder pattern diffraction, XPS spectroscopy, transmission electron microscopy and thermogravimetric analysis. The results showed that cyclodextrins and citrate plays a key role in order to obtain a lower size of coated MNPs and proved to be an efficient strategy to obtain a more stable colloidal dispersion, avoiding the nanoparticles oxidation, enhancing the irinotecan incorporation and release. Furthermore, citrate-coated BCD-MNPs showed the same cytotoxicity of the free IRI.

  19. Utility of Aspergillus niger citrate synthase promoter for heterologous expression.

    PubMed

    Dave, Kashyap; Punekar, Narayan S

    2011-09-10

    Citrate synthase is a central player in the acidogenic metabolism of Aspergillus niger. The 5' upstream sequence (0.9kb DNA) of citrate synthase gene (citA) from A. niger NCIM 565 was analyzed and its promoter function demonstrated through the heterologous expression of two proteins. The cloned citrate synthase promoter (PcitA) sequence was able to express bar coding sequence thereby conferring phosphinothricin resistance. This sequence was further analyzed by systematic deletions to define an effective but compact functional promoter. The PcitA driven egfp expression showed that PcitA was active in all differentiation cell-stages of A. niger. EGFP expression was highest on non-repressible carbon sources like acetate and glycerol. Mycelial EGFP levels increased during acidogenic growth suggesting that PcitA is functional throughout this cultivation. A. niger PcitA is the first Krebs cycle gene promoter used to express heterologous proteins in filamentous fungi.

  20. Strongly bound citrate stabilizes the apatite nanocrystals in bone

    SciTech Connect

    Hu, Y.-Y.; Rawal, A.; Schmidt-Rohr, K.

    2010-10-12

    Nanocrystals of apatitic calcium phosphate impart the organic-inorganic nanocomposite in bone with favorable mechanical properties. So far, the factors preventing crystal growth beyond the favorable thickness of ca. 3 nm have not been identified. Here we show that the apatite surfaces are studded with strongly bound citrate molecules, whose signals have been identified unambiguously by multinuclear magnetic resonance (NMR) analysis. NMR reveals that bound citrate accounts for 5.5 wt% of the organic matter in bone and covers apatite at a density of about 1 molecule per (2 nm){sup 2}, with its three carboxylate groups at distances of 0.3 to 0.45 nm from the apatite surface. Bound citrate is highly conserved, being found in fish, avian, and mammalian bone, which indicates its critical role in interfering with crystal thickening and stabilizing the apatite nanocrystals in bone

  1. Automated regional citrate anticoagulation: technological barriers and possible solutions.

    PubMed

    Szamosfalvi, Balazs; Frinak, Stanley; Yee, Jerry

    2010-01-01

    Large-scale adoption of regional citrate anticoagulation (RCA) is prevented by risks of the technique as practiced traditionally. Safe RCA protocols with automated delivery on customized dialysis systems are needed. We applied kinetic analysis of solute fluxes during RCA to design a protocol for sustained low-efficiency dialysis (SLED) for critically ill patients. We used a high-flux hemodialyzer, a zero-calcium (Ca) dialysate, a dialysis machine with online clearance and access recirculation monitoring, and a separate optical hematocrit (Hct) sensor. Flow rates were Q(B) = 200 ml/min for blood; Q(D) = 400 ml/min for dialysate, with Na = 140 mmol/l and HCO(3) = 32 mmol/l; Q(citrate) = 400 ml/h of acid citrate dextrose A; ultrafiltration as indicated. The Q(Ca) was infused into the return blood line, adjusted hourly based on online Hct and a <24-hour-old albumin level. Using the SLED-RCA protocol in an anhepatic, ex vivo dialysis system, ionized Ca (iCa) was >1 mmol/l in the blood reservoir and <0.3 mmol/l in the blood circuit after citrate but before Ca infusion (Q(Ca)) with normal electrolyte composition of the blood returning to the reservoir. Clinically, SLED-RCA completely abrogated clotting, without adverse electrolyte effects. The Q(Ca) prediction algorithm maintained normal systemic iCa (0.95-1.4 mmol/l) in all patients. The high citrate extraction on the dialyzer prevented systemic citrate accumulation even in shock liver patients. Safety analysis shows that building a dialysis system for automated SLED-RCA is feasible. Using predictive Q(Ca) dosing and integrating control of the infusion pumps with the dialysis machine, SLED-RCA can be near-automated today to provide a user-friendly and safe system. Copyright (c) 2010 S. Karger AG, Basel.

  2. Supplementation of total parenteral nutrition solutions with ferrous citrate.

    PubMed

    Sayers, M H; Johnson, D K; Schumann, L A; Ivey, M F; Young, J H; Finch, C A

    1983-01-01

    Daily infusion of a total parenteral nutrition (TPN) formulation containing 1 liter of 5.5% Travasol provides less than 0.1 milligrams of iron. By comparison, a formulation which includes a liter of 10% Travamin provides 2 milligrams of iron per day. To meet iron requirements in patients infusing formulations containing Travasol, iron was added as ferrous citrate. In in virto experiments, 74% of this iron was available to transferrin. In seven patients in whom in vivo availability was tested by red cell incorporation, the mean availability was 81%. Ferrous citrate is recommended as a safe, effective additive to TPN solutions for adult patients requiring iron supplements.

  3. Peroxisomal and mitochondrial citrate synthase in CAM plants.

    PubMed

    Zafra, M F; Segovia, J L; Alejandre, M J; García-Peregrín, E

    1981-12-01

    Citrate synthase wa studied for the first time in peroxisomes and mitochondria of crassulacean acid metabolism plants. Cellular organelles were isolated from Agave americana leaves by sucrose density gradient centrifugation and characterized by the use of catalase and cytochrome oxidase as marker enzymes, respectively. 48,000 X g centrifugation caused the breakdown of the cellular organelles. The presence of a glyoxylate cycle enzyme (citrate synthase) and a glycollate pathway enzyme (catalase) in the same organelles, besides the absence of another glyoxalate cycle enzyme (malate synthase) is reported for the first time, suggesting that peroxisomal and glyoxysomal proteins are synthesized at the same time and housed in he same organelle.

  4. Sildenafil citrate attenuates the deleterious effects of elevated ammonia.

    PubMed

    Arafa, Manar H; Atteia, Hebatallah H

    2013-07-01

    Ammonia is a bi-product of protein metabolism in the body. It is able to cross the blood-brain barrier and elevated ammonia levels are toxic to the brain. Rats with hyperammonemia showed impaired learning ability and impaired function of the glutamate-nitric oxide-cyclic guanosine monophosphate (glutamate-NO-cGMP) pathway in the brain. Chronic treatment with sildenafil restored learning ability. We therefore tested the hypothesis that sildenafil has a protective effect on the brains of hyperammonemic rats. Hyperammonemia was induced in male rats by daily intraperitoneal (i.p.) injection of ammonium chloride (100 mg/kg body weight) for 8 weeks. Sildenafil citrate was administered intraperitoneally (10 mg/kg body weight/3 days) for 8 weeks. Treatment with sildenafil resulted in a significant reduction in plasma liver enzymes, lipid profile as well as brain lipid peroxidation and caspase-3 mRNA. Meanwhile, plasma NO as well as cGMP, antioxidants and endothelial nitric oxide synthase (eNOS) gene expression were significantly elevated in the brains of hyperammonemic rats. Our results showed that sildenafil exerts a protective effect on the brain by reversing oxidative stress during hyperammonemia and this could be due to (i) cytoprotective, antioxidant and anti-apoptotic effects (ii) increasing cGMP and enhancing the proper metabolism of fats which could suppress oxygen radical generation and thus preventing oxidative damage in the brain. The exact protective mechanism of sildenafil has to be still investigated and further studies are warranted. Consequently, therapeutic modulation of the NO/cGMP pathway might have important clinical applications to improve brain functions in patients with hyperammonemia or clinical hepatic encephalopathy.

  5. 21 CFR 582.1751 - Sodium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose Food Additives § 582... recognized as safe when used in accordance with good manufacturing or feeding practice. ...

  6. Citrate-release-mediated aluminum resistance is coupled to the inducible expression of mitochondrial citrate synthase gene in Paraserianthes falcataria.

    PubMed

    Osawa, Hiroki; Kojima, Katsumi

    2006-05-01

    Aluminum (Al) resistance in some leguminous plants is achieved by enhanced citrate release from roots. Enhancement requires several hours for complete activation and is postulated to involve Al-responsive genes or components. We examined the mechanism of Al-induced citrate release by studying the relationship between citrate release and expression of the mitochondrial citrate synthase (mCS) gene in three leguminous trees. Root elongation in Leucaena leucocephala (Lam.) de Wit was arrested within 24 h by 30 microM Al, whereas root elongation in Paraserianthes falcataria (L.) Neilson and Acacia mangium Willd. was inhibited < 50% by a 48-h treatment with 100 microM Al in calcium chloride solution. Roots of P. falcataria and A. mangium maintained enhanced release and accumulation of citrate for at least 28 days in response to Al treatment. Aluminum increased the accumulation of mCS transcripts in P. falcataria roots, but not in L. leucocephala roots, and thus up-regulation decreased following removal of Al. Lanthanum did not alter the expression level of mCS. Aluminum increased mCS activity concomitantly with enhanced mCS gene expression in P. falcataria, whereas it did not affect mCS activity in L. leucocephala. Aluminum content in root apices of P. falcataria was increased by cycloheximide, supporting the idea that de novo synthesis of proteins is a prerequisite for Al resistance. Our findings suggest that Al-inducible expression of mCS coupled with enhanced citrate release mediates Al resistance in P. falcataria.

  7. A test of the citrate method of PMI estimation from skeletal remains.

    PubMed

    Wilson, Sarah J; Christensen, Angi M

    2017-01-01

    Citrate content in bone has been shown to be associated with the postmortem interval (PMI), with citrate decreasing after death as a function of time. Here we test this method using porcine ribs for the period of 1-165days after death, and also assess citrate content and variation from samples placed into two different postmortem environments (terrestrial and aquatic). Higher citrate variation, lower citrate recovery, and a weaker association with time were found in this study as compared to others. Citrate content, however, was found to decrease with increasing PMI, and the method was found to be easy and inexpensive to apply. No significant differences were found in citrate loss between terrestrial and aquatic environments. Although more research is needed, citrate content appears to be a promising new approach in estimating PMI from skeletal remains. Published by Elsevier B.V.

  8. A Low-Tech Analytical Method for Diethylcarbamazine Citrate in Medicated Salt

    PubMed Central

    Weaver, Abigail; Brown, Patrick; Huey, Shannon; Magallon, Marco; Bollman, E. Brennan; Mares, Dominique; Streit, Thomas G.; Lieberman, Marya

    2011-01-01

    The World Health Organization has called for an effort to eliminate Lymphatic Filariasis (LF) around the world. In regions where the disease is endemic, local production and distribution of medicated salt dosed with diethylcarbamazine (DEC) has been an effective method for eradicating LF. A partner of the Notre Dame Haiti program, Group SPES in Port-au-Prince, Haiti, produces a medicated salt called Bon Sel. Coarse salt is pre-washed and sprayed with a solution of DEC citrate and potassium iodate. Iodine levels are routinely monitored on site by a titrimetric method. However, the factory had no method for monitoring DEC. Critical analytical issues include 1) determining whether the amount of DEC in each lot of Bon Sel is within safe and therapeutically useful limits, 2) monitoring variability within and between production runs, and 3) determining the effect of a common local practice (washing salt before use) on the availability of DEC. This paper describes a novel titrimetric method for analysis of DEC citrate in medicated salt. The analysis needs no electrical power and requires only a balance, volumetric glassware, and burets that most salt production programs have on hand for monitoring iodine levels. The staff of the factory used this analysis method on site to detect underloading of DEC on the salt by their sprayer and to test a process change that fixed the problem. PMID:21347443

  9. A low-tech analytical method for diethylcarbamazine citrate in medicated salt.

    PubMed

    Weaver, Abigail; Brown, Patrick; Huey, Shannon; Magallon, Marco; Bollman, E Brennan; Mares, Dominique; Streit, Thomas G; Lieberman, Marya

    2011-02-08

    The World Health Organization has called for an effort to eliminate Lymphatic Filariasis (LF) around the world. In regions where the disease is endemic, local production and distribution of medicated salt dosed with diethylcarbamazine (DEC) has been an effective method for eradicating LF. A partner of the Notre Dame Haiti program, Group SPES in Port-au-Prince, Haiti, produces a medicated salt called Bon Sel. Coarse salt is pre-washed and sprayed with a solution of DEC citrate and potassium iodate. Iodine levels are routinely monitored on site by a titrimetric method. However, the factory had no method for monitoring DEC. Critical analytical issues include 1) determining whether the amount of DEC in each lot of Bon Sel is within safe and therapeutically useful limits, 2) monitoring variability within and between production runs, and 3) determining the effect of a common local practice (washing salt before use) on the availability of DEC. This paper describes a novel titrimetric method for analysis of DEC citrate in medicated salt. The analysis needs no electrical power and requires only a balance, volumetric glassware, and burets that most salt production programs have on hand for monitoring iodine levels. The staff of the factory used this analysis method on site to detect underloading of DEC on the salt by their sprayer and to test a process change that fixed the problem.

  10. Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.

    PubMed

    Bristow, Sarah M; Gamble, Greg D; Stewart, Angela; Horne, Lauren; House, Meaghan E; Aati, Opetaia; Mihov, Borislav; Horne, Anne M; Reid, Ian R

    2014-11-28

    Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

  11. Development and validation of an UPLC method for rapid determination of ibuprofen and diphenhydramine citrate in the presence of impurities in combined dosage form.

    PubMed

    Rao, Dantu Durga; Sait, Shakil S; Mukkanti, K

    2011-04-01

    A novel, stability-indicating gradient reverse-phase ultra-performance liquid chromatographic method was developed for the simultaneous determination of ibuprofen and diphenhydramine citrate in the presence of degradation products and process related impurities in combined dosage form. The method was developed using C18 column with mobile phase containing a gradient mixture of solvent A and B. The eluted compounds were monitored at 220 nm. Ibuprofen and diphenhydramine citrate were subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Major unknown impurity formed under oxidative degradation was identified using LC-MS-MS study. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantitation, accuracy, precision and robustness. The described method was linear over the range of 0.20-6.00 μg/mL (r>0.998) for Ibuprofen and 0.084-1.14 μg/mL for diphenhydramine citrate (r>0.998). The limit of detection results were ranged from 0.200-0.320 μg/mL for ibuprofen impurities and 0.084-0.099 μg/mL for diphenhydramine citrate impurities. The limit of quantitation results were ranged from 0.440 to 0.880 μg/mL for ibuprofen impurities and 0.258 to 0.372 μg/mL for diphenhydramine citrate impurities. The recovery of ibuprofen impurities were ranged from 98.1% to 100.5% and the recovery of diphenhydramine citrate impurities were ranged from 97.5% to 102.1%. This method is also suitable for the simultaneous assay determination of ibuprofen and diphenhydramine citrate in pharmaceutical dosage forms.

  12. 21 CFR 184.1296 - Ferric ammonium citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE... brown or garnet red scales or granules or as a brownish-yellowish powder. (2) Ferric ammonium citrate... occurs as thin transparent green scales, as granules, as a powder, or as transparent green crystals....

  13. 21 CFR 184.1296 - Ferric ammonium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE... brown or garnet red scales or granules or as a brownish-yellowish powder. (2) Ferric ammonium citrate... occurs as thin transparent green scales, as granules, as a powder, or as transparent green crystals....

  14. 21 CFR 73.1025 - Ferric ammonium citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Ferric ammonium citrate. 73.1025 Section 73.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF... general and ophthalmic surgery subject to the following conditions: (1) The dyed suture shall conform...

  15. 21 CFR 73.1025 - Ferric ammonium citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Ferric ammonium citrate. 73.1025 Section 73.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF... general and ophthalmic surgery subject to the following conditions: (1) The dyed suture shall conform...

  16. 21 CFR 73.1025 - Ferric ammonium citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Ferric ammonium citrate. 73.1025 Section 73.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF... general and ophthalmic surgery subject to the following conditions: (1) The dyed suture shall conform...

  17. 21 CFR 73.1025 - Ferric ammonium citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Ferric ammonium citrate. 73.1025 Section 73.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF... general and ophthalmic surgery subject to the following conditions: (1) The dyed suture shall conform...

  18. Development of Injectable Citrate-Based Bioadhesive Bone Implants

    PubMed Central

    Xie, Denghui; Guo, Jinshan; Mehdizadeh, Mohammadreza; Tran, Richard T.; Chen, Ruisong; Sun, Dawei; Qian, Guoying; Jin, Dadi; Bai, Xiaochun; Yang, Jian

    2014-01-01

    Injectable bone implants have been widely used in bone tissue repairs including the treatment of comminuted bone fractures (CBF). However, most injectable bone implants are not suitable for the treatment of CBF due to their weak tissue adhesion strengths and minimal osteoinduction. Citrate has been recently reported to promote bone formation through enhanced bioceramic integration and osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF treatment. iCMBA/HA can be set within 2–4 minutes and the as-prepared (wet) iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to 3.2±0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and osteoinductivity. This is also the first time to demonstrate that citrate supplementation in osteogenic medium and citrate released from iCMBA/HA degradation can promote the mineralization of osteoblastic committed human mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit comminuted radial fracture model showed significantly increased bone formation with markedly enhanced three-point bending strength compared to the negative control. Neovascularization and bone ingrowth as well as highly organized bone formation were also observed showing the potential of iCMBA/HA in treating CBF. PMID:25580247

  19. 21 CFR 184.1307c - Ferrous citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... 23383-11-1) is a slightly colored powder or white crystals. It is prepared from the reaction of sodium citrate with ferrous sulfate or by direct action of citric acid on iron filings. (b) The ingredient must... accordance with section 412(g) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 350a(g)) or...

  20. 21 CFR 184.1307c - Ferrous citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the reaction of sodium citrate with ferrous sulfate or by direct action of citric acid on iron filings... (the act) (21 U.S.C. 350a(g)) or with regulations promulgated under section 412(a)(2) of the act (21 U.S.C. 350a(a)(2)). (d) Prior sanctions for this ingredient different from the uses established in...

  1. 21 CFR 184.1307c - Ferrous citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the reaction of sodium citrate with ferrous sulfate or by direct action of citric acid on iron filings... (the act) (21 U.S.C. 350a(g)) or with regulations promulgated under section 412(a)(2) of the act (21 U.S.C. 350a(a)(2)). (d) Prior sanctions for this ingredient different from the uses established in...

  2. 21 CFR 184.1307c - Ferrous citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the reaction of sodium citrate with ferrous sulfate or by direct action of citric acid on iron filings... (the act) (21 U.S.C. 350a(g)) or with regulations promulgated under section 412(a)(2) of the act (21 U.S.C. 350a(a)(2)). (d) Prior sanctions for this ingredient different from the uses established in...

  3. 40 CFR 721.7285 - Amines, N-cocoalkyltrimethylenedi-, citrates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Amines, N-cocoalkyltrimethylenedi... Specific Chemical Substances § 721.7285 Amines, N-cocoalkyltrimethylenedi-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

  4. 40 CFR 721.7285 - Amines, N-cocoalkyltrimethylenedi-, citrates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Amines, N-cocoalkyltrimethylenedi... Specific Chemical Substances § 721.7285 Amines, N-cocoalkyltrimethylenedi-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

  5. 40 CFR 721.7286 - Amines, N-tallowalkyltripropylenetetra-, citrates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Amines, N-tallowalkyltripropylenetetra... Specific Chemical Substances § 721.7286 Amines, N-tallowalkyltripropylenetetra-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

  6. 40 CFR 721.7286 - Amines, N-tallowalkyltripropylenetetra-, citrates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Amines, N-tallowalkyltripropylenetetra... Specific Chemical Substances § 721.7286 Amines, N-tallowalkyltripropylenetetra-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

  7. 40 CFR 721.7286 - Amines, N-tallowalkyltripropylenetetra-, citrates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-tallowalkyltripropylenetetra-, citrates (PMN P-93-881; CAS No. 189120-62-5) is subject to reporting under this section for the...), (g)(4)(iii), and (g)(5). (ii) Release to water. Requirements as specified in § 721.90 (a)(1), (b)(1....125 (a), (b), (c), (f), (g), (h), and (k) are applicable to manufacturers, importers, and processors...

  8. 40 CFR 721.7285 - Amines, N-cocoalkyltrimethylenedi-, citrates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-cocoalkyltrimethylenedi-, citrates. (PMN P-93-880; CAS No. 189120-63-6) is subject to reporting under this section for the...), (g)(4)(iii), and (g)(5). (ii) Release to water. Requirements as specified in § 721.90 (a)(1), (b)(1....125 (a), (b), (c), (f), (g), (h), and (k) are applicable to manufacturers, importers, and processors...

  9. Complex transcriptional regulation of citrate metabolism in Clostridium perfringens.

    PubMed

    Yuan, Yonghui; Ohtani, Kaori; Yoshizawa, Satoko; Shimizu, Tohru

    2012-02-01

    A Gram-positive, spore-forming bacterium, Clostridium perfringens, possesses genes for citrate metabolism, which might play an important role in the utilization of citrate as a sole carbon source. In this study, we identified a chromosomal citCDEFX-mae-citS operon in C. perfringens strain 13, which is transcribed on three mRNAs of different sizes. Expression of the cit operon was significantly induced when 5 mM extracellular citrate was added to the growth medium. Most interestingly, three regulatory systems were found to be involved in the regulation of the expression of cit genes: 1) the two upstream divergent genes citG and citI; 2) two different two-component regulatory systems, CitA/CitB (TCS6 consisted of CPE0531/CPE0532) and TCS5 (CPE0518/CPE0519); and 3) the global two-component VirR/VirS-VR-RNA regulatory system known to regulate various genes for toxins and degradative enzymes. Our results suggest that in C. perfringens the citrate metabolism might be strictly controlled by a complex regulatory system.

  10. 40 CFR 721.7286 - Amines, N-tallowalkyltripropylenetetra-, citrates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amines, N-tallowalkyltripropylenetetra... Specific Chemical Substances § 721.7286 Amines, N-tallowalkyltripropylenetetra-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines,...

  11. 40 CFR 721.7285 - Amines, N-cocoalkyltrimethylenedi-, citrates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amines, N-cocoalkyltrimethylenedi... Specific Chemical Substances § 721.7285 Amines, N-cocoalkyltrimethylenedi-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines,...

  12. 40 CFR 721.7285 - Amines, N-cocoalkyltrimethylenedi-, citrates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amines, N-cocoalkyltrimethylenedi... Specific Chemical Substances § 721.7285 Amines, N-cocoalkyltrimethylenedi-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

  13. 40 CFR 721.7286 - Amines, N-tallowalkyltripropylenetetra-, citrates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amines, N-tallowalkyltripropylenetetra... Specific Chemical Substances § 721.7286 Amines, N-tallowalkyltripropylenetetra-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

  14. 21 CFR 520.622d - Diethylcarbamazine citrate capsules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Diethylcarbamazine citrate capsules. (a) Specifications. Each capsule contains 12.5, 50, 200, or 400 milligrams (mg... dogs—(1) Amount/indications for use. 3 mg per pound (/lb) body weight daily for prevention of heartworm disease (Dirofilaria immitis); 25 to 50 mg/lb body weight in a single dose as an aid in the treatment...

  15. 21 CFR 520.622d - Diethylcarbamazine citrate capsules.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Diethylcarbamazine citrate capsules. (a) Specifications. Each capsule contains 12.5, 50, 200, or 400 milligrams (mg... dogs—(1) Amount/indications for use. 3 mg per pound (/lb) body weight daily for prevention of heartworm disease (Dirofilaria immitis); 25 to 50 mg/lb body weight in a single dose as an aid in the treatment...

  16. 78 FR 63228 - Determination That Potassium Citrate, 10 Milliequivalents/Packet and 20 Milliequivalents/Packet...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Determination That Potassium Citrate, 10 Milliequivalents...) has determined that Potassium Citrate, 10 milliequivalents/packet (mEq/packet) and 20 mEq/ packet, was... approve abbreviated new drug applications (ANDAs) for Potassium Citrate, 10 mEq/packet and 20 mEq/packet...

  17. 75 FR 14491 - Listing of Color Additives Exempt From Certification; Bismuth Citrate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-26

    ... level of bismuth citrate as a color additive in cosmetics intended for coloring hair on the scalp. This... citrate as a color additive in cosmetics intended for coloring hair on the scalp from 0.5 percent (weight... bismuth citrate in cosmetics intended for coloring scalp hair to 2.0 percent (w/v) with no changes to the...

  18. 78 FR 64914 - Citric Acid and Certain Citrate Salts From Canada: Final Results of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-30

    ... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Final Results of... of the antidumping duty order on citric acid and certain citrate salts from Canada.\\1\\ The review... period of review (POR) is May 1, 2011, through April 30, 2012. \\1\\ See Citric Acid and Certain Citrate...

  19. 77 FR 24461 - Citric Acid and Certain Citrate Salts From Canada: Final Results of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-24

    ... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Final Results of... the preliminary results of the administrative review of the antidumping duty order on citric acid and... citric acid and certain citrate salts from Canada. See Citric Acid and Certain Citrate Salts from Canada...

  20. Mayenite Synthesized Using the Citrate Sol-Gel Method

    SciTech Connect

    Ude, Sabina N; Rawn, Claudia J; Meisner, Roberta A; Kirkham, Melanie J; Jones, Gregory L.; Payzant, E Andrew

    2014-01-01

    A citrate sol-gel method has been used to synthesize mayenite (Ca12Al14O33). X-ray powder diffraction data show that the samples synthesized using the citrate sol-gel method contained CaAl2O4 and CaCO3 along with mayenite when fired ex-situ in air at 800 C but were single phase when fired at 900 C and above. Using high temperature x-ray diffraction, data collected in-situ in air at temperatures of 600 C and below showed only amorphous content; however, data collected at higher temperatures indicated the first phase to crystallize is CaCO3. High temperature x-ray diffraction data collected in 4% H2/96% N2 does not show the presence of CaCO3, and Ca12Al14O33 starts to form around 850 C. In comparison, x-ray powder diffraction data collected ex-situ on samples synthesized using traditional solid-state synthesis shows that single phase was not reached until samples were fired at 1350 C. DTA/TGA data collected either in a nitrogen environment or air on samples synthesized using the citrate gel method suggest the complete decomposition of metastable phases and the formation of mayenite at 900 C, although the phase evolution is very different depending on the environment. Brunauer-Emmett-Teller (BET) measurements showed a slightly higher surface area of 7.4 0.1 m2/g in the citrate gel synthesized samples compared to solid-state synthesized sample with a surface area of 1.61 0.02 m2/g. SEM images show a larger particle size for samples synthesized using the solid-state method compared to those synthesized using the citrate gel method.

  1. Preparation of xylan citrate--a potential adsorbent for industrial wastewater treatment.

    PubMed

    Shuaiyang, Wang; Huiling, Li; Junli, Ren; Chuanfu, Liu; Feng, Peng; Runcang, Sun

    2013-02-15

    The novel and degradable xylan citrate was prepared by the environmental-friendly semi-dry oven method. Xylan reacted with citric acid (CA) to yield xylan citrate at high temperature. The influence of the different weight ratios of CA and xylan on the product yield, the carboxyl group content and degree of esterification were comparatively discussed. The results showed that there were higher carboxyl group content and degree of esterification in modified xylan than native xylan. The product yield of 128.2%, the carboxyl group content of 1174.3 meq/100 g and degree of esterification of 33.1% were achieved at the CA/xylan weight ratio of 2.4 in the absence of catalyst. Furthermore, the adsorption capacity of xylan after modification was improved greatly. These materials with better properties can enhance their water affinity, and improve their adsorption of copper ions and methyl orange in aqueous solution due to carboxyl groups. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Acute effect of citrate bath on postdialysis alkalaemia.

    PubMed

    Ortiz, Patricia De Sequera; Ramón, Marta Albalate; Pérez-García, Rafael; Prats, Elena Corchete; Cobo, Patricia Arribas; Arroyo, Roberto Alcázar; Díaz, Maira Ortega; Carretero, Marta Puerta

    2015-01-01

    The correction of metabolic acidosis caused by renal failure is achieved by adding bicarbonate during dialysis. In order to avoid the precipitation of calcium carbonate and magnesium carbonate that takes place in the dialysis fluid (DF) when adding bicarbonate, it is necessary to add an acid, usually acetate, which is not free of side effects. Thus, citrate appears as an advantageous alternative to acetate, despite the fact that its acute effects are not accurately known. To assess the acute effect of a dialysis fluid containing citrate instead of acetate on acid-base balance and calcium-phosphorus metabolism parameters. A prospective crossover study was conducted with twenty-four patients (15 male subjects and 9 female subjects). All patients underwent dialysis with AK-200-Ultra-S monitor with SoftPac® dialysis fluid, made with 3 mmol/L of acetate and SelectBag Citrate®, with 1 mmol/L of citrate and free of acetate. The following were measured before and after dialysis: venous blood gas monitoring, calcium (Ca), ionic calcium (Cai), phosphorus (P) and parathyroid hormone (PTH). Differences (p<0.05) were found when using the citrate bath (C) compared to acetate (A) in the postdialysis values of: pH, C: 7.43 (0.04) vs. A: 7.47 (0.05); bicarbonate, C: 24.7 (2.7) vs. A: 27.3 (2.1) mmol/L; base excess (BEecf), C: 0.4 (3.1) vs. A: 3.7 (2.4) mmol/L; corrected calcium (Cac), C: 9.8 (0.8) vs. A: 10.1 (0.7) mg/dL; and Cai, C: 1.16 (0.05) vs. A: 1.27 (0.06) mmol/L. No differences were found in either of the parameters measured before dialysis. Dialysis with citrate provides better control of postdialysis acid-base balance, decreases/avoids postdialysis alkalaemia, and lowers the increase in Cac and Cai. This finding is of special interest in patients with predisposing factors for arrhythmia and patients with respiratory failure, carbon dioxide retention, calcifications and advanced liver disease. Copyright © 2015. Published by Elsevier España, S.L.U.

  3. Modification by food of the calcium absorbability and physicochemical effects of calcium citrate

    NASA Technical Reports Server (NTRS)

    Wabner, C. L.; Pak, C. Y.

    1992-01-01

    The food-calcium (Ca) interaction was examined in 12 healthy women (mean age 38 years) maintained on a constant metabolic diet. They underwent three phases of study, comprised of control (no Ca), Ca citrate (1 g Ca/day) during meals, and Ca citrate separately from meals. Each phase was 7 days in length and two 24-hour urine samples were collected on days 6 and 7. The rise from the control phase in urinary Ca was slightly more prominent when Ca citrate was given with meals than without (68 and 62%, respectively). The fall in urinary phosphorus was equivalent at about 25% between Ca citrate phases. The rise in urinary citrate and pH and the decline in urinary ammonium were more prominent when Ca citrate was given with meals; however, the changes were small or nonsignificant. The urinary saturation of Ca oxalate, brushite or monosodium urate did not differ between the two Ca citrate phases. There was a nonsignificant rise in serum iron during Ca citrate phases. The results suggest that: 1) dissolution and absorption of Ca citrate might be slightly greater when given with food than without; 2) that the ability of Ca citrate to attenuate crystallization of stone-forming Ca salts in urine is not modified by food; and 3) that Ca citrate may not impair iron absorption from food.

  4. Modification by food of the calcium absorbability and physicochemical effects of calcium citrate

    NASA Technical Reports Server (NTRS)

    Wabner, C. L.; Pak, C. Y.

    1992-01-01

    The food-calcium (Ca) interaction was examined in 12 healthy women (mean age 38 years) maintained on a constant metabolic diet. They underwent three phases of study, comprised of control (no Ca), Ca citrate (1 g Ca/day) during meals, and Ca citrate separately from meals. Each phase was 7 days in length and two 24-hour urine samples were collected on days 6 and 7. The rise from the control phase in urinary Ca was slightly more prominent when Ca citrate was given with meals than without (68 and 62%, respectively). The fall in urinary phosphorus was equivalent at about 25% between Ca citrate phases. The rise in urinary citrate and pH and the decline in urinary ammonium were more prominent when Ca citrate was given with meals; however, the changes were small or nonsignificant. The urinary saturation of Ca oxalate, brushite or monosodium urate did not differ between the two Ca citrate phases. There was a nonsignificant rise in serum iron during Ca citrate phases. The results suggest that: 1) dissolution and absorption of Ca citrate might be slightly greater when given with food than without; 2) that the ability of Ca citrate to attenuate crystallization of stone-forming Ca salts in urine is not modified by food; and 3) that Ca citrate may not impair iron absorption from food.

  5. Artificial citrate operon and Vitreoscilla hemoglobin gene enhanced mineral phosphate solubilizing ability of Enterobacter hormaechei DHRSS.

    PubMed

    Yadav, Kavita; Kumar, Chanchal; Archana, G; Kumar, G Naresh

    2014-10-01

    Mineral phosphate solubilization by bacteria is mediated through secretion of organic acids, among which citrate is one of the most effective. To overproduce citrate in bacterial systems, an artificial citrate operon comprising of genes encoding NADH-insensitive citrate synthase of E. coli and Salmonella typhimurium sodium-dependent citrate transporter was constructed. In order to improve its mineral phosphate solubilizing (MPS) ability, the citrate operon was incorporated into E. hormaechei DHRSS. The artificial citrate operon transformant secreted 7.2 mM citric acid whereas in the native strain, it was undetectable. The transformant released 0.82 mM phosphate in flask studies in buffered medium containing rock phosphate as sole P source. In fermenter studies, similar phenotype was observed under aerobic conditions. However, under microaerobic conditions, no citrate was detected and P release was not observed. Therefore, an artificial citrate gene cluster containing Vitreoscilla hemoglobin (vgb) gene under its native promoter, along with artificial citrate operon under constitutive tac promoter, was constructed and transformed into E. hormaechei DHRSS. This transformant secreted 9 mM citric acid under microaerobic conditions and released 1.0 mM P. Thus, incorporation of citrate operon along with vgb gene improves MPS ability of E. hormaechei DHRSS under buffered, microaerobic conditions mimicking rhizospheric environment.

  6. Validated stability-indicating reversed-phase-HPLC method for simultaneous determination of orphenadrine citrate, caffeine and aspirin.

    PubMed

    Darwish, Khaled; Salama, Ismail; Mostafa, Samia; El-Sadek, Mohamed

    2012-01-01

    New, simple, rapid and precise reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of orphenadrine citrate, caffeine and aspirin in presence of aspirin degradation products, orphenadrine citrate and caffeine process related impurities, and excipients. Good resolution and quantization were achieved on reversed-phase column [Phenomenex™ Luna ODS C(18) (25 cm×4.6 mm, 5 µm particles)]. Gradient elution based on; eluant [A]: 0.1% triethylamine in aqueous potassium dihydrogen phosphate buffer (50 mM; pH 3.0), while as, eluant [B]: acetonitrile, at a flow rate of 1.5 mL min(-1). UV quantitation was set at 215 nm. Linearity was exhibited for orphenadrine citrate, caffeine and aspirin within 0.5-150, 0.5-360 or 0.7-301 µg mL(-1) ranges, respectively. Satisfactory validation results were ascertained in terms of low limits of quantiation (6.33×10(-2)-7.94×10(-2)), mean percentage recovery (98.9-101.4%), precision (<2%) and robustness. The proposed method was proved to be specific, robust and accurate for the determination of cited drugs in pharmaceutical preparations in presence of their degradation products.

  7. Citrate anticoagulation during continuous renal replacement therapy in pediatric critical care.

    PubMed

    Davis, T Keefe; Neumayr, Tara; Geile, Kira; Doctor, Allan; Hmeil, Paul

    2014-06-01

    To provide the pediatric intensivist an in-depth understanding of citrate as regional anticoagulant during continuous renal replacement therapy. We searched the PubMed.gov database using the initial key words: citrate anticoagulation [title] AND continuous; citrate [title] AND pediatric AND continuous; prospective pediatric renal replacement AND citrate; and regional citrate anticoagulation. Additional searchers were performed using EMBASE, CINAHL, and SCOPUS with similar keywords and limits. Further articles were gathered from bibliographic references of relevant studies and reviews. Only articles published in English were reviewed. In the pediatric population, there are no prospective interventional or randomized studies comparing regional versus systemic anticoagulation. However, there are 11 (retrospective and prospective observational studies) in the pediatric population using citrate anticoagulation. These studies have shown that regional citrate anticoagulation in the pediatric population can be effective, provide equivalent circuit survival, and decrease bleeding compared with heparin anticoagulation. In the adult population, there are six prospective randomized controlled trials comparing the efficacy of regional citrate anticoagulation versus heparin. Two systematic reviews with meta-analysis of these six trials have been performed. The adult data on the use of regional citrate anticoagulation during continuous renal replacement therapy show a decreased risk of bleeding and at the least equivalent circuit survival as compared to heparin. Current pediatric and adult studies support regional citrate anticoagulation as an effective alternative to systemic heparin anticoagulation in most patient populations. Continuous renal replacement therapy is the most common modality of renal replacement in the critical care setting. Regional anticoagulation is an ideal option in a critically ill child after recent surgery or with coagulopathy. Therefore, regional

  8. Purification and Characterization of the Reconstitutively Active Citrate Carrier from Maize Mitochondria1

    PubMed Central

    Genchi, Giuseppe; Spagnoletta, Anna; De Santis, Aurelio; Stefanizzi, Luisa; Palmieri, Ferdinando

    1999-01-01

    The citrate carrier from maize (Zea mays) shoot mitochondria was solubilized with Triton X-100 and purified by sequential chromatography on hydroxyapatite and hydroxyapatite/celite in the presence of cardiolipin. SDS-gel electrophoresis of the purified fraction showed a single polypeptide band with an apparent molecular mass of 31 kD. When reconstituted into liposomes, the citrate carrier catalyzed a pyridoxal 5′-P-sensitive citrate/citrate exchange. It was purified 224-fold with a recovery of 50% and a protein yield of 0.22% with respect to the mitochondrial extract. In the reconstituted system the purified citrate carrier catalyzed a first-order reaction of citrate/citrate (0.065 min−1) or citrate/malate exchange (0.075 min−1). Among the various substrates and inhibitors tested, the reconstituted protein transported citrate, cis-aconitate, isocitrate, l-malate, succinate, malonate, glutarate, α-ketoglutarate, oxaloacetate, and α-ketoadipate and was inhibited by pyridoxal 5′-P, phenylisothiocyanate, mersalyl, and p-hydroxymercuribenzoate (but not N-ethylmaleimide), 1,2,3-benzentricarboxylate, benzylmalonate, and butylmalonate. The activation energy of the citrate/citrate exchange was 66.5 kJ/mol between 10°C and 35°C; the half-saturation constant (Km) for citrate was 0.65 ± 0.05 mm and the maximal rate (Vmax) of the citrate/citrate exchange was 13.0 ± 1.0 μmol min−1 mg−1 protein at 25°C. PMID:10398720

  9. Citrate sensing by the C4-dicarboxylate/citrate sensor kinase DcuS of Escherichia coli: binding site and conversion of DcuS to a C4-dicarboxylate- or citrate-specific sensor.

    PubMed

    Krämer, J; Fischer, J D; Zientz, E; Vijayan, V; Griesinger, C; Lupas, A; Unden, G

    2007-06-01

    The histidine protein kinase DcuS of Escherichia coli senses C(4)-dicarboxylates and citrate by a periplasmic domain. The closely related sensor kinase CitA binds citrate, but no C(4)-dicarboxylates, by a homologous periplasmic domain. CitA is known to bind the three carboxylate and the hydroxyl groups of citrate by sites C1, C2, C3, and H. DcuS requires the same sites for C(4)-dicarboxylate sensing, but only C2 and C3 are highly conserved. It is shown here that sensing of citrate by DcuS required the same sites. Binding of citrate to DcuS, therefore, was similar to binding of C(4)-dicarboxylates but different from that of citrate binding in CitA. DcuS could be converted to a C(4)-dicarboxylate-specific sensor (DcuS(DC)) by mutating residues of sites C1 and C3 or of some DcuS-subtype specific residues. Mutations around site C1 aimed at increasing the size and accessibility of the site converted DcuS to a citrate-specific sensor (DcuS(Cit)). DcuS(DC) and DcuS(Cit) had complementary effector specificities and responded either to C(4)-dicarboxylates or to citrate and mesaconate. The results imply that DcuS binds citrate (similar to the C(4)-dicarboxylates) via the C(4)-dicarboxylate part of the molecule. Sites C2 and C3 are essential for binding of two carboxylic groups of citrate or of C(4)-dicarboxylates; sites C1 and H are required for other essential purposes.

  10. 77 FR 56188 - Citric Acid and Certain Citrate Salts from the People's Republic of China: Notice of Rescission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... the order includes all grades and granulation sizes of citric acid, sodium citrate, and potassium... also includes blends of citric acid, sodium citrate, and potassium citrate; as well as blends with... potassium citrate constitute 40 percent or more, by weight, of the blend. The scope of the order also...

  11. Calcium citrate for vulvar vestibulitis. A case report.

    PubMed

    Solomons, C C; Melmed, M H; Heitler, S M

    1991-12-01

    A woman had suffered from vulvar vestibulitis (vulvodynia) for four years. Pain from the disorder had disrupted her ability to function at work and home as well as sexually. An initial full range of treatments, including multiple operations, had produced no relief. Examination of the urine for evidence of excess oxalate, which has been shown to cause epithelial reactions similar to those found in vulvodynia, showed periodic hyperoxaluria and pH elevations related to the symptoms. Calcium citrate was given to modify the oxalate crystalluria. The symptoms were significantly reduced in three months, and the patient was pain free after one year. She was able to resume normal work, family, sexual and recreational activities. Withdrawal of the calcium citrate resulted in a return of the symptoms; reinstitution alleviated them. These findings suggest that further study of individualized metabolic factors that may underlie vulvodynia is warranted.

  12. Trisodium citrate, Na3(C6H5O7)

    PubMed Central

    Rammohan, Alagappa; Kaduk, James A.

    2016-01-01

    The crystal structure of anhydrous tris­odium citrate, Na3(C6H5O7), has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory (DFT). There are two independent five-coordinate Na+ and one six-coordinate Na+ cations in the asymmetric unit. The [NaO5] and [NaO6] polyhedra share edges and corners to form a three-dimensional framework. There are channels parallel to the a and b axes in which the remainder of the citrate anions reside. The only hydrogen bonds are an intra­molecular one between the hy­droxy group and one of the terminal carboxyl­ate O atoms and an intermolecular one between a methylene group and the hydroxyl O atom. PMID:27308044

  13. Diagnosis of mycotic abdominal aortic aneurysm using 67-gallium citrate

    SciTech Connect

    Blumoff, R.L.; McCartney, W.; Jaques, P.; Johnson, G. Jr.

    1982-11-01

    Mycotic aneurysms of the abdominal aorta are uncommon, but potentially lethal problems. Clinical subtleties may suggest their presence, but in the past, definitive diagnosis has been dependent on surgical exploration or autopsy findings. A case is presented in which 67-gallium citrate abdominal scanning localized the site of sepsis in an abdominal aortic aneurysm and allowed for prompt and successful surgical therapy. This noninvasive technique is recommended as a adjunct in the diagnosis of mycotic abdominal aortic aneurysms.

  14. Phylogenetic relationships of rhizobia based on citrate synthase gene sequences.

    PubMed

    Hernández-Lucas, Ismael; Rogel-Hernández, Marco Antonio; Segovia, Lorenzo; Rojas-Jiménez, Keilor; Martínez-Romero, Esperanza

    2004-11-01

    Partial nucleotide sequences of the citrate synthase (gltA) gene from different rhizobia genera were determined. Tree topologies based on this housekeeping gene were similar to that obtained using 16S rRNA sequences. However gltA appeared to be more reliable at determining phylogenetic relationships of closely related taxa. We propose gltA sequences as an additional tool to be used in molecular phylogenetic studies.

  15. Clomiphene citrate and its effects upon ovulation and estrogen.

    PubMed

    Shirai, E; Iizuka, R; Notake, Y

    1972-05-01

    This paper reports a clinical evaluation of the mechanism of action of clomiphene citrate and describes selection of the most responsive patients. Patients were 121 women, aged 21-37 years, who desired pregnancy. Their infertility was diagnosed as being due to anovulation. Primary amenorrhea or special endocrine disorders were not present. All the women who had no vaginal bleeding for more than 2 months were diagnosed amenorrhea and treated with 65 mg of progesterone capronate intramuscularly. They were then divided into two subgroups on the basis of the presence or absence of vaginal bleeding within 2 weeks. Clinical studies included: basal body temperature charts; daily vaginal smears evaluated by the ink acidophilic stain index (ISI); cervical mucus evaluated by amount, spresence of spinnbarkeit, and ferning; 24-hour urines examined for estrogen and total gonadotropic activity; and a pregnanediol determination. Each group received daily 50 mg doses of clomiphene citrate for 5 days. Estrogen inhibiting effect of the drug was suggested by vaginal cytology and the disappearance of ferning and decrease in quantity of cervical mucus. However, the excretion of the total urinary estrogen was increased in ovulatory cases (81 of the 121 patients). In 17 patients having no bleeding within 2 weeks after progesterone injection no ovulation could be induced. In patients with withdrawal flow 54 of 70 achieved ovulation. Of 37 patients with previous anovulatory bleeding 27 achieved ovulation. There were 11 of the 121 who became pregnant. In those with early ovulation the antiestrogen effect is believed to be in the hypothalamus and pituitary bringing about the estrogen surge and stimulating LH secretion. In those with later ovulation the antiestrogenic effect increased FSH secretion followed by ovulation. The type of patient most likely to respond to clomiphene citrate is one with nearly normal pituitary-gonadal axis. Inducing withdrawal bleeding with progesterone in those

  16. Gold/silver core-shell 20 nm nanoparticles extracted from citrate solution examined by XPS

    SciTech Connect

    Engelhard, Mark H.; Smith, Jordan N.; Baer, Donald R.

    2016-06-01

    Silver nanoparticles of many types are widely used in consumer and medical products. The surface chemistry of particles and the coatings that form during synthesis or use in many types of media can significantly impact the behaviors of particles including dissolution, transformation and biological or environmental impact. Consequently it is useful to be able to extract information about the thickness of surface coatings and other attributes of nanoparticles produced in a variety of ways. It has been demonstrated that X-ray Photoelectron Spectroscopy (XPS) can be reliably used to determine the thickness of organic and other nanoparticles coatings and shells. However, care is required to produce reliable and consistent information. Here we report the XPS spectra from gold/silver core-shell nanoparticles of nominal size 20 nm removed from a citrate saturated solution after one and two washing cycles. The Simulation of Electron Spectra for Surface Analysis (SESSA) program had been used to model peak amplitudes to obtain information on citrate coatings that remain after washing and demonstrate the presence of the gold core. This data is provided so that others can compare use of SESSA or other modeling approaches to quantify the nature of coatings to those already published and to explore the impacts particle non-uniformities on XPS signals from core-shell nanoparticles.

  17. Characterization of sildenafil citrate tablets of different sources by near infrared chemical imaging and chemometric tools.

    PubMed

    Sabin, Guilherme P; Lozano, Valeria A; Rocha, Werickson F C; Romão, Wanderson; Ortiz, Rafael S; Poppi, Ronei J

    2013-11-01

    The chemical imaging technique by near infrared spectroscopy was applied for characterization of formulations in tablets of sildenafil citrate of six different sources. Five formulations were provided by Brazilian Federal Police and correspond to several trademarks of prohibited marketing and one was an authentic sample of Viagra. In a first step of the study, multivariate curve resolution was properly chosen for the estimation of the distribution map of concentration of the active ingredient in tablets of different sources, where the chemical composition of all excipients constituents was not truly known. In such cases, it is very difficult to establish an appropriate calibration technique, so that only the information of sildenafil is considered independently of the excipients. This determination was possible only by reaching the second-order advantage, where the analyte quantification can be performed in the presence of unknown interferences. In a second step, the normalized histograms of images from active ingredient were grouped according to their similarities by hierarchical cluster analysis. Finally it was possible to recognize the patterns of distribution maps of concentration of sildenafil citrate, distinguishing the true formulation of Viagra. This concept can be used to improve the knowledge of industrial products and processes, as well as, for characterization of counterfeit drugs.

  18. Substrate- and plant-mediated removal of citrate-coated silver nanoparticles in constructed wetlands.

    PubMed

    Auvinen, Hannele; Sepúlveda, Viviana Vásquez; Rousseau, Diederik P L; Du Laing, Gijs

    2016-11-01

    The growing production and commercial application of engineered nanoparticles (ENPs), such as Ag, CeO2, and TiO2 nanoparticles, induce a risk to the environment as ENPs are released during their use. The comprehensive assessment of the environmental risk that the ENPs pose involves understanding their fate and behavior in wastewater treatment systems. Therefore, in this study, we investigate the effect of plants and different substrates on the retention and distribution of citrate-coated silver nanoparticles (Ag-NPs) in batch experimental setups simulating constructed wetlands (CWs). Sand, zeolite, and biofilm-coated gravel induce efficient removal (85, 55, and 67 %, respectively) of Ag from the water phase indicating that citrate-coated Ag-NPs are efficiently retained in CWs. Plants are a minor factor in retaining Ag as a large fraction of the recovered Ag remains in the water phase (0.42-0.58). Most Ag associated with the plant tissues is attached to or taken up by the roots, and only negligible amounts (maximum 3 %) of Ag are translocated to the leaves under the applied experimental conditions.

  19. Severe citrate toxicity complicating volunteer apheresis platelet donation.

    PubMed

    Bell, A M; Nolen, J D L; Knudson, C M; Raife, T J

    2007-02-01

    We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.

  20. CitI, a Transcription Factor Involved in Regulation of Citrate Metabolism in Lactic Acid Bacteria†

    PubMed Central

    Martin, Mauricio G.; Magni, Christian; de Mendoza, Diego; López, Paloma

    2005-01-01

    A large variety of lactic acid bacteria (LAB) can utilize citrate under fermentative conditions. Although much information concerning the metabolic pathways leading to citrate utilization by LAB has been gathered, the mechanisms regulating these pathways are obscure. In Weissella paramesenteroides (formerly called Leuconostoc paramesenteroides), transcription of the citMDEFCGRP citrate operon and the upstream divergent gene citI is induced by the presence of citrate in the medium. Although genetic experiments have suggested that CitI is a transcriptional activator whose activity can be modulated in response to citrate availability, specific details of the interaction between CitI and DNA remained unknown. In this study, we show that CitI recognizes two A+T-rich operator sites located between citI and citM and that the DNA-binding affinity of CitI is increased by citrate. Subsequently, this citrate signal propagation leads to the activation of the cit operon through an enhanced recruitment of RNA polymerase to its promoters. Our results indicate that the control of CitI by the cellular pools of citrate provides a mechanism for sensing the availability of citrate and adjusting the expression of the cit operon accordingly. In addition, this is the first reported example of a transcription factor directly functioning as a citrate-activated switch allowing the cell to optimize the generation of metabolic energy. PMID:16030208

  1. Transcriptional Control of the Citrate-Inducible citMCDEFGRP Operon, Encoding Genes Involved in Citrate Fermentation in Leuconostoc paramesenteroides

    PubMed Central

    Martín, Mauricio; Magni, Christian; López, Paloma; de Mendoza, Diego

    2000-01-01

    In this study we describe the expression pattern of the Leuconostoc paramesenteroides citMCDEFGRP operon in response to the addition of citrate to the growth medium. An 8.8-kb polycistronic transcript, which includes the citMCDEFGRP genes, was identified; its synthesis was dramatically induced upon addition of citrate to the growth medium. We also found that expression of the cit operon is subjected to posttranscriptional regulation, since processing sites included in four complex secondary structures (I, II, III, and IV) were identified by Northern blot analysis and mapped by primer extension. Upstream of the citMCDEFGRP operon a divergent open reading frame, whose expression was also increased by citrate, was identified by DNA sequencing and designated citI. The start and end sites of transcription of the cit operon and citI gene were mapped. The start sites are separated by a stretch of 188 bp with a very high A+T content of 77% and are preceded by transcriptional promoters. The end sites of the transcripts are located next to the 3′ end of two secondary structures characteristic of ρ-independent transcriptional terminators. The effect of the citI gene on expression of the cit operon was studied in Escherichia coli. The presence of the citI gene in cis and in trans resulted in increased activity of the cit promoter. These data provide the first evidence that citrate fermentation in Leuconostoc is regulated at the transcriptional level by a transcriptional activator rather than by a repressor. PMID:10869065

  2. Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria.

    PubMed

    Krieger, Nancy S; Asplin, John R; Frick, Kevin K; Granja, Ignacio; Culbertson, Christopher D; Ng, Adeline; Grynpas, Marc D; Bushinsky, David A

    2015-12-01

    Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation. Copyright © 2015 by the American Society of Nephrology.

  3. Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria

    PubMed Central

    Asplin, John R.; Frick, Kevin K.; Granja, Ignacio; Culbertson, Christopher D.; Ng, Adeline; Grynpas, Marc D.; Bushinsky, David A.

    2015-01-01

    Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation. PMID:25855777

  4. Ferric Citrate Controls Phosphorus and Delivers Iron in Patients on Dialysis

    PubMed Central

    Sika, Mohammed; Koury, Mark J.; Chuang, Peale; Schulman, Gerald; Smith, Mark T.; Whittier, Frederick C.; Linfert, Douglas R.; Galphin, Claude M.; Athreya, Balaji P.; Nossuli, A. Kaldun Kaldun; Chang, Ingrid J.; Blumenthal, Samuel S.; Manley, John; Zeig, Steven; Kant, Kotagal S.; Olivero, Juan Jose; Greene, Tom; Dwyer, Jamie P.

    2015-01-01

    Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of −2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin. PMID:25060056

  5. Ferric citrate controls phosphorus and delivers iron in patients on dialysis.

    PubMed

    Lewis, Julia B; Sika, Mohammed; Koury, Mark J; Chuang, Peale; Schulman, Gerald; Smith, Mark T; Whittier, Frederick C; Linfert, Douglas R; Galphin, Claude M; Athreya, Balaji P; Nossuli, A Kaldun Kaldun; Chang, Ingrid J; Blumenthal, Samuel S; Manley, John; Zeig, Steven; Kant, Kotagal S; Olivero, Juan Jose; Greene, Tom; Dwyer, Jamie P

    2015-02-01

    Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin. Copyright © 2015 by the American Society of Nephrology.

  6. Performance characteristics of an ion chromatographic method for the quantitation of citrate and phosphate in pharmaceutical solutions.

    PubMed

    Jenke, Dennis; Sadain, Salma; Nunez, Karen; Byrne, Frances

    2007-01-01

    The performance of an ion chromatographic method for measuring citrate and phosphate in pharmaceutical solutions is evaluated. Performance characteristics examined include accuracy, precision, specificity, response linearity, robustness, and the ability to meet system suitability criteria. In general, the method is found to be robust within reasonable deviations from its specified operating conditions. Analytical accuracy is typically 100 +/- 3%, and short-term precision is not more than 1.5% relative standard deviation. The instrument response is linear over a range of 50% to 150% of the standard preparation target concentrations (12 mg/L for phosphate and 20 mg/L for citrate), and the results obtained using a single-point standard versus a calibration curve are essentially equivalent. A small analytical bias is observed and ascribed to the relative purity of the differing salts, used as raw materials in tested finished products and as reference standards in the analytical method. The assay is specific in that no phosphate or citrate peaks are observed in a variety of method-related solutions and matrix blanks (with and without autoclaving). The assay with manual preparation of the eluents is sensitive to the composition of the eluent in the sense that the eluent must be effectively degassed and protected from CO(2) ingress during use. In order for the assay to perform effectively, extensive system equilibration and conditioning is required. However, a properly conditioned and equilibrated system can be used to test a number of samples via chromatographic runs that include many (> 50) injections.

  7. D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects.

    PubMed

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Yorita, K; Chung, S P; Tran, D H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-10-01

    Angiogenesis is critical for cancer growth and metastasis. Steps of angiogenesis are energy consuming, while vascular endothelial cells are highly glycolytic. Glioblastoma multiforme (GBM) is a highly vascular tumor and this enhances its aggressiveness. D-amino acid oxidase (DAO) is a promising therapeutic protein that induces oxidative stress upon acting on its substrates. Oxidative stress-energy depletion (OSED) therapy was recently reported (El Sayed et al., Cancer Gene Ther, 19, 1-18, 2012). OSED combines DAO-induced oxidative stress with energy depletion caused by glycolytic inhibitors such as 3-bromopyruvate (3BP), a hexokinase II inhibitor that depleted ATP in cancer cells and induced production of hydrogen peroxide. 3BP disturbs the Warburg effect and antagonizes effects of lactate and pyruvate (El Sayed et al., J Bioenerg Biomembr, 44, 61-79, 2012). Citrate is a natural organic acid capable of inhibiting glycolysis by targeting phosphofructokinase. Here, we report that DAO, 3BP and citrate significantly inhibited angiogenesis, decreased the number of vascular branching points and shortened the length of vascular tubules. OSED delayed the growth of C6/DAO glioma cells. 3BP combined with citrate delayed the growth of C6 glioma cells and decreased significantly the number and size of C6 glioma colonies in soft agar. Human GBM cells (U373MG) were resistant to chemotherapy e.g. cisplatin and cytosine arabinoside, while 3BP was effective in decreasing the viability and disturbing the morphology of U373MG cells.

  8. Synthesis and characterization of starch citrate-chitosan foam with superior water and saline absorbance properties.

    PubMed

    Salam, Abdus; Pawlak, Joel J; Venditti, Richard A; El-tahlawy, Khaled

    2010-06-14

    The objective of this research was to synthesize and characterize high-value foam gel materials with unique absorptive and mechanical properties from starch citrate-chitosan. The effects of starch citrate concentration, pH, solid to liquid ratio, reaction time, and temperature on absorbency, weight loss in water, and strength were determined. The cross-linked starch citrate-chitosan foam is flexible and elastic and has significantly increased absorbance and strength and decreased weight loss in water compared to starch-chitosan foam. A unique characteristic of the starch citrate-chitosan foam is that it absorbs more saline solution than pure water, which is the opposite of current commercial super absorbents. An increased strength, increased degradation temperature, increased storage modulus, and decreased weight loss in water for starch citrate-chitosan relative to starch-chitosan are in agreement with amide bonds formed between the carboxyl group of starch citrate and the amino group of chitosan.

  9. Citrate uptake into tonoplast vesicles from acid lime (Citrus aurantifolia) juice cells.

    PubMed

    Brune, A; Gonzalez, P; Goren, R; Zehavi, U; Echeverria, E

    1998-12-01

    Citrate transport into the vacuoles of acid lime juice cells was investigated using isolated tonoplast vesicles. ATP stimulated citrate uptake in the presence or in the absence of a Delta mu H+. Energization of the vesicles only by an artificial K+ gradient (establishing an inside-positive Delta psi) also resulted in citrate uptake as was the case of a Delta pH dominated Delta mu H+. Addition of inhibitors to endomembrane ATPases showed no direct correlation between the inhibition to the tonoplast bound H+/ATPase and citrate uptake. The data indicated that, although some citrate uptake can be accounted for by Delta psi and by a direct primary active transport mechanism involving ATP, under in vivo conditions of vacuolar pH of 2.0, citrate uptake is driven by Delta pH.

  10. Transport of citrate-coated silver nanoparticles in unsaturated sand

    NASA Astrophysics Data System (ADS)

    Kumahor, Samuel; Hron, Pavel; Metreveli, George; Schaumann, Gabriele; Vogel, Hans-Jörg

    2015-04-01

    Chemical factors and physical constraints lead to coupled effects during particle transport in unsaturated porous media. Unlike for saturated transport, studies on unsaturated transport as typical for soil are currently scarce. We investigated the mobility of citrate-coated Ag NPs in unsaturated sand (grain diameter: 0.1-0.3 mm). For three flux rates and a given pore-water ionic strength (1 mM KNO3), the citrate-coated Ag NPs were less mobile at pH = 5 compared to pH = 9. The classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory suggests unfavorable deposition conditions at both, the air-water interface and solid-water interface. Breakthrough curves measured under quasi-steady state unsaturated flow showed retardation of the citrate-coated Ag NPs compared to inert solute (KBr). After flushing with nanoparticle-free 1 mM KNO3 solution (pH-adjusted), retention was much lower in deeper depths compared to the surface where the particles entered the flow field. The results show a non-linear dependence of nanoparticle (NP) mobility on flux rate and water content. Especially the observed retardation similar to equilibrium sorption is in contrast to observations under saturated flow conditions. A convection-dispersion and reaction model that combines a reversible equilibrium process and a non-equilibrium interaction process reproduced the measured breakthrough curves reasonably well. From comparison between saturated and unsaturated experiments we conclude that the air-water interface is responsible for the reversible equilibrium process while the water-solid interface accounts for irreversible soption.

  11. Engineering genetically encoded nanosensors for real-time in vivo measurements of citrate concentrations.

    PubMed

    Ewald, Jennifer C; Reich, Sabrina; Baumann, Stephan; Frommer, Wolf B; Zamboni, Nicola

    2011-01-01

    Citrate is an intermediate in catabolic as well as biosynthetic pathways and is an important regulatory molecule in the control of glycolysis and lipid metabolism. Mass spectrometric and NMR based metabolomics allow measuring citrate concentrations, but only with limited spatial and temporal resolution. Methods are so far lacking to monitor citrate levels in real-time in-vivo. Here, we present a series of genetically encoded citrate sensors based on Förster resonance energy transfer (FRET). We screened databases for citrate-binding proteins and tested three candidates in vitro. The citrate binding domain of the Klebsiella pneumoniae histidine sensor kinase CitA, inserted between the FRET pair Venus/CFP, yielded a sensor highly specific for citrate. We optimized the peptide linkers to achieve maximal FRET change upon citrate binding. By modifying residues in the citrate binding pocket, we were able to construct seven sensors with different affinities spanning a concentration range of three orders of magnitude without losing specificity. In a first in vivo application we show that E. coli maintains the capacity to take up glucose or acetate within seconds even after long-term starvation.

  12. Structures of citrate synthase and malate dehydrogenase of Mycobacterium tuberculosis.

    PubMed

    Ferraris, Davide M; Spallek, Ralf; Oehlmann, Wulf; Singh, Mahavir; Rizzi, Menico

    2015-02-01

    The tricarboxylic acid (TCA) cycle is a central metabolic pathway of all aerobic organisms and is responsible for the synthesis of many important precursors and molecules. TCA cycle plays a key role in the metabolism of Mycobacterium tuberculosis and is involved in the adaptation process of the bacteria to the host immune response. We present here the first crystal structures of M. tuberculosis malate dehydrogenase and citrate synthase, two consecutive enzymes of the TCA, at 2.6 Å and 1.5 Å resolution, respectively. General analogies and local differences with the previously reported homologous protein structures are described. © 2014 Wiley Periodicals, Inc.

  13. Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

    PubMed

    Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

    2013-02-16

    Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite

  14. Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

    PubMed Central

    2013-01-01

    Background Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report

  15. In vitro evidence that D-serine disturbs the citric acid cycle through inhibition of citrate synthase activity in rat cerebral cortex.

    PubMed

    Zanatta, Angela; Schuck, Patrícia Fernanda; Viegas, Carolina Maso; Knebel, Lisiane Aurélio; Busanello, Estela Natacha Brandt; Moura, Alana Pimentel; Wajner, Moacir

    2009-11-17

    The present work investigated the in vitro effects of D-serine (D-Ser) on important parameters of energy metabolism in cerebral cortex of young rats. The parameters analyzed were CO(2) generation from glucose and acetate, glucose uptake and the activities of the respiratory chain complexes I-IV, of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase and of creatine kinase and Na(+),K(+)-ATPase. Our results show that D-Ser significantly reduced CO(2) production from acetate, but not from glucose, reflecting an impairment of the citric acid cycle function. Furthermore, D-Ser did not affect glucose uptake. We also observed that the activity of the mitochondrial enzyme citrate synthase from mitochondrial preparations and purified citrate synthase was significantly inhibited by D-Ser, whereas the other activities of the citric acid cycle as well as the activities of complexes I-III, II-III, II and IV of the respiratory chain, creatine kinase and Na(+),K(+)-ATPase were not affected by this D-amino acid. We also found that L-serine did not affect citrate synthase activity from mitochondrial preparations and purified enzyme. The data indicate that D-Ser impairs the citric acid cycle activity via citrate synthase inhibition, therefore compromising energy metabolism production in cerebral cortex of young rats. Therefore, it is presumed that this mechanism may be involved at least in part in the neurological damage found in patients affected by disorders in which D-Ser metabolism is impaired, with altered cerebral concentrations of this D-amino acid.

  16. Effect of potassium sodium tartrate and sodium citrate on the preparation of {alpha}-calcium sulfate hemihydrate from flue gas desulfurization gypsum in a concentrated electrolyte solution

    SciTech Connect

    Shen, Z.X.; Guan, B.H.; Fu, H.L.; Yang, L.C.

    2009-12-15

    Flue gas desulfurization (FGD) gypsum mainly composed of calcium sulfate dihydrate (DH) was used as a raw material to obtain alpha-calcium sulfate hemihydrate ({alpha}-HH) through dehydration in a Ca-Mg-K-Cl-solution medium at 95{sup o}C under atmospheric pressure. The effects of potassium sodium tartrate and sodium citrate on the preparation of alpha-HH in the electrolyte solution were investigated. The results revealed that the addition of potassium sodium tartrate (1.0 x 10{sup -2} - 2.5 x 10{sup -2}M) decreased the dehydration rate of FGD gypsum and increased the length/width (l/w) ratio of {alpha}-HH crystals, which could yield unfavorable strength properties. Addition of sodium citrate (1.0 x 10{sup -5} - 2.0 x 10{sup -5}M) slightly increased the dehydration rate of FGD gypsum and decreased the l/w ratio of {alpha}-HH crystals, which could be beneficial to increase strength. However, it also led to a partial formation of anhydrite (AH) crystals. AH was also the only dehydration product when the concentration of sodium citrate increased to 1.0 x 10{sup -4}M. Therefore, sodium citrate rather than potassium sodium tartrate could be used as an additive in Ca-Mg-K-Cl electrolyte solutions if alpha-HH with a shorter l/w ratio is the desired product from FGD gypsum dehydration. The concentration of sodium citrate should be properly controlled to reduce the formation of AH.

  17. Acetate- and Citrate-Specific Ion Effects on Unfolding and Temperature-Dependent Aggregation Rates of Anti-Streptavidin IgG1.

    PubMed

    Barnett, Gregory V; Razinkov, Vladimir I; Kerwin, Bruce A; Hillsley, Alexander; Roberts, Christopher J

    2016-03-01

    Controlling and predicting unwanted degradation, such as non-native aggregation, is a long-standing challenge for mAbs and other protein-based products. mAb aggregation rates are typically sensitive to temperature, pH, and the addition of excipients. Quantitatively comparing temperature-dependent aggregation rates across multiple possible formulations is a challenge in product development. A parallel temperature initial rate method is used to efficiently and accurately determine initial rates for anti-streptavidin (AS) IgG1 aggregation as a function of pH, [NaCl], and in the presence of acetate versus citrate buffer. Parallel temperature initial rates are shown to agree with results from a traditional, isothermal method and permits direct comparison of the formulations across almost 3 orders of magnitude of aggregation rates. The apparent midpoint unfolding temperatures (through differential scanning calorimetry) and the effective activation energy values (Ea) are generally higher in acetate buffer compared with citrate buffer, which is consistent with preferential accumulation of citrate ions compared with acetate ions that was speculated in previous work (Barnett et al., J Phys Chem B, 2015). Static light scattering and Kirkwood-Buff analysis show that AS-IgG1 has stronger net repulsive protein-protein interactions in acetate compared with citrate buffer, also consistent with increased values of Ea. In an extreme case, aggregation of AS-IgG1 is effectively eliminated across all practical temperatures at pH 4 in 10 mM sodium acetate but proceeds readily in citrate buffer. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy.

    PubMed

    Carneiro, Marcella L B; Nunes, Eloiza S; Peixoto, Raphael C A; Oliveira, Ricardo G S; Lourenço, Luiza H M; da Silva, Izabel C R; Simioni, Andreza R; Tedesco, Antônio C; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

    2011-03-28

    Rhodium (II) citrate (Rh(2)(H(2)cit)(4)) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates (Rh(2)(H(2)cit)(4)) as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh(2)(H(2)cit)(4) and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh(2)(H(2)cit)(4)) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures. Treatment with free Rh(2)(H(2)cit)(4) induced cytotoxicity that was dependent on dose, time, and cell line. The IC(50) values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh(2)(H(2)cit)(4)-loaded maghemite nanoparticles (Mag(h)-Rh(2)(H(2)cit)(4)) and Rh(2)(H(2)cit)(4)-loaded magnetoliposomes (Lip-Magh-Rh(2)(H(2)cit)(4)) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh(2)(H(2)cit)(4), were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh(2)(H(2)cit)(4) induces cell death by apoptosis. The treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity

  19. Phenotypes of gene disruptants in relation to a putative mitochondrial malate-citrate shuttle protein in citric acid-producing Aspergillus niger.

    PubMed

    Kirimura, Kohtaro; Kobayashi, Keiichi; Ueda, Yuka; Hattori, Takasumi

    2016-09-01

    The mitochondrial citrate transport protein (CTP) functions as a malate-citrate shuttle catalyzing the exchange of citrate plus a proton for malate between mitochondria and cytosol across the inner mitochondrial membrane in higher eukaryotic organisms. In this study, for functional analysis, we cloned the gene encoding putative CTP (ctpA) of citric acid-producing Aspergillus niger WU-2223L. The gene ctpA encodes a polypeptide consisting 296 amino acids conserved active residues required for citrate transport function. Only in early-log phase, the ctpA disruptant DCTPA-1 showed growth delay, and the amount of citric acid produced by strain DCTPA-1 was smaller than that by parental strain WU-2223L. These results indicate that the CTPA affects growth and thereby citric acid metabolism of A. niger changes, especially in early-log phase, but not citric acid-producing period. This is the first report showing that disruption of ctpA causes changes of phenotypes in relation to citric acid production in A. niger.

  20. Pretreatment With Caffeine Citrate to Increase Seizure Duration During Electroconvulsive Therapy: A Case Series.

    PubMed

    Pinkhasov, Aaron; Biglow, Michael; Chandra, Subhash; Pica, Tiffany

    2016-04-01

    Due to the shortage of parenteral caffeine and sodium benzoate, patients were pretreated with caffeine citrate to increase therapeutic seizure duration during electroconvulsive therapy (ECT). To date, no data are available on the use of caffeine citrate during ECT. This retrospective case series was done to demonstrate utilization of caffeine citrate as a substitute for caffeine and sodium benzoate in optimizing ECT. Medical records were reviewed to identify patients who received ECT and caffeine citrate. Physician notes were reviewed to determine the parameters of the ECT procedure, the seizure length, and the dose of caffeine citrate. Each chart was thoroughly studied to find the relationship between seizure duration and dose of caffeine citrate. Of the 12 ECT treatments utilizing caffeine citrate, 9 achieved at least 1 session lasting >30 seconds with an average seizure duration of 35 seconds. Increase in seizure duration ranged from -41% to 276% with an average increase of 48%. Only 3 treatment sessions utilizing caffeine citrate showed no increase in seizure duration. Doses ranged from 120 to 600 mg of both oral and parenteral caffeine citrate. Although increase in seizure duration was achieved for the majority of the ECT sessions, no dose-response correlation could be made. No significant adverse reactions were noted with the use of caffeine citrate during ECT. It was determined that, much like caffeine and sodium benzoate, caffeine citrate does increase the seizure duration. However, this response did vary due to many reasons including small sample size, concomitant medications, duration of illness, and number of ECTs they received in the past and how long ago they received the last ECT. Further research is required to elucidate the effect of these variables on seizure duration. © The Author(s) 2014.

  1. Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets

    PubMed Central

    Aslani, Abolfazl; Fattahi, Fatemeh

    2013-01-01

    Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Results: Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pH<6, friability < 1%, water percentage < 0.5% and accurate content uniformity. In panel test, both of combination flavors; (orange - lemon) and (strawberry - raspberry) had good acceptability. Conclusion: The prepared tablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates. PMID:24312839

  2. ATP citrate lyase inhibitors as novel cancer therapeutic agents.

    PubMed

    Zu, Xu-Yu; Zhang, Qing-Hai; Liu, Jiang-Hua; Cao, Ren-Xian; Zhong, Jing; Yi, Guang-Hui; Quan, Zhi-Hua; Pizzorno, Giuseppe

    2012-05-01

    ATP citrate lyase (ACL or ACLY) is an extra-mitochondrial enzyme widely distributed in various human and animal tissues. ACL links glucose and lipid metabolism by catalyzing the formation of acetyl-CoA and oxaloacetate from citrate produced by glycolysis in the presence of ATP and CoA. ACL is aberrantly expressed in many immortalized cells and tumors, such as breast, liver, colon, lung and prostate cancers, and is correlated reversely with tumor stage and differentiation, serving as a negative prognostic marker. ACL is an upstream enzyme of the long chain fatty acid synthesis, providing acetyl-CoA as an essential component of the fatty acid synthesis. Therefore, ACL is a key enzyme of cellular lipogenesis and potent target for cancer therapy. As a hypolipidemic strategy of metabolic syndrome and cancer treatment, many small chemicals targeting ACL have been designed and developed. This review article provides an update for the research and development of ACL inhibitors with a focus on their patent status, offering a new insight into their potential application.

  3. Bioequivalence study of sildenafil citrate tablets in healthy human volunteers.

    PubMed

    Mandal, U; Musmade, Prashant; Chakraborty, Mita; Rajan, D Senthil; Chakravarti, M; Pal, T K; Chattaraj, T K

    2004-11-01

    Newly developed sildenafil citrate (SC), a selective inhibitor of cyclic guanosine monophosphate (c-GMP) specific phosphodiesterase type 5 (PDE 5) in the corpus cavernosum is used for the oral treatment of erectile dysfunction. A convenient, sensitive and simple method for the determination of sildenafil in human plasma is presented. The analytical technique was based on reversed-phase high-performance liquid chromatography coupled with UV detector set at 295 nm. Rofecoxib was used as internal standard (I.S). Liquid-liquid extraction using diethyl ether was performed to recover sildenafil and rofecoxib. The retention time of I.S and sildenafil were 5.5 minutes and 7.2 minutes respectively. The method was validated over a linear range of 10 to 1000 ng/ml from plasma. Separate stability study showed that sildenafil is stable under conditions of analysis. The extraction efficiency from plasma varied from 79.69% to 81.13 %. The minimum quantifiable concentration was set at 10 ng/ml. (%o CV<12.5%). The method was used for Bioequivalence Study of Two Brands of Sildenafil citrate 50 mg tablets in healthy human volunteers. All pharmacokinetic parameter were calculated along with statistical evaluation.

  4. Inkjet printing of silver citrate conductive ink on PET substrate

    NASA Astrophysics Data System (ADS)

    Nie, Xiaolei; Wang, Hong; Zou, Jing

    2012-11-01

    Direct synthesis of silver conductive film on PET substrate by inkjet printing silver citrate conductive ink was presented in this paper. This kind of conductive ink contained silver citrate as silver precursor, 1,2-diaminopropane as complex agent dissolving the silver salt and methanol and isopropanol as a media adjusting the viscosity and surface tension. The formation of silver-amine complex reduced the decomposition temperature from 180 °C to 135 °C, thus the ink could be cured at relatively low temperature. The film reached the lowest resistivity of 17 μΩ cm after cured at 150 °C for 50 min, 3.1 μΩ cm at 230 °C and possessed high reflection and excellent adhesive property. Electrical conductivity, surface morphology and composition were investigated by four-point probe method, scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDS). It is demonstrated how the cured condition affects the silver film. Moreover, radio-frequency identification (RFID) antenna was fabricated by inkjet printing, which opens up routes for the flexible electronics fabrication.

  5. Why sildenafil and sildenafil citrate monohydrate crystals are not stable?

    PubMed

    Sawatdee, Somchai; Pakawatchai, Chaveng; Nitichai, Kwanjai; Srichana, Teerapol; Phetmung, Hirihattaya

    2015-10-01

    Sildenafil citrate was crystallized by various techniques aiming to determine the behavior and factors affecting the crystal growth. There are only 2 types of sildenafil obtaining from crystallization: sildenafil (1) and sildenafil citrate monohydrate (2). The used techniques were (i) crystallization from saturated solutions, (ii) addition of an antisolvent, (iii) reflux and (iv) slow solvent evaporation method. By pursuing these various methods, our work pointed that the best formation of crystal (1) was obtained from technique no. (i). Surprisingly, the obtained crystals (1) were perfected if the process was an acidic pH at a cold temperature then perfect crystals occurred within a day. Crystals of compound (2) grew easily using technique no. (ii) which are various polar solvents over a wide range of pH and temperature preparation processes. The infrared spectroscopy and nuclear magnetic resonance spectra fit well with these two X-ray crystal structures. The crystal structures of sildenafil free base and salt forms were different from their different growing conditions leading to stability difference.

  6. Transcriptional regulation of Bacillus subtilis citrate synthase genes.

    PubMed

    Jin, S; Sonenshein, A L

    1994-08-01

    The Bacillus subtilis citrate synthase genes citA and citZ were repressed during early exponential growth phase in nutrient broth medium and were induced as cells reached the end of exponential phase. Both genes were also induced by treatment of cells with the drug decoyinine. After induction, the steady-state level of citZ mRNA was about five times higher than that of citA mRNA. At least some of the citZ transcripts read through into the isocitrate dehydrogenase (citC) gene. Transcription from an apparent promoter site located near the 3' end of the citZ gene also contributed to expression of citC. In minimal medium, citA transcription was about 6-fold lower when glucose was the sole carbon source than it was when succinate was the carbon source. Expression of the citZ gene was repressed 2-fold by glucose and 10-fold when glucose and glutamate were present simultaneously. This latter synergistic repression is similar to the effect of glucose and glutamate on steady-state citrate synthase enzyme activity. CitR, a protein of the LysR family, appeared to be a repressor of citA but not of citZ.

  7. Why sildenafil and sildenafil citrate monohydrate crystals are not stable?

    PubMed Central

    Sawatdee, Somchai; Pakawatchai, Chaveng; Nitichai, Kwanjai; Srichana, Teerapol; Phetmung, Hirihattaya

    2015-01-01

    Sildenafil citrate was crystallized by various techniques aiming to determine the behavior and factors affecting the crystal growth. There are only 2 types of sildenafil obtaining from crystallization: sildenafil (1) and sildenafil citrate monohydrate (2). The used techniques were (i) crystallization from saturated solutions, (ii) addition of an antisolvent, (iii) reflux and (iv) slow solvent evaporation method. By pursuing these various methods, our work pointed that the best formation of crystal (1) was obtained from technique no. (i). Surprisingly, the obtained crystals (1) were perfected if the process was an acidic pH at a cold temperature then perfect crystals occurred within a day. Crystals of compound (2) grew easily using technique no. (ii) which are various polar solvents over a wide range of pH and temperature preparation processes. The infrared spectroscopy and nuclear magnetic resonance spectra fit well with these two X-ray crystal structures. The crystal structures of sildenafil free base and salt forms were different from their different growing conditions leading to stability difference. PMID:26594116

  8. Phosphodiesterase-5 inhibition by sildenafil citrate in a rat model of bleomycin-induced lung fibrosis.

    PubMed

    Yildirim, Alper; Ersoy, Yasemin; Ercan, Feriha; Atukeren, Pinar; Gumustas, Koray; Uslu, Unal; Alican, Inci

    2010-06-01

    the effect of sildenafil on GSH content. In conclusion, sildenafil citrate administration to rats with bleomycin-induced lung fibrosis seems to be beneficial via prevention of lipid peroxidation, cytokine production and/or release and neutrophil accumulation.

  9. Citrate and the conversion of carbohydrate in fat. The activities of citrate-cleavage enzyme and acetate thiokinase in livers of starved and re-fed rats

    PubMed Central

    Kornacker, Melodee S.; Lowenstein, J. M.

    1965-01-01

    1. The activity of citrate-cleavage enzyme varies in accordance with the nutritional state of the animal. It is suppressed on starvation and restored on re-feeding after starvation. 2. The increase in enzyme activity that occurs on re-feeding starved animals depends on the diet. It is largest on diets high in carbohydrate and low in fat, and smallest on diets high in fat. Intermediate increases are obtained with balanced diets. 3. The ratio of activities of citrate-cleavage enzyme to acetate thiokinase varies from 2·5 for animals maintained on a balanced diet to 20 for animals re-fed with a diet high in carbohydrate. 4. The changes in activity of citrate-cleavage enzyme correlate with changes in the rate of fatty acid synthesis and provide evidence for the involvement of the citrate-cleavage reaction in fatty acid synthesis. PMID:14342232

  10. 76 FR 5782 - Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-02

    ... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of... administrative review of the antidumping duty order on citric acid and certain citrate salts (citric acid) from... citric acid from Canada with respect to JBL Canada covering the period November 20, 2008, through May 19...

  11. 78 FR 34648 - Citric Acid and Certain Citrate Salts: Preliminary Results of Countervailing Duty Administrative...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-10

    ... International Trade Administration Citric Acid and Certain Citrate Salts: Preliminary Results of Countervailing... review of the countervailing duty (CVD) order on citric acid and citrate salts from the People's Republic... (202) 482-1503. Scope of the Order The merchandise subject to the order is citric acid and certain...

  12. 76 FR 34044 - Citric Acid and Certain Citrate Salts From Canada: Final Results of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Final Results of... preliminary results of the first administrative review of the antidumping duty order on citric acid and certain citrate salts (citric acid) from Canada. The review covers one manufacturer/exporter of the...

  13. 77 FR 6061 - Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-07

    ... International Trade Administration Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of... administrative review of the antidumping duty order on citric acid and certain citrate salts (citric acid) from... initiation of an administrative review of the antidumping duty order on citric acid from Canada with respect...

  14. Renal excretion of aluminium in the rat: effect of citrate infusion.

    PubMed

    Lote, C J; Willmott, K; Wood, J A; Thewles, A; Freeman, M

    1995-12-01

    When aluminium is administered intravenously to rats, the speciation of the aluminium has a major effect on its renal excretion. Aluminium administered as citrate is much more effectively excreted than that administered as chloride or sulphate. This suggests that citrate could be therapeutically useful in patients who have been exposed to aluminium. Accordingly, we have performed two series of experiments in rats, in which a citrate infusion (intravenous), was begun either immediately after, or one hour after, the administration of an intravenous aluminium sulphate bolus. Both protocols led to markedly enhanced aluminium excretion compared to controls in which only 0.7% NaCl was infused. The enhancement of aluminium excretion was 783% if citrate infusion was begun immediately after aluminium administration, and 335% if the citrate infusion began after an hour delay. The increased excretion was due to an increase in the freely filterable fraction of aluminium. In the control experiments, in which aluminium sulphate administration was followed by 0.7% NaCl infusion, aluminium was found to be deposited in the liver. Administration of citrate one hour after the aluminium bolus did not reduce this liver deposition. The results indicate that a fraction of the plasma aluminium is accessible to the citrate infused and can thereby be converted into a filterable form which can be excreted. It appears that, for maximum therapeutic effect, citrate should be infused as rapidly as possible after an aluminium load, to limit aluminium binding to ligands which allow it to enter cells.

  15. Comparison of citrated and fresh whole blood for viscoelastic coagulation testing during elective neurosurgery.

    PubMed

    Silverberg, E; Tornqvist, F; Kander, T; Bengzon, J; Solomon, C; Bonnevier, J; Schött, U

    2017-08-01

    Previous viscoelastic haemostatic tests studies have often indicated a hypercoagulative test signal with citrated blood, which could influence clinical decision makings. The aim of this study was to compare fresh and citrated whole blood using two non-automated viscoelastic ROTEM and Sonoclot tests. Our hypothesis was that citrated blood would demonstrate a hypercoagulative response in this setting, not tested before. Perioperative viscoelastic coagulation changes were evaluated with a ROTEM and Sonoclot in 38 patients undergoing elective brain tumor surgery. The citrated samples were recalcified with CaCl2. Wilcoxon nonparametric-paired tests and Bland-Altman plots were performed to compare the fresh and citrated blood analyses. The citrated blood showed a hypercoagulative response in ROTEM NATEM-clot formation time and α-angle, Sonoclot-clot rate and platelet function, as compared to fresh blood (p<0.0001). Fresh whole blood may theoretically reflect in vivo haemostasis more closely than citrated analyses, which indicated a hypercoagulative response as compared to the fresh whole blood analyses Bland-Altman plots also indicated that ROTEM reference ranges in patients undergoing brain surgery should be redefined. Future studies must establish the correlation between viscoelastic test results using fresh or citrate anticoagulated blood and clinical outcomes, such as bleeding, transfusion or reoperation for postoperative haematoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Characterization of citrate utilization in Corynebacterium glutamicum by transcriptome and proteome analysis.

    PubMed

    Polen, Tino; Schluesener, Daniela; Poetsch, Ansgar; Bott, Michael; Wendisch, Volker F

    2007-08-01

    Corynebacterium glutamicum grows aerobically on a variety of carbohydrates and organic acids as single or combined sources of carbon and energy. To characterize the citrate utilization in C. glutamicum on a genomewide scale, a comparative analysis was carried out by combining transcriptome and proteome analysis. In cells grown on citrate, transcriptome analysis revealed highest expression changes for two different citrate-uptake systems encoded by citM and tctCBA, whereas genes encoding uptake systems for the glucose- (ptsG), sucrose- (ptsS) and fructose- (ptsF) specific PTS components and permeases for gluconate (gntP) and glutamate (gluC) displayed decreased mRNA levels in citrate-grown cells. This pattern was also observed when cells grown in Luria-Bertani (LB) medium plus citrate were compared with cells grown in LB medium, indicating some kind of catabolite repression. Genes encoding enzymes of the tricarboxylic acid cycle (aconitase, succinyl-CoA synthetase, succinate dehydrogenase and fumarase), malic enzyme, PEP carboxykinase, gluconeogenic glyceraldehyde-3-phosphate dehydrogenase and ATP synthase displayed increased expression in cells grown on citrate. Accordingly, proteome analysis revealed elevated protein levels of these enzymes and showed a good correlation with the mRNA levels. In conclusion, this study revealed the citrate stimulon in C. glutamicum and the regulated central metabolic genes when grown on citrate.

  17. Citrate anticoagulation protocol for slow extended hemodialysis with the Genius dialysis system in acute renal failure.

    PubMed

    Schneider, M; Liefeldt, L; Slowinski, T; Peters, H; Neumayer, H-H; Morgera, S

    2008-01-01

    The Genius dialysis system is increasingly used as an intermittent hemodialysis device in the setting of acute renal failure. Slow extended hemodialysis is preferred in the case of critical ill patients. In this study we established a safe and feasible citrate anticoagulation protocol for slow extended hemodialysis (SLED) with the Genius system. We compared six anticoagulation protocols using SLED in 34 critically ill patients with acute renal failure. One group (A) received only citrate anticoagulation. Four groups (B - D) were treated with citrate and different additional systemic anticoagulation. Patients in the last group (F) were anticoagulated with heparin and were free of citrate anticoagulation. The total number of treatments was 103. A 4% sodium citrate solution was infused into the arterial line of the dialysis device for citrate anticoagulation. The dialysis solution contained one mmol/L of calcium. No additional calcium supplementation was done. We monitored electrolyte, acid-base and cardiovascular status prospectively. Hemodialysis was well tolerated hemodynamically. Electrolytes remained stable throughout hemodialysis in all groups. The decrease in ionized and total calcium was within the expected, clinically acceptable range. Bicarbonate and pH levels increased during dialysis, especially if citrate was used. Slow extended Genius hemodialysis with citrate is well tolerated and offers a safe and effective alternative to systemic anticoagulation.

  18. Enzymatic Analysis of the Requirement for Sodium in Aerobic Growth of Salmonella typhimurium on Citrate

    PubMed Central

    O'Brien, R. W.; Frost, G. M.; Stern, Joseph R.

    1969-01-01

    Na+ was required for the aerobic growth of Salmonella typhimurium on citrate, but not on l-malate, glucose, or glycerol. The maximal growth rate and the maximal total growth occurred with 6 to 7 mm Na+. Na+ could not be replaced by K+, NH4+, Li+, Rb+, or Cs+. Sonically treated extracts of citrate-grown cells contained the enzymes of the citrate fermentation pathway (citritase and oxalacetate decarboxylase) and all of the enzymes of the citric acid cycle. Thus, two separate routes of citrate catabolism appeared to be operational in the cells. Two discrete oxalacetate (OAA) decarboxylases were also demonstrated. One was of the “classic” type, being activated by Mn++ and inhibited by ethylenediaminetetracetate (EDTA). It was present in the cell sap. The second decarboxylase closely resembled the Na+-activated OAA decarboxylase of citrate-grown Aerobacter aerogenes, whose growth also requires, or is increased, by Na+. This decarboxylase was EDTA-insensitive, specifically activated by Na+ and inhibited by avidin, and it had a high affinity for OAA. It was induced by growth on citrate, but not l-malate or glycerol. It is suggested that the Na+ requirement for growth reflects the need to activate this OAA decarboxylase as a component of the citrate fermentation pathway and that citrate catabolism via the citric acid cycle, which should be independent of Na+, is somehow dependent upon the activity of the Na+-activated enzyme. PMID:4980062

  19. A novel citrate selective electrode based on surfactant modified nano-clinoptilolite.

    PubMed

    Hasheminejad, Mahdieh; Nezamzadeh-Ejhieh, Alireza

    2015-04-01

    A citrate-selective sensor was prepared by modification of a PVC membrane with modified nano-clinoptilolite particles by hexadecyltrimethyl ammonium surfactant (SMZ). A Nernstian slope of 29.9 ± 0.2 mV per decade of citrate concentration was obtained over the concentration range of 5.0 × 10(-5)-5.0 × 10(-2) mol L(-1) of citrate. The electrode showed a fast response time (⩽ 10 s) and a detection limit of 1.3 × 10(-5) mol L(-1) of citrate. The linear range and detection limit were respectively changed to 1.0 × 10(-4)-5.0 × 10(-2) mol L(-1) and 1.0 × 10(-4) mol L(-1) of citrate when the micronized clinoptilolite particles were used. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Struvite crystal growth inhibition by trisodium citrate and the formation of chemical complexes in growth solution

    NASA Astrophysics Data System (ADS)

    Prywer, Jolanta; Mielniczek-Brzóska, Ewa; Olszynski, Marcin

    2015-05-01

    Effect of trisodium citrate on the crystallization of struvite was studied. To evaluate such an effect an experiment of struvite growth from artificial urine was performed. The investigations are related to infectious urinary stones formation. The crystallization process was induced by the addition of aqueous ammonia solution to mimic the bacterial activity. The spectrophotometric results demonstrate that trisodium citrate increases induction time with respect to struvite formation and decreases the growth efficiency of struvite. The inhibitory effect of trisodium citrate on the nucleation and growth of struvite is explained in base of chemical speciation analysis. Such an analysis demonstrates that the inhibitory effect is related with the fact that trisodium citrate binds NH4 + and Mg2+ ions in the range of pH from 7 to 9.5 characteristic for struvite precipitation. The most important is the MgCit- complex whose concentration strongly depends on an increase in pH rather than on an increase in citrate concentrations.

  1. Optimization and validation of a rapid method to determine citrate and inorganic phosphate in milk by capillary electrophoresis.

    PubMed

    Izco, J M; Tormo, M; Harris, A; Tong, P S; Jimenez-Flores, R

    2003-01-01

    Quantification of phosphate and citrate compounds is very important because their distribution between soluble and colloidal phases of milk and their interactions with milk proteins influence the stability and some functional properties of dairy products. The aim of this work was to optimize and validate a capillary electrophoresis method for the rapid determination of these compounds in milk. Various parameters affecting analysis have been optimized, including type, composition, and pH of the electrolyte, and sample extraction. Ethanol, acetonitrile, sulfuric acid, water at 50 degrees C or at room temperature were tested as sample buffers (SB). Water at room temperature yielded the best overall results and was chosen for further validation. The extraction time was checked and could be shortened to less than 1 min. Also, sample preparation was simplified to pipet 12 microl of milk into 1 ml of water containing 20 ppm of tartaric acid as an internal standard. The linearity of the method was excellent (R2 > 0.999) with CV values of response factors <3%. The detection limits for phosphate and citrate were 5.1 and 2.4 nM, respectively. The accuracy of the method was calculated for each compound (103.2 and 100.3%). In addition, citrate and phosphate content of several commercial milk samples were analyzed by this method, and the results deviated less than 5% from values obtained when analyzing the samples by official methods. To study the versatility of the technique, other dairy productssuch as cream cheese, yogurt, or Cheddar cheese were analyzed and accuracy was similar to milk in all products tested. The procedure is rapid and offers a very fast and simple sample preparation. Once the sample has arrived at the laboratory, less than 5 min (including handling, preparation, running, integration, and quantification) are necessary to determine the concentration of citric acid and inorganic phosphate. Because of the speed and accuracy of this method, it is promising as an

  2. Clomiphene citrate as a preventive treatment for intractable chronic cluster headache: a second reported case with long-term follow-up.

    PubMed

    Rozen, Todd D

    2015-04-01

    To describe a second case of treatment refractory chronic cluster headache responsive to clomiphene citrate and with long-term follow-up. Case report with 7-year evaluation. A 63-year-old man with a 17-year history of chronic cluster headache preceded to have significant adverse events or was nonresponsive to multiple cluster headache preventive medications including verapamil, lithium, valproic acid, topiramate, baclofen as well as greater occipital nerve blocks and inpatient hospitalization. The patient experienced 3-5 headaches per day. On clomiphene citrate 100 mg/day he became 100% pain-free and remained so for 3.5 years with only mild fatigue as a side effect. He then had cluster headache recurrence and did well on gabapentin for another 3 years with repeat headache recurrence. Clomiphene was restarted, and he became pain-free once again. This is the second reported case of the effective use of clomiphene citrate for the preventive treatment of medicinal refractory chronic cluster headache. This is the first case to report long-term follow-up of this neurohormonal treatment. Clomiphene citrate appears to be safe for extended use in chronic cluster headache even in an elderly sufferer and has a minimal side effect profile. The mechanism of action of how clomiphene prevents cluster headache may involve both its ability to enhance testosterone production and its ability to bind to hypothalamic estrogen receptors. Clomiphene citrate should join the list of alternative cluster headache prophylactic treatments to be considered by headache specialists when conventional cluster headache preventives are ineffective. © 2015 American Headache Society.

  3. Improving methionine and ATP availability by MET6 and SAM2 co-expression combined with sodium citrate feeding enhanced SAM accumulation in Saccharomyces cerevisiae.

    PubMed

    Chen, Hailong; Wang, Zhou; Wang, Zhilai; Dou, Jie; Zhou, Changlin

    2016-04-01

    S-adenosyl-L-methionine (SAM), biosynthesized from methionine and ATP, exhibited diverse pharmaceutical applications. To enhance SAM accumulation in S. cerevisiae CGMCC 2842 (wild type), improvement of methionine and ATP availability through MET6 and SAM2 co-expression combined with sodium citrate feeding was investigated here. Feeding 6 g/L methionine at 12 h into medium was found to increase SAM accumulation by 38 % in wild type strain. Based on this result, MET6, encoding methionine synthase, was overexpressed, which caused a 59 % increase of SAM. To redirect intracellular methionine into SAM, MET6 and SAM2 (encoding methionine adenosyltransferase) were co-expressed to obtain the recombinant strain YGSPM in which the SAM accumulation was 2.34-fold of wild type strain. The data obtained showed that co-expression of MET6 and SAM2 improved intracellular methionine availability and redirected the methionine to SAM biosynthesis. To elevate intracellular ATP levels, 6 g/L sodium citrate, used as an auxiliary energy substrate, was fed into the batch fermentation medium, and an additional 19 % increase of SAM was observed after sodium citrate addition. Meanwhile, it was found that addition of sodium citrate improved the isocitrate dehydrogenase activity which was associated with the intracellular ATP levels. The results demonstrated that addition of sodium citrate improved intracellular ATP levels which promoted conversion of methionine into SAM. This study presented a feasible approach with considerable potential for developing highly SAM-productive strains based on improving methionine and ATP availability.

  4. Alkali replacement raises urinary citrate excretion in patients with topiramate-induced hypocitraturia.

    PubMed

    Jhagroo, R Allan; Wertheim, Margaret L; Penniston, Kristina L

    2016-01-01

    The aims of this study were to assess (1) the magnitude and temporality of decreased urinary citrate excretion in patients just starting topiramate and (2) the effect of alkali replacement on topiramate-induced hypocitraturia. Study 1 was a prospective, non-intervention study in which patients starting topiramate for headache remediation provided pre- and post-topiramate 24 h urine collections for measurement of urine citrate. Study 2 was a clinical comparative effectiveness study in which patients reporting to our stone clinic for kidney stones and who were treated with topiramate were prescribed alkali therapy. Pre- and post-alkali 24 h urinary citrate excretion was compared. Data for 12 and 22 patients (studies 1 and 2 respectively) were evaluated. After starting topiramate, urinary citrate excretion dropped significantly by 30 days (P = 0.016) and 62% of patients had hypocitraturia (citrate <320 mg day(-1) ). At 60 days, urine citrate was even lower than at baseline (P = 0.0032) and 86% of patients had developed hypocitraturia. After starting alkali, urine citrate increased in stone-forming patients on topiramate (198 ± 120 to 408 ± 274 mg day(-1) ; P = 0.042 for difference). 85% of patients were hypocitraturic on topiramate alone vs. 40% after adding alkali. The increase in urinary citrate was greater in patients provided ≥ 90 mEq potassium citrate. Our study is the first to provide clinical evidence that alkali therapy can raise urinary citrate excretion in patients who form kidney stones while being treated with topiramate. Clinicians should consider alkali therapy for reducing the kidney stone risk of patients benefitting from topiramate treatment for migraine headaches or other conditions. © 2015 The British Pharmacological Society.

  5. Heterotopic pregnancy following induction of ovulation with clomiphene citrate

    PubMed Central

    Ghandi, Sedigheh; Ahmadi, Raheleh; Fazel, Mahmoud

    2011-01-01

    Background: Although heterotopic gestation is common in assisted reproductive techniques, it is very rare in natural conception and clomiphene induced pregnancy. Diagnosis and appropriate intervention of heterotopic pregnancy requires a high index of suspicious. Case: In this paper a case of heterotopic pregnancy in a 30-year old woman with hemoperitoneum from ruptured tubal pregnancy with live intrauterine gestation at 9 weeks of gestation is reported. Conclusion: This case suggests that a heterotopic pregnancy must always be considered particularly after the induction of ovulation by clomiphene citrate or assisted reproductive technology. Every clinician treating women of reproductive age should keep this diagnosis in mind. It also demonstrates that early diagnosis is essential in order to salvage the intrauterine pregnancy and avoid maternal morbidity and mortality. PMID:26396583

  6. Sildenafil citrate for the treatment of pulmonary hypertension.

    PubMed

    Hrometz, Sandra L; Shields, Kelly M

    2006-12-01

    Pulmonary arterial hypertension is a progressive disease that has a high rate of mortality. For these reasons, early treatment is essential. Treatment choices for pulmonary arterial hypertension are limited by drug tolerability, drug cost and inconvenience associated with administration techniques and dosing schedules. Therefore, a therapy that provides oral dosing with limited side effects would prove useful in managing many patients. Sildenafil citrate, the first and highly publicized oral medication to receive approval from the U.S. Food and Drug Administration for erectile dysfunction, has recently been approved for treatment of pulmonary arterial hypertension. This review summarizes the normal physiology of the pulmonary vasculature, and the pathophysiology involved in pulmonary arterial hypertension and the role of sildenafil in its treatment.

  7. Response of patients with indolent systemic mastocytosis to tamoxifen citrate.

    PubMed

    Butterfield, Joseph H; Chen, Dong

    2016-01-01

    We examined whether tamoxifen citrate at 20mg/day for 1 year had a beneficial effect on laboratory findings, bone marrow mastocytosis, common clinical symptoms, or quality-of-life assessment for 5 women and 2 men with indolent systemic mastocytosis. Tamoxifen was well tolerated. We found significant reductions in the platelet count, serum alkaline phosphatase, and 24-h urinary excretion of N-methylhistamine and significant increases in serum lactate dehydrogenase and (excluding 2 patients taking aspirin) in 24-h urinary excretion of 11β-prostaglandin F2α. Overall, no change occurred in percent involvement of bone marrow by mastocytosis. Symptom scores were mild and did not change during the treatment. The 36-Item Short Form Health Survey scores for quality of life physical and mental components showed no marked changes. Tamoxifen, an older, nonhematotoxic medication, has limited activity in systemic mastocytosis at the dosage used in this study.

  8. Citrate anticoagulation for continuous renal replacement therapy in small children.

    PubMed

    Soltysiak, Jolanta; Warzywoda, Alfred; Kociński, Bartłomiej; Ostalska-Nowicka, Danuta; Benedyk, Anna; Silska-Dittmar, Magdalena; Zachwieja, Jacek

    2014-03-01

    Regional citrate anticoagulation (RCA) is one of the methods used to prevent clotting in continuous renal replacement therapy (CRRT). The aim of this study was to describe the outcomes and complications of RCA-CRRT in comparison to heparin anticoagulation (HA)-CRRT in critically ill children. This study was a retrospective review of 30 critically ill children (16 on RCA- and 14 on HA-CRRT) who underwent at least 24 h of CRRT. The mean body weight of the children was 8.69 ± 5.63 kg. RCA-CRRT was performed with a commercially available pre-dilution citrate solution (Prismocitrate 18/0). The mean time on RCA-CRRT and HA-CRRT was 148.73 ± 131.58 and 110.24 ± 105.38 h, respectively. Circuit lifetime was significantly higher in RCA-CRRT than in HA-CRRT (58.04 ± 51.18 h vs. 37.64 ± 32.51 h, respectively; p = 0.030). Circuit clotting was observed in 11.63 % of children receiving RCA-CRRT and 34.15 % of those receiving HA-CRRT. Episodic electrolyte and metabolic disturbances were more common in children receiving RCA-CRRT. The survival at discharge from the hospital was 37.5 and 14.3 % among children receiving RCA-CRRT and HA-CRRT, respectively. In critically ill children with a low body weight, RCA appeared to be safe and easy to used. Among our patient cohort, RCA was more effective in preventing circuit clotting and provided a better circuit lifetime than HA.

  9. 76 FR 77772 - Citric Acid and Certain Citrate Salts from the People's Republic of China: Final Results of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-14

    ... International Trade Administration Citric Acid and Certain Citrate Salts from the People's Republic of China... of the antidumping duty order on citric acid and certain citrate salts (``citric acid'') from the... Citric Acid and Certain Citrate Salts from the People's Republic of China: Preliminary Results of the...

  10. 76 FR 17835 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Extension of Time...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... International Trade Administration A-570-937] Citric Acid and Certain Citrate Salts From the People's Republic... order on citric acid and certain citrate salts (``citric acid'') from the People's Republic of China.... See Citric Acid and Certain Citrate Salts from the People's Republic of China: Notice of Extension of...

  11. 76 FR 82275 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Extension of Time...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ... International Trade Administration Citric Acid and Certain Citrate Salts From the People's Republic of China... countervailing duty order on citric acid and certain citrate salts from the People's Republic of China (PRC). See... and Certain Citrate Salts, 74 FR 25705 (May 29, 2009). On May 2, 2011, the Department published...

  12. 77 FR 22560 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Extension of Time...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ... International Trade Administration Citric Acid and Certain Citrate Salts From the People's Republic of China... acid and certain citrate salts (``citric acid'') from the People's Republic of China (``PRC'').\\1\\ On...). \\2\\ See Citric Acid and Certain Citrate Salts From the People's Republic of China: Extension of...

  13. 77 FR 74171 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Final Results of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-13

    ... International Trade Administration Citric Acid and Certain Citrate Salts From the People's Republic of China... certain citrate salts from the People's Republic of China (``PRC'') on June 6, 2012.\\1\\ The period of... Citric Acid and Certain Citrate Salts from the People's Republic of China: Post- Preliminary...

  14. 77 FR 9891 - Citric Acid and Certain Citrate Salts from the People's Republic of China: Amended Final Results...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-21

    ... International Trade Administration Citric Acid and Certain Citrate Salts from the People's Republic of China... antidumping duty order on citric acid and certain citrate salts (``citric acid'') from the People's Republic... Act of 1930, as amended (``the Act''). \\1\\ See Citric Acid and Certain Citrate Salts from the...

  15. Citrate anticoagulation during plasma exchange in a patient with thrombotic thrombocytopenic purpura: short heparin-free hemodialysis helps to attenuate citrate load.

    PubMed

    Buturović-Ponikvar, Jadranka; Pernat, Andreja Marn; Ponikvar, Rafael

    2005-06-01

    The treatment of thrombotic thrombocytopenic purpura requires plasma exchange using fresh frozen plasma as a replacement solution once or even twice daily. If citrate anticoagulation is needed, the citrate load (both from fresh frozen plasma and citrate as an anticoagulant) can be significant, causing metabolic complications. The aim of our report is to present our experience with citrate anticoagulation in a patient with thrombotic thrombocytopenic purpura treated with daily membrane plasma exchange. Twenty-six plasma exchange procedures were performed during 20 days of treatment in a 46-year-old female. The blood flow was 98 +/- 8 mL/min; 4% trisodium citrate was infused into the arterial line (134 +/- 11 mL/h) and 1 M CaCl2 into the venous line (11.4 +/- 1.8 mL/h). Fresh frozen plasma (first 7 procedures) or cryo-poor plasma (19 procedures) were used as a replacement solution, 3176 +/- 536 mL per procedure. A total of 88,930 mL of plasma was exchanged. No serious side-effects occurred. iCa before plasma exchange was significantly higher than afterwards (1.23 +/- 0.12 vs. 1.12 +/- 0.12, P = 0.0047). Significant alkalosis occurred after three plasma exchanges (pH 7.64, bicarbonate 36.2 mmol/L), and was corrected by 3-h heparin-free hemodialysis with dialysate as follows: K 4.0 mmol/L, calcium 1.5 mmol/L, and bicarbonate set to 24 mmol/L. After dialysis, pH was 7.45 and bicarbonate 29.4 mmol/L. Another (2-h) heparin-free hemodialysis procedure was repeated after six plasma exchanges. Citrate anticoagulation can be safely performed in patients treated with plasma exchange once or twice daily. Periodically performed short heparin-free hemodialysis can correct metabolic alkalosis and attenuate the citrate load.

  16. Genome-wide identification of citrus ATP-citrate lyase genes and their transcript analysis in fruits reveals their possible role in citrate utilization.

    PubMed

    Hu, Xiao-Mei; Shi, Cai-Yun; Liu, Xiao; Jin, Long-Fei; Liu, Yong-Zhong; Peng, Shu-Ang

    2015-02-01

    ATP-citrate lyase (ACL, EC4.1.3.8) catalyzes citrate to oxaloacetate and acetyl-CoA in the cell cytosol, and has important roles in normal plant growth and in the biosynthesis of some secondary metabolites. We identified three ACL genes, CitACLα1, CitACLα2, and CitACLβ1, in the citrus genome database. Both CitACLα1 and CitACLα2 encode putative ACL α subunits with 82.5 % amino acid identity, whereas CitACLβ1 encodes a putative ACL β subunit. Gene structure analysis showed that CitACLα1 and CitACLα2 had 12 exons and 11 introns, and CitACLβ1 had 16 exons and 15 introns. CitACLα1 and CitACLβ1 were predominantly expressed in flower, and CitACLα2 was predominantly expressed in stem and fibrous roots. As fruits ripen, the transcript levels of CitACLα1, CitACLβ1, and/or CitACLα2 in cultivars 'Niuher' and 'Owari' increased, accompanied by significant decreases in citrate content, while their transcript levels decreased significantly in 'Egan No. 1' and 'Iyokan', although citrate content also decreased. In 'HB pummelo', in which acid content increased as fruit ripened, and in acid-free pummelo, transcript levels of CitACLα2, CitACLβ1, and/or CitACLα1 increased. Moreover, mild drought stress and ABA treatment significantly increased citrate contents in fruits. Transcript levels of the three genes were significantly reduced by mild drought stress, and the transcript level of only CitACLβ1 was significantly reduced by ABA treatment. Taken together, these data indicate that the effects of ACL on citrate use during fruit ripening depends on the cultivar, and the reduction in ACL gene expression may be attributed to citrate increases under mild drought stress or ABA treatment.

  17. Comparative transcriptome analysis reveals a global insight into molecular processes regulating citrate accumulation in sweet orange (Citrus sinensis).

    PubMed

    Lu, Xiaopeng; Cao, Xiongjun; Li, Feifei; Li, Jing; Xiong, Jiang; Long, Guiyou; Cao, Shangyin; Xie, Shenxi

    2016-12-01

    Citrate, the predominant organic acid in citrus, determines the taste of these fruits. However, little is known about the synergic molecular processes regulating citrate accumulation. Using 'Dahongtiancheng' (Citrus sinensis) and 'Bingtangcheng' (C. sinensis) with significant difference in citrate, the objectives of this study were to understand the global mechanisms of high-citrate accumulation in sweet orange. 'Dahongtiancheng' and 'Bingtangcheng' exhibit significantly different patterns in citrate accumulation throughout fruit development, with the largest differences observed at 50-70 days after full bloom (DAFB). Comparative transcriptome profiling was performed for the endocarps of both cultivars at 50 and 70 DAFB. Over 34.5 million clean reads per library were successfully mapped to the reference database and 670-2630 differentially expressed genes (DEGs) were found in four libraries. Among the genes, five transcription factors were ascertained to be the candidates regulating citrate accumulation. Functional assignments of the DEGs indicated that photosynthesis, the citrate cycle and amino acid metabolism were significantly altered in 'Dahongtiancheng'. Physiological and molecular analyses suggested that high photosynthetic efficiency and partial impairment of citrate catabolism were crucial for the high-citrate trait, and amino acid biosynthesis was one of the important directions for citrate flux. The results reveal a global insight into the gene expression changes in a high-citrate compared with a low-citrate sweet orange. High accumulating efficiency and impaired degradation of citrate may be associated with the high-citrate trait of 'Dahongtiancheng'. Findings in this study increase understanding of the molecular processes regulating citrate accumulation in sweet orange. © 2016 Scandinavian Plant Physiology Society.

  18. ROLES OF CITRATE AND ACETOIN IN THE METABOLISM OF STREPTOCOCCUS DIACETILACTIS

    PubMed Central

    Harvey, R. J.; Collins, E. B.

    1963-01-01

    Harvey, R. J. (University of California, Davis), and E. B. Collins. Roles of citrate and acetoin in the metabolism of Streptococcus diacetilactis. J. Bacteriol. 86:1301–1307. 1963.—Streptococcus diacetilactis was unable to use citrate as a source of energy for growth, but the addition of citrate to a lactose-containing medium increased the specific growth rate 35%. Besides serving as the precursor of acetoin, some of the pyruvate formed from citrate was incorporated into cell material, primarily into lipids. A constant fraction of the weight of new cells was synthesized from the pyruvate formed from citrate. The rate of entry of citrate into cells was independent of the growth rate, and the usual result was that more pyruvate was formed from citrate than was required for cell synthesis. All excess pyruvate was converted to acetoin. Thus, acetoin formation acts as a detoxification mechanism, a means of removing intracellular pyruvate not required for synthesis of cell material. PMID:14086105

  19. Preparation and Quality Control of (68)Ga-Citrate for PET Applications.

    PubMed

    Aghanejad, Ayuob; Jalilian, Amir Reza; Ardaneh, Khosro; Bolourinovin, Fatemeh; Yousefnia, Hassan; Samani, Ali Bahrami

    2015-01-01

    In nuclear medicine studies, gallium-68 ((8)Ga) citrate has been recently known as a suitable infection agent in positron emission tomography (PET). In this study, by applying an in-house produced (68)Ge/(68)Ga generator, a simple technique for the synthesis and quality control of (68)Ga-citrate was introduced; followed by preliminary animal studies. (68)GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC), chemical purity (assessed by ICP-EOS), radionuclide purity (evaluated by HPGe), and breakthrough. (68)Ga-citrate was prepared from eluted (68)GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370C, followed by biodistribution studies in rats for 120 min. (68)Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC), specific activity (4-6 GBq/mM), chemical purity (Sn, Fe<0.3 ppm and Zn<0.2 ppm) within 15 min at 500C. The biodistribution of (68)Ga-citrate was consistent with former reports up to 120 minutes. This study demonstrated the possible in-house preparation and quality control of (68)Ga-citrate, using a commercially available (68)Ge/(68)Ga generator for PET imaging throughout the country.

  20. Preparation and Quality Control of 68Ga-Citrate for PET Applications

    PubMed Central

    Aghanejad, Ayuob; Jalilian, Amir Reza; Ardaneh, Khosro; Bolourinovin, Fatemeh; Yousefnia, Hassan; Samani, Ali Bahrami

    2015-01-01

    Objective(s): In nuclear medicine studies, gallium-68 (8Ga) citrate has been recently known as a suitable infection agent in positron emission tomography (PET). In this study, by applying an in-house produced 68Ge/68Ga generator, a simple technique for the synthesis and quality control of 68Ga-citrate was introduced; followed by preliminary animal studies. Methods: 68GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC), chemical purity (assessed by ICP-EOS), radionuclide purity (evaluated by HPGe), and breakthrough. 68Ga-citrate was prepared from eluted 68GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370C, followed by biodistribution studies in rats for 120 min. Results: 68Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC), specific activity (4-6 GBq/mM), chemical purity (Sn, Fe<0.3 ppm and Zn<0.2 ppm) within 15 min at 500C. The biodistribution of 68Ga-citrate was consistent with former reports up to 120 minutes. Conclusion: This study demonstrated the possible in-house preparation and quality control of 68Ga-citrate, using a commercially available 68Ge/68Ga generator for PET imaging throughout the country. PMID:27408889

  1. Citrate, calcium, phosphate and magnesium in sows' milk at initiation of lactation.

    PubMed

    Kent, J C; Arthur, P G; Hartmann, P E

    1998-02-01

    Colostrum and milk were collected from ten sows at frequent intervals from before farrowing until 9 d after farrowing. Ionized calcium, pH, and total concentrations of citrate, calcium, phosphate and magnesium were measured in whole milk. The diffusible fraction of the mammary secretion was separated by ultrafiltration and was used for the measurement of diffusible citrate, calcium, phosphate and magnesium. The pH before farrowing was 5.7, and increased to 6.5 on day 4 as total calcium and phosphate also increased. Before farrowing, total and diffusible citrate were 7.8 and 7.3 mM respectively, while diffusible phosphate was 11.9 mM, and these concentrations all decreased during the study period. Total magnesium ranged between 3.3 and 4.1 mM, while diffusible magnesium ranged between 2.0 and 3.1 mM. While these concentrations and patterns of change of diffusible calcium and citrate are quite different from those of women's milk during the first week after birth, theoretical physicochemical relationships between diffusible calcium and citrate, and ionized calcium and HPO4(2-) were corroborated by these results. We conclude that diffusible citrate plays an important role in the determination of the concentration of diffusible calcium. However, while citrate may be the major determinant of the total concentration of calcium in women's milk, this is not the case in sows' milk.

  2. The Citrate Carrier CitS Probed by Single-Molecule Fluorescence Spectroscopy

    PubMed Central

    Kästner, Christopher N.; Prummer, Michael; Sick, Beate; Renn, Alois; Wild, Urs P.; Dimroth, Peter

    2003-01-01

    A prominent region of the Na+-dependent citrate carrier (CitS) from Klebsiella pneumoniae is the highly conserved loop X-XI, which contains a putative citrate binding site. To monitor potential conformational changes within this region by single-molecule fluorescence spectroscopy, the target cysteines C398 and C414 of the single-Cys mutants (CitS-sC398, CitS-sC414) were selectively labeled with the thiol-reactive fluorophores AlexaFluor 546/568 C5 maleimide (AF546, AF568). While both single-cysteine mutants were catalytically active citrate carriers, labeling with the fluorophore was only tolerated at C398. Upon citrate addition to the functional protein fluorophore conjugate CitS-sC398-AF546, complete fluorescence quenching of the majority of molecules was observed, indicating a citrate-induced conformational change of the fluorophore-containing domain of CitS. This quenching was specific for the physiological substrate citrate and therefore most likely reflecting a conformational change in the citrate transport mechanism. Single-molecule studies with dual-labeled CitS-sC398-AF546/568 and dual-color detection provided strong evidence for a homodimeric association of CitS. PMID:12609868

  3. The role of ammonium citrate washing on the characteristics of mechanochemical-hydrothermal derived magnesium-containing apatites.

    PubMed

    Chen, Chun-Wei; Suchanek, Wojciech L; Shuk, Pavel; Byrappa, Kullaiah; Oakes, Charles; Riman, Richard E; Brown, Kelly; Tenhuisen, Kevor S; Janas, Victor F

    2007-07-01

    The role of citrate washing on the physical and chemical characteristics of magnesium-substituted apatites (HAMgs) was performed. HAMgs were synthesized by a mechanochemical-hydrothermal route at room temperature in as little as 1 h, which is five times faster than our previous work. Magnesium-substituted apatites had concentrations as high as 17.6 wt% Mg with a corresponding specific surface area (SSA) of 216 m(2)/g. A systematic study was performed to examine the influence of increasing magnesium content on the physical and chemical characteristics of the reaction products. As the magnesium content increased from 0 to 17.6 wt%, magnesium-doped apatite crystallite size decreased from 12 to 8.8 nm. The Mg/(Mg + Ca) ratio in the product was enriched relative to that used for the reacting precursor solution. During mechanochemical-hydrothermal reaction, magnesium doped apatites co-crystallize with magnesium hydroxide. Citrate washing serves to remove the magnesium hydroxide phase. The concomitant increase in surface area results because of the removal of this phase. Possible mechanisms for magnesium hydroxide leaching are discussed to explain the measured trends.

  4. Effects of citrate and NaCl on size, morphology, crystallinity and microstructure of calcium phosphates obtained from aqueous solutions at acidic or near-neutral pH.

    PubMed

    Mekmene, Omar; Rouillon, Thierry; Quillard, Sophie; Pilet, Paul; Bouler, Jean-Michel; Pezennec, Stéphane; Gaucheron, Frédéric

    2012-05-01

    Precipitation of calcium phosphates occurs in dairy products and depending on pH and ionic environment, several salts with different crystallinity can form. The present study aimed to investigate the effects of NaCl and citrate on the characteristics of precipitates obtained from model solutions of calcium phosphate at pH 6·70 maintained constant or left to drift. The ion speciation calculations showed that all the starting solutions were supersaturated with respect to dicalcium phosphate dihydrate (DCPD), octacalcium phosphate (OCP) and hydroxyapatite (HAP) in the order HAP>OCP>DCPD. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) analyses of the precipitates showed that DCPD was formed at drifting pH (acidic final pH) whereas poor crystallised calcium deficient apatite was mainly formed at constant pH (6·70). Laser light scattering measurements and electron microscopy observations showed that citrate had a pronounced inhibitory effect on the crystallisation of calcium phosphates both at drifting and constant pH. This resulted in the decrease of the particle sizes and the modification of the morphology and the microstructure of the precipitates. The inhibitory effect of citrate mainly acted by the adsorption of the citrate molecules onto the surfaces of newly formed nuclei of calcium phosphate, thereby changing the morphology of the growing particles. These findings are relevant for the understanding of calcium phosphate precipitation from dairy byproducts that contain large amounts of NaCl and citrate.

  5. 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects.

    PubMed

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Chung, S P; Diem, T H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-02-01

    Oxidative stress-energy depletion therapy using oxidative stress induced by D-amino acid oxidase (DAO) and energy depletion induced by 3-bromopyruvate (3BP) was reported recently (El Sayed et al., Cancer Gene Ther., 19, 1-18, 2012). Even in the presence of oxygen, cancer cells oxidize glucose preferentially to produce lactate (Warburg effect) which seems vital for cancer microenvironment and progression. 3BP is a closely related structure to lactate and pyruvate and may antagonize their effects as a novel mechanism of its action. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP. Lactate and pyruvate enhanced migratory power of C6 glioma which was blocked by 3BP. Pyruvate and lactate did not protect against C6 glioma cell death induced by other glycolytic inhibitors e.g. citrate (inhibitor of phosphofructokinase) and sodium fluoride (inhibitor of enolase). Serial doses of 3BP were synergistic with citrate in decreasing viability of C6 glioma cells and spheroids. Glycolysis subjected to double inhibition using 3BP with citrate depleted ATP, clonogenic power and migratory power of C6 glioma cells. 3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time-dependent manner.

  6. Physiologically relevant divalent cations modulate citrate recognition by the McpS chemoreceptor.

    PubMed

    Lacal, Jesús; García-Fontana, Cristina; Callejo-García, Carla; Ramos, Juan-Luis; Krell, Tino

    2011-01-01

    The McpS chemoreceptor of Pseudomonas putida KT2440 recognizes six different tricarboxylic acid (TCA) cycle intermediates. However, the magnitude of the chemotactic response towards these compounds differs largely, which has led to distinguish between strong attractants (malate, succinate, fumarate, oxaloacetate) and weak attractants (citrate, isocitrate). Citrate is abundantly present in plant tissues and root exudates and can serve as the only carbon source for growth. Citrate is known to form complexes with divalent cations which are also abundantly present in natural habitats of this bacterium. We have used isothermal titration calorimetry to study the formation of citrate-metal ion complexes. In all cases binding was entropy driven but significant differences in affinity were observed ranging from K(D)=157 µM (for Mg(2+)) to 3 µM (for Ni(2+)). Complex formation occurred over a range of pH and ionic strength. The ligand binding domain of McpS (McpS-LBD) was found to bind free citrate, but not complexes with physiologically relevant Mg(2+) and Ca(2+). In contrast, complexes with divalent cations which are present as trace elements (Co(2+), Cd(2+) and Ni(2+)) were recognized by McpS-LBD. This discrimination differs from other citrate sensing proteins. These results are discussed in the context of the three dimensional structure of free citrate and its complex with Mg(2+). Chemotaxis assays using P. putida revealed that taxis towards the strong attractant malate is strongly reduced in the presence of free citrate. However, this reduction is much less important in the presence of citrate-Mg(2+) complexes. The physiological relevance of these findings is discussed.

  7. Citrate-enhanced release of arsenic during pyrite oxidation at circumneutral conditions.

    PubMed

    Zhang, Peng; Yao, Weiyu; Yuan, Songhu

    2017-02-01

    The release of arsenic (As) from the oxidation of As-rich pyrite is an important source of the high arsenic in groundwater. As a widespread low-molecular-weight organic acid, citrate plays an important role on the cycling of Fe(II)/Fe(III) through complexation in circumneutral subsurface environments, while the influence of citrate on the release of As from the oxidation of As-rich pyrite is poorly understood. In this study, As was loaded onto pyrite particles under anoxic conditions, and its release was investigated in the presence of 0-1 mM citrate at pH 7.4 under oxic conditions. As-loaded pyrite suspension was prepared by the equilibrium of 2.67 μM As(III) in 10 g/L pyrite under anoxic conditions with the decrease in dissolved As(III) concentration to 1 μM. The suspension was subsequently exposed to air for oxygenation. In the absence of citrate, the oxygenation decreased the partitioning of As in the solution because of the re-adsorption of aqueous As by the in situ generated Fe(III) oxyhydroxides. However, with the increase in citrate concentration from 0.1 to 1 mM, the As partitioned in the solution increased from 0.3 to 2.67 μM. In the presence of 1 mM citrate, the As(III) was almost completely oxidized to As(V) during the oxygenation. The mechanisms of citrate-enhanced release of As were mainly attributed to the ligand exchange of citrate with As for pyrite surface sites, the competitive adsorption of citrate with As on Fe(III) oxyhydroxides and pyrite, and the partitioning of As on the newly formed Fe(III) colloids. This finding presents an overlooked mechanism of the release of pyrite-associated As under oxic and circumneutral conditions.

  8. Polymyxin B Direct Hemoperfusion Using Regional Citrate-Calcium Anticoagulation: A Case Report.

    PubMed

    Sidoti, Anna; Brogi, Etrusca; Morse, Joshua; Collareta, Michele; Vetrugno, Luigi; Giunta, Francesco; Forfori, Francesco

    2016-12-01

    Direct hemoperfusion with polymyxin B (PMX-DHP) is an extracorporeal treatment to add to conventional therapy during unresponsive endotoxic septic shock. So far, only heparin has been used as an anticoagulant during polymyxin B therapy. We present a case report of a postsurgical septic patient treated with 2 cycles of PMX-DHP using citrate anticoagulation. Monitoring of serum calcium, postcartridge calcium, and acid-base balance was performed. The treatments were accomplished without complications. To our knowledge, this is the first published report on the use of citrate anticoagulation during PMX-DHP. We conclude that citrate anticoagulation is feasible during hemoperfusion therapy in patients with increased hemorrhagic risk.

  9. Effect of citrate ions on laser ablation of Ag foil in aqueous medium

    NASA Astrophysics Data System (ADS)

    Sisková, K.; Vlcková, B.; Turpin, P.-Y.; Fayet, C.; Hromádková, J.; Slouf, M.

    2007-04-01

    Promoting effect of citrate in 1 × 10-5-1×10-2 M concentrations on laser ablation (LA) of a Ag foil in aqueous solution performed by ns laser pulses at 1064 nm is reported. Furthermore, adsorption of citrate ions was found to increase markedly the stability of the resulting LA-Ag hydrosol. The results are discussed on the basis of comparison of surface plasmon extinction spectral characteristics, transmission electron microscopy images, nanoparticle size distributions and surface-enhanced Raman scattering (SERS) spectral tests of hydrosols resulting from LA in neutral and acidic aqueous citrate solutions and in pure water.

  10. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study

    PubMed Central

    2012-01-01

    Introduction Liver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. The aim of this study was to investigate the predictive capability of baseline liver function parameters regarding citrate accumulation, expressed as an increase in the calcium total/calcium ionized (Catot/Caion) ratio ≥2.5, and to describe the feasibility of citrate CVVHD in liver failure patients. Methods We conducted a prospective observational study in medical ICU patients treated in a German university hospital. We performed 43 CVVHD runs using citrate for regional anticoagulation in 28 critically ill patients with decompensated liver cirrhosis or acute liver failure (maximum of two CVVHD runs per patient). Liver function was characterized before CVVHD using laboratory parameters, calculation of Child-Pugh and Model of End-stage Liver Disease scores, and determination of the plasma disappearance rate of indocyanine green. In addition to blood gas analysis, we measured total calcium and citrate in serum at baseline and after definitive time points for each CVVHD run. Results Accumulation of citrate in serum correlated with an increase in the Catot/Caion ratio. Although the critical upper threshold of Catot/Caion ratio ≥2.5 was exceeded 10 times in seven different CVVHD runs, equalization of initial metabolic acidosis was possible without major disturbances of acid-base and electrolyte status. Standard laboratory liver function parameters showed poor predictive capabilities regarding citrate accumulation in terms of an elevated Catot/Caion ratio ≥2.5. In contrast, serum lactate ≥3.4 mmol/l and prothrombin time ≤26% predicted an increase in the Catot/Caion ratio ≥2.5 with high sensitivity (86% for both lactate and prothrombin time) and specificity (86% for lactate, 92% for prothrombin time). Conclusions Despite substantial accumulation of citrate in serum, CVVHD with regional citrate

  11. Purification of L-glutamate-dependent citrate lyase from Clostridium sphenoides and electron microscopic analysis of citrate lyase isolated from Rhodopseudomonas gelatinosa, Streptococcus diacetilactis and C. sphenoides.

    PubMed

    Antranikian, G; Klinner, C; Kümmel, A; Schwanitz, D; Zimmermann, T; Mayer, F; Gottschalk, G

    1982-08-01

    Citrate lyase from Clostridium sphenoides was purified 72-fold with a yield of 11%. In contrast to citrate lyase from other sources the activity of this enzyme was strictly dependent on the presence of L-glutamate. The purified enzyme was only stable in the presence of 150 mM L-glutamate or 7 mM L-glutamate plus glycerol, sucrose or bovine serum albumin. Changes of the L-glutamate pool and of enzyme activity in growing cells of C. sphenoides indicated that citrate lyase activity in this organism was regulated by the intracellular L-glutamate concentration. Citrate lyase isolated from C. sphenoides, Rhodopseudomonas gelatinosa and Streptococcus diacetilactis was investigated by electron microscopy using the negative staining technique. Three different projections of enzyme molecules were observed: 'star' form, 'ring' form and 'triangle' form. In samples from R. gelatinosa and S. diacetilactis, star and ring forms occurred in a ratio of about 1:9. Using the enzyme from S. diacetilactis it was demonstrated that this ratio could be altered in favour of the star form by the addition of citrate or tricarballylate. The triangle form was observed in less than 1% of all evaluated molecules and may represent a transition form. In lyase samples from C. sphenoides there existed a correlation between enzyme activity and the proportion of stars and rings at varying concentrations of L-glutamate.

  12. A Process-Based Model of TCA Cycle Functioning to Analyze Citrate Accumulation in Pre- and Post-Harvest Fruits

    PubMed Central

    Etienne, Audrey; Génard, Michel; Bugaud, Christophe

    2015-01-01

    Citrate is one of the most important organic acids in many fruits and its concentration plays a critical role in organoleptic properties. The regulation of citrate accumulation throughout fruit development, and the origins of the phenotypic variability of the citrate concentration within fruit species remain to be clarified. In the present study, we developed a process-based model of citrate accumulation based on a simplified representation of the TCA cycle to predict citrate concentration in fruit pulp during the pre- and post-harvest stages. Banana fruit was taken as a reference because it has the particularity of having post-harvest ripening, during which citrate concentration undergoes substantial changes. The model was calibrated and validated on the two stages, using data sets from three contrasting cultivars in terms of citrate accumulation, and incorporated different fruit load, potassium supply, and harvest dates. The model predicted the pre and post-harvest dynamics of citrate concentration with fairly good accuracy for the three cultivars. The model suggested major differences in TCA cycle functioning among cultivars during post-harvest ripening of banana, and pointed to a potential role for NAD-malic enzyme and mitochondrial malate carriers in the genotypic variability of citrate concentration. The sensitivity of citrate accumulation to growth parameters and temperature differed among cultivars during post-harvest ripening. Finally, the model can be used as a conceptual basis to study citrate accumulation in fleshy fruits and may be a powerful tool to improve our understanding of fruit acidity. PMID:26042830

  13. A Process-Based Model of TCA Cycle Functioning to Analyze Citrate Accumulation in Pre- and Post-Harvest Fruits.

    PubMed

    Etienne, Audrey; Génard, Michel; Bugaud, Christophe

    2015-01-01

    Citrate is one of the most important organic acids in many fruits and its concentration plays a critical role in organoleptic properties. The regulation of citrate accumulation throughout fruit development, and the origins of the phenotypic variability of the citrate concentration within fruit species remain to be clarified. In the present study, we developed a process-based model of citrate accumulation based on a simplified representation of the TCA cycle to predict citrate concentration in fruit pulp during the pre- and post-harvest stages. Banana fruit was taken as a reference because it has the particularity of having post-harvest ripening, during which citrate concentration undergoes substantial changes. The model was calibrated and validated on the two stages, using data sets from three contrasting cultivars in terms of citrate accumulation, and incorporated different fruit load, potassium supply, and harvest dates. The model predicted the pre and post-harvest dynamics of citrate concentration with fairly good accuracy for the three cultivars. The model suggested major differences in TCA cycle functioning among cultivars during post-harvest ripening of banana, and pointed to a potential role for NAD-malic enzyme and mitochondrial malate carriers in the genotypic variability of citrate concentration. The sensitivity of citrate accumulation to growth parameters and temperature differed among cultivars during post-harvest ripening. Finally, the model can be used as a conceptual basis to study citrate accumulation in fleshy fruits and may be a powerful tool to improve our understanding of fruit acidity.

  14. Citrate Attenuates Adenine-Induced Chronic Renal Failure in Rats by Modulating the Th17/Treg Cell Balance.

    PubMed

    Ou, Yan; Li, Shuiqin; Zhu, Xiaojing; Gui, Baosong; Yao, Ganglian; Ma, Liqun; Zhu, Dan; Fu, Rongguo; Ge, Heng; Wang, Li; Jia, Lining; Tian, Lifang; Duan, Zhaoyang

    2016-02-01

    Citrate is commonly used as an anticoagulant in hemodialysis for chronic renal failure (CRF) and for the regulation of the immune dysfunction in CRF patients. The objective of this study was to investigate the effect of citrate on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in CRF. The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were significantly increased in the CRF model group compared to the control group, and were decreased in the citrate-treated groups. Citrate treatment inhibited the viability of Th17 cells while elevating the viability of Treg cells in CRF rats. Moreover, Th17-related cytokines significantly decreased while the Treg-related cytokines significantly increased with citrate treatment. Moreover, citrate had a negative influence on the deviation of Th17/Treg cells in CRF rats. Therefore, our study suggests that citrate had an anti-inflammatory effect on CRF through the modulation of the Th17/Treg balance.

  15. [Comparative estimation of antilithogenic activity of porcine kidney derived biomedical substance and sodium citrate in experimental urolithiasis].

    PubMed

    Pavlyashik, G V; Zharikov, A Yu; Kiselev, V I

    2017-06-01

    to compare the anti-lithogenic activity of biomedical substance derived from freeze-dried porcine kidney and sodium citrate. The experiments were conducted on Wistar rats divided into three groups of 15 animals each: control group (disease control), comparison group (sodium citrate treatment) and experimental group (treatment with biomedical substance from porcine kidneys). Experimental urolithiasis was modeled using the ethylene glycol model. On every 7th day of the 6 week experiment testing was done calcium and oxalate urine concentration and the activity of marker enzymes of renal epithelial damage: lactate dehydrogenase (LDH), -glutamyl transferase (GGT), and N-acetyl--D-glucosaminidase (NAG). At the end of the experiment, a part of the rats were decapitated and the renal tissue was tested for the oxidant status indicators of (renal thiobarbiturate reactive product content, TBRP, and total prooxidant activity, TPA) and antioxidant enzyme activities: glutathione peroxidase (GPO), superoxide dismutase (SOD) and catalase (CAT). To measure the number and size of calcium deposits formed in the renal papillary area, the Koss histochemical method was used. The experimental findings showed developing oxalate nephrolithiasis in the control group, as indicated by urinary supersaturation of oxalate ion, increased activity of marker enzymes, oxidative stress and the formation of numerous calcium deposits in the renal papillary area. In the comparison group, the 3-week use of sodium citrate contributed to a significant decrease in nephrolithiasis: a 3 to 4-fold decrease in the activity of marker enzymes in the urine, a 3.8-fold increase in the concentration of TBRP, normalization of GPO activity; the number and size of urinary calcium deposits decreased by 3.4 and 1.9 times, respectively. In the experimental group, using biomedical substance led to an even greater therapeutic effect. LDH activity and concentration of TPRP showed 1.9 times and by 26.2% greater decrease than

  16. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... piperazine citrate). (b) Sponsor. See 054628 in § 510.600(c) of this chapter. (c) (d) Conditions of use—(1... for administration by stomach tube, it shall be labeled: “Federal law restricts this drug to use by...

  17. Preventing serpin aggregation: The molecular mechanism of citrate action upon antitrypsin unfolding

    SciTech Connect

    Pearce, Mary C.; Morton, Craig J.; Feil, Susanne C.; Hansen, Guido; Adams, Julian J.; Parker, Michael W.; Bottomley, Stephen P.

    2008-11-21

    The aggregation of antitrypsin into polymers is one of the causes of neonatal hepatitis, cirrhosis, and emphysema. A similar reaction resulting in disease can occur in other human serpins, and collectively they are known as the serpinopathies. One possible therapeutic strategy involves inhibiting the conformational changes involved in antitrypsin aggregation. The citrate ion has previously been shown to prevent antitrypsin aggregation and maintain the protein in an active conformation; its mechanism of action, however, is unknown. Here we demonstrate that the citrate ion prevents the initial misfolding of the native state to a polymerogenic intermediate in a concentration-dependent manner. Furthermore, we have solved the crystal structure of citrate bound to antitrypsin and show that a single citrate molecule binds in a pocket between the A and B beta-sheets, a region known to be important in maintaining antitrypsin stability.

  18. Kinetic studies of the regulation of mitochondrial malate dehydrogenase by citrate.

    PubMed Central

    Gelpí, J L; Dordal, A; Montserrat, J; Mazo, A; Cortés, A

    1992-01-01

    Mitochondrial malate dehydrogenase shows a complex regulation pattern in the presence of citrate. Previously published results indicate that this enzyme is activated by citrate in the NAD(+)----NADH direction and inhibited in the opposite direction. Moreover, high concentrations of L-malate or oxaloacetate produce deviations from the Michaelis-Menten behaviour. Results reported in this paper clearly show that citrate both activates and inhibits mitochondrial malate dehydrogenase in the same direction (NAD(+)----NADH), and in the same reaction medium, depending on substrate concentration. This surprising effect has made it necessary to propose a new kinetic mechanism that extends those previously suggested and allows us to explain both the citrate effect (activating or inhibitory) and the effect of high concentrations of L-malate and oxaloacetate. PMID:1567375

  19. Pharmacokinetics of bismuth and ranitidine following single doses of ranitidine bismuth citrate

    PubMed Central

    KOCH, K M; DAVIS, I M; GOODING, A E; YIN, Y

    1996-01-01

    The pharmacokinetics of bismuth and ranitidine derived from ranitidine bismuth citrate given in single oral doses ranging from 200 mg to 1600 mg were evaluated in healthy subjects. Bismuth was only minimally absorbed (<0.5% of the amount dosed) after administration of ranitidine bismuth citrate, and peak plasma concentrations never exceeded 33 ng ml−1 in any subject. Plasma concentrations and urinary recoveries of bismuth at doses up to and including 800 mg were relatively constant and not proportional to dose. Bismuth absorption was increased more than proportionally with the dose at 1600 mg. The pharmacokinetics of ranitidine after administration of ranitidine bismuth citrate were dose-proportional and consistent with previous observations for ranitidine administered alone. Ranitidine bismuth citrate was well-tolerated in single oral doses of up to 1600 mg. PMID:8864318

  20. Closed circuit recovery of copper, lead and iron from electronic waste with citrate solutions.

    PubMed

    Torres, Robinson; Lapidus, Gretchen T

    2017-02-01

    An integral closed circuit hydrometallurgical process is presented for base metal recovery from electronic waste. The leaching medium consists of a sodium citrate solution, from which base metals are retrieved by direct electrowinning, and the barren solution is recycled back to the leaching stage. This leaching-electrowinning cycle was repeated four times. The redox properties of the fresh citrate solution, as well as the leach liquors, were characterized by cyclic voltammetry to determine adequate conditions for metal reduction, as well as to limit citrate degradation. The leaching efficiency of electronic waste, employing the same solution after four complete cycles was 71, 83 and 94% for copper, iron and lead, respectively, compared to the original leach with fresh citrate solution.

  1. The effect of post annealing treatment on the citrate sol-gel derived nanocrystalline BaFe12O19 powder: structural, morphological, optical and magnetic properties

    NASA Astrophysics Data System (ADS)

    Brightlin, B. C.; Balamurugan, S.

    2016-11-01

    The nanocrystalline BaFe12O19 powders were obtained from citrate sol-gel combustion-derived powder upon annealing at 800-1100 °C, and explored their structural, micro-structural, optical and magnetic properties. The thermal decomposition of citrate sol-gel combustion product was verified by means of thermogravimetric and differential thermal analysis. Structural identification of the citrate sol-gel combustion powder and annealed samples were investigated by powder X-ray diffraction. Though the combustion product exhibits cubic spinel phase material, the annealed powder yields good quality nanocrystalline hexagonal BaFe12O19 phase materials. The thin plate-like flakes morphology with random particle sizes of 100-200 nm with slightly agglomerated particles of BaFe12O19 phase is analyzed by high resolution scanning electron microscopy for the good quality annealed sample. Photoluminescence emission spectrum of BaFe12O19 material reveals broad emission peak at 360 nm under the excitation wavelength of 270 nm. Interestingly, the near infrared relative reflectivity of the nanocrystalline BaFe12O19 materials obtained by citrate sol-gel synthesis method is higher than the nanocrystalline BaFe12O19 materials obtained by mechano-thermal and co-precipitation method. The present dark brown colored BaFe12O19 materials can be applied as a ceramic color pigment which includes several applications. The room temperature magnetic hysteresis loop of the annealed BaFe12O19 sample exhibits a ferromagnetic saturation magnetization, M s of 55.774 emu/g at 15 kOe.

  2. Citrate influences microbial Fe hydroxide reduction via a dissolution-disaggregation mechanism

    NASA Astrophysics Data System (ADS)

    Braunschweig, Juliane; Klier, Christine; Schröder, Christian; Händel, Matthias; Bosch, Julian; Totsche, Kai U.; Meckenstock, Rainer U.

    2014-08-01

    Microbial reduction of ferric iron is partly dependent on Fe hydroxide particle size: nanosized Fe hydroxides greatly exceed the bioavailability of their counterparts larger than 1 μm. Citrate as a low molecular weight organic acid can likewise stabilize colloidal suspensions against aggregation by electrostatic repulsion but also increase Fe bioavailability by enhancing Fe hydroxide solubility. The aim of this study was to see whether adsorption of citrate onto surfaces of large ferrihydrite aggregates results in the formation of a stable colloidal suspension by electrostatic repulsion and how this effect influences microbial Fe reduction. Furthermore, we wanted to discriminate between citrate-mediated colloid stabilization out of larger aggregates and ferrihydrite dissolution and their influence on microbial Fe hydroxide reduction. Dissolution kinetics of ferrihydrite aggregates induced by different concentrations of citrate and humic acids were compared to microbial reduction kinetics with Geobacter sulfurreducens. Dynamic light scattering results showed the formation of a stable colloidal suspension and colloids with hydrodynamic diameters of 69 (±37) to 165 (± 65) nm for molar citrate:Fe ratios of 0.1 to 0.5 and partial dissolution of ferrihydrite at citrate:Fe ratios ⩾ 0.1. No dissolution or colloid stabilization was detected in the presence of humic acids. Adsorption of citrate, necessary for dissolution, reversed the surface charge and led to electrostatic repulsion between sub-aggregates of ferrihydrite and colloid stabilization when the citrate:Fe ratio was above a critical value (⩽ 0.1). Lower ratios resulted in stronger ferrihydrite aggregation instead of formation of a stable colloidal suspension, owing to neutralization of the positive surface charge. At the same time, microbial ferrihydrite reduction increased from 0.029 to 0.184 mM h-1 indicating that colloids stabilized by citrate addition enhanced microbial Fe reduction. Modelling of

  3. Self nanoprecipitating preconcentrate of tamoxifen citrate for enhanced bioavailability.

    PubMed

    Kapse, Sonali V; Gaikwad, Rajiv V; Samad, Abdul; Devarajan, Padma V

    2012-06-15

    We disclose a self nanoprecipitating preconcentrate (SNP) of tamoxifen citrate (TMX), which forms TMX loaded polymeric nanoparticles, on dilution with aqueous media. SNP comprised TMX, polymer (Kollidon SR) and surfactant/s dissolved in a pharmaceutically acceptable vehicle. Binary surfactant mixtures of Aerosol OT (AOT) with Tween 80 revealed synergistic reduction in surface tension to enable both high entrapment efficiency (EE) and low particle size (PS). Synergism of the surfactants was confirmed by molecular interaction parameter(β(σ)). Combination of AOT and Tween 80 resulted in EE (∼85%) and PS (<250nm). Formation of TMX-KSR nanoparticles in situ was reproducible under most experimental conditions and exhibited pH independent behavior. Dilution volume (>80mL) influenced both PS and EE while dilution temperature influenced only PS. Marginal increase in size was evident at the end of 1h nevertheless was not of concern as TMX SNP exhibited near complete release in 1h. DSC and XRD studies revealed amorphous nature of TMX in nanoparticles. FTIR imaging confirmed uniform distribution of TMX in nanoparticles. ESEM and TEM revealed spherical nanoparticles. Biodistribution studies of (99m)Tc labeled TMX SNP in rats revealed no significant absorption however oral pharmacokinetics revealed enhanced oral bioavailability of TMX (165%) compared to TMX suspension. SNP presents a new in situ approach, for design of drug loaded polymeric nanoparticles. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Assembly of citrate gold nanoparticles on hydrophilic monolayers

    NASA Astrophysics Data System (ADS)

    Vikholm-Lundin, Inger; Rosqvist, Emil; Ihalainen, Petri; Munter, Tony; Honkimaa, Anni; Marjomäki, Varpu; Albers, Willem M.; Peltonen, Jouko

    2016-08-01

    Self-assembled monolayers (SAMs) as model surfaces were linked onto planar gold films thorough lipoic acid or disulfide groups. The molecules used were polyethylene glycol (EG-S-S), N-[tris-(hydroxymethyl)methyl]acrylamide polymers with and without lipoic acid (Lipa-pTHMMAA and pTHMMAA) and a lipoic acid triazine derivative (Lipa-MF). All the layers, but Lipa-MF with a primary amino group were hydroxyl terminated. The layers were characterized by contact angle measurements and atomic force microscopy, AFM. Citrate stabilized nanoparticles, AuNPs in water and phosphate buffer were allowed to assemble on the layers for 10 min and the binding was followed in real-time with surface plasmon resonance, SPR. The SPR resonance curves were observed to shift to higher angles and become increasingly damped, while also the peaks strongly broaden when large nanoparticles assembled on the surface. Both the angular shift and the damping of the curve was largest for nanoparticles assembling on the EG-S-S monolayer. High amounts of particles were also assembled on the pTHMMAA layer without the lipoic acid group, but the damping of the curve was considerably lower with a more even distribution of the particles. Topographical images confirmed that the highest number of particles were assembled on the polyethylene glycol monolayer. By increasing the interaction time more particles could be assembled on the surface.

  5. Clomiphene citrate treatment for late onset hypogonadism: rise and fall.

    PubMed

    Marconi, Marcelo; Souper, Renato; Hartmann, Jonathan; Alvarez, Matías; Fuentes, Ignacio; Guarda, Francisco J

    2016-01-01

    Previous series have demonstrated that Clomiphene Citrate (CC) is an effective treatment to increase Total Testosterone (TT) in Late Onset Hypogonadism (LOH) patients. However, what happens to TT levels after ending CC treatment is still debatable. The objective of this study is to evaluate TT levels 3 months after the discontinuation of CC in patients with LOH who were previously successfully treated with the same drug. Twenty-seven patients with LOH that were successfully treated (achieved TT levels >11nmol/l) with CC 50mgs daily for 50 days were prospectively recruited in our Andrological outpatient clinic. CC was then stopped for 3 months and TT levels were measured at the end of this period. Mean TT level before discontinuation of CC was 22.7±8.1nmol/L (mean±SD). Three months after discontinuation, mean TT level significantly decreased in all pa¬tients, 10.2±3.9nmol/l (p < 0.01). Twenty-one patients (78%) decreased TT levels under 11nmol/L. Six patients (22%) had TT levels that remained within the normal recommended range (≥11nmol/l). No statistical significant differences were observed between both groups. In the short term LOH does not seem to be a reversible condition in most patients after CC treatment. More studies with longer follow-up are needed to evaluate the kinetics of TT in LOH. Copyright® by the International Brazilian Journal of Urology.

  6. Clomiphene citrate treatment for late onset hypogonadism: rise and fall

    PubMed Central

    Marconi, Marcelo; Souper, Renato; Hartmann, Jonathan; Alvarez, Matías; Fuentes, Ignacio; Guarda, Francisco J.

    2016-01-01

    ABSTRACT Objective: Previous series have demonstrated that Clomiphene Citrate (CC) is an effective treatment to increase Total Testosterone (TT) in Late Onset Hypogonadism (LOH) patients. However, what happens to TT levels after ending CC treatment is still debatable. The objective of this study is to evaluate TT levels 3 months after the discontinuation of CC in patients with LOH who were previously successfully treated with the same drug. Materials and Methods: Twenty-seven patients with LOH that were successfully treated (achieved TT levels >11nmol/l) with CC 50mgs daily for 50 days were prospectively recruited in our Andrological outpatient clinic. CC was then stopped for 3 months and TT levels were measured at the end of this period. Results: Mean TT level before discontinuation of CC was 22.7±8.1nmol/L (mean±SD). Three months after discontinuation, mean TT level significantly decreased in all patients, 10.2±3.9nmol/l (p<0.01). Twenty-one patients (78%) decreased TT levels under 11nmol/L. Six patients (22%) had TT levels that remained within the normal recommended range (≥11nmol/l). No statistical significant differences were observed between both groups. Conclusion: In the short term LOH does not seem to be a reversible condition in most patients after CC treatment. More studies with longer follow-up are needed to evaluate the kinetics of TT in LOH. PMID:27622282

  7. Pseudohypernatremia secondary to trisodium citrate (Citra-LockTM)

    PubMed Central

    Milliere, Janice; Corriveau, Daryl; Parmar, Malvinder S.

    2016-01-01

    Introduction Hypernatremia is common among hospitalized patients especially in the intensive care units and presents an independent risk factor for mortality. Mild hypernatremia is often asymptomatic but severe hypernatremia causes central nervous system dysfunction with initial non-specific symptoms of encephalopathy that may progress to seizures, coma and death, if left untreated. Severe hypernatremia is a medical emergency and requires emergent medical attention. Materials and methods A haemodialysis patient who arrived for his scheduled haemodialysis treatment had monthly blood work drawn and was reported to have severe hypernatremia with serum sodium concentration of 183 mmol/L. The possibility of technique or laboratory error was considered and systematically evaluated. Results The serum sodium measurement using another analyser showed similar value of 182 mmolL. A repeat serum sodium level on a sample drawn 2 h later showed normal value of 139–140 mmol/L. A step-wise evaluation of the complete procedure from blood collection to analysis of the sample revealed this to be spuriously elevated serum sodium concentration secondary to contamination of the sample during sample collection with trisodium citrate, a catheter-lock solution, commonly used in dialysis units to maintain patency of dialysis catheters. Conclusions Spuriously elevated plasma sodium concentration (pseudohypernatremia) of mild degree is common but severe pseudohypernatremia is rare and the possibility of sample contaminations or laboratory error should be considered. Vigilance is required by both the medical and the laboratory staff to resolve such issues in a timely fashion to avoid unintended consequences. PMID:27346973

  8. Reductive defluorination of perfluorooctanoic acid by titanium(III) citrate with vitamin B12 and copper nanoparticles.

    PubMed

    Lee, Yu-Chi; Chen, Yi-Pei; Chen, Meng-Jia; Kuo, Jeff; Lo, Shang-Lien

    2017-10-15

    Perfluorooctanoic acid (PFOA) is widespread in the environment, which causes serious health and safety concerns. A mechanistic study on reductive defluorination of PFOA by titanium(III) citrate in the presence of catalysts was conducted. Vitamin B12 was used to catalyze reduction reactions by shuttling electrons from a reducing agent (electron donor) to PFOA to produce a Co-carbon bond intermediates. In the presence of copper nanoparticles, a precursor complex, B12-C7F14COOH, adsorbed on the metal surface, followed by a hydrogenolytic reaction to form less-fluorinated products. The synergistic effect between vitamin B12 and copper nanoparticles enhances the reductive activities by electron-transfer reactions and hydrogenolysis. The efficient reduction of PFOA to less-noxious compounds was demonstrated with a copper dose of 2gL(-1), titanium(III) citrate (45mM), and vitamin B12 (0.2mM) with an initial pH of 9.0 and 70°C. In this anoxic aqueous solution, the biomimetic reductive system effectively removed 65% of PFOA. The mass balance on fluoride matched the observed degradation of PFOA, while no short-chain intermediates were detected. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The influence of Citrate or PEG coating on silver nanoparticle toxicity to a human keratinocyte cell line.

    PubMed

    Bastos, V; Ferreira de Oliveira, J M P; Brown, D; Jonhston, H; Malheiro, E; Daniel-da-Silva, A L; Duarte, I F; Santos, C; Oliveira, H

    2016-05-13

    Surface coating of silver nanoparticles may influence their toxicity, in a way yet to decipher. In this study, human keratinocytes (HaCaT cells) were exposed for 24 and 48h to well-characterized 30nm AgNPs coated either with citrate (Cit30 AgNPs) or with poly(ethylene glycol) (PEG30 AgNPs), and assessed for cell viability, reactive oxygen species (ROS), cytokine release, apoptosis and cell cycle dynamics. The results showed that Cit30 AgNPs and PEG30 AgNPs decreased cell proliferation and viability, the former being more cytotoxic. The coating molecules per se were not cytotoxic. Moreover, Ag(+) release and ROS production were similar for both AgNP types. Cit30 AgNPs clearly induced apoptotic death, while cells exposed to PEG30 AgNPs appeared to be at an earlier phase of apoptosis, supported by changes in BAX, BCL2 and CASP-3 expressions. Concerning the impact on cell cycle dynamics, both Cit30 and PEG30 AgNPs affected cell cycle regulation of HaCaT cells, but, again, citrate-coating induced more drastic effects, showing earlier downregulation of cyclin B1 gene and cellular arrest at the G2 phase. Overall, this study has shown that the surface coating of AgNPs influences their toxicity by differently regulating cell-cycle and cell death mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Bowel preparation for CT colonography: blinded comparison of magnesium citrate and sodium phosphate for catharsis.

    PubMed

    Borden, Zachary S; Pickhardt, Perry J; Kim, David H; Lubner, Meghan G; Agriantonis, Demetrios J; Hinshaw, J Louis

    2010-01-01

    To compare colonic cleansing and fluid retention of double-dose magnesium citrate with those of single-dose sodium phosphate in patients undergoing computed tomographic (CT) colonography. This retrospective HIPAA-compliant clinical study had institutional review board approval; informed consent was waived. The study included 118 consecutive patients given single-dose sodium phosphate for bowel catharsis and 115 consecutive patients at risk for phosphate nephropathy, who were instead given double-dose magnesium citrate. The bowel preparation regimen was otherwise identical. Four-point scales were used to assess residual stool and fluid in the six colonic segments, and attenuation of residual fluid was measured. An a priori power analysis was performed, and unpaired t tests with Welch correction were used to compare the two groups on stool and fluid scores and fluid attenuation. Both cathartic regimens offered excellent colon cleansing, with no significant difference for residual stool in any of the six segments. Stool scores of 1 or 2 (ie, no residual stool or residual stool <5 mm) were recorded in 88.6% (627 of 708) of colonic segments in the sodium phosphate group and in 88.1% (608 of 690) in the magnesium citrate group. No clinically important differences were seen in residual fluid scores in any of the six segments, with the only significant difference seen in the sigmoid colon (2.17 for sodium phosphate vs 2.44 for magnesium citrate; P< 0.01). Fluid attenuation was significantly different between magnesium citrate and sodium phosphate groups (790 HU +/- 216 vs 978 HU +/- 160; P <.001). Both sodium phosphate and magnesium citrate provided excellent colon cleansing for CT colonography. Residual stool and fluid were similar in both groups, and fluid attenuation values were closer to optimal in the magnesium citrate group. Since bowel preparation provided by both cathartics was comparable, magnesium citrate should be considered for CT colonography, particularly in

  11. Synergistic iron reduction and citrate dissimilation by Shewanella alga and Aeromonas veronii

    PubMed

    Knight; Caccavo; Wudyka; Blakemore

    1996-10-17

    Two bacterial isolates from Great Bay Estuary, New Hampshire, in co-culture carried out anaerobic dissimilation of citric acid with Fe(III) as the terminal electron acceptor. Neither isolate oxidized citrate with Fe(III) anaerobically in axenic culture. The Fe(III) reducer, Shewanella alga strain BrY, did not grow anaerobically with citrate as an energy source. The citrate utilizer, Aeromonas veronii, did not reduce iron axenically with a variety of electron donors including citrate. The onset of iron reduction by the co-culture occurred after initiation of citrate dissimilation and just prior to initiation of growth by either organism (as measured by viable plate counts). Anaerobic culture growth rates and final cell densities of each bacterial strain were greater in co-culture than in axenic cultures. By 48 h of growth, the co-culture had consumed 27 mM citrate as compared with 12 mM dissimilated by the axenic culture of A. veronii. By 48 h the co-culture produced half as much formate (6 mM) and twice as much acetate (40 mM) as did A. veronii grown axenically (12 mM and 20 mM, respectively). Formate produced from citrate by A. veronii appeared to have supported growth and Fe(III) reduction by S. alga.Although not obligatory, nutrient coupling between these two organisms illustrates that fermentative (A. veronii-type) organisms can convert organic compounds such as citrate to those used as substrates by dissimilatory Fe(III) reducers, including S. alga. This synergism broadens the range of substrates available for iron reduction, stimulates the extent and rate of organic electron donor degradation (and that of iron reduction) and enhances the growth of each participant.

  12. [THE MODERN PROSPECT FOR CITRATE MIXTURES IN THE TREATMENT OF UROLITHIASIS].

    PubMed

    Chepurov, A K; Pronkin, E A; Bolotov, A D

    2015-01-01

    The authors present a review of literature on the use of litholytic citrate medications for conservative management of urolithiasis. Urate urolithiasis is the most common clinical condition encountered by urologists. Citrate agents, in particular Blemaren, not only may be employed in a conservative therapy of uric acid stones, but can also be successfully used in the treatment of the calcium urolithiasis, i.e. mixed composition stones, which is supported by current international urology guidelines.

  13. The role of citrate and phthalate during Co(II) coprecipitation with calcite

    NASA Astrophysics Data System (ADS)

    Lee, Young J.; Reeder, Richard J.

    2006-05-01

    The influence of citrate and phthalate on Co coprecipitation with calcite was investigated using a combination of batch experiments, Fourier-transform infra-red (FT-IR) spectroscopy, and thermogravimetric analysis (TGA) over a wide range of precipitation rates. Steady-state growth conditions (at constant [Ca], [Co], DIC, and pH) were generally achieved within 3-5 h, after which Co(II) partitioning into calcite was evaluated. Only minor differences are observed in the partition coefficient ( Kd) trends with and without citrate and phthalate as a function of calcite precipitation rate except at very low rates. Slight inhibition of calcite growth is observed in the presence of citrate or phthalate, which can be attributed to adsorption at surface sites. TGA curves for samples coprecipitated with citrate show a significant mass loss between 375 and 550 °C, whereas the weight-loss curves for the Co-phthalate coprecipitates are indistinguishable from those of the organic-free Co coprecipitates. This indicates that citrate is incorporated into calcite during calcite crystallization, whereas phthalate is excluded. FT-IR spectra for the sample with citrate show a broad absorption in the range 3700-3100 cm -1, which is attributable to water molecules coordinated to citrate coprecipitated with calcite. The preferential incorporation of citrate over phthalate likely reflects differences in both aqueous speciation and conformation of the carboxylate groups. This new finding may provide new insight to the factors that control the behavior of macromolecules and their incorporation into the structure of calcium carbonate during biomineralization.

  14. Anaerobic regulation of citrate fermentation by CitAB in Escherichia coli.

    PubMed

    Yamamoto, Kaneyoshi; Matsumoto, Fumika; Oshima, Taku; Fujita, Nobuyuki; Ogasawara, Naotake; Ishihama, Akira

    2008-11-01

    In Escherichia coli, CitB, a cognate response regulator of CitA, specifically bound to the promoter regions for mdh, citA, citC, and exuT. Transcription of these genes was induced by citrate under anaerobic conditions in a CitAB-dependent manner. Taking this together, we conclude that CitAB is the master regulatory system that activates the set of genes involved in citrate fermentation in E. coli.

  15. The synergic role of collagen and citrate in stabilizing amorphous calcium phosphate precursors with platy morphology.

    PubMed

    Delgado-López, José Manuel; Bertolotti, Federica; Lyngsø, Jeppe; Pedersen, Jan Skov; Cervellino, Antonio; Masciocchi, Norberto; Guagliardi, Antonietta

    2017-02-01

    Bioinspired in vitro collagen mineralization experiments have been performed in the presence of citrate and the combined role of the two bone organic matrix components in controlling mineral formation was investigated for the first time. Mineralized and non-mineralized collagen fibrils have been in depth characterized by combining small- and wide-angle X-ray scattering (SAXS/WAXS) techniques with Atomic Force Microscopy (AFM) imaging. A synergic effect of collagen and citrate in driving the formation of long-term stable amorphous calcium phosphate (ACP) nanoparticles with platy morphology was found. AFM images on mineralized collagen fibrils revealed that some of the ACP nanoparticles were deposited on the intramolecular nanoscopic holes of collagen fibrils. Citrate is an important component of the bone organic matrix but its specific role in bone mineralization is presently unclear. In this work, bioinspired in vitro collagen mineralization experiments in the presence of citrate have been carried out and the combined role of collagen and citrate in controlling mineral formation has been addressed for the first time. Through X-ray scattering and Atomic Force Microscopy characterizations on mineralized and non-mineralized collagen fibrils, we have found that citrate in synergy with collagen stabilizes an amorphous calcium phosphate (ACP) phase with platy morphology over one week and controls its deposition on collagen fibrils. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Assessment of Multiplate® platelet aggregometry using Citrate, Heparin or Hirudin in Rhesus macaques

    PubMed Central

    Dugan, Greg; O’Donnell, Lisa; Hanbury, David B.; Cline, J. Mark; Caudell, David L.

    2016-01-01

    Electrical impedance aggregometry (EIA) has gained popularity for clinical and research applications. Nonhuman primates are used to study disease and drug-related mechanisms that affect hemostasis, therefore normal establishing normal EIA parameters are necessary. The anticoagulants sodium heparin, hirudin and sodium citrate and three agonists, ADP, ASPI, and collagen were evaluated. Whole blood from 12 adult male rhesus macaques was collected to evaluate anticoagulants, sodium heparin, hirudin and sodium citrate using three agonists (ADP, ASPI and collagen), on the Multiplate® 5.0 Analyzer. Platelet function was reported for three parameters: Area under the curve (AUC), aggregation, and aggregation velocity. There was a significant difference in mean AUC between citrate and heparin samples, and citrate and hirudin samples regardless of the agonist used. There was no difference in AUC between heparin and hirudin. ADP-activated samples showed an increase in impedance with hirudin samples compared to citrate. Furthermore heparin and hirudin out-perform citrate as the anticoagulant for EIA in the macaque. Finally, this study demonstrates the utility of the Multiplate® system in this model and provides important insight into anticoagulant choice when using EIA. PMID:25549285

  17. Effects of the Oral Administration of Mosapride Citrate on Capsule Endoscopy Completion Rate

    PubMed Central

    Ida, Yosuke; Hosoe, Naoki; Imaeda, Hiroyuki; Bessho, Rieko; Ichikawa, Riko; Naganuma, Makoto; Kanai, Takanori; Hibi, Toshifumi

    2012-01-01

    Background/Aims In capsule endoscopy (CE), the capsule does not always reach the cecum within its battery life, which may reduce its diagnostic yield. We evaluated the effect of mosapride citrate, a 5-hydroxytryptamine-4 agonist that increases gastrointestinal motility, on CE completion. Methods In a retrospective study, we performed univariate and multivariate analyses for 232 CE procedures performed at our hospital. To identify factors that affect CE completion, the following data were systematically collected: gender, age, gastric transit time (GTT), nonsteroidal anti-inflammatory drug administration, previous abdominal surgery, hospitalization, use of a polyethylene glycol solution, use of mosapride citrate (10 mg), body mass index (BMI), and total recording time. Results The univariate analysis showed that oral mosapride citrate, GTT, and BMI were associated with improved CE completion. Multivariate analyses showed that oral mosapride citrate (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.01 to 3.91) and GTT (OR, 2.34; 95% CI, 1.13 to 4.87) were significant factors for improving the CE completion. Oral mosapride citrate significantly shortened the GTT and small bowel transit time (SBTT). Conclusions Oral mosapride citrate reduced the GTT and SBTT during CE and improved the CE completion rate. PMID:22844562

  18. Overexpression of Citrus junos mitochondrial citrate synthase gene in Nicotiana benthamiana confers aluminum tolerance.

    PubMed

    Deng, Wei; Luo, Keming; Li, Zhengguo; Yang, Yingwu; Hu, Nan; Wu, Yu

    2009-07-01

    Aluminum (Al) toxicity is one of the major factors that limit plant growth in acid soils. Al-induced release of organic acids into rhizosphere from the root apex has been identified as a major Al-tolerance mechanism in many plant species. In this study, Al tolerance of Yuzu (Citrus Junos Sieb. ex Tanaka) was tested on the basis of root elongation and the results demonstrated that Yuzu was Al tolerant compared with other plant species. Exposure to Al triggered the exudation of citrate from the Yuzu root. Thus, the mechanism of Al tolerance in Yuzu involved an Al-inducible increase in citrate release. Aluminum also elicited an increase of citrate content and increased the expression level of mitochondrial citrate synthase (CjCS) gene and enzyme activity in Yuzu. The CjCS gene was cloned from Yuzu and overexpressed in Nicotiana benthamiana using Agrobacterium tumefaciens-mediated methods. Increased expression level of the CjCS gene and enhanced enzyme activity were observed in transgenic plants compared with the wild-type plants. Root growth experiments showed that transgenic plants have enhanced levels of Al tolerance. The transgenic Nicotiana plants showed increased levels of citrate in roots compared to wild-type plants. The exudation of citrate from roots of the transgenic plants significantly increased when exposed to Al. The results with transgenic plants suggest that overexpression of mitochondrial CS can be a useful tool to achieve Al tolerance.

  19. Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS.

    PubMed

    Westergaard, Niels; Waagepetersen, Helle S; Belhage, Bo; Schousboe, Arne

    2017-01-05

    Citrate is key constituent of the tricarboxylic acid (TCA) cycle, serves as substrate for fatty acid and sterol biosynthesis, and functions as a key regulator of intermediary energy metabolism. Ursula Sonnewald had initiated studies using for the first time both proton- and (13)C-NMR to investigate metabolic processes in cultured neurons and astrocytes resulting in the important observation that citrate was specifically synthesized in and released from astrocytes in large amounts which is in keeping with the high concentration found in the CSF. The aim of this review is to highlight the possible roles of citrate in physiological and pathophysiological processes in the CNS. An interesting feature of citrate is its ability to chelate Ca(2+), Mg(2+) and Zn(2+)and thereby playing a pivotal role as an endogenous modulator of glutamate receptors and in particular the NMDA subtypes of these receptors in the CNS. Besides its presence in cerebrospinal fluid (CSF) citrate is also found in high amounts in prostate fluid reaching concentrations as high as 180 mM and here Zn(2+) seems also to play an important role, which makes prostate cells interesting for comparison of features of citrate and Zn(2+) between these cells and cells in the CNS.

  20. Citrate and celecoxib induce apoptosis and decrease necrosis in synergistic manner in canine mammary tumor cells.

    PubMed

    Vahidi, R; Safi, S; Farsinejad, A; Panahi, N

    2015-10-16

    Celecoxib and citrate have been shown to possess antitumor activity in a variety of cancer cells. However, the antitumor activities of these agents in canine mammary tumors have not been well demonstrated. The aim of our study was to investigate the apoptotic and antiproliferative effects of citrate and celecoxib, individually and in combination, on canine mammary tumor cell line CF41—Mg. MTT assay was performed to determine cell viability, and Annexin—PI test was performed to evaluate apoptosis induction. MTT assay results revealed that compared with the control groups, treatment groups, as both single and combined treatments, showed significant inhibition of tumor growth in a dose—dependent manner. IC50 concentrations of citrate and celecoxib were defined 26mM and 22μM, respectively. In another set of experiment, significant increase in cell apoptosis was observed at IC50 concentrations of citrate and celecoxib after 48h incubation. In spite of that, simultaneous treatment of cells with citrate and celecoxib eventuated with meaningful toxicity augmentation and induction of apoptosis at lower concentrations. Also necrotic cells were decreased by coadministration of the two agents. In conclusion, the present study indicates significant cytotoxic and apoptotic effects of citrate and celecoxib coadministration on CF41—Mg cells, and proposes new strategies for counteracting cancer cells proliferation and overcoming chemo resistance.

  1. OsFRDL1 is a citrate transporter required for efficient translocation of iron in rice.

    PubMed

    Yokosho, Kengo; Yamaji, Naoki; Ueno, Daisei; Mitani, Namiki; Ma, Jian Feng

    2009-01-01

    Multidrug and toxic compound extrusion (MATE) transporters represent a large family in plants, but their functions are poorly understood. Here, we report the function of a rice (Oryza sativa) MATE gene (Os03g0216700, OsFRDL1), the closest homolog of barley (Hordeum vulgare) HvAACT1 (aluminum [Al]-activated citrate transporter 1), in terms of metal stress (iron [Fe] deficiency and Al toxicity). This gene was mainly expressed in the roots and the expression level was not affected by either Fe deficiency or Al toxicity. Knockout of this gene resulted in leaf chlorosis, lower leaf Fe concentration, higher accumulation of zinc and manganese concentration in the leaves, and precipitation of Fe in the root's stele. The concentration of citrate and ferric iron in the xylem sap was lower in the knockout line compared to the wild-type rice. Heterologous expression of OsFRDL1 in Xenopus oocytes showed transport activity for citrate. Immunostaining showed that OsFRDL1 was localized at the pericycle cells of the roots. On the other hand, there was no difference in the Al-induced secretion of citrate from the roots between the knockout line and the wild-type rice. Taken together, our results indicate that OsFRDL1 is a citrate transporter localized at the pericycle cells, which is necessary for efficient translocation of Fe to the shoot as a Fe-citrate complex.

  2. Transport of citrate across renal brush border membrane: effects of dietary acid and alkali loading

    SciTech Connect

    Jenkins, A.D.; Dousa, T.P.; Smith, L.H.

    1985-10-01

    Dietary acid or alkali loading was given to rats by providing 150 mM NH4Cl or 150 mM NaHCO3 in place of drinking water for 6 days; control animals received 150 mM NaCl. After 6 days, the citrate clearance was 0.04 +/- 0.01 ml/min (mean +/- SE) in the acid-loaded group, 0.9 +/- 0.1 ml/min in the control group, and 2.5 +/- 0.2 ml/min in the alkali-loaded group. At the end of the experiment, the rats were killed, and the Na gradient-dependent citrate uptake was measured in brush border membrane (BBM) vesicles prepared from each group. At 0.3 min, the ( UC)citrate uptake was 198 +/- 8 pmol/mg protein (mean +/- SE) in the acid-loaded group, 94 +/- 16 pmol/mg protein in the control group, and 94 +/- 13 pmol/mg protein in the alkali-loaded group. The rate of Na -independent (NaCl in medium replaced by KCl) ( UC)-citrate uptake by BBM vesicles was the same for acid-loaded, control, and alkali-loaded animals. Thus, the increased capacity of the proximal tubular BBM to transport citrate from the tubular lumen into the cell interior may be an important factor that contributes to decreased urinary citrate in the presence of metabolic acidosis induced by chronic dietary acid loading.

  3. Clinical review: Anticoagulation for continuous renal replacement therapy - heparin or citrate?

    PubMed Central

    2011-01-01

    Heparin is the most commonly prescribed anticoagulant for continuous renal replacement therapy. There is, however, increasing evidence questioning its safety, particularly in the critically ill. Heparin mainly confers its anticoagulant effect by binding to antithrombin. Heparin binds to numerous other proteins and cells as well, however, compromising its efficacy and safety. Owing to antithrombin consumption and degradation, and to the binding of heparin to acute phase proteins, and to apoptotic and necrotic cells, critical illness confers heparin resistance. The nonspecific binding of heparin further leads to an unpredictable interference with inflammation pathways, microcirculation and phagocytotic clearance of dead cells, with possible deleterious consequences for patients with sepsis and systemic inflammation. Regional anticoagulation with citrate does not increase the patient's risk of bleeding. The benefits of citrate further include a longer or similar circuit life, and possibly better patient and kidney survival. This needs to be confirmed in larger randomized controlled multicenter trials. The use of citrate might be associated with less inflammation and has useful bio-energetic implications. Citrate can, however, with inadequate use cause metabolic derangements. Full advantages of citrate can only be realized if its risks are well controlled. These observations suggest a greater role for citrate. PMID:21345279

  4. Kinetic analysis of the hydrolysis of methyl parathion using citrate-stabilized 10 nm gold nanoparticles.

    PubMed

    Nita, Rafaela; Trammell, Scott A; Ellis, Gregory A; Moore, Martin H; Soto, Carissa M; Leary, Dagmar H; Fontana, Jake; Talebzadeh, Somayeh F; Knight, D Andrew

    2016-02-01

    "Ligand-free" citrate-stabilized 10 nm gold nanoparticles (AuNPs) promote the hydrolysis of the thiophosphate ester methyl parathion (MeP) on the surface of gold as a function of pH and two temperature values. At 50 °C, the active surface gold atoms show catalytic turnover ∼4 times after 8 h and little turnover of gold surface atoms at 25 °C with only 40% of the total atoms being active. From Michaelis-Menten analysis, k(cat) increases between pH 8 and 9 and decreases above pH 9. A global analysis of the spectral changes confirmed the stoichiometric reaction at 25 °C and the catalytic reaction at 50 °C and mass spectrometry confirmed the identity of p-nitrophenolate (PNP) product. Additional decomposition pathways involving oxidation and hydrolysis independent of the formation of PNP were also seen at 50 °C for both catalyzed and un-catalyzed reactions. This work represents the first kinetic analysis of ligand-free AuNP catalyzed hydrolysis of a thiophosphate ester.

  5. Physicochemical and Microbiological Stability of the Extemporaneous Sildenafil Citrate Oral Suspension

    PubMed Central

    Sae Yoon, Attawadee; Sawatdee, Somchai; Woradechakul, Chuthamas; Sae Chee, Kridsada; Atipairin, Apichart

    2015-01-01

    Sildenafil is a potent and selective phosphodiesterase-5 inhibitor that is effectively used in the treatment of pulmonary arterial hypertension. In several countries, hospital pharmacists prepare the drug in an extemporaneous liquid preparation as there are no liquid formulations available for pediatric and adult uses. The purpose of this study was to evaluate the stability of an extemporaneous sildenafil citrate oral suspension for 90 days, according to the ASEAN guideline on stability studies of drug products. The results showed that the preparation was a white suspension with a sweet taste. It was a viscous and weakly acidic mixture with pseudoplastic behavior. The drug content was in the range between 99.23% and 102.23%, and the microbial examination met the general requirements throughout the study period. Therefore, the extemporaneously compounded sildenafil suspensions were physically, chemically, and microbiologically stable for at least 90 days when stored at 30° and 40°C. Furthermore, the in-use stability study showed that the preparations had acceptable attributes at least 14 days after the first-time use. This might provide an alternative option when the commercial suspension is unavailable. PMID:26839846

  6. Colorimetric determination of sildenafil citrate (Viagra) through ion-associate complex formation.

    PubMed

    Amin, Alaa S; Moustafa, Moustafa E; El-Dosoky, Reham

    2009-01-01

    A simple, quick, accurate, and sensitive colorimetric method is described for the determination of sildenafil citrate (SLD). The method is based on the reaction of SLD with Congo Red, Sudan II, and Gentian Violet in buffered aqueous solutions at pH 2.5, 6.5, and 11.0, respectively, to give highly colored soluble ion-associate complex species; the colored products are quantitated colorimetrically at 523, 554, and 569 nm, respectively. The various experimental conditions were optimized. The stoichiometric ratio was found to be 1:1 for all ion associates; the calculated logarithmic stability constants were 8.51, 7.79, and 5.58, respectively. Beer's law was obeyed over the concentration range of 0.2-7.0 microg/mL, whereas the Ringbom optimum concentration range was 0.4-6.5 microg/mL. Values for molar absorptivity, Sandell sensitivity, and detection and quantification limits were also calculated. The proposed method was successfully applied to the determination of SLD in Viagra tablets and in serum samples by using the technique of standard additions with mean accuracy values of 100.06 +/- 1.14, 99.87 +/- 0.70, and 99.86 +/- 0.97% for Viagra tablets and 99.88 +/- 0.60, 99.90 +/- 0.90, and 100.24 +/- 0.80% for serum samples, respectively.

  7. Physicochemical and Microbiological Stability of the Extemporaneous Sildenafil Citrate Oral Suspension.

    PubMed

    Sae Yoon, Attawadee; Sawatdee, Somchai; Woradechakul, Chuthamas; Sae Chee, Kridsada; Atipairin, Apichart

    2015-01-01

    Sildenafil is a potent and selective phosphodiesterase-5 inhibitor that is effectively used in the treatment of pulmonary arterial hypertension. In several countries, hospital pharmacists prepare the drug in an extemporaneous liquid preparation as there are no liquid formulations available for pediatric and adult uses. The purpose of this study was to evaluate the stability of an extemporaneous sildenafil citrate oral suspension for 90 days, according to the ASEAN guideline on stability studies of drug products. The results showed that the preparation was a white suspension with a sweet taste. It was a viscous and weakly acidic mixture with pseudoplastic behavior. The drug content was in the range between 99.23% and 102.23%, and the microbial examination met the general requirements throughout the study period. Therefore, the extemporaneously compounded sildenafil suspensions were physically, chemically, and microbiologically stable for at least 90 days when stored at 30° and 40°C. Furthermore, the in-use stability study showed that the preparations had acceptable attributes at least 14 days after the first-time use. This might provide an alternative option when the commercial suspension is unavailable.

  8. Sensitive and selective SERS probe for trivalent chromium detection using citrate attached gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Ye, Yingjie; Liu, Honglin; Yang, Liangbao; Liu, Jinhuai

    2012-09-01

    In this article, we have demonstrated a sensitive and selective surface enhanced Raman spectroscopy (SERS) probe, based on citrate-capped gold nanoparticles (AuNPs), for trivalent chromium (Cr3+) detection. After introducing Tween 20 to a solution of citrate-capped AuNPs, the as-prepared Tween 20/citrate-AuNP probe could recognize Cr3+ at a 50 × 10-9 M level in an aqueous medium at a pH of 6.0. Tween 20 can stabilize the citrate-capped AuNPs against conditions of high ionic strength. Due to the chelation between Cr3+ and citrate ions, AuNPs undergo aggregation. As a result, it formed several hot spots and provided a significant enhancement of the Raman signal intensity through electromagnetic (EM) field enhancements. A detailed mechanism for tremendous SERS intensity change had been discussed. The selectivity of this system toward Cr3+ was 400-fold, remarkably greater than other metal ions.In this article, we have demonstrated a sensitive and selective surface enhanced Raman spectroscopy (SERS) probe, based on citrate-capped gold nanoparticles (AuNPs), for trivalent chromium (Cr3+) detection. After introducing Tween 20 to a solution of citrate-capped AuNPs, the as-prepared Tween 20/citrate-AuNP probe could recognize Cr3+ at a 50 × 10-9 M level in an aqueous medium at a pH of 6.0. Tween 20 can stabilize the citrate-capped AuNPs against conditions of high ionic strength. Due to the chelation between Cr3+ and citrate ions, AuNPs undergo aggregation. As a result, it formed several hot spots and provided a significant enhancement of the Raman signal intensity through electromagnetic (EM) field enhancements. A detailed mechanism for tremendous SERS intensity change had been discussed. The selectivity of this system toward Cr3+ was 400-fold, remarkably greater than other metal ions. Electronic supplementary information (ESI) available: Fig. S1-S5. See DOI: 10.1039/c2nr31985c

  9. Potassium citrate decreases urine calcium excretion in patients with hypocitraturic calcium oxalate nephrolithiasis.

    PubMed

    Song, Yan; Hernandez, Natalia; Shoag, Jonathan; Goldfarb, David S; Eisner, Brian H

    2016-04-01

    Two previous studies (<10 patients each) have demonstrated that alkali therapy may reduce urine calcium excretion in patients with calcium oxalate nephrolithiasis. The hypothesized mechanisms are (1) a decrease in bone turnover due to systemic alkalinization by the medications; (2) binding of calcium by citrate in the gastrointestinal tract; (3) direct effects on TRPV5 activity in the distal tubule. We performed a retrospective review of patients on potassium citrate therapy to evaluate the effects of this medication on urinary calcium excretion. A retrospective review was performed of a metabolic stone database at a tertiary care academic hospital. Patients were identified with a history of calcium oxalate nephrolithiasis and hypocitraturia who were on potassium citrate therapy for a minimum of 3 months. 24-h urine composition was assessed prior to the initiation of potassium citrate therapy and after 3 months of therapy. Patients received 30-60 mEq potassium citrate by mouth daily. Inclusion criterion was a change in urine potassium of 20 mEq/day or greater, which suggests compliance with potassium citrate therapy. Paired t test was used to compare therapeutic effect. Twenty-two patients were evaluated. Mean age was 58.8 years (SD 14.0), mean BMI was 29.6 kg/m(2) (SD 5.9), and gender prevalence was 36.4% female:63.6% male. Mean pre-treatment 24-h urine values were as follows: citrate 280.0 mg/day, potassium 58.7 mEq/day, calcium 216.0 mg/day, pH 5.87. Potassium citrate therapy was associated with statistically significant changes in each of these parameters-citrate increased to 548.4 mg/day (p < 0.0001), potassium increased to 94.1 mEq/day (p < 0.0001), calcium decreased to 156.5 mg/day (p = 0.04), pH increased to 6.47 (p = 0.001). Urine sodium excretion was not different pre- and post-therapy (175 mEq/day pre-therapy versus 201 mEq/day post-therapy, p = NS). Urinary calcium excretion decreased by a mean of 60 mg/day on potassium citrate therapy-a nearly 30

  10. Anticaries effect of dentifrices with calcium citrate and sodium trimetaphosphate

    PubMed Central

    DELBEM, Alberto Carlos Botazzo; BERGAMASCHI, Maurício; RODRIGUES, Eliana; SASSAKI, Kikue Takebayashi; VIEIRA, Ana Elisa de Mello; MISSEL, Emilene Macario Coimbra

    2012-01-01

    Because of the growing concerns regarding fluoride ingestion by young children and dental fluorosis, it is necessary to develop new dentifrices. Objective The aim of this study was to evaluate the effect of dentifrices with calcium citrate (Cacit) and sodium trimetaphosphate (TMP) on enamel demineralization. Material and Methods Enamel blocks (n=70), previously selected through surface hardness analysis, were submitted to daily treatment with dentifrices diluted in artificial saliva and to a pH-cycling model. The fluoride concentration in dentifrices was 0, 250, 450, 550, 1,000 and 1,100 µg F/g. CrestTM was used as a positive control (1,100 mg F/g). Cacit (0.25%) and TMP (0.25%) were added to dentifrices with 450 and 1,000 µg F/g. Surface hardness was measured again and integrated loss of subsurface hardness and fluoride concentration in enamel were calculated. Parametric and correlation tests were used to determine difference (p<0.05) and dose-response relationship between treatments. Results The addition of Cacit and TMP did not provide a higher fluoride concentration in enamel, however it reduced (p<0.05) mineral loss when compared to other dentifrices; the dentifrice with Cacit and TMP and a low fluoride concentration presented similar results when compared to a dentifrice with 1,100 mg F/g (p>0.05). Conclusions Dentifrices with 450 and 1,000 µg F/g, Cacit and TMP were as effective as a gold standard one. PMID:22437685

  11. Transport of citrate-coated silver nanoparticles in unsaturated sand.

    PubMed

    Kumahor, Samuel K; Hron, Pavel; Metreveli, George; Schaumann, Gabriele E; Vogel, Hans-Jörg

    2015-12-01

    Chemical factors and physical constraints lead to coupled effects during particle transport in unsaturated porous media. Studies on unsaturated transport as typical for soils are currently scarce. In unsaturated porous media, particle mobility is determined by the existence of an air-water interface in addition to a solid-water interface. To this end, we measured breakthrough curves and retention profiles of citrate-coated Ag nanoparticles in unsaturated sand at two pH values (5 and 9) and three different flow rates corresponding to different water contents with 1 mM KNO3 as background electrolyte. The classical DLVO theory suggests unfavorable deposition conditions at the air-water and solid-water interfaces. The breakthrough curves indicate modification in curve shapes and retardation of nanoparticles compared to inert solute. Retention profiles show sensitivity to flow rate and pH and this ranged from almost no retention for the highest flow rate at pH=9 to almost complete retention for the lowest flow rate at pH=5. Modeling of the breakthrough curves, thus, required coupling two parallel processes: a kinetically controlled attachment process far from equilibrium, responsible for the shape modification, and an equilibrium sorption, responsible for particle retardation. The non-equilibrium process and equilibrium sorption are suggested to relate to the solid-water and air-water interfaces, respectively. This is supported by the DLVO model extended for hydrophobic interactions which suggests reversible attachment, characterized by a secondary minimum (depth 3-5 kT) and a repulsive barrier at the air-water interface. In contrast, the solid-water interface is characterized by a significant repulsive barrier and the absence of a secondary minimum suggesting kinetically controlled and non-equilibrium interaction. This study provides new insights into particle transport in unsaturated porous media and offers a model concept representing the relevant processes.

  12. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia.

    PubMed

    Hardies, Katia; de Kovel, Carolien G F; Weckhuysen, Sarah; Asselbergh, Bob; Geuens, Thomas; Deconinck, Tine; Azmi, Abdelkrim; May, Patrick; Brilstra, Eva; Becker, Felicitas; Barisic, Nina; Craiu, Dana; Braun, Kees P J; Lal, Dennis; Thiele, Holger; Schubert, Julian; Weber, Yvonne; van 't Slot, Ruben; Nürnberg, Peter; Balling, Rudi; Timmerman, Vincent; Lerche, Holger; Maudsley, Stuart; Helbig, Ingo; Suls, Arvid; Koeleman, Bobby P C; De Jonghe, Peter

    2015-11-01

    The epileptic encephalopathies are a clinically and aetiologically heterogeneous subgroup of epilepsy syndromes. Most epileptic encephalopathies have a genetic cause and patients are often found to carry a heterozygous de novo mutation in one of the genes associated with the disease entity. Occasionally recessive mutations are identified: a recent publication described a distinct neonatal epileptic encephalopathy (MIM 615905) caused by autosomal recessive mutations in the SLC13A5 gene. Here, we report eight additional patients belonging to four different families with autosomal recessive mutations in SLC13A5. SLC13A5 encodes a high affinity sodium-dependent citrate transporter, which is expressed in the brain. Neurons are considered incapable of de novo synthesis of tricarboxylic acid cycle intermediates; therefore they rely on the uptake of intermediates, such as citrate, to maintain their energy status and neurotransmitter production. The effect of all seven identified mutations (two premature stops and five amino acid substitutions) was studied in vitro, using immunocytochemistry, selective western blot and mass spectrometry. We hereby demonstrate that cells expressing mutant sodium-dependent citrate transporter have a complete loss of citrate uptake due to various cellular loss-of-function mechanisms. In addition, we provide independent proof of the involvement of autosomal recessive SLC13A5 mutations in the development of neonatal epileptic encephalopathies, and highlight teeth hypoplasia as a possible indicator for SLC13A5 screening. All three patients who tried the ketogenic diet responded well to this treatment, and future studies will allow us to ascertain whether this is a recurrent feature in this severe disorder.

  13. Potential for quantifying expression of the Geobacteraceae citrate synthase gene to assess the activity of Geobacteraceae in the subsurface and on current-harvesting electrodes

    USGS Publications Warehouse

    Holmes, Dawn E.; Nevin, Kelly P.; O'Neil, Regina A.; Ward, Joy E.; Adams, Lorrie A.; Woodard, Trevor L.; Vrionis, Helen A.; Lovely, Derek R.

    2005-01-01

    The Geobacteraceae citrate synthase is phylogenetically distinct from those of other prokaryotes and is a key enzyme in the central metabolism of Geobacteraceae. Therefore, the potential for using levels of citrate synthase mRNA to estimate rates of Geobacter metabolism was evaluated in pure culture studies and in four different Geobacteraceae-dominated environments. Quantitative reverse transcription-PCR studies with mRNA extracted from cultures of Geobacter sulfurreducens grown in chemostats with Fe(III) as the electron acceptor or in batch with electrodes as the electron acceptor indicated that transcript levels of the citrate synthase gene, gltA, increased with increased rates of growth/Fe(III) reduction or current production, whereas the expression of the constitutively expressed housekeeping genes recA, rpoD, and proC remained relatively constant. Analysis of mRNA extracted from groundwater collected from a U(VI)-contaminated site undergoing in situ uranium bioremediation revealed a remarkable correspondence between acetate levels in the groundwater and levels of transcripts of gltA. The expression of gltA was also significantly greater in RNA extracted from groundwater beneath a highway runoff recharge pool that was exposed to calcium magnesium acetate in June, when acetate concentrations were high, than in October, when the levels had significantly decreased. It was also possible to detect gltA transcripts on current-harvesting anodes deployed in freshwater sediments. These results suggest that it is possible to monitor the in situ metabolic rate of Geobacteraceae by tracking the expression of the citrate synthase gene.

  14. Quantitative metabolic flux analysis reveals an unconventional pathway of fatty acid synthesis in cancer cells deficient for the mitochondrial citrate transport protein.

    PubMed

    Jiang, Lei; Boufersaoui, Adam; Yang, Chendong; Ko, Bookyung; Rakheja, Dinesh; Guevara, Gerardo; Hu, Zeping; DeBerardinis, Ralph J

    2017-09-01

    The mitochondrial citrate transport protein (CTP), encoded by SLC25A1, accommodates bidirectional trafficking of citrate between the mitochondria and cytosol, supporting lipid biosynthesis and redox homeostasis. Genetic CTP deficiency causes a fatal neurodevelopmental syndrome associated with the accumulation of L- and D-2-hydroxyglutaric acid, and elevated CTP expression is associated with poor prognosis in several types of cancer, emphasizing the importance of this transporter in multiple human pathologies. Here we describe the metabolic consequences of CTP deficiency in cancer cells. As expected from the phenotype of CTP-deficient humans, somatic CTP loss in cancer cells induces broad dysregulation of mitochondrial metabolism, resulting in accumulation of lactate and of the L- and D- enantiomers of 2-hydroxyglutarate (2HG) and depletion of TCA cycle intermediates. It also eliminates mitochondrial import of citrate from the cytosol. To quantify the impact of CTP deficiency on metabolic flux, cells were cultured with a set of (13)C-glucose and (13)C-glutamine tracers with resulting data integrated by metabolic flux analysis (MFA). CTP-deficient cells displayed a major restructuring of central carbon metabolism, including suppression of pyruvate dehydrogenase (PDH) and induction of glucose-dependent anaplerosis through pyruvate carboxylase (PC). We also observed an unusual lipogenic pathway in which carbon from glucose supplies mitochondrial production of alpha-ketoglutarate (AKG), which is then trafficked to the cytosol and used to supply reductive carboxylation by isocitrate dehydrogenase 1 (IDH1). The resulting citrate is cleaved to produce lipogenic acetyl-CoA, thereby completing a novel pathway of glucose-dependent reductive carboxylation. In CTP deficient cells, IDH1 inhibition suppresses lipogenesis from either glucose or glutamine, implicating IDH1 as a required component of fatty acid synthesis in states of CTP deficiency. Copyright © 2016 International

  15. Potential for Quantifying Expression of the Geobacteraceae Citrate Synthase Gene To Assess the Activity of Geobacteraceae in the Subsurface and on Current-Harvesting Electrodes

    PubMed Central

    Holmes, Dawn E.; Nevin, Kelly P.; O'Neil, Regina A.; Ward, Joy E.; Adams, Lorrie A.; Woodard, Trevor L.; Vrionis, Helen A.; Lovley, Derek R.

    2005-01-01

    The Geobacteraceae citrate synthase is phylogenetically distinct from those of other prokaryotes and is a key enzyme in the central metabolism of Geobacteraceae. Therefore, the potential for using levels of citrate synthase mRNA to estimate rates of Geobacter metabolism was evaluated in pure culture studies and in four different Geobacteraceae-dominated environments. Quantitative reverse transcription-PCR studies with mRNA extracted from cultures of Geobacter sulfurreducens grown in chemostats with Fe(III) as the electron acceptor or in batch with electrodes as the electron acceptor indicated that transcript levels of the citrate synthase gene, gltA, increased with increased rates of growth/Fe(III) reduction or current production, whereas the expression of the constitutively expressed housekeeping genes recA, rpoD, and proC remained relatively constant. Analysis of mRNA extracted from groundwater collected from a U(VI)-contaminated site undergoing in situ uranium bioremediation revealed a remarkable correspondence between acetate levels in the groundwater and levels of transcripts of gltA. The expression of gltA was also significantly greater in RNA extracted from groundwater beneath a highway runoff recharge pool that was exposed to calcium magnesium acetate in June, when acetate concentrations were high, than in October, when the levels had significantly decreased. It was also possible to detect gltA transcripts on current-harvesting anodes deployed in freshwater sediments. These results suggest that it is possible to monitor the in situ metabolic rate of Geobacteraceae by tracking the expression of the citrate synthase gene. PMID:16269721

  16. Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism: a pharmacodynamic and pharmacokinetic study

    PubMed Central

    Wiehle, Ronald; Cunningham, Glenn R; Pitteloud, Nelly; Wike, Jenny; Hsu, Kuang; Fontenot, Gregory K; Rosner, Michele; Dwyer, Andrew; Podolski, Joseph

    2013-01-01

    Objectives To determine the pharmacodynamic profile of serum total testosterone and luteinizing hormone (LH) levels in men with secondary hypogonadism after initial and chronic daily oral doses of enclomiphene citrate vs transdermal testosterone. To determine the effects of daily oral doses of enclomiphene citrate in comparison with transdermal testosterone on other hormones and markers in men with secondary hypogonadism. Patients and Methods This was a randomized, single-blind, two-centre, phase II study to evaluate the effects of three different doses of enclomiphene citrate (6.25, 12.5 and 25 mg) vs transdermal testosterone on 24-h LH and total testosterone in otherwise normal healthy men with secondary hypogonadism. Forty-eight men were enrolled in the trial (the intent-to-treat population), but four men had testosterone levels >350 ng/dL at baseline. Forty-four men completed the study per protocol. All subjects enrolled in this trial had serum total testosterone in the low range (<350 ng/dL) and had low to normal LH (<12 IU/L) on at least two occasions. Total testosterone and LH levels were assessed each hour for 24 h to examine the effects at each of three treatment doses of enclomiphene citrate vs a standard dose (5 g) of transdermal testosterone. In the initial profile, total testosterone and LH were determined in a naïve population after a single initial oral or transdermal treatment (day 1). This was contrasted to that seen after 6 weeks of continuous daily oral or transdermal treatment (day 42). The pharmacokinetics of enclomiphene citrate were assessed in a select subpopulation. Serum samples were obtained over the course of the study to determine the levels of various hormones and lipids. Results After 6 weeks of continuous use, the mean (sd) concentration of total testosterone at day 42 was 604 (160) ng/dL for men taking the highest dose of enclomiphene citrate (enclomiphene citrate, 25 mg daily) and 500 (278) ng in those men treated with transdermal

  17. Inflammatory responses of a human keratinocyte cell line to 10 nm citrate- and PEG-coated silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Bastos, V.; Brown, D.; Johnston, H.; Daniel-da-Silva, A. L.; Duarte, I. F.; Santos, C.; Oliveira, H.

    2016-07-01

    Silver nanoparticles (AgNPs) are among the most commonly used engineered NPs and various commercially available products are designed to come in direct contact with the skin (wound dressings, textiles, creams, among others). Currently, there is limited understanding of the influence of coatings on the toxicity of AgNPs and in particular their ability to impact on AgNP's mediated inflammatory responses. As AgNPs are often stabilized by different coatings, including citrate and polyethyleneglycol (PEG), in this study we investigate the influence of citrate (Cit10) or PEG (PEG10) coatings to 10 nm AgNP on skin, using human HaCaT keratinocytes. AgNPs cytotoxicity and inflammatory response (nuclear factor (NF)-κB induction and cytokine production) of HaCaT were assessed after in vitro exposure to 10 and 40 µg/mL after 4, 24, and 48 h. Results showed that although both types of coated AgNPs decreased cell proliferation and viability, Cit10 AgNPs were more toxic. NF-κB inhibition was observed for the highest concentration (40 µg/mL) of PEG10 AgNPs, and the putative link to early apoptotic pathways observed in these cells is discussed. No production of IL-1β, IL-6, IL-10, and TNFα was stimulated by AgNPs. Furthermore, Cit10 and PEG10 AgNPs decreased the release of MCP-1 by HaCaT cells after 48 h of exposure. As cytokines are vital for the immunologic regulation in the human body, and it is demonstrated that they may interfere with NPs, more research is needed to understand how different AgNPs affect the immune system.

  18. Genotoxicity of citrate-coated silver nanoparticles to human keratinocytes assessed by the comet assay and cytokinesis blocked micronucleus assay.

    PubMed

    Bastos, V; Duarte, I F; Santos, C; Oliveira, H

    2017-02-01

    Silver nanoparticles (AgNPs) are widely used in industrial, cosmetic, and biomedical products, and humans are frequently exposed to these products through the skin. It is widely recognized that the characteristics of AgNPs (e.g., size, coating) may influence their cytotoxic effects, but their correlation with DNA damage and mitotic disorders remains poorly explored. In this study, human keratinocytes (HaCaT cell line) were exposed to well-characterized 30 nm AgNPs coated with citrate, and their effects on viability, DNA fragmentation (assessed by the comet assay), and micronuclei (MNi) induction (assessed by the cytokinesis-block micronucleus cytome assays, CBMN) were investigated. The results showed that 10 and 40 μg/mL AgNPs decreased cell proliferation and viability, and induced a significant genetic damage. This was observed by an increase of DNA amount in comet tail, which linearly correlated with dose and time of exposure. Also, cytostaticity (increase of mononucleated cells) and MNi rates increased in treated cells. In contrast, no significant changes were observed in nucleoplasmatic bridges (NPBs) or nuclear buds (NBUDs), although NBUDs tended to increase in all conditions and periods. The cytostatic effects on HaCaT cells were also shown by the decrease of their nuclear division index. Thus, both comet and CBMN assays supported the observation that citrate-AgNPs induced genotoxic effects on HaCaT cells. Considering that AgNPs are present in a vast number of consumer products and also in multiple nanomedicine skin applications and formulations, more research is needed to determine the properties that confer less toxicity of AgNPs to different cell lines.

  19. Fresh and citrated whole-blood specimens can produce different thromboelastography results in patients on extracorporeal membrane oxygenation.

    PubMed

    Gilman, Elizabeth A; Koch, Christopher D; Santrach, Paula J; Schears, Gregory J; Karon, Brad S

    2013-08-01

    To compare thromboelastography (TEG) tracings obtained from fresh and citrated whole-blood samples in patients on extracorporeal membrane oxygenation (ECMO) or after cardiopulmonary bypass and in healthy volunteers. Samples of fresh and citrated whole blood were analyzed for 25 patients and 4 healthy volunteers. Thromboelastography analysis was performed in both plain and heparinase cups. In 5 of 6 patients on ECMO, use of citrated samples resulted in apparent partial or complete heparin reversal. In TEG tracings from patients following cardiopulmonary bypass, there was a slight hypercoagulable appearance in the citrated sample. No differences were noted between fresh and citrated samples from healthy volunteers whose blood was spiked with heparin. In some patients on ECMO, use of samples collected in sodium citrate tubes for TEG analysis results in significant artifacts, which could lead to heparin overdosing in these patients.

  20. Localization of the calcium-regulated citrate transport process in proximal tubule cells.

    PubMed

    Hering-Smith, Kathleen S; Mao, Weibo; Schiro, Faith R; Coleman-Barnett, Joycelynn; Pajor, Ana M; Hamm, L Lee

    2014-06-01

    Urinary citrate is an important inhibitor of calcium-stone formation. Most of the citrate reabsorption in the proximal tubule is thought to occur via a dicarboxylate transporter NaDC1 located in the apical membrane. OK cells, an established opossum kidney proximal tubule cell line, transport citrate but the characteristics change with extracellular calcium such that low calcium solutions stimulate total citrate transport as well as increase the apparent affinity for transport. The present studies address several fundamental properties of this novel process: the polarity of the transport process, the location of the calcium-sensitivity and whether NaDC1 is present in OK cells. OK cells grown on permeable supports exhibited apical >basolateral citrate transport. Apical transport of both citrate and succinate was sensitive to extracellular calcium whereas basolateral transport was not. Apical calcium, rather than basolateral, was the predominant determinant of changes in transport. Also 2,3-dimethylsuccinate, previously identified as an inhibitor of basolateral dicarboxylate transport, inhibited apical citrate uptake. Although the calcium-sensitive transport process in OK cells is functionally not typical NaDC1, NaDC1 is present in OK cells by Western blot and PCR. By immunolocalization studies, NaDC1 was predominantly located in discrete apical membrane or subapical areas. However, by biotinylation, apical NaDC1 decreases in the apical membrane with lowering calcium. In sum, OK cells express a calcium-sensitive/regulated dicarboxylate process at the apical membrane which responds to variations in apical calcium. Despite the functional differences of this process compared to NaDC1, NaDC1 is present in these cells, but predominantly in subapical vesicles.

  1. Differential modulation of citrate synthesis and release by fatty acids in perfused working rat hearts.

    PubMed

    Vincent, Genevieve; Bouchard, Bertrand; Khairallah, Maya; Des Rosiers, Christine

    2004-01-01

    The objective of this study was to test the effect of increasing fatty acid concentrations on substrate fluxes through pathways leading to citrate synthesis and release in the heart. This was accomplished using semirecirculating work-performing rat hearts perfused with substrate mixtures mimicking the in situ milieu (5.5 mM glucose, 8 nM insulin, 1 mM lactate, 0.2 mM pyruvate, and 0.4 mM oleate-albumin) and 13C methods. Raising the fatty acid concentration from 0.4 to 1 mM with long-chain oleate or medium-chain octanoate resulted in a lowering ( approximately 20%) of cardiac output and efficiency with unaltered O2 consumption. At the metabolic level, beyond the expected effects of high fatty acid levels on the contribution of pyruvate decarboxylation (reduced >3-fold) and beta-oxidation (enhanced approximately 3-fold) to citrate synthesis, there was also a 2.4-fold lowering of anaplerotic pyruvate carboxylation. Despite the dual inhibitory effect of high fatty acids on pyruvate decarboxylation and carboxylation, tissue citrate levels were twofold higher, but citrate release rates remained unchanged at 11-14 nmol/min, representing <0.5% of citric acid cycle flux. A similar trend was observed for most metabolic parameters after oleate or octanoate addition. Together, these results emphasize a differential modulation of anaplerotic pyruvate carboxylation and citrate release in the heart by fatty acids. We interpret the lack of effects of high fatty acid concentrations on citrate release rates as suggesting that, under physiological conditions, this process is maximal, probably limited by the activity of its mitochondrial or plasma membrane transporter. Limited citrate release at high fatty acid concentrations may have important consequences for the heart's fuel metabolism and function.

  2. Citrate-permeable channels in the plasma membrane of cluster roots from white lupin.

    PubMed

    Zhang, Wen-Hao; Ryan, Peter R; Tyerman, Stephen D

    2004-11-01

    White lupin (Lupinus albus) is well adapted to phosphorus deficiency by developing cluster roots that release large amounts of citrate into the rhizosphere to mobilize the sparingly soluble phosphorus. To determine the mechanism underlying citrate release from cluster roots, we isolated protoplasts from different types of roots of white lupin plants grown in phosphorus-replete (+P) and phosphorus-deficient (-P) conditions and used the patch-clamp technique to measure the whole-cell currents flowing across plasma membrane of these protoplasts. Two main types of anion conductance were observed in protoplasts prepared from cluster root tissue: (1) an inwardly rectifying anion conductance (IRAC) activated by membrane hyperpolarization, and (2) an outwardly rectifying anion conductance (ORAC) that became more activated with membrane depolarization. Although ORAC was an outward rectifier, it did allow substantial inward current (anion efflux) to occur. Both conductances showed citrate permeability, with IRAC being more selective for citrate3- than Cl- (PCit/PCl = 26.3), while ORAC was selective for Cl- over citrate (PCl/PCit = 3.7). Both IRAC and ORAC were sensitive to the anion channel blocker anthracene-9-carboxylic acid. These currents were also detected in protoplasts derived from noncluster roots of -P plants, as well as from normal (noncluster) roots of plants grown with 25 microm phosphorus (+P). No differences were observed in the magnitude or frequency of IRAC and ORAC currents between the cluster roots and noncluster roots of -P plants. However, the IRAC current from +P plants occurred less frequently than in the -P plants. IRAC was unaffected by external phosphate, but ORAC had reduced inward current (anion efflux) when phosphate was present in the external medium. Our data suggest that IRAC is the main pathway for citrate efflux from white lupin roots, but ORAC may also contribute to citrate efflux.

  3. Interaction of ligands with pig heart citrate synthase: conformational changes and catalysis.

    PubMed

    Johnson, J K; Srivastava, D K

    1991-06-01

    The fluorescence polarization of 8-hydroxypyrene (1,3,6)trisulfonate (HPT) increases upon interaction with pig heart citrate synthase. Titration of HPT with increasing concentrations of citrate synthase exhibits a hyperbolic saturation behavior, from which the dissociation constant of the enzyme-HPT complex (3.64 +/- 0.3 microM) was determined. The enzyme-HPT interaction is competitively inhibited by oxaloacetate (but not affected by acetyl CoA) with a Ki of 4.3 +/- 1.8 microM. This value is similar to the dissociation constant (Kd = 4.5 +/- 1.6 microM) for the enzyme-oxalocetate complex (determined in the absence of any effector ligand), as well as to the Km for oxaloacetate (3.9 +/- 0.7 microM) in a steady-state citrate synthase catalyzed reaction at a saturating concentration of acetyl CoA. However, the dissociation constant for the citrate synthase-oxaloacetate complex determined by the urea denaturation method is at least 25-fold lower than those determined by the other methods. This suggests an effector role of urea in strengthening the enzyme-oxaloacetate interaction. At low nondenaturing concentrations, urea inhibits the citrate synthase catalyzed reaction in an uncompetitive manner with respect to oxaloacetate, i.e., the Km for oxaloacetate decreases with an increase in urea concentration. This further suggests that urea stabilizes the interaction between citrate synthase and oxaloacetate. The effect of urea is specific for the substrate oxaloacetate, and not for the substrate analogue, HPT, although both these ligands bind citrate synthase with equal affinities, and protect the enzyme against thermal denaturation with equal magnitudes. The results presented herein are discussed in the light of known conformational states of the enzyme.

  4. Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats.

    PubMed

    Taskin, Mine Islimye; Yay, Arzu; Adali, Ertan; Balcioglu, Esra; Inceboz, Umit

    2015-04-01

    The aim of this study is to evaluate the effects of sildenafil citrate on cisplatin-induced ovarian toxicity. Thirty-two female rats were divided into four groups. Group 1: saline control; group 2: cisplatin; group 3: sildenafil citrate; and group 4: cisplatin plus sildenafil citrate group. In groups 2 and 4, the rats were injected with 5 mg/kg cisplatin intraperitoneally (i.p.). In groups 3 and 4, the rats were injected with 1.4 mg/kg sildenafil citrate i.p. The ovaries were removed two weeks later in all groups. Histopathologic examination, follicle counting and classification were performed. The expression of anti-Müllerian hormone (AMH) was detected immunohistochemically in the ovarian tissues. Sildenafil alleviated cisplatin-induced histopathological changes in the ovarian tissue. Primordial, secondary and tertiary follicles were diminished in group 2 compared with group 1 (p < 0.05). Pretreatment with sildenafil citrate preserved primordial follicle count in group 4 compared with group 2, and the difference was statistically significant (p < 0.05). According to our results, immunoreactivity intensity of AMH was lower in group 2 compared with group 1 (92.4 ± 3.97 versus 88.8 ± 1.77) but not significantly, whereas immunoreactivity intensity of AMH was higher in group 4 compared with group 2 (88.8 ± 1.77 versus 94.1 ± 2.36; p < 0.05). Our results demonstrated that pretreatment with sildenafil citrate is beneficial for protecting the ovaries from cisplatin-induced damage. Sildenafil citrate can be a choice for fertility preservation.

  5. [Insulin sensitivity in patients not responding to ovulation induction using clomiphene citrate].

    PubMed

    Vital Reyes, Víctor Saúl; Téllez Velasco, Sergio; Ríos Castillo, Brendha; Badillo Buenfil, Manuel; Hinojosa Cruz, Juan Carlos

    2012-07-01

    The role of insulin resistance (IR) of infertile patients with chronic anovulation in their therapeutic failure to clomiphene citrate (CC) is not quite clear. Determine the sensitivity to insulin in patients with chronic anovulation and failure to the treatment with clomiphene citrate. A cross-sectional clinical study in infertile patients with clomiphene citrate resistance and in patients with adequate response to clomiphene citrate was carried out. In all patients insulin resistance was determined by the rate of glucose/insulin, HOMA (Homestatic Model Assessment) and the insulin sensitivity test. For the inferential statistical analysis, a Student's t test for independent samples was used. The average total basal insulin was 19.6 +/- 8.1 microU/mL. We observed higher concentrations in the clomiphene citrate resistance group (22.1 +/- 8.9 vs. 15.8 +/- 5.1 mU/mL p = 0.07). The glucose/insulin rate was statistically minor in patients with resistance to clomiphene citrate (4.2 +/- 1.9 versus 6.9 +/- 2.1 p = 0.02), but HOMA was not significantly different in both groups (4.3 +/- 1.4 vs. 3.9 +/- 1.3 p = 0.6). The total rate of glucose disappearance (KIIT) was 4.1 +/- 1.2. However, the statistical analysis did not show significant statistical differences between the two groups. Our preliminary results suggest that insulin resistance can be a mechanism involved in the pharmacologic response to ovulation induction in infertile patients, but coexisting pathophysiological mechanisms such as hyperandrogenism might also account for the lack of response to clomiphene citrate.

  6. The Aqueous Complexation of Thorium with Citrate under Neutral to Basic Conditions

    SciTech Connect

    Felmy, Andrew R; Cho, Herman M; Dixon, David A; Xia, Yuanxian; Hess, Nancy J; Wang, Zheming

    2006-04-20

    The aqueous complexation of thorium with citrate was investigated under neutral to basic conditions and over a broad range of ionic strengths. The solubility data for ThO2(am) as a function of citrate concentration indicate the presence of stable species with citrate-to-metal ratios of between two to three. The dependence of the ThO2(am) solubilities on hydrogen ion concentration can also be readily explained by the classical assumption of hydrolysis of the central Th(IV) ion to form mixed thorium-hydroxide-citrate complexes. 13C NMR spectra of the species in solution confirm that the citrate-to-metal ratio of the species in solution is between two and three and show that the citrate attaches to the metal in a bidentate fashion through oxygens on the -carboxylate and -alkoxyl groups, rather than through the carboxylate groups. The 13C NMR spectra, as well as a density functional theory (DFT) electronic structure study of the presumptive complexes, suggests that the associated α-hydroxyl proton can be displaced during complex formation. These findings indicate an alternative explanation for the observed changes in solubility as a function of hydrogen ion concentration, the displacement of protons from the citrate alkoxyl groups via metal binding. Removal of protons from the alkoxyl groups or hydrolysis of the central Th(IV) cannot be distinguished by thermodynamic measurements, however the species with the α-hydroxyl proton removed (i.e., ThOH(Cit)25- and Th(Cit)38-) would appear to better represent the microscopic binding. Apparent equilibrium constants for the solution phase reactions of these species and the hydrous thorium oxide have been calculated as a function of ionic strength.

  7. Optimalization of Poly(neutral red) Coated-wire Electrode for Determination of Citrate in Soft Drinks

    PubMed Central

    Broncová, Gabriela; Shishkanova, Tatiana V.; Krondak, Martin; Volf, Radko; Král, Vladimír

    2008-01-01

    This report presents an optimization of potentiometric measurements with citrate-selective electropolymerized poly(neutral red) electrodes. The optimal background electrolyte for these measurements is a TRIS buffer with nitrate at pH 8.5. The electrodes described here exhibit stable and reproducible near-Nernstian response to citrates with a low detection limit of 6 × 10-6 M. Electrodes polymerized from sulfuric acid and acetonitrile are compared in detail. Simple and sensitive method for quantification of citrate in real-life samples by potentiometry with poly(neutral red) electrodes are presented. Data from potentiometric measurements of citrate are compared with capillary electrophoresis. PMID:27879724

  8. Catabolite repression of the citrate fermentation genes in Klebsiella pneumoniae: evidence for involvement of the cyclic AMP receptor protein.

    PubMed

    Meyer, M; Dimroth, P; Bott, M

    2001-09-01

    Klebsiella pneumoniae is able to grow anaerobically with citrate as a sole carbon and energy source by a fermentative pathway involving the Na(+)-dependent citrate carrier CitS, citrate lyase, and oxaloacetate decarboxylase. The corresponding genes are organized in the divergent citC and citS operons, whose expression is strictly dependent on the citrate-sensing CitA-CitB two-component system. Evidence is provided here that the citrate fermentation genes are subject to catabolite repression, since anaerobic cultivation with a mixture of citrate and glucose or citrate and gluconate resulted in diauxic growth. Glucose, gluconate, and also glycerol decreased the expression of a chromosomal citS-lacZ fusion by 60 to 75%, whereas a direct inhibition of the citrate fermentation enzymes was not observed. The purified cyclic AMP (cAMP) receptor protein (CRP) of K. pneumoniae bound to two sites in the citC-citS intergenic region, which were centered at position -41.5 upstream of the citC and citS transcriptional start sites. Binding was apparently stimulated by the response regulator CitB. These data indicate that catabolite repression of the citrate fermentation genes is exerted by CRP and that in the absence of repressing carbon sources the cAMP-CRP complex serves to enhance the basal, CitB-dependent transcription level.

  9. Generation of circularly permuted fluorescent-protein-based indicators for in vitro and in vivo detection of citrate.

    PubMed

    Honda, Yuki; Kirimura, Kohtaro

    2013-01-01

    Indicators for citrate, particularly those applicable to its in vivo detection and quantitation, have attracted much interest in both biochemical studies and industrial applications since citrate is a key metabolic intermediate playing important roles in living cells. We generated novel fluorescence indicators for citrate by fusing the circularly permuted fluorescent protein (cpFP) and the periplasmic domain of the bacterial histidine kinase CitA, which can bind to citrate with high specificity. The ratiometric fluorescent signal change was observed with one of these cpFP-based indicators, named CF98: upon addition of citrate, the excitation peak at 504 nm increased proportionally to the decrease in the peak at 413 nm, suitable for build-in quantitative estimation of the binding compound. We confirmed that CF98 can be used for detecting citrate in vitro at millimolar levels in the range of 0.1 to 50 mM with high selectivity; even in the presence of other organic acids such as isocitrate and malate, the fluorescence intensity of CF98 remains unaffected. We finally demonstrated the in vivo applicability of CF98 to estimation of the intracellular citrate concentration in Escherichia coli co-expressing the genes encoding CF98 and the citrate carrier CitT. The novel indicator CF98 can be a specific and simple detection tool for citrate in vitro and a non-invasive tool for real-time estimation of intracellular concentrations of the compound in vivo.

  10. Inhibition of calcium oxalate monohydrate growth by citrate and the effect of the background electrolyte

    NASA Astrophysics Data System (ADS)

    Weaver, Matthew L.; Qiu, S. Roger; Hoyer, John R.; Casey, William H.; Nancollas, George H.; De Yoreo, James J.

    2007-08-01

    Pathological mineralization is a common phenomenon in broad range of plants and animals. In humans, kidney stone formation is a well-known example that afflicts approximately 10% of the population. Of the various calcium salt phases that comprise human kidney stones, the primary component is calcium oxalate monohydrate (COM). Citrate, a naturally occurring molecule in the urinary system and a common therapeutic agent for treating stone disease, is a known inhibitor of COM. Understanding the physical mechanisms of citrate inhibition requires quantification of the effects of both background electrolytes and citrate on COM step kinetics. Here we report the results of an in situ AFM study of these effects, in which we measure the effect of the electrolytes LiCl, NaCl, KCl, RbCl, and CsCl, and the dependence of step speed on citrate concentration for a range of COM supersaturations. We find that varying the background electrolyte results in significant differences in the measured step speeds and in step morphology, with KCl clearly producing the smallest impact and NaCl the largest. The kinetic coefficient for the former is nearly three times larger than for the latter, while the steps change from smooth to highly serrated when KCl is changed to NaCl. The results on the dependence of step speed on citrate concentration show that citrate produces a dead zone whose width increases with citrate concentration as well as a continual reduction in kinetic coefficient with increasing citrate level. We relate these results to a molecular-scale view of inhibition that invokes a combination of kink blocking and step pinning. Furthermore, we demonstrate that the classic step-pinning model of Cabrera and Vermilyea (C-V model) does an excellent job of predicting the effect of citrate on COM step kinetics provided the model is reformulated to more realistically account for impurity adsorption, include an expression for the Gibbs-Thomson effect that is correct for all supersaturations

  11. Stabilizing effect of citrate buffer on the photolysis of riboflavin in aqueous solution

    PubMed Central

    Ahmad, Iqbal; Sheraz, Muhammad Ali; Ahmed, Sofia; Kazi, Sadia Hafeez; Mirza, Tania; Aminuddin, Mohammad

    2011-01-01

    In the present investigation the photolysis of riboflavin (RF) in the presence of citrate species at pH 4.0–7.0 has been studied. A specific multicomponent spectrophotometric method has been used to assay RF in the presence of photoproducts during the reactions. The overall first-order rate constants (kobs) for the photolysis of RF range from 0.42 to 1.08×10–2 min−1 in the region. The values of kobs have been found to decrease with an increase in citrate concentration indicating an inhibitory effect of these species on the rate of reaction. The second-order rate constants for the interaction of RF with total citrate species causing inhibition range from 1.79 to 5.65×10–3 M−1 min−1 at pH 4.0–7.0. The log k–pH profiles for the reactions at 0.2–1.0 M citrate concentration show a gradual decrease in kobs and the value at 1.0 M is more than half compared to that of k0, i.e., in the absence of buffer, at pH 5.0. Divalent citrate ions cause a decrease in RF fluorescence due to the quenching of the excited singlet state resulting in a decrease in the rate of reaction and consequently leading to the stabilization of RF solutions. The greater quenching of fluorescence at pH 4.0 compared to that of 7.0 is in accordance with the greater concentration of divalent citrate ions (99.6%) at that pH. The trivalent citrate ions exert a greater inhibitory effect on the rate of RF photolysis compared to that of the divalent citrate ions probably as a result of excited triplet state quenching. The values of second-order rate constants for the interaction of divalent and trivalent citrate ions are 0.44×10–2 and 1.06×10–3 M–1 min–1, respectively, indicating that the trivalent ions exert a greater stabilizing effect, compared to the divalent ions, on RF solutions. PMID:25755977

  12. Films based on neutralized chitosan citrate as innovative composition for cosmetic application.

    PubMed

    Libio, Illen C; Demori, Renan; Ferrão, Marco F; Lionzo, Maria I Z; da Silveira, Nádya P

    2016-10-01

    In this work, citrate and acetate buffers, were investigated as neutralizers to chitosan salts in order to provide biocompatible and stable films. To choose the appropriate film composition for this study, neutralized chitosan citrate and acetate films, with and without the plasticizer glycerol, were prepared and characterized by thickness, moisture content, degree of swelling, total soluble matter in acid medium, simultaneous thermal analysis and differential scanning calorimetry. Chitosan films neutralized in citrate buffer showed greater physical integrity resulted from greater thicknesses, lower moisture absorbance, lower tendency to solubility in the acid medium, and better swelling capacities. According to thermal analyses, these films had higher interaction with water which is considered an important feature for cosmetic application. Since the composition prepared in citrate buffer without glycerol was considered to present better physical integrity, it was applied to investigate hyaluronic acid release in a skin model. Skins treated with those films, with or without hyaluronic acid, show stratum corneum desquamation and hydration within 10min. The results suggest that the neutralized chitosan citrate film prepared without glycerol promotes a cosmetic effect for skin exfoliation in the presence or absence of hyaluronic acid.

  13. Artificial Citrate Operon Confers Mineral Phosphate Solubilization Ability to Diverse Fluorescent Pseudomonads

    PubMed Central

    Adhikary, Hemanta; Sanghavi, Paulomi B.; Macwan, Silviya R.; Archana, Gattupalli; Naresh Kumar, G.

    2014-01-01

    Citric acid is a strong acid with good cation chelating ability and can be very efficient in solubilizing mineral phosphates. Only a few phosphate solubilizing bacteria and fungi are known to secrete citric acids. In this work, we incorporated artificial citrate operon containing NADH insensitive citrate synthase (gltA1) and citrate transporter (citC) genes into the genome of six-plant growth promoting P. fluorescens strains viz., PfO-1, Pf5, CHAO1, P109, ATCC13525 and Fp315 using MiniTn7 transposon gene delivery system. Comprehensive biochemical characterization of the genomic integrants and their comparison with plasmid transformants of the same operon in M9 minimal medium reveals the highest amount of ∼7.6±0.41 mM citric and 29.95±2.8 mM gluconic acid secretion along with ∼43.2±3.24 mM intracellular citrate without affecting the growth of these P. fluorescens strains. All genomic integrants showed enhanced citric and gluconic acid secretion on Tris-Cl rock phosphate (TRP) buffered medium, which was sufficient to release 200–1000 µM Pi in TRP medium. This study demonstrates that MPS ability could be achieved in natural fluorescent pseudomonads by incorporation of artificial citrate operon not only as plasmid but also by genomic integration. PMID:25259527

  14. The FRD3 citrate effluxer promotes iron nutrition between symplastically disconnected tissues throughout Arabidopsis development.

    PubMed

    Roschzttardtz, Hannetz; Séguéla-Arnaud, Mathilde; Briat, Jean-François; Vert, Grégory; Curie, Catherine

    2011-07-01

    We present data supporting a general role for FERRIC REDICTASE DEFECTIVE3 (FRD3), an efflux transporter of the efficient iron chelator citrate, in maintaining iron homeostasis throughout plant development. In addition to its well-known expression in root, we show that FRD3 is strongly expressed in Arabidopsis thaliana seed and flower. Consistently, frd3 loss-of-function mutants are defective in early germination and are almost completely sterile, both defects being rescued by iron and/or citrate supply. The frd3 fertility defect is caused by pollen abortion and is associated with the male gametophytic expression of FRD3. Iron imaging shows the presence of important deposits of iron on the surface of aborted pollen grains. This points to a role for FRD3 and citrate in proper iron nutrition of embryo and pollen. Based on the findings that iron acquisition in embryo, leaf, and pollen depends on FRD3, we propose that FRD3 mediated-citrate release in the apoplastic space represents an important process by which efficient iron nutrition is achieved between adjacent tissues lacking symplastic connections. These results reveal a physiological role for citrate in the apoplastic transport of iron throughout development, and provide a general model for multicellular organisms in the cell-to-cell transport of iron involving extracellular circulation.

  15. Enhancing radium solubilization in soils by citrate, EDTA, and EDDS chelating amendments.

    PubMed

    Prieto, C; Lozano, J C; Blanco Rodríguez, P; Tomé, F Vera

    2013-04-15

    The effect of three chelating agents (citrate, EDTA, and EDDS) on the solubilization of radium from a granitic soil was studied systematically, considering different soil pH values, chelating agent concentrations, and leaching times. For all the chelating agents tested, the amount of radium leached proved to be strongly dependent on the pH of the substrate: only for acidic conditions did the amount of radium released increase significantly relative to the controls. Under the best conditions, the radium released from the amended soil was greater by factors of 20 in the case of citrate, 18 for EDTA, and 14 for EDDS. The greatest improvement in the release of radium was obtained for the citrate amendment at the highest concentration tested (50 mmol kg(-1)). A slightly lower amount of radium was leached with EDTA at 5 mmol kg(-1) soil, but the solubilization over time was very different from that observed with citrate or EDDS. With EDTA, a maximum in radium leaching was reached on the first day after amendment, while with citrate, the maximum was attained on the fourth day. With EDDS, radium leaching increased slightly but steadily with time (until the sixth day), but the net effect for the period tested was the lowest of the three reagents.

  16. Fate of uranyl in a quaternary system composed of uranyl, citrate, goethite, and Pseudomonas fluorescens.

    PubMed

    Bencheikh-Latmani, Rizlan; Leckie, James O; Bargar, John R

    2003-08-15

    This study investigated the partitioning of uranyl within a quaternary system made up of uranyl, citrate, goethite, and the bacterium Pseudomonas fluorescens. In the absence of cells, uranyl was sorbed to goethite as a complex involving surface groups and/or citrate. Measurements of the evolution of CO2 indicated that the addition of bacterial cells lead to the gradual biodegradation of citrate. Throughout the biodegradation process, uranyl remained sorbed to the insoluble fraction comprised of goethite and cells. EXAFS (Extended X-ray Absorption Fine Structure) measurements showed that bacterial cells outcompeted goethite for uranyl under the experimental conditions and caused the repartitioning of uranyl from goethite to cell matter, independently from citrate degradation. Citrate degradation caused further release of uranyl from goethite surfaces, followed by subsequent association of uranyl with cells. At long equilibration times (3 months), cell lysis and phosphate release resulted in the precipitation of an autunite-like phase. This work suggests that bacterial degradation of uranyl-complexing ligands in contaminated subsurface media containing iron oxides should not necessarily lead to an increase in the mobility of uranyl.

  17. Effect of ranitidine bismuth citrate on postprandial plasma gastrin and pepsinogens.

    PubMed Central

    Fraser, A G; Lam, W M; Luk, Y W; Sercombe, J; Sawyerr, A M; Hudson, M; Samloff, I M; Pounder, R E

    1993-01-01

    Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate. PMID:8472980

  18. Effect of topically applied sildenafil citrate on wound healing: experimental study.

    PubMed

    Gürsoy, Koray; Oruç, Melike; Kankaya, Yüksel; Ulusoy, Mustafa Gürhan; Koçer, Uğur; Kankaya, Duygu; Gürsoy, Reyhan Neslihan; Çevik, Özge; Öğüş, Elmas; Fidanci, Vildan

    2014-08-16

    Wound healing is a complex process that necessitates organization of different cell types and several signalling molecules. The aim of this study is to evaluate the effect of different concentrations of sildenafil citrate, which decreases cGMP degradation, on wound healing by secondary intention.This study was performed using 25 Sprague Dawley rats weighing 200-250 grams. 4 dorsal defects were created. Four different treatment modalities which were 1% and 5% sildenafil citrate gel prepared with carbopol, pure carbopol gel without any drug in it and 0,9% NaCl solution; were applied to each lesion of the same rat. Randomly selected five rats (25 rats in total) were sacrificed on 3rd, 5th, 7th, 10th, and 14th days; and the effect of each modality was evaluated by means of defect area measurement, histopathological examination and measurement of tissue hydroxyproline levels.Sildenafil citrate gel application decreased the defect areas in a dose independent manner starting from 3rd day and dose dependent manner after 7th day. By means of vascularization, sildenafil citrate increased vascularity starting from 3rd day. The strength of acute inflammation was superior in sildenafil groups starting from 5th day; and the amount and maturation of granulation in the wound bed, as well as the strength of chronic inflammation were superior in defects treated with sildenafil citrate as early as 7th day.

  19. Sodium citrate blood contamination by K2 -ethylenediaminetetraacetic acid (EDTA): impact on routine coagulation testing.

    PubMed

    Lima-Oliveira, G; Salvagno, G L; Danese, E; Favaloro, E J; Guidi, G C; Lippi, G

    2015-06-01

    The potential cross-contamination of additives between primary blood tubes is a well-known problem during sample collection. The aim of this study was to assess the impact of citrated blood contamination with different amounts of dipotassium ethylenediaminetetraacetic (K2 EDTA blood) on activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen. Blood was collected from 15 ostensibly healthy volunteers into four 0.109 m citrate blood tubes followed by one K2 EDTA blood tube. The citrate tubes of each subject were pooled and divided in five aliquots. The whole blood of the K2 EDTA tube was then added in scalar amounts to autologous citrated blood aliquots, to obtain K2 EDTA contamination ranging from 0% to 43%, and thus mimic potential pre-analytical contamination. A statistically and clinically significant prolongation was observed for both APTT and PT between 29% and 43% K2 EDTA contamination, whereas the decrease of fibrinogen values became statistically and clinically significant at 43% K2 EDTA contamination. The results of this investigation show that contamination of citrated blood with as much as 29% of K2 EDTA blood generates a significant bias in results of routine clotting assays. This has serious implications for patient safety and management. © 2014 John Wiley & Sons Ltd.

  20. Artificial citrate operon confers mineral phosphate solubilization ability to diverse fluorescent pseudomonads.

    PubMed

    Adhikary, Hemanta; Sanghavi, Paulomi B; Macwan, Silviya R; Archana, Gattupalli; Naresh Kumar, G

    2014-01-01

    Citric acid is a strong acid with good cation chelating ability and can be very efficient in solubilizing mineral phosphates. Only a few phosphate solubilizing bacteria and fungi are known to secrete citric acids. In this work, we incorporated artificial citrate operon containing NADH insensitive citrate synthase (gltA1) and citrate transporter (citC) genes into the genome of six-plant growth promoting P. fluorescens strains viz., PfO-1, Pf5, CHAO1, P109, ATCC13525 and Fp315 using MiniTn7 transposon gene delivery system. Comprehensive biochemical characterization of the genomic integrants and their comparison with plasmid transformants of the same operon in M9 minimal medium reveals the highest amount of ∼7.6±0.41 mM citric and 29.95±2.8 mM gluconic acid secretion along with ∼43.2±3.24 mM intracellular citrate without affecting the growth of these P. fluorescens strains. All genomic integrants showed enhanced citric and gluconic acid secretion on Tris-Cl rock phosphate (TRP) buffered medium, which was sufficient to release 200-1000 µM Pi in TRP medium. This study demonstrates that MPS ability could be achieved in natural fluorescent pseudomonads by incorporation of artificial citrate operon not only as plasmid but also by genomic integration.

  1. The role of tannic acid and sodium citrate in the synthesis of silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Ranoszek-Soliwoda, Katarzyna; Tomaszewska, Emilia; Socha, Ewelina; Krzyczmonik, Pawel; Ignaczak, Anna; Orlowski, Piotr; Krzyzowska, Małgorzata; Celichowski, Grzegorz; Grobelny, Jaroslaw

    2017-08-01

    We describe herein the significance of a sodium citrate and tannic acid mixture in the synthesis of spherical silver nanoparticles (AgNPs). Monodisperse AgNPs were synthesized via reduction of silver nitrate using a mixture of two chemical agents: sodium citrate and tannic acid. The shape, size and size distribution of silver particles were determined by UV-Vis spectroscopy, dynamic light scattering (DLS) and scanning transmission electron microscopy (STEM). Special attention is given to understanding and experimentally confirming the exact role of the reagents (sodium citrate and tannic acid present in the reaction mixture) in AgNP synthesis. The oxidation and reduction potentials of silver, tannic acid and sodium citrate in their mixtures were determined using cyclic voltammetry. Possible structures of tannic acid and its adducts with citric acid were investigated in aqueous solution by performing computer simulations in conjunction with the semi-empirical PM7 method. The lowest energy structures found from the preliminary conformational search are shown, and the strength of the interaction between the two molecules was calculated. The compounds present on the surface of the AgNPs were identified using FT-IR spectroscopy, and the results are compared with the IR spectrum of tannic acid theoretically calculated using PM6 and PM7 methods. The obtained results clearly indicate that the combined use of sodium citrate and tannic acid produces monodisperse spherical AgNPs, as it allows control of the nucleation, growth and stabilization of the synthesis process. [Figure not available: see fulltext.

  2. Separation of Ni and Co by D2EHPA in the Presence of Citrate Ion

    NASA Astrophysics Data System (ADS)

    Nadimi, Hamed; Haghshenas Fatmehsari, Davoud; Firoozi, Sadegh

    2017-10-01

    Recycling processes for the recovery of metallic content from the electronic wastes are environmentally friendly and economical. This paper reports a method for the recovery and separation of Ni and Co from the sulfate solution by the use of D2EHPA. In this regard, the influence of citrate ion, as a carboxylate ligand, was examined in the separation conditions of Ni and Co via D2EHPA (a poor selective extractant for Ni and Co separation). It was found that the Δ {pH}_{0.5}^{Ni-Co} (the difference between pH values corresponding to 50 pct extraction of metallic ion) increases to 1.5 at the citrate concentration of 0.05 M; this Δ {pH}_{0.5}^{Ni-Co} value is much higher than that obtained in the absence of citrate ion (0.1). Fourier Transform Infrared Spectroscopy (FT-IR) indicated that the citrate ion is co-absorbed during the metallic ions absorption by D2EHPA meaning that the metal-organic complexes contain Co/Ni and citrate ion. Also, the stoichiometric coefficients of the Ni and Co extraction reaction were proposed by applying the slope analysis method.

  3. Requirement for Sodium in the Anaerobic Growth of Aerobacter aerogenes on Citrate

    PubMed Central

    O'Brien, R. W.; Stern, Joseph R.

    1969-01-01

    Anaerobic growth of Aerobacter aerogenes on citrate as a carbon source required the presence of Na+. The growth rate increased with increasing Na+ concentration and was optimal at 0.10 m Na+. The requirement was specific for Na+, which could not be replaced by K+, NH4+, Li+, Rb+, or Cs+. K+ was required for growth in the presence of Na+, the optimal K+ concentration being 0.15 mm. Enzyme profiles were determined on cells grown in three different media: (i) intermediate Na+, high K+ concentration, (ii) high Na+, high K+ concentration, and (c) high Na+, low K+ concentration. All cells contained the enzymes of the citrate fermentation pathway, namely, citritase and the Na+-requiring oxalacetate (OAA) decarboxylase. All of the enzymes of the citric acid cycle were present, except α-ketoglutarate dehydrogenase which could not be detected. The incomplete citric acid cycle was, in effect, converted into two biosynthetic pathways leading to glutamate and succinate, respectively. The specific activities of citritase and OAA decarboxylase were lowest in medium (i), and under these conditions the activity of OAA decarboxylase appeared to be limited in vivo by the availability of Na+. Failure of A. aerogenes to grow anaerobically on citrate in the absence of Na+ can be explained at the enzymatic level by the Na+ requirement of the OAA decarboxylase step of the citrate fermentation pathway and by the absence of an alternate pathway of citrate catabolism. PMID:5784198

  4. Radiolabeled porphyrin versus gallium-67 citrate for the detection of human melanoma in athymic mice

    SciTech Connect

    Maric, N.; Chan, S. Ming; Hoffer, P.B.; Duray, P.

    1987-01-01

    We performed the biodistribution and imaging studies of /sup 111/In and /sup 67/Ga labeled tetra(4-N-methylpyridyl) porphine, (T4NMPYP), and compared it to that of /sup 67/Ga citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both /sup 111/In and /sup 67/Ga labeled T4NMPYP (3, 6, 24, and 48 hours) were similar but differed from that of /sup 67/Ga citrate (48 hours). The optimum tumor uptake of both radiolabeled porphyrins was at 6 hours postinjection and was lower than the tumor uptake of /sup 67/Ga citrate at 48 hours postinjection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of /sup 67/Ga citrate. The imaging studies performed with /sup 111/In T4NMPYP and /sup 67/Ga citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of /sup 111/In T4NMPYP. 15 refs., 3 figs., 5 tabs.

  5. Nitrate Protects Cucumber Plants Against Fusarium oxysporum by Regulating Citrate Exudation.

    PubMed

    Wang, Min; Sun, Yuming; Gu, Zechen; Wang, Ruirui; Sun, Guomei; Zhu, Chen; Guo, Shiwei; Shen, Qirong

    2016-09-01

    Fusarium wilt causes severe yield losses in cash crops. Nitrogen plays a critical role in the management of plant disease; however, the regulating mechanism is poorly understood. Using biochemical, physiological, bioinformatic and transcriptome approaches, we analyzed how nitrogen forms regulate the interactions between cucumber plants and Fusarium oxysporum f. sp. cucumerinum (FOC). Nitrate significantly suppressed Fusarium wilt compared with ammonium in both pot and hydroponic experiments. Fewer FOC colonized the roots and stems under nitrate compared with ammonium supply. Cucumber grown with nitrate accumulated less fusaric acid (FA) after FOC infection and exhibited increased tolerance to chemical FA by decreasing FA absorption and transportation in shoots. A lower citrate concentration was observed in nitrate-grown cucumbers, which was associated with lower MATE (multidrug and toxin compound extrusion) family gene and citrate synthase (CS) gene expression, as well as lower CS activity. Citrate enhanced FOC spore germination and infection, and increased disease incidence and the FOC population in ammonium-treated plants. Our study provides evidence that nitrate protects cucumber plants against F. oxysporum by decreasing root citrate exudation and FOC infection. Citrate exudation is essential for regulating disease development of Fusarium wilt in cucumber plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. [Cost-effectiveness analysis of preventive treatment of urinary lithiasis recurrence using potassium citrate].

    PubMed

    Gisbert Gelonch, R; Fernández Augusto, L

    1997-05-01

    This study evaluated two possible alternatives of potassium citrate administration-granulate (liquid) and tablet (wax matrix)-versus treatment with diet and/or fluid to prevent recurrence of urinary lithiasis. The cost-effectiveness of the alternative modalities were analyzed using data from the studies conducted by Barceló (1993), Pak (1985) and Preminger (1985). The variables utilized for effectiveness were 'avoided relapse' and 'avoided intervention'. Since the data from the foregoing studies did not make any distinction between the two alternative forms of potassium citrate administration, the incidence of side effects and the dropout rate were included. These data were obtained from the studies conducted by Barceló (1993). Campoy (1994) and Conte (1994). Potassium citrate is effective in the prevention of recurrence of urinary lithiasis; relapses and interventions were significantly avoided. Both forms of potassium citrate are similarly effective and the only differences found were in regard to the side effects and the dropout rate; however, further studies are warranted to determine the possible differences with more precision. Potassium citrate in granulated form in much more cost-effective than the diet and fluid regimen than the tablet alternative, with a difference significantly in favor of the former in the order of 8:1. Price was the most important variable and therefore it is important to determine the appropriate dosage since it will influence the cost-effectiveness ratio and the allocation of resources.

  7. Double-blind, randomized, placebo-controlled study of a lotion containing triethyl citrate and ethyl linoleate in the treatment of acne vulgaris.

    PubMed

    Charakida, A; Charakida, M; Chu, A C

    2007-09-01

    Acne vulgaris is a major clinical problem; despite a vast array of treatment modalities available for acne, there is considerable dissatisfaction in acne treatment among patients and doctors. Rising antibiotic drug resistance consequent to the widespread use of topical antibiotics is causing concern and effective nonantibiotic treatments are needed. To evaluate the efficacy and tolerability of a novel lotion containing triethyl citrate and ethyl linoleate in the treatment of mild to moderate acne vulgaris. This was a double-blind, placebo-controlled, randomized study comparing the active lotion containing triethyl citrate and ethyl linoleate with its vehicle as a placebo control. Patients were assessed by the modified Leeds acne grading system as well as by counting inflammatory and noninflammatory lesions on the face at weeks 0, 4, 8 and 12. Sebum production was assessed by the Sebutape method at weeks 0 and 12. All adverse events were recorded. Forty patients were recruited into the study, of whom 33 completed the study. Active treatment was statistically superior to placebo in reduction of Leeds grading and total, inflammatory and noninflammatory lesion counts. The active lotion showed a rapid response with obvious reduction in lesion counts and acne grading by 4 weeks. Sebum production was significantly reduced in the actively treated group, with a mean reduction of 53% in sebum production compared with baseline. One patient developed irritation to the active lotion and withdrew from the study. The new lotion containing triethyl citrate and ethyl linoleate has been shown to be an effective treatment for mild to moderate acne, with an effect on both inflammatory and noninflammatory acne lesions. The new lotion worked quickly and was generally well tolerated. A surprising finding was the significant impact the new lotion has on sebum production, suggesting a role in patients with seborrhoea. This nonantibiotic preparation will be a very useful addition to

  8. Amino acid-dependent transformations of citrate-coated silver nanoparticles: impact on morphology, stability and toxicity.

    PubMed

    Shi, Junpeng; Sun, Xia; Zou, Xiaoyan; Zhang, Hongwu

    2014-08-17

    Humans face the risk of exposure to silver nanoparticles (AgNPs) due to their extensive application in consumer products. AgNPs can interact with many substances in the human body due to their chemically unstable nature and high activity properties, which might result in unknown hazards and even some serious diseases for humans. As the basic constituent element of human bodies, amino acids (AAs) differ in concentration and variety in different cells and tissues. Thus, understanding the transformation of citrate-coated AgNPs in the presence of AAs is crucial for determining their fate and toxicity in the human body. Our study focused on the transformation of the morphology, dissolution behavior and reaction product of AgNPs in different AA-containing systems and then evaluated the effect of these transformations on the cytotoxicity of AgNPs. The obtained results indicated that the addition of glycine with the lowest Ag(+) binding energy had little effect on the transformations and toxicity of AgNPs. While in the presence of histidine with higher Ag(+) binding energy, the Ag(+) release and particle size of AgNPs obviously increased. These transformations resulted in a decrease in the cytotoxicity of AgNPs due to the formation of Ag-His complex and the growth of AgNPs. Furthermore, l-cysteine with the highest Ag(+) binding energy could easily interact with AgNPs, transforming them completely to form [Ag(Cys)n](+) and Ag2S precipitates, which induced the largest decrease in AgNP toxicity. In summary, our results may provide useful information to understand the fate, transformation, and toxicity of citrate-coated AgNPs in the human body.

  9. Effects of Sodium Citrate Concentration on Electroless Ni-Fe Bath Stability and Deposition

    NASA Astrophysics Data System (ADS)

    Jung, Myung-Won; Kang, Sung K.; Lee, Jae-Ho

    2014-01-01

    In this research, electroless Ni-Fe bath stability and deposition characteristics were investigated for various sodium citrate concentrations. Complexing agents such as sodium citrate are one of the main components of such electroless plating baths. Since they could play various roles such as maintaining pH stability, preventing precipitation of metal salts, and reducing the concentrations of free metal ions, the concentration of complexing agents in the plating bath is an important parameter for electroless deposition processes. In this research, unstable baths were obtained for insufficient sodium citrate concentrations, and these phenomena were analyzed with ChemEQL. Moreover, the deposition characteristics of electroless Ni-Fe for under bump metallurgy diffusion barriers were also investigated using energy-dispersive spectroscopy and field-emission scanning electron microscopy.

  10. SECONDARY HYPERPARATHYROIDISM AFTER BARIATRIC SURGERY: TREATMENT IS WITH CALCIUM CARBONATE OR CALCIUM CITRATE?

    PubMed Central

    BARETTA, Giorgio Alfredo Pedroso; CAMBI, Maria Paula Carlini; RODRIGUES, Arieli Luz; MENDES, Silvana Aparecida

    2015-01-01

    Background : Bariatric surgery, especially Roux-en-Y gastric bypass, can cause serious nutritional complications arising from poor absorption of essential nutrients. Secondary hyperparathyroidism is one such complications that leads to increased parathyroid hormone levels due to a decrease in calcium and vitamin D, which may compromise bone health. Aim : To compare calcium carbonate and calcium citrate in the treatment of secondary hyperparathyroidism. Method : Patients were selected on the basis of their abnormal biochemical test and treatment was randomly done with citrate or calcium carbonate. Results : After 60 days of supplementation, biochemical tests were repeated, showing improvement in both groups. Conclusion : Supplementation with calcium (citrate or carbonate) and vitamin D is recommended after surgery for prevention of secondary hyperparathyroidism. PMID:26537273

  11. SECONDARY HYPERPARATHYROIDISM AFTER BARIATRIC SURGERY: TREATMENT IS WITH CALCIUM CARBONATE OR CALCIUM CITRATE?

    PubMed

    Baretta, Giorgio Alfredo Pedroso; Cambi, Maria Paula Carlini; Rodrigues, Arieli Luz; Mendes, Silvana Aparecida

    2015-01-01

    Bariatric surgery, especially Roux-en-Y gastric bypass, can cause serious nutritional complications arising from poor absorption of essential nutrients. Secondary hyperparathyroidism is one such complications that leads to increased parathyroid hormone levels due to a decrease in calcium and vitamin D, which may compromise bone health. To compare calcium carbonate and calcium citrate in the treatment of secondary hyperparathyroidism. Patients were selected on the basis of their abnormal biochemical test and treatment was randomly done with citrate or calcium carbonate. After 60 days of supplementation, biochemical tests were repeated, showing improvement in both groups. Supplementation with calcium (citrate or carbonate) and vitamin D is recommended after surgery for prevention of secondary hyperparathyroidism.

  12. Phloretin and citrate promote the differentiation rate from epimastigote to metacyclic forms of Trypanosoma cruzi.

    PubMed

    Adroher, F J; Osuna, A; Lupiáñez, J A

    1991-11-01

    We have investigated the effects of the metabolic inhibitors, phloretin, 2-deoxy-D-glucose, maleate and trans-aconitate, as well as two intermediates of the tricarboxylic-acid cycle, acetate and citrate, on the growth and metacyclogenesis of Trypanosoma cruzi. 0.1 mM phloretin increased the percentage of metacyclic forms about 2.7-fold without affecting growth rate, whereas the other inhibitors had no apparent effect on either growth or differentiation rates. The addition of 5 mM citrate stimulated differentiation by about 2.6-fold. When either 10 mM citrate or 10 mM acetate were added, on the other hand, both the growth and differentiation rates were severely inhibited.

  13. Comparison of fluorine-18-2-fluorodeoxyglucose and gallium-67 citrate imaging for detection of lymphoma

    SciTech Connect

    Paul, R.

    1987-03-01

    Patients with lymphomas are conventionally imaged with (/sup 67/Ga)citrate for tumor detection and determination of dissemination. Fluorine-18-2-fluoro-2-deoxy-D-glucose (( /sup 18/F)FDG) is a radiopharmaceutical that accumulates into tissues where glucose utilization is enhanced, such as tumors. Six cancer patients (five non-Hodgkin's lymphomas, one endodermal retroperitoneal sinus carcinoma) were imaged with (/sup 18/F)FDG and (/sup 67/Ga)citrate whole-body scintigraphies in order to compare the sensitivities of these two tumor imaging radiopharmaceuticals. Among the five untreated lymphoma patients, two /sup 67/Ga scans and four (/sup 18/F)FDG scans were positive; in the patient with the retroperitoneal carcinoma who had a positive (/sup 18/F)FDG scan before treatment, both scans were negative after treatment. Fluorine-18 FDG may be a more sensitive tumor-detecting radiopharmaceutical for non-Hodgkin's lymphoma than (/sup 67/Ga)citrate.

  14. Sildenafil citrate for the management of fetal growth restriction and oligohydramnios.

    PubMed

    Choudhary, Rana; Desai, Kavita; Parekh, Hetal; Ganla, Kedar

    2016-01-01

    Fetal growth restriction (FGR) and preeclampsia are the major causes of neonatal morbidity and mortality, which affect up to 8% of all pregnancies. The pathogenesis in FGR is an abnormal trophoblastic invasion leading to compromised uteroplacental circulation. However, in spite of this understanding and identification of high-risk patients, the management options are limited. There are some new studies which have demonstrated the role of sildenafil citrate in improving vasodilatation of small myometrial vessels and therefore improvement in amniotic fluid index, fetal weight, and even uterine and umbilical artery Doppler patterns. We report here the case of a 31-year-old female with infertility and preconceptional thin endometrium responding well to sildenafil citrate, followed by conception. However, she presented with an early-onset FGR at 26 weeks of gestation, and again after treatment with sildenafil citrate, showed improvement in amniotic fluid index and fetal weight, finally resulting in delivery of a full-term healthy baby with uneventful neonatal course.

  15. Tamoxifen citrate loaded ethosomes for transdermal drug delivery system: preparation and characterization.

    PubMed

    Sarwa, Khomendra Kumar; Suresh, Preeti K; Debnath, Manabendra; Ahmad, Mohammad Zaki

    2013-08-01

    Long term tamoxifen citrate therapy is imperative to treat several dermatological and hormonal sensitive disorders. Successful oral and parenteral administration of tamoxifen citrate has been challenging since it undergoes enzymatic degradation and has poor aqueous solubility issues. In the present work, tamoxifen citrate loaded ethosomes were prepared and characterized for transdermal applications. The prepared formulations were characterized for morphological features, particle size distribution, calorimetric attributes, zeta potential and drug entrapment. Permeation profile of prepared ethosomes was compared with liposomes and hydroethonalic solution across cellophane membrane and human cadaver skin. Results of the permeation studies indicate that ethosomes were able to deliver >90% drug within 24 hours of application, while liposomes and hydroethanolic solution delivered only 39.04% and 36.55% respectively. Skin deposition and stability studies are also reported.

  16. [Fenibut and its citrate prevent psychoneurological disorders caused by chronic stress (paradoxical sleep deprivation)].

    PubMed

    Tiurenkov, I N; Bagmetova, V V; Borodkina, L E; Berestovitskaia, V M; Vasil'eva, O S

    2012-01-01

    The antistress protective action of two structural analogs of GABA, fenibut and its salt with citric acid (fenibut citrate, citrocard, RGPU-147), has been studied using a model of chronic stress caused by seven-fold 24-h deprivation of paradoxical sleep phase at an interval of 24 h between the deprivations. It is established that fenibut and fenibut citrate produce a protective action by (i) reducing the intensity of emotional disorders in the open-field test and elevated plus maze test, (ii) decreasing cognitive disorders in the tests for conditioned avoidance response and extrapolatory deliverance; and (iii) limiting stress reaction due to a decrease in the intensity of adrenal hypertrophy, thymus involution, and stomach mucous membrane ulceration. Fenibut citrate surpasses fenibut in the intensity of antistress protective action.

  17. Interaction of monolaurin, eugenol and sodium citrate on growth of common meat spoilage and pathogenic organisms.

    PubMed

    Blaszyk, M; Holley, R A

    1998-02-17

    Interactions of monolaurin, eugenol (phenolic compound) and sodium citrate (chelator) on the growth of six organisms including common meat spoilage (Lactobacillus curvatus, Lactobacillus sake, Leuconostoc mesenteroides, Brochothrix thermosphacta) and pathogenic (Escherichia coli O157:H7 and Listeria monocytogenes) organisms were investigated. The combinations of 100 to 250 ppm monolaurin with 500 and 1000 ppm eugenol, and 0.2 and 0.4% sodium citrate were more effective than each component separately. More than one combination prevented detectable growth of each organism. Lactic acid bacteria (LAB) and E. coli O157:H7 were most resistant and L. monocytogenes and B. thermosphacta most sensitive to control by the chosen combinations. The presence of sodium citrate was necessary to yield potent inhibition of Lb. curvatus and Lb. sake growth by the monolaurin and eugenol combinations.

  18. Dietary and Lifestyle Factors and Medical Conditions Associated with Urinary Citrate Excretion

    PubMed Central

    Taylor, Eric N.; Curhan, Gary C.

    2013-01-01

    Summary Background and objectives Lower urinary citrate excretion is a risk factor for nephrolithiasis and associated with metabolic acidosis and higher prevalence of hypertension and insulin resistance. This study sought to quantify the independent predictors of urinary citrate excretion in population-based cohorts. Design, setting, participants, & measurements A cross-sectional study of 2561 individuals from the Health Professionals Follow-Up Study and Nurses’ Health Studies I and II who provided two 24-hour urine collections was conducted. Dietary data were ascertained from the semiquantitative food frequency questionnaire. Lifestyle and disease data were derived from responses to biennial questionnaires. Multivariable linear regression was used to quantify the predictors of urinary citrate excretion. Results After adjusting for age, urinary creatinine, dietary, and other factors, higher intake of nondairy animal protein (per 10 g/d; −20 mg/d; 95% confidence interval [−29 to −11]), higher body mass index (per 1 kg/m2; −4 mg/d; [−6 to −2]), and history of nephrolithiasis (−57 mg/d; [−79 to −36]), hypertension (−95 mg/d; [−119 to −71]), gout (−104 mg/d; [−155 to −54]), and thiazide use (−34 mg/d; [−68 to −1]) were independently associated with lower 24-hour urinary citrate excretion. Higher intake of potassium (per 1000 mg/d; 53 mg/d; [33 to 74]), higher urinary sodium (per 100 mEq/d; 56 mg/d; [31 to 80]), and history of diabetes (61 mg/d; [21 to 100]) were independently associated with higher citrate excretion. Conclusions Several dietary and lifestyle factors and medical conditions are independently associated with urinary citrate excretion. PMID:23449767

  19. Light wavelength influence on surface plasmon resonance in citrate-gold nanosystems

    NASA Astrophysics Data System (ADS)

    Lupusoru, Raoul-Vasile; Pricop, Daniela A.; Andries, Maria; Creanga, Dorina

    2016-12-01

    Citrate-gold particles were yielded according to classical method of auric salt reduction in two different synthesis media aiming to use them further applications in biomedical and environmental domains. The analysis of citrate-gold interaction was done through UV-vis and IR spectroscopy as well as by Transmission Electron Microscopy (TEM) and Dark Field (DF) Microscopy. Average particle size was higher for citrate-gold NPs synthesized with NaOH (32.5 nm) than for NPs synthesized with NaCl (15 nm). Dimensional histograms of one year aged colloidal suspensions presented mean size of 29 nm and respectively 18 nm. The influence of 90 min light exposure, analyzed by UV-vis, evidenced that for both NaOH synthesis protocol and NaCl protocol, plasmon band maxima at 528 nm and respectively 538 nm didn't changed, neither for white nor for green light. For one year aged samples this band shifted to 540 nm for green light irradiation in the case of citrate-gold NPs synthesized with NaOH. Also, for these NPs, both green and white light exposures resulted in plasmon band intensity changes for native as well as for aged samples. FTIR investigation showed also different changes at the level of the intensity of main vibration bands of citrate-gold after exposure to light, suggesting stronger adsorption of citrate in the case of NaCl addition in the initial reaction medium than in the case of NaOH. Finally, the utilization of NaCl in the synthesis protocol seems to favor the synthesis of more stable and lower toxicity colloidal suspensions, both during time and under the light irradiation.

  20. Use of Potassium Citrate to Reduce the Risk of Renal Stone Formation During Spaceflight

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Pietrzyk, R. A.; Sams, C. F.; Jones, J. A.; Nelman-Gonzalez, M.; Hudson, E. K.

    2008-01-01

    Introduction: NASA s Vision for Space Exploration centers on exploration class missions including the goals of returning to the moon and landing on Mars. One of NASA s objectives is to focus research on astronaut health and the development of countermeasures that will protect crewmembers during long duration voyages. Exposure to microgravity affects human physiology and results in changes in the urinary chemical composition favoring urinary supersaturation and an increased risk of stone formation. Nephrolithiasis is a multifactorial disease and development of a renal stone is significantly influenced by both dietary and environmental factors. Previous results from long duration Mir and short duration Shuttle missions have shown decreased urine volume, pH, and citrate levels and increased calcium. Citrate, an important inhibitor of calcium-containing stones, binds with urinary calcium reducing the amount of calcium available to form stones. Citrate inhibits renal stone recurrence by preventing crystal growth, aggregation, and nucleation and is one of the most common therapeutic agents used to prevent stone formation. Methods: Thirty long duration crewmembers (29 male, 1 female) participated in this study. 24-hour urines were collected and dietary monitoring was performed pre, in, and postflight. Crewmembers in the treatment group received two potassium citrate (KCIT) pills, 10 mEq/pill, ingested daily beginning 3 days before launch, all inflight days and through 14 days postflight. Urinary biochemical and dietary analyses were completed. Results: KCIT treated subjects exhibited decreased urinary calcium excretion and maintained the levels of calcium oxalate supersaturation risk at their preflight levels. The increased urinary pH levels in these subjects reduced the risk of uric acid stones. Discussion: The current study investigated the use of potassium citrate as a countermeasure to minimize the risk of stone formation during ISS missions. Results suggest that

  1. Chitosan citrate as multifunctional polymer for vaginal delivery. Evaluation of penetration enhancement and peptidase inhibition properties.

    PubMed

    Bonferoni, Maria Cristina; Sandri, Giuseppina; Rossi, Silvia; Ferrari, Franca; Gibin, Sara; Caramella, Carla

    2008-02-05

    In the present work the employment of chitosan citrate (Chs citrate) as multifunctional polymer in vaginal applications was evaluated. Potential properties of penetration enhancement and protease inhibition could be expected because of the capability of citrate to bind divalent cations such as calcium, that is involved in the regulation of gap and tight junctions, and zinc, that is essential co-factor for some proteases. A comparison was performed with chitosan HCl (Chs HCl). Ex vivo drug permeation experiments were performed on pig vaginal mucosa, by application of 3.0% (w/w) chitosan gels. Acyclovir (5.0%, w/w) and ciprofloxacin HCl (0.3%, w/w) were used as low molecular weight model drugs. Fluorescein isothiocyanate dextran MW 4400 (FD4) was used as hydrophilic high molecular weight fluorescent probe (0.2%, w/w). In the case of low MW drugs the amount penetrated into pig vaginal mucosa was measured by extraction from tissue slices and HPLC detection. From the samples maintained in contact with FD4, slices were cut perpendicularly to the surface and observed by means of confocal laser scanning microscopy (CLSM). FD4 permeation was also measured in in-vitro cell culture model (Caco-2). The penetration enhancing capacity of Chs citrate was comparable to that of Chs HCl. Both Chs citrate and Chs HCl were tested for the inhibition of the proteolytic enzymes carboxypeptidase A and leucine aminopeptidase. In both cases Chs citrate showed a significantly higher inhibition of enzymatic activity with respect to Chs HCl.

  2. Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers.

    PubMed

    Pratt, Raymond D; Swinkels, Dorine W; Ikizler, T Alp; Gupta, Ajay

    2017-03-01

    Ferric pyrophosphate citrate (Triferic) is a water-soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double-blind, randomized, placebo-controlled, single-, ascending-dose study was conducted to evaluate the pharmacokinetics and safety of intravenous ferric pyrophosphate citrate in 48 healthy iron-replete subjects (drug, n = 36; placebo, n = 12). Single doses of 2.5, 5.0, 7.5, or 10 mg of ferric pyrophosphate citrate or placebo were administered over 4 hours, and single doses of 15 or 20 mg of ferric pyrophosphate citrate or placebo were administered over 12 hours via intravenous infusion. Serum total iron (sFetot ), transferrin-bound iron (TBI), hepcidin-25, and biomarkers of oxidative stress and inflammation were determined using validated assays. Marked diurnal variation in sFetot was observed in placebo-treated subjects. Concentrations of sFetot and TBI increased rapidly after drug administration, with maximum serum concentrations (Cmax ) reached at the end of infusion. Increases in baseline-corrected Cmax and area under the concentration-time curve from 0 to the time of the last quantifiable concentration (AUC0-t ) were dose proportional up to 100% transferrin saturation. Iron was rapidly cleared (apparent terminal phase half-life 1.2-2 hours). No significant changes from baseline in serum hepcidin-25 concentration were observed at end of infusion for any dose. Biomarkers of oxidative stress and inflammation were unaffected. Intravenous doses of ferric pyrophosphate citrate were well tolerated. These results demonstrate that intravenous ferric pyrophosphate citrate is rapidly bound to transferrin and cleared from the circulation without increasing serum hepcidin levels or biomarkers of oxidative stress or inflammation. © 2016 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  3. Sildenafil citrate monohydrate-cyclodextrin nanosuspension complexes for use in metered-dose inhalers.

    PubMed

    Sawatdee, Somchai; Phetmung, Hirihattaya; Srichana, Teerapol

    2013-10-15

    Sildenafil is a selective phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension. Sildenafil citrate monohydrate was complexed with α-, hydroxypropyl-β- and γ-cyclodextrin (α-CD, HP-β-CD and γ-CD, respectively) to enhance its water solubility. The complexes of sildenafil citrate monohydrate with all types of CDs were characterized by phase solubility diagrams, (1)H and (13)C NMR, and dielectric constants. Sildenafil citrate monohydrate complexed with CDs was developed as nanosuspensions for use in a pressurized metered-dose inhaler (pMDI). Sildenafil citrate monohydrate pMDI formulations were prepared by a bottom-up process using dried ethanol as a solvent and HFA-134a as an antisolvent and propellant in order to form nanosuspensions. A 3×3 factorial design was applied for the contents of the dried ethanol and HFA-134a propellant. The phase solubility profiles of the sildenafil and cyclodextrins were described as AL type with a mole ratio 1:1. The piperazine moiety of sildenafil formed an inclusion in the cavity of the CDs. The particle diameters of the sildenafil citrate monohydrate suspensions in pMDIs were all within a nanosuspension size range. An assay of the sildenafil content showed that the formation of complexes with CDs was close to 100%. In the case of the formulations with CDs, the emitted doses varied within 97.4±10.8%, the fine particle fractions (FPFs) were in a range of 45-81%, the fine particle dose (FPD) was 12.6±2.0 μg and the mass median aerodynamic diameters (MMADs) were 1.86±0.41 μm. In contrast, the formulations without CDs produced a low emitted dose of sildenafil (<60%). Therefore, only sildenafil citrate monohydrate pMDI formulations containing CDs were suitable for use as aerosols.

  4. Regional citrate anticoagulation for continuous venovenous hemodiafiltration using calcium-containing dialysate.

    PubMed

    Gupta, Monika; Wadhwa, Nand K; Bukovsky, Rose

    2004-01-01

    Regional anticoagulation with trisodium citrate for continuous venovenous hemodiafiltration (CVVHDF) is an effective and safe alternative to heparin, especially in patients at high risk for bleeding. However, regional citrate anticoagulation is not used widely because current protocols are complex, labor intensive, and cumbersome. Existing protocols require the use of calcium-free dialysate with a continuous systemic calcium infusion to prevent hypocalcemia. We evaluated Anticoagulant Citrate Dextrose Formula A (ACD-A) solution for regional anticoagulation in CVVHDF in combination with a commercially available calcium-containing dialysis solution. Thirty-eight patients in the intensive care units underwent citrate-based CVVHDF using low-calcium peritoneal dialysis solution (calcium, 5.0 mg/dL [1.25 mmol/L]). ACD-A infusion rate was adjusted to maintain postfilter ionized calcium (iCa++) levels at 1.0 to 2.0 mg/dL (0.25 to 0.5 mmol/L). Calcium chloride (10%) solution was administered intravenously every 6 hours on an as-needed basis to maintain systemic serum iCa++ levels at 3.5 to 4.0 mg/dL (0.88 to 1.0 mmol/L). CVVHDF was performed for a total of 394 days using 149 hemofilters. Mean hemofilter life span was 63.5 +/- 27.1 hours. Seventy-five percent, 61%, and 49% of hemofilters were patent at 24, 48, and 72 hours, respectively. No patient experienced a change in clinical status caused by hypocalcemia and/or signs and symptoms of citrate toxicity. Four patients developed metabolic alkalosis requiring 0.1 N of hydrochloric acid infusion. Our simplified technique of regional citrate anticoagulation for CVVHDF using calcium-containing dialysate is not associated with increased hemofilter clotting and obviates the need for a continuous systemic calcium infusion and calcium-free dialysate.

  5. Selective cytopheretic inhibitory device with regional citrate anticoagulation and portable sorbent dialysis.

    PubMed

    Pino, Christopher J; Farokhrani, Amin; Lou, Liandi; Smith, Peter L; Johnston, Kimberly; Buffington, Deborah A; Humes, H David

    2013-02-01

    Selective cytopheretic inhibitory device (SCD) therapy is an immunomodulatory treatment provided by a synthetic biomimetic membrane in an extracorporeal circuit, which has shown promise in preclinical large animal models of severe sepsis as well as in clinical trials treating patients with acute kidney injury and multiple organ failure. During SCD therapy, citrate is administered to lower ionized calcium levels in blood for anticoagulation and inhibition of leukocyte activation. Historically, citrate has been known to interfere with sorbent dialysis, therefore, posing a potential issue for the use of SCD therapy with a portable dialysis system. This sorbent dialysis SCD (sorbent SCD) would be well suited for battlefield and natural disaster applications where the water supply for standard dialysis is limited, and the types of injuries in those settings would benefit from SCD therapy. In order to explore the compatibility of sorbent and SCD technologies, a uremic porcine model was tested with the Allient sorbent dialysis system (Renal Solutions Incorporated, Fresenius Medical Care, Warrendale, PA, USA) and concurrent SCD therapy with regional citrate anticoagulation. The hypothesis to be assessed was whether the citrate load required by the SCD could be metabolized prior to recirculation from systemic blood back into the therapeutic circuit. Despite the fact that the sorbent SCD maintained urea clearance without any adverse hematologic events, citrate load for SCD therapy caused an interaction with the sorbent column resulting in elevated, potentially toxic aluminum levels in dialysate and in systemic blood. Alternative strategies to implement sorbent-SCD therapy will be required, including development of alternate urease-sorbent column binding chemistry or further changes to the sorbent-SCD therapeutic circuit along with determining the minimum citrate concentration required for efficacious SCD treatment.

  6. Comparison of Elaeagnus angustifolia Extract and Sildenafil Citrate on Female Orgasmic Disorders: A Randomized Clinical Trial

    PubMed Central

    Akbarzadeh, Marzieh; Zeinalzadeh, Sanaz; Zolghadri, Jaleh; Mohagheghzadeh, Abdolali; Faridi, Pouya; Sayadi, Mehrab

    2014-01-01

    Background Orgasmic disorder can create a feeling of deprivation and failure and provide mental problems, incompatibility and marital discord. This study aimed to compare the effects of Elaeagnus angustifolia flower extract and sildenafil citrate on female orgasmic disorder in women in 2013. Methods In this randomized clinical trial, 125 women between 18-40 years old who suffered from orgasmic disorder were divided into three E. angustifolia, sildenafil citrate and control groups. The data were gathered using Female Sexual Function Index and through measurement of TSH and prolactin. The first intervention group had to consume 4.5 gr E. angustifolia extract in two divided doses for 35 days and the second one had to use 50 mg sildenafil citrate tablets for 4 weeks one hour before their sexual relationship. However, the control group had to consume the placebo. The data were analyzed using paired t-test, one-way ANOVA, and Bonferroni posthoc test and p<0.05 was considered significant. Results The frequency of orgasmic disorder before the intervention was 41.5%, 40.5%, and 57.1% in E. angustifolia, sildenafil citrate, and control groups, respectively (p=0.23). However, these measures were respectively 29.3%, 16.7%, and 50% after the intervention (p=0.004). A significant difference between the two groups regarding sexual satisfaction after the intervention (p=0.003) compared to the beginning of the study (p=0.356). Besides, the highest reduction of changes after the intervention (58.82%) was observed in the sildenafil citrate group. Conclusion Both E. angustifolia extract and sildenafil citrate were effective in reduction of the frequency of orgasmic disorder in women. PMID:25473627

  7. Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?

    PubMed

    Bagis, Selda; Karabiber, Mehmet; As, Ismet; Tamer, Lülüfer; Erdogan, Canan; Atalay, Ayçe

    2013-01-01

    The aims of this study were to investigate the relationship between magnesium levels and fibromyalgia symptoms and to determine the effect of magnesium citrate treatment on these symptoms. Sixty premenopausal women diagnosed with fibromyalgia according to the ACR criteria and 20 healthy women whose age and weight matched the premenopausal women were evaluated. Pain intensity, pain threshold, the number of tender points, the tender point index, the fibromyalgia impact questionnaire (FIQ), the Beck depression and Beck anxiety scores and patient symptoms were evaluated in all the women. Serum and erythrocyte magnesium levels were also measured. The patients were divided into three groups. The magnesium citrate (300 mg/day) was given to the first group (n = 20), amitriptyline (10 mg/day) was given to the second group (n = 20), and magnesium citrate (300 mg/day) + amitriptyline (10 mg/day) treatment was given to the third group (n = 20). All parameters were reevaluated after the 8 weeks of treatment. The serum and erythrocyte magnesium levels were significantly lower in patients with fibromyalgia than in the controls. Also there was a negative correlation between the magnesium levels and fibromyalgia symptoms. The number of tender points, tender point index, FIQ and Beck depression scores decreased significantly with the magnesium citrate treatment. The combined amitriptyline + magnesium citrate treatment proved effective on all parameters except numbness. Low magnesium levels in the erythrocyte might be an etiologic factor on fibromyalgia symptoms. The magnesium citrate treatment was only effective tender points and the intensity of fibromyalgia. However, it was effective on all parameters when used in combination with amitriptyline.

  8. Aggregation Kinetics of Citrate and Polyvinylpyrrolidone Coated Silver Nanoparticles in Monovalent and Divalent Electrolyte Solutions

    PubMed Central

    Huynh, Khanh An; Chen, Kai Loon

    2011-01-01

    The aggregation kinetics of silver nanoparticles (AgNPs) that were coated with two commonly used capping agents—citrate and polyvinylpyrrolidone (PVP)—were investigated. Time-resolved dynamic light scattering (DLS) was employed to measure the aggregation kinetics of the AgNPs over a range of monovalent and divalent electrolyte concentrations. The aggregation behavior of citrate-coated AgNPs in NaCl was in excellent agreement with the predictions based on Derjaguin–Landau–Verwey–Overbeek (DLVO) theory, and the Hamaker constant of citrate-coated AgNPs in aqueous solutions was derived to be 3.7 × 10-20 J. Divalent electrolytes were more efficient in destabilizing the citrate-coated AgNPs, as indicated by the considerably lower critical coagulation concentrations (2.1 mM CaCl2 and 2.7 mM MgCl2 vs. 47.6 mM NaCl). The PVP-coated AgNPs were significantly more stable than citrate-coated AgNPs in both NaCl and CaCl2, which is likely due to steric repulsion imparted by the large, non-charged polymers. The addition of humic acid resulted in the adsorption of the macromolecules on both citrate- and PVP-coated AgNPs. The adsorption of humic acid induced additional electrosteric repulsion that elevated the stability of both nanoparticles in suspensions containing NaCl or low concentrations of CaCl2. Conversely, enhanced aggregation occurred for both nanoparticles at high CaCl2 concentrations due to interparticle bridging by humic acid clusters. PMID:21630686

  9. Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers

    PubMed Central

    Swinkels, Dorine W.; Ikizler, T. Alp; Gupta, Ajay

    2016-01-01

    Abstract Ferric pyrophosphate citrate (Triferic) is a water‐soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double‐blind, randomized, placebo‐controlled, single‐, ascending‐dose study was conducted to evaluate the pharmacokinetics and safety of intravenous ferric pyrophosphate citrate in 48 healthy iron‐replete subjects (drug, n = 36; placebo, n = 12). Single doses of 2.5, 5.0, 7.5, or 10 mg of ferric pyrophosphate citrate or placebo were administered over 4 hours, and single doses of 15 or 20 mg of ferric pyrophosphate citrate or placebo were administered over 12 hours via intravenous infusion. Serum total iron (sFetot), transferrin‐bound iron (TBI), hepcidin‐25, and biomarkers of oxidative stress and inflammation were determined using validated assays. Marked diurnal variation in sFetot was observed in placebo‐treated subjects. Concentrations of sFetot and TBI increased rapidly after drug administration, with maximum serum concentrations (Cmax) reached at the end of infusion. Increases in baseline‐corrected Cmax and area under the concentration‐time curve from 0 to the time of the last quantifiable concentration (AUC0‐t) were dose proportional up to 100% transferrin saturation. Iron was rapidly cleared (apparent terminal phase half‐life 1.2‐2 hours). No significant changes from baseline in serum hepcidin‐25 concentration were observed at end of infusion for any dose. Biomarkers of oxidative stress and inflammation were unaffected. Intravenous doses of ferric pyrophosphate citrate were well tolerated. These results demonstrate that intravenous ferric pyrophosphate citrate is rapidly bound to transferrin and cleared from the circulation without increasing serum hepcidin levels or biomarkers of oxidative stress or inflammation. PMID:27557937

  10. Modulation of calcium oxalate monohydrate crystallization by citrate through selective binding to atomic steps

    SciTech Connect

    Qiu, S R; Wierzbicki, A; Salter, E A; Zepeda, S; Orme, C A; Hoyer, J R; Nancollas, G H; Cody, A M; De Yoreo, J J

    2004-10-19

    The majority of human kidney stones are composed primarily of calcium oxalate monohydrate (COM) crystals. Thus, determining the molecular mechanisms by which urinary constituents modulate calcium oxalate crystallization is crucial for understanding and controlling urolithiassis in humans. A comprehensive molecular-scale view of COM shape modification by citrate, a common urinary constituent, obtained through a combination of in situ atomic force microscopy (AFM) and molecular modeling is now presented. We show that citrate strongly influences the growth morphology and kinetics on the (-101) face but has much lower effect on the (010) face. Moreover, binding energy calculations show that the strength of the citrate-COM interaction is much greater at steps than on terraces and is highly step-specific. The maximum binding energy, -166.5 kJ {center_dot} mol{sup -1}, occurs for the [101] step on the (-101) face. In contrast, the value is only -56.9 kJ {center_dot} mol-1 for the [012] step on the (010) face. The binding energies on the (-101) and (010) terraces are also much smaller, -65.4 and -48.9 kJ {center_dot} mol{sup -1} respectively. All other binding energies lie between these extremes. This high selectivity leads to preferential binding of citrate to the acute [101] atomic steps on the (-101) face. The strong citrate-step interactions on this face leads to pinning of all steps, but the anisotropy in interaction strength results in anisotropic reductions in step kinetics. These anisotropic changes in step kinetics are, in turn, responsible for changes in the shape of macroscopic COM crystals. Thus, the molecular scale growth morphology and the bulk crystal habit in the presence of citrate are similar, and the predictions of molecular simulations are fully consistent with the experimental observations.

  11. Isoexergonic Conformations of Surface-Bound Citrate Regulated Bioinspired Apatite Nanocrystal Growth.

    PubMed

    Wang, Ziqiu; Xu, Zhijun; Zhao, Weilong; Chen, Wei; Miyoshi, Toshikazu; Sahai, Nita

    2016-10-05

    The superior biomechanical properties of bone and dentin are dictated, in part, by the unique plate-like morphology of hydroxyapatite (HAP) nanocrysals within a hierarchically assembled collagen matrix. Understanding the mechanism of crystal growth and thus morphology is important to the rational design of bioinspired apatite nanocrystals for orthopedic and dental applications. Citrate has long been proposed to modulate apatite crystal growth, but major questions exist regarding the HAP-bound citrate conformations and the identities of the interacting functional groups and HAP surface sites. Here, we conducted a comprehensive investigation of the mechanism from the angstrom to submicrometer scale by detailed correlation of the results of high-level metadynamics simulations, employing force-fields benchmarked to experiment and density functional theory calculations with the results of high resolution transmission electron microscopy, nuclear magnetic resonance spectroscopy, solution analysis, and thermogravimetric analysis. Crystal morphology changed from needle- to plate-like with increasing citrate concentration. Citrate adsorbed more strongly on the HAP (100) face than on the (001) face, thus resulting in preferential growth in the [001] direction and the plate-like morphology. Two very different bound conformations were obtained, involving interactions of either one or both terminal carboxyl groups with three or five surface calcium ions, respectively, and a hydrogen bond between the citrate hydroxyl and the HAP surface. Remarkably, despite fewer interaction sites in the single bound carboxyl conformation, the structures were isoexergonic, so both exist at equilibrium. Identification of the former conformation is significant because it allows a greater adsorption density than is traditionally assumed and can help explain concentration-dependence of citrate in modulating crystal morphology. These unique results were enabled first by the application of advanced

  12. Thermosensitive bioadhesive gels for the vaginal delivery of sildenafil citrate: in vitro characterization and clinical evaluation in women using clomiphene citrate for induction of ovulation.

    PubMed

    Soliman, Ghareb M; Fetih, Gihan; Abbas, Ahmed M

    2017-03-01

    The objective of this study is to develop and characterize in situ thermosensitive gels for the vaginal administration of sildenafil as a potential treatment of endometrial thinning occurring as a result of using clomiphene citrate for ovulation induction in women with type II eugonadotrophic anovulation. While sildenafil has shown promising results in the treatment of infertility in women, the lack of vaginal pharmaceutical preparation and the side effects associated with oral sildenafil limit its clinical effectiveness. Sildenafil citrate in situ forming gels were prepared using different grades of Pluronic(®) (PF-68 and PF-127). Mucoadhesive polymers as sodium alginate and hydroxyethyl cellulose were added to the gels in different concentrations and the effect on gel properties was studied. The formulations were evaluated in terms of viscosity, gelation temperature (Tsol-gel), mucoadhesion properties, and in vitro drug release characteristics. Selected formulations were evaluated in women with clomiphene citrate failure due to thin endometrium (Clinicaltrial.gov identifier NCT02766725). The Tsol-gel decreased with increasing PF-127 concentration and it was modulated by addition of PF-68 to be within the acceptable range of 28-37 °C. Increasing Pluronic® concentration increased gel viscosity and mucoadhesive force but decreased drug release rate. Clinical results showed that the in situ sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow with no reported side effects. Further, these results were achieved at lower frequency and duration of drug administration. Sildenafil thermosensitive vaginal gels might result in improved potential of pregnancy in anovulatory patients with clomiphene citrate failure due to thin endometrium.

  13. Calcium absorption from apple and orange juice fortified with calcium citrate malate (CCM).

    PubMed

    Andon, M B; Peacock, M; Kanerva, R L; De Castro, J A

    1996-06-01

    Determine calcium (Ca) absorption from Ca fortified orange and apple juice. Absorbability was assessed by measuring 45Ca absorption in healthy women (mean age 57 years, n = 57/group) and whole body 47Ca retention in adult female beagle dogs (n = 6/group) and young adult male rats (n = 6/group). Women received 6.24 mmol (250 mg) Ca as calcium citrate malate fortified orange juice (CCM-OJ) or apple juice (CCM-AJ). Dogs received 3.12 mmol (125 mg) Ca as CCM-OJ or CCM-AJ. Rats were administered 0.15 mmol (6 mg) Ca as either milk, CCM-OJ, or CCM-AJ. Additional 47Ca whole body retention experiments in rats measured the effects of differences in the carbohydrate and organic acid contents of the juices on Ca absorption. Mean +/- SEM percent Ca fractional absorption was greater (p < 0.003) in women who consumed CCM-AJ (42 +/- 2%) than those who consumed CCM-OJ (36 +/- 1%). Ca retention in dogs was 15 +/- 1% for CCM-OJ and 29 +/- 2% for CCM-AJ (p < 0.001). Ca retention was significantly different (p < 0.05) in rats administered milk (42 +/- 2%), CCM-OJ (52 +/- 2%), or CCM-AJ (61 +/- 2%). By manipulating the carbohydrate and organic acid concentrations of test solutions to mimic the composition of Ca fortified juices, we found that the greater fructose and lower organic acid content of apple juice accounted for its greater Ca absorbability. CCM fortified versions of orange and apple juice have high Ca absorbability and are potentially important vehicles for increasing dietary Ca intake. The greater Ca absorption from CCM-AJ compared with CCM-OJ is accounted for by differences in the carbohydrate and organic acid content of the juices. These data suggest that by modifying common beverage ingredients, products with even greater Ca absorbability could be formulated.

  14. The health benefits of calcium citrate malate: a review of the supporting science.

    PubMed

    Reinwald, Susan; Weaver, Connie M; Kester, Jeffrey J

    2008-01-01

    There has been considerable investigation into the health benefits of calcium citrate malate (CCM) since it was first patented in the late 1980s. This chapter is a comprehensive summary of the supporting science and available evidence on the bioavailability and health benefits of consuming CCM. It highlights the important roles that CCM can play during various life stages. CCM has been shown to facilitate calcium retention and bone accrual in children and adolescents. In adults, it effectively promotes the consolidation and maintenance of bone mass. In conjunction with vitamin D, CCM also decreases bone fracture risk in the elderly, slows the rate of bone loss in old age, and is of benefit to the health and well-being of postmenopausal women. CCM is exceptional in that it confers many unique benefits that go beyond bone health. Unlike other calcium sources that necessitate supplementation be in conjunction with a meal to ensure an appreciable benefit is derived, CCM can be consumed with or without food and delivers a significant nutritional benefit to individuals of all ages. The chemistry of CCM makes it a particularly beneficial calcium source for individuals with hypochlorydia or achlorydia, which generally includes the elderly and those on medications that decrease gastric acid secretion. CCM is also recognized as a calcium source that does not increase the risk of kidney stones, and in fact it protects against stone-forming potential. The versatile nature of CCM makes it a convenient and practical calcium salt for use in moist foods and beverages. The major factor that may preclude selection of CCM as a preferred calcium source is the higher cost compared to other sources of calcium commonly used for fortification (e.g., calcium carbonate and tricalcium phosphate). However, formation of CCM directly within beverages or other fluid foods and/or preparations, and the addition of a concentrated CCM solution or slurry, are relatively cost-effective methods by

  15. In vitro enamel remineralization by low-fluoride toothpaste with calcium citrate and sodium trimetaphosphate.

    PubMed

    Hirata, Edo; Danelon, Marcelle; Freire, Isabelle Rodrigues; Delbem, Alberto Carlos Botazzo

    2013-01-01

    The objective of this study was to evaluate in vitro the effect of a low fluoride toothpaste (450 µgF/g, NaF) combined with calcium citrate (Cacit) and sodium trimetaphosphate (TMP) on enamel remineralization. Bovine enamel blocks had the enamel surface polished sequentially to determine the surface hardness. After production of artificial carious lesions, the blocks selected by their surface hardness were submitted to remineralization pH cycling and daily treatment with dentifrice suspensions (diluted in deionized water or artificial saliva): placebo, 275, 450, 550 and 1,100 µgF/g and commercial dentifrice (positive control, 1,100 µgF/g). Finally, the surface and cross-section hardness was determined for calculating the change of surface hardness (%SH) and mineral content (%∆Z). Fluoride in enamel was also determined. The data from %SH, %∆Z and fluoride were subjected to two-way analysis of variance followed by Student-Newman-Keuls's test (p<0.05). The mineral gain (%SH and %∆Z) was higher for toothpastes diluted in saliva (p<0.05), except for the 450 µgF/g dentifrice with Cacit/TMP (p>0.05). The 450 Cacit/TMP toothpaste and the positive control showed similar results (p>0.05) when diluted in water. A dose-response was observed between fluoride concentration in toothpastes and fluoride present in enamel, regardless of dilution. It was concluded that it is possible to enhance the remineralization capacity of low F concentration toothpaste by of organic (Cacit) and inorganic (TMP) compounds with affinity to hydroxyapatite.

  16. Comparison of samples obtained from 3.2% sodium citrate glass and two 3.2% sodium citrate plastic blood collection tubes used in coagulation testing.

    PubMed

    Gosselin, Robert C; Janatpour, Kim; Larkin, Edward C; Lee, Yanlap P; Owings, John T

    2004-12-01

    We sought to compare coagulation test results obtained from patients using 2 plastic blood collection tubes and the traditional glass blood collection tube. Blood specimens were obtained from 241 patients in 3.2% buffered sodium citrate using standard glass tubes, in 3.2% buffered sodium citrate in plastic tubes, and in 3.2% sodium citrate "sandwich" tubes (plastic within plastic). All samples were obtained and processed contemporaneously and tested for prothrombin time (PT) and activated partial thromboplastin time (aPTT). Residual plasma was frozen at -70 degrees C for future testing, including fibrinogen, antithrombin, plasminogen, protein C and protein S (functional and antigenic), dilute Russell viper venom time (DRVVT), ristocetin cofactor, factor XIII, D dimer, anti-Xa activity, and prothrombin fragment. Although paired t test analysis revealed statistically significant differences (P < .05) between glass and plastic for PT, aPTT, fibrinogen, protein C (functional and antigenic), functional protein S, DRVVT and confirmation method, antithrombin, and factor XIII, these differences were not considered clinically significant.

  17. 76 FR 47146 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Extension of Time...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-04

    ... International Trade Administration Citric Acid and Certain Citrate Salts From the People's Republic of China...'') published the initiation of the administrative review of the antidumping duty order on citric acid and certain citrate salts (``citric acid'') from the People's Republic of China (``PRC''). See Initiation of...

  18. 76 FR 77206 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Final Results of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-12

    ... International Trade Administration Citric Acid and Certain Citrate Salts From the People's Republic of China...'') has completed its administrative review of the countervailing duty (``CVD'') order on citric acid and... Citric Acid and Certain Citrate Salts from the People's Republic of China: Preliminary Results of...

  19. 77 FR 47370 - Citric Acid and Certain Citrate Salts from the People's Republic of China: Intent To Rescind...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-08

    ... International Trade Administration Citric Acid and Certain Citrate Salts from the People's Republic of China... countervailing duty (CVD) order on citric acid and certain citrate salts from the People's Republic of China.\\1...). Scope of the Order The scope of the order includes all grades and granulation sizes of citric acid...

  20. 77 FR 1455 - Citric Acid and Certain Citrate Salts From the People's Republic of China: Extension of Time...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-10

    ... International Trade Administration Citric Acid and Certain Citrate Salts From the People's Republic of China... acid and certain citrate salts (``citric acid'') from the People's Republic of China (``PRC''). See... of the administrative review of citric acid from the PRC within this time limit. Specifically...