Seasonal variations of low molecular weight hydroxy-dicarboxylic acids and oxaloacetic acid in remote marine aerosols from Chichijima Island in the western North Pacific (December 2010-November 2011)

Science.gov (United States)

Gowda, Divyavani; Kawamura, Kimitaka

2018-05-01

Concentrations of homologous hydroxy-dicarboxylic acids (diacids) (hC3-hC6) and keto-diacid (oxaloacetic acid) were measured in the atmospheric aerosols collected at Chichijima Island (27.04° N, 142.13° E) in the western North Pacific from December 2010 to November 2011. The monthly averaged concentrations of hydroxy-diacids and oxaloacetic acid were significantly higher in spring followed by winter and autumn. Molecular distributions of hydroxy-diacids demonstrated that malic acid was the most abundant species in all four seasons, followed by tartronic acid in winter and spring and 3- and 2-hydroxyglutaric acids in summer and autumn. Hydroxy-diacids and keto-diacid maximized in spring and winter when air masses originated from the Asian continent with westerly winds. The concentrations of total hydroxy-diacids and oxaloacetic acid ranged from 0.1 to 27.3 ng m-3 and Asia to remote Chichijima Island followed by photochemical processing of organic aerosols. Seasonal molecular distribution of hydroxy-diacids and oxaloacetic acid was found to be dependent on the source strengths and plausible photochemical processing to form smaller diacids. Moderate to strong correlations among hydroxy-diacids, oxaloacetic acid and low molecular weight (LMW) diacids suggest that hydroxy-diacids and oxaloacetic acid are the intermediates in the photochemical oxidation of LMW diacid. Hence, photochemical formation of the most abundant LMW diacids, i.e., oxalic acid, could be produced from hydroxy- and keto-diacid as intermediates.

Development of a novel ultrasensitive enzyme immunoassay for human glutamic acid decarboxylase 65 antibody.

Science.gov (United States)

Numata, Satoshi; Katakami, Hideki; Inoue, Shinobu; Sawada, Hirotake; Hashida, Seiichi

2016-07-01

We developed a novel, ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for determination of glutamic acid decarboxylase autoantibody concentrations in serum samples from patients with type 2 diabetes. We developed an immune complex transfer enzyme immunoassay for glutamic acid decarboxylase autoantibody and measured glutamic acid decarboxylase autoantibody from 22 patients with type 1 diabetes, 29 patients with type 2 diabetes, and 32 healthy controls. A conventional ELISA kit identified 10 patients with type 1 diabetes and one patient with type 2 diabetes as glutamic acid decarboxylase autoantibody positive, whereas 15 patients with type 1 diabetes and six patients with type 2 diabetes were identified as glutamic acid decarboxylase autoantibody positive using immune complex transfer enzyme immunoassay. Immune complex transfer enzyme immunoassay is a highly sensitive and specific assay for glutamic acid decarboxylase autoantibody and might be clinically useful for diabetic onset prediction and early diagnosis. © The Author(s) 2016.

Glutamic acid decarboxylase isoform distribution in transgenic mouse septum: an anti-GFP immunofluorescence study.

Science.gov (United States)

Verimli, Ural; Sehirli, Umit S

2016-09-01

The septum is a basal forebrain region located between the lateral ventricles in rodents. It consists of lateral and medial divisions. Medial septal projections regulate hippocampal theta rhythm whereas lateral septal projections are involved in processes such as affective functions, memory formation, and behavioral responses. Gamma-aminobutyric acidergic neurons of the septal region possess the 65 and 67 isoforms of the enzyme glutamic acid decarboxylase. Although data on the glutamic acid decarboxylase isoform distribution in the septal region generally appears to indicate glutamic acid decarboxylase 67 dominance, different studies have given inconsistent results in this regard. The aim of this study was therefore to obtain information on the distributions of both of these glutamic acid decarboxylase isoforms in the septal region in transgenic mice. Two animal groups of glutamic acid decarboxylase-green fluorescent protein knock-in transgenic mice were utilized in the experiment. Brain sections from the region were taken for anti-green fluorescent protein immunohistochemistry in order to obtain estimated quantitative data on the number of gamma-aminobutyric acidergic neurons. Following the immunohistochemical procedures, the mean numbers of labeled cells in the lateral and medial septal nuclei were obtained for the two isoform groups. Statistical analysis yielded significant results which indicated that the 65 isoform of glutamic acid decarboxylase predominates in both lateral and medial septal nuclei (unpaired two-tailed t-test p glutamic acid decarboxylase isoform 65 in the septal region in glutamic acid decarboxylase-green fluorescent protein transgenic mice.

Investigation of the biosynthesis of acetyl-CoA and oxaloacetic acid from pyruvic acid and the quantitative evaluation of incorporated 13C-labeled l-alanine in Arthrobacter hyalinus

International Nuclear Information System (INIS)

Katsumi Iida

2014-01-01

Studies on the contribution to acetyl-CoA and oxaloacetic acid from the pyruvic acid transformation from l-alanine in Arthrobacter hyalinus were conducted by means of feeding experiments with l-[1- 13 C]alanine and l-[3- 13 C]alanine, followed by an analysis of the labeling patterns of coproporphyrinogen III using 13 C NMR spectroscopy. The results demonstrated that l-alanine was transformed via pyruvic acid to both acetyl-CoA and oxaloacetic acid. Additionally, the quantitative analysis indicated that pyruvic acid was transformed to acetyl-CoA and oxaloacetic acid in the ratio of 1:0.8. (author)

Ornithine decarboxylase, polyamines, and pyrrolizidine alkaloids in senecio and crotalaria.

Science.gov (United States)

Birecka, H; Birecki, M; Cohen, E J; Bitonti, A J; McCann, P P

1988-01-01

When tested for ornithine and arginine decarboxylases, pyrrolizidine alkaloid-bearing Senecio riddellii, S. longilobus (Compositae), and Crotalaria retusa (Leguminosae) plants exhibited only ornithine decarboxylase activity. This contrasts with previous studies of four species of pyrrolizidine alkaloid-bearing Heliotropium (Boraginaceae) in which arginine decarboxylase activity was very high relative to that of ornithine decarboxylase. Unlike Heliotropium angiospermum and Heliotropium indicum, in which endogenous arginine was the only detectable precursor of putrescine channeled into pyrrolizidines, in the species studied here-using difluoromethylornithine and difluoromethylarginine as the enzyme inhibitors-endogenous ornithine was the main if not the only precursor of putrescine converted into the alkaloid aminoalcohol moiety. In S. riddellii and C. retusa at flowering, ornithine decarboxylase activity was present mainly in leaves, especially the young ones. However, other very young organs such as inflorescence and growing roots exhibited much lower or very low activities; the enzyme activity in stems was negligible. There was no correlation between the enzyme activity and polyamine or alkaloid content in either species. In both species only free polyamines were detected except for C. retusa roots and inflorescence-with relatively very high levels of these compounds-in which conjugated putrescine, spermidine, and spermine were also found; agmatine was not identified by HPLC in any plant organ except for C. retusa roots with rhizobial nodules. Organ- or age-dependent differences in the polyamine levels were small or insignificant. The highest alkaloid contents were found in young leaves and inflorescence.

A systematic review on aromatic L-amino acid decarboxylase (5-hydroxytryptophan decarboxylase)

International Nuclear Information System (INIS)

Rahman, M.K.; Nagatsu, T.

1988-11-01

Aromatic L-amino acid decarboxylase (AADC, EC. 4.1.1.28) with L-5-hydroxytryptophan as a substrate (also called L-5-hydroxytryptophan decarboxylase, 5-HTPDC) decarboxylates L-5-hydroxytryptophan to serotonin (5-HT), an important neurotransmitter that involved in the regulation of neuronal functions, behaviour and emotion of higher animals. As it is an important enzyme, many researchers are now working on its physiological functions and properties and also on its isolation, purification and characterization from mammalian tissues. But up to now no systematic review studies have been done on this enzyme. We made systematic studies on this enzyme in tissues and brains of rats, and human subjects. We also developed highly sensitive assay methods of the enzyme. This new method led us to discover the enzyme in the sera of various animals. We examined the developmental changes of 5-HTPDC in the sera of animals. We discovered an endogenous inhibitor of the enzyme in the monkey blood. The purification of the enzyme were performed by us and other researches from the sera, brains, adrenals, liver and kidneys of mammals. These and other results of up to date research papers on 5-HTPDC have been reviewed in this paper. (author). 71 refs, 10 figs, 14 tabs

Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions

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Mario U Manto

2015-03-01

Full Text Available Autoantibodies to the smaller isoform of glutamate decarboxylase can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct glutamate decarboxylase autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal glutamate decarboxylase antibodies. We found that glutamate decarboxylase autoantibodies present in patients with stiff person syndrome (n = 7 and cerebellar ataxia (n = 15 recognized an epitope distinct from that recognized by glutamate decarboxylase autoantibodies present in patients with type 1 diabetes mellitus (n = 10 or limbic encephalitis (n = 4. We demonstrated that the administration of a monoclonal glutamate decarboxylase antibody representing this epitope specificity (1 disrupted in vitro the association of glutamate decarboxylase with γ-Aminobutyric acid containing synaptic vesicles, (2 depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect, (3 significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task, (4 markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm, and (5 induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of glutamate decarboxylase by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such glutamate decarboxylase antibodies could be envisioned.

Serum Glutamic-Oxaloacetic Transaminase (GOT) and Glutamic-Pyruvic Transaminase (GPT) Levels in Children and Adolescents with Intellectual Disabilities

Science.gov (United States)

Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

2010-01-01

The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or…

Systems-wide metabolic pathway engineering in Corynebacterium glutamicum for bio-based production of diaminopentane.

Science.gov (United States)

Kind, Stefanie; Jeong, Weol Kyu; Schröder, Hartwig; Wittmann, Christoph

2010-07-01

In the present work the Gram-positive bacterium Corynebacterium glutamicum was engineered into an efficient, tailor-made production strain for diaminopentane (cadaverine), a highly attractive building block for bio-based polyamides. The engineering comprised expression of lysine decarboxylase (ldcC) from Escherichia coli, catalyzing the conversion of lysine into diaminopentane, and systems-wide metabolic engineering of central supporting pathways. Substantially re-designing the metabolism yielded superior strains with desirable properties such as (i) the release from unwanted feedback regulation at the level of aspartokinase and pyruvate carboxylase by introducing the point mutations lysC311 and pycA458, (ii) an optimized supply of the key precursor oxaloacetate by amplifying the anaplerotic enzyme, pyruvate carboxylase, and deleting phosphoenolpyruvate carboxykinase which otherwise removes oxaloacetate, (iii) enhanced biosynthetic flux via combined amplification of aspartokinase, dihydrodipicolinate reductase, diaminopimelate dehydrogenase and diaminopimelate decarboxylase, and (iv) attenuated flux into the threonine pathway competing with production by the leaky mutation hom59 in the homoserine dehydrogenase gene. Lysine decarboxylase proved to be a bottleneck for efficient production, since its in vitro activity and in vivo flux were closely correlated. To achieve an optimal strain having only stable genomic modifications, the combination of the strong constitutive C. glutamicum tuf promoter and optimized codon usage allowed efficient genome-based ldcC expression and resulted in a high diaminopentane yield of 200 mmol mol(-1). By supplementing the medium with 1 mgL(-1) pyridoxal, the cofactor of lysine decarboxylase, the yield was increased to 300 mmol mol(-1). In the production strain obtained, lysine secretion was almost completely abolished. Metabolic analysis, however, revealed substantial formation of an as yet unknown by-product. It was identified as an

Keto-isovalerate decarboxylase enzymes and methods of use thereof

Science.gov (United States)

McElvain, Jessica; O'Keefe, Daniel P.; Paul, Brian James; Payne, Mark S.; Rothman, Steven Cary; He, Hongxian

2016-01-19

Provided herein are polypeptides and polynucleotides encoding such polypeptides which have ketoisovalerate decarboxylase activity. Also provided are recombinant host cells comprising such polypeptides and polynucleotides and methods of use thereof.

Ornithine Decarboxylase Activity Is Required for Prostatic Budding in the Developing Mouse Prostate.

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Melissa Gamat

Full Text Available The prostate is a male accessory sex gland that produces secretions in seminal fluid to facilitate fertilization. Prostate secretory function is dependent on androgens, although the mechanism by which androgens exert their effects is still unclear. Polyamines are small cationic molecules that play pivotal roles in DNA transcription, translation and gene regulation. The rate-limiting enzyme in polyamine biosynthesis is ornithine decarboxylase, which is encoded by the gene Odc1. Ornithine decarboxylase mRNA decreases in the prostate upon castration and increases upon administration of androgens. Furthermore, testosterone administered to castrated male mice restores prostate secretory activity, whereas administering testosterone and the ornithine decarboxylase inhibitor D,L-α-difluromethylornithine (DFMO to castrated males does not restore prostate secretory activity, suggesting that polyamines are required for androgens to exert their effects. To date, no one has examined polyamines in prostate development, which is also androgen dependent. In this study, we showed that ornithine decarboxylase protein was expressed in the epithelium of the ventral, dorsolateral and anterior lobes of the adult mouse prostate. Ornithine decarboxylase protein was also expressed in the urogenital sinus (UGS epithelium of the male and female embryo prior to prostate development, and expression continued in prostatic epithelial buds as they emerged from the UGS. Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens. DFMO also significantly decreased the expression of developmental regulatory gene Notch1. Other genes implicated in prostatic development including Sox9, Wif1 and Srd5a2 were unaffected by DFMO. Together these results indicate that Odc1 and polyamines are required for androgens to exert their

Screening method for detection of immediate amino acid decarboxylases--producing bacteria implicated in food poisoning.

Science.gov (United States)

Hussain, Husniza; Mohd Fuat, A R; Vimala, B; Ghazali, H M

2011-08-01

Assessment of amino acid decarboxylase activity can be conducted using tubed broth or plated agar. In this study, the test was carried out in microtitre plates containing lysine, ornithine, arginine, tyrosine, tryptophan, phenylalanine or histidine as biogenic amine precursors. Møller decarboxylase base broth (MDB) with or without 1% of a known amino acid were added to wells of a 96 well-microtitre plate. The wells were inoculated with Escherichia coli, Klebsiella pneumoniae, Acinetobacter anitratus or Staphylococcus aureus to the final concentration of 6.0 x 10(7) cfu/ml and incubated at 35ºC. The absorbance of the culture broth was read at 570 nm at 0, 1.0, 2.0, 3.0, 4.0, 5.5, 6.5 and 7.5 hour. Comparison of means of A'(570) between 0 hour and a specified incubation time was determined statistically. Positive decarboxylase activities were detected in the media inoculated with E. coli and K. pneumoniae in less than 6 hours. The current method is suitable for immediate producers of amino acid decarboxylase enzymes. It costs less as it uses less amino acid and it has the potential to be used for screening aliquots of food materials for amino acid decarboxylase activities.

Diurnal changes in polyamine content, arginine and ornithine decarboxylase, and diamine oxidase in tobacco leaves

Czech Academy of Sciences Publication Activity Database

Gemperlová, Lenka; Nováková, Marie; Vaňková, Radomíra; Eder, Josef; Cvikrová, Milena

2006-01-01

Roč. 57, č. 6 (2006), s. 1413-1421 ISSN 0022-0957 R&D Projects: GA ČR GA206/03/0369 Institutional research plan: CEZ:AV0Z50380511 Keywords : Arginine decarboxylase * diamine oxidase * ornithine decarboxylase Subject RIV: ED - Physiology Impact factor: 3.630, year: 2006

Sensing and adaptation to low pH mediated by inducible amino acid decarboxylases in Salmonella.

Science.gov (United States)

Viala, Julie P M; Méresse, Stéphane; Pocachard, Bérengère; Guilhon, Aude-Agnès; Aussel, Laurent; Barras, Frédéric

2011-01-01

During the course of infection, Salmonella enterica serovar Typhimurium must successively survive the harsh acid stress of the stomach and multiply into a mild acidic compartment within macrophages. Inducible amino acid decarboxylases are known to promote adaptation to acidic environments. Three low pH inducible amino acid decarboxylases were annotated in the genome of S. Typhimurium, AdiA, CadA and SpeF, which are specific for arginine, lysine and ornithine, respectively. In this study, we characterized and compared the contributions of those enzymes in response to acidic challenges. Individual mutants as well as a strain deleted for the three genes were tested for their ability (i) to survive an extreme acid shock, (ii) to grow at mild acidic pH and (iii) to infect the mouse animal model. We showed that the lysine decarboxylase CadA had the broadest range of activity since it both had the capacity to promote survival at pH 2.3 and growth at pH 4.5. The arginine decarboxylase AdiA was the most performant in protecting S. Typhimurium from a shock at pH 2.3 and the ornithine decarboxylase SpeF conferred the best growth advantage under anaerobiosis conditions at pH 4.5. We developed a GFP-based gene reporter to monitor the pH of the environment as perceived by S. Typhimurium. Results showed that activities of the lysine and ornithine decarboxylases at mild acidic pH did modify the local surrounding of S. Typhimurium both in culture medium and in macrophages. Finally, we tested the contribution of decarboxylases to virulence and found that these enzymes were dispensable for S. Typhimurium virulence during systemic infection. In the light of this result, we examined the genomes of Salmonella spp. normally responsible of systemic infection and observed that the genes encoding these enzymes were not well conserved, supporting the idea that these enzymes may be not required during systemic infection.

Sensing and adaptation to low pH mediated by inducible amino acid decarboxylases in Salmonella.

Directory of Open Access Journals (Sweden)

Julie P M Viala

Full Text Available During the course of infection, Salmonella enterica serovar Typhimurium must successively survive the harsh acid stress of the stomach and multiply into a mild acidic compartment within macrophages. Inducible amino acid decarboxylases are known to promote adaptation to acidic environments. Three low pH inducible amino acid decarboxylases were annotated in the genome of S. Typhimurium, AdiA, CadA and SpeF, which are specific for arginine, lysine and ornithine, respectively. In this study, we characterized and compared the contributions of those enzymes in response to acidic challenges. Individual mutants as well as a strain deleted for the three genes were tested for their ability (i to survive an extreme acid shock, (ii to grow at mild acidic pH and (iii to infect the mouse animal model. We showed that the lysine decarboxylase CadA had the broadest range of activity since it both had the capacity to promote survival at pH 2.3 and growth at pH 4.5. The arginine decarboxylase AdiA was the most performant in protecting S. Typhimurium from a shock at pH 2.3 and the ornithine decarboxylase SpeF conferred the best growth advantage under anaerobiosis conditions at pH 4.5. We developed a GFP-based gene reporter to monitor the pH of the environment as perceived by S. Typhimurium. Results showed that activities of the lysine and ornithine decarboxylases at mild acidic pH did modify the local surrounding of S. Typhimurium both in culture medium and in macrophages. Finally, we tested the contribution of decarboxylases to virulence and found that these enzymes were dispensable for S. Typhimurium virulence during systemic infection. In the light of this result, we examined the genomes of Salmonella spp. normally responsible of systemic infection and observed that the genes encoding these enzymes were not well conserved, supporting the idea that these enzymes may be not required during systemic infection.

Perturbation of the Monomer-Monomer Interfaces of the Benzoylformate Decarboxylase Tetramer

Energy Technology Data Exchange (ETDEWEB)

Andrews, Forest H.; Rogers, Megan P.; Paul, Lake N.; McLeish, Michael J. [IUPUI; (Purdue)

2014-08-14

The X-ray structure of benzoylformate decarboxylase (BFDC) from Pseudomonas putida ATCC 12633 shows it to be a tetramer. This was believed to be typical of all thiamin diphosphate-dependent decarboxylases until recently when the structure of KdcA, a branched-chain 2-keto acid decarboxylase from Lactococcus lactis, showed it to be a homodimer. This lent credence to earlier unfolding experiments on pyruvate decarboxylase from Saccharomyces cerevisiae that indicated that it might be active as a dimer. To investigate this possibility in BFDC, we sought to shift the equilibrium toward dimer formation. Point mutations were made in the noncatalytic monomer–monomer interfaces, but these had a minimal effect on both tetramer formation and catalytic activity. Subsequently, the R141E/Y288A/A306F variant was shown by analytical ultracentrifugation to be partially dimeric. It was also found to be catalytically inactive. Further experiments revealed that just two mutations, R141E and A306F, were sufficient to markedly alter the dimer–tetramer equilibrium and to provide an ~450-fold decrease in k_cat. Equilibrium denaturation studies suggested that the residual activity was possibly due to the presence of residual tetramer. The structures of the R141E and A306F variants, determined to <1.5 Å resolution, hinted that disruption of the monomer interfaces will be accompanied by movement of a loop containing Leu109 and Leu110. As these residues contribute to the hydrophobicity of the active site and the correct positioning of the substrate, it seems that tetramer formation may well be critical to the catalytic activity of BFDC.

Characterization of Trypanosoma brucei brucei S-adenosyl-L-methionine decarboxylase and its inhibition by Berenil, pentamidine and methylglyoxal bis(guanylhydrazone).

Science.gov (United States)

Bitonti, A J; Dumont, J A; McCann, P P

1986-01-01

Trypanosoma brucei brucei S-adenosyl-L-methionine (AdoMet) decarboxylase was found to be relatively insensitive to activation by putrescine as compared with the mammalian enzyme, being stimulated by only 50% over a 10,000-fold range of putrescine concentrations. The enzyme was not stimulated by up to 10 mM-Mg2+. The Km for AdoMet was 30 microM, similar to that of other eukaryotic AdoMet decarboxylases. T.b. brucei AdoMet decarboxylase activity was apparently irreversibly inhibited in vitro by Berenil and reversibly by pentamidine and methylglyoxal bis(guanylhydrazone). Berenil also inhibited trypanosomal AdoMet decarboxylase by 70% within 4 h after administration to infected rats and markedly increased the concentration of putrescine in trypanosomes that were exposed to the drug in vivo. Spermidine and spermine blocked the curative effect of Berenil on model mouse T.b. brucei infections. This effect of the polyamines was probably not due to reversal of Berenil's inhibitory effects on the AdoMet decarboxylase. PMID:3800910

Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain

DEFF Research Database (Denmark)

Nilsson, Tatjana; Bogdanovic, Nenad; Volkman, Inga

2006-01-01

The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD...

Arginase and Arginine Decarboxylase - Where Do the Putative Gate Keepers of Polyamine Synthesis Reside in Rat Brain?

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Daniela Peters

Full Text Available Polyamines are important regulators of basal cellular functions but also subserve highly specific tasks in the mammalian brain. With this respect, polyamines and the synthesizing and degrading enzymes are clearly differentially distributed in neurons versus glial cells and also in different brain areas. The synthesis of the diamine putrescine may be driven via two different pathways. In the "classical" pathway urea and carbon dioxide are removed from arginine by arginase and ornithine decarboxylase. The alternative pathway, first removing carbon dioxide by arginine decarboxlyase and then urea by agmatinase, may serve the same purpose. Furthermore, the intermediate product of the alternative pathway, agmatine, is an endogenous ligand for imidazoline receptors and may serve as a neurotransmitter. In order to evaluate and compare the expression patterns of the two gate keeper enzymes arginase and arginine decarboxylase, we generated polyclonal, monospecific antibodies against arginase-1 and arginine decarboxylase. Using these tools, we immunocytochemically screened the rat brain and compared the expression patterns of both enzymes in several brain areas on the regional, cellular and subcellular level. In contrast to other enzymes of the polyamine pathway, arginine decarboxylase and arginase are both constitutively and widely expressed in rat brain neurons. In cerebral cortex and hippocampus, principal neurons and putative interneurons were clearly labeled for both enzymes. Labeling, however, was strikingly different in these neurons with respect to the subcellular localization of the enzymes. While with antibodies against arginine decarboxylase the immunosignal was distributed throughout the cytoplasm, arginase-like immunoreactivity was preferentially localized to Golgi stacks. Given the apparent congruence of arginase and arginine decarboxylase distribution with respect to certain cell populations, it seems likely that the synthesis of agmatine

AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

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N. V. Piven

2011-01-01

Full Text Available Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to glutamic acid decarboxylase by means of ELISA approach. (Med. Immunol., 2011, vol. 13, N 2-3, pp 257-260

l-Histidine Decarboxylase and Tourette's Syndrome

Science.gov (United States)

Ercan-Sencicek, A. Gulhan; Stillman, Althea A.; Ghosh, Ananda K.; Bilguvar, Kaya; O'Roak, Brian J.; Mason, Christopher E.; Abbott, Thomas; Gupta, Abha; King, Robert A.; Pauls, David L.; Tischfield, Jay A.; Heiman, Gary A.; Singer, Harvey S.; Gilbert, Donald L.; Hoekstra, Pieter J.; Morgan, Thomas M.; Loring, Erin; Yasuno, Katsuhito; Fernandez, Thomas; Sanders, Stephan; Louvi, Angeliki; Cho, Judy H.; Mane, Shrikant; Colangelo, Christopher M.; Biederer, Thomas; Lifton, Richard P.; Gunel, Murat; State, Matthew W.

2010-01-01

Summary Tourette's syndrome is a common developmental neuropsychiatric disorder characterized by chronic motor and vocal tics. Despite a strong genetic contribution, inheritance is complex, and risk alleles have proven difficult to identify. Here, we describe an analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding l-histidine decarboxylase, the rate-limiting enzyme in histamine biosynthesis. Our findings, together with previously published data from model systems, point to a role for histaminergic neurotransmission in the mechanism and modulation of Tourette's syndrome and tics. PMID:20445167

Characterisation of a thiamine diphosphate-dependent alpha-keto acid decarboxylase from Proteus mirabilis JN458.

Science.gov (United States)

Wang, Biying; Bai, Yajun; Fan, Taiping; Zheng, Xiaohui; Cai, Yujie

2017-10-01

Alpha-keto acid decarboxylases can convert keto acids to their corresponding aldehydes, which are often volatile aroma compounds. The gene encoding α-keto acid decarboxylase in Proteus mirabilis JN458 was cloned, and the enzyme overexpressed in Escherichia coli BL21 (DE3), purified in high yield, and characterised. The molecular weight is 62.291kDa by MALDI-TOF MS, and optimum activity at pH 6.0 and 40-50°C. The enzyme is a typical decarboxylase, dependent on thiamine diphosphate and Mg 2+ as cofactors. For the decarboxylation reaction, the enzyme displayed a broad substrate range. Kinetic parameters were determined using 4-methyl-2-oxopentanoic acid, phenyl pyruvate and 3-methyl-2-oxopentanoic acid as substrates. K m and k cat values for phenyl pyruvate were 0.62mM and 77.38s -1 , respectively, and the k cat /K m value was 124.81mM -1 s -1 . The enzyme properties suggest it may act effectively under cheese ripening conditions. Copyright © 2017. Published by Elsevier Ltd.

EFFECT OF AERO-/ANAEROBIOSIS ON DECARBOXYLASE ACTIVITY OF SELECTED LACTIC ACID BACTERIA

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Stanislav Kráčmar

2010-05-01

Full Text Available Biogenic amines are undesirable compounds produced in foods mainly through bacterial decarboxylase activity. The aim of this study was to investigate some environmental conditions (particularly aero/anaerobiosis, sodium chloride concentration (0–2% w/w, and amount of lactose (0–1% w/w on the activity of tyrosine decarboxylase enzymes of selected six technological important Lactococcus lactis strains. The levels of parameters tested were chosen according to real situation in fermented dairy products technology (especially cheese-making. Tyramine was determined by the ion-exchange chromatography with post-column ninhydrine derivatization and spectrophotometric detection. Tyrosine decarboxylation occurred during the active growth phase. Under the model conditions used, oxygen availability had influence on tyramine production, anaerobiosis seemed to favour the enzyme activity because all L. lactis strains produced higher tyramine amount. doi:10.5219/43

Effect of hexoses on the levels of pyruvate decarboxylase in Mucor rouxii.

OpenAIRE

Barrera, C R; Corral, J

1980-01-01

Pyruvate decarboxylase activity in the dimorphic fungus Mucor rouxii increased 25- to 35-fold in yeastlike and mycelial cells grown in the presence of glucose as compared to the activity observed in mycelial cultures grown in the absence of glucose.

Glutamate decarboxylase activity in rat brain during experimental epileptic seizures induced by pilocarpine

Energy Technology Data Exchange (ETDEWEB)

Netopilova, M; Drsata, J [Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, 50005 Hradec Kralove (Czech Republic); Haugvicova, R; Kubova, H; Mares, P [Institute of Physiology, Czech Academy of Sciences, 14220 Prague (Czech Republic)

1998-07-01

Glutamate decarboxylase (GAD) activity was studied rat brain parts in a pilocarpine model of epileptic seizures. An increased enzyme activity was found in hippocampus a cerebellum during the acute phase of seizures, while the cortex and cerebellum showed increased GAD activity in the chronic phase of the process. Systematic administration of pilocarpine to rats induces status epilepticus. The aim of this research was to find out if seizures induced by pilocarpine are connected changes in glutamate decarboxylase activity, the enzyme that catalyzes synthesis of inhibitory neurotransmitter GABA. GAD was assayed by means of radiometric method using {sup 14}C-carboxyl-labelled glutamate and measurement of {sup 14}CO{sub 2} radioactivity. Obtained results suggest that pilocarpine seizures are connected with changes of GAD activity in individual parts of rat brain. (authors)

Glutamate decarboxylase activity in rat brain during experimental epileptic seizures induced by pilocarpine

International Nuclear Information System (INIS)

Netopilova, M.; Drsata, J.; Haugvicova, R.; Kubova, H.; Mares, P.

1998-01-01

Glutamate decarboxylase (GAD) activity was studied rat brain parts in a pilocarpine model of epileptic seizures. An increased enzyme activity was found in hippocampus a cerebellum during the acute phase of seizures, while the cortex and cerebellum showed increased GAD activity in the chronic phase of the process. Systematic administration of pilocarpine to rats induces status epilepticus. The aim of this research was to find out if seizures induced by pilocarpine are connected changes in glutamate decarboxylase activity, the enzyme that catalyzes synthesis of inhibitory neurotransmitter GABA. GAD was assayed by means of radiometric method using 14 C-carboxyl-labelled glutamate and measurement of 14 CO 2 radioactivity. Obtained results suggest that pilocarpine seizures are connected with changes of GAD activity in individual parts of rat brain. (authors)

Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid

International Nuclear Information System (INIS)

Kido, H.; Fukusen, N.; Katunuma, N.

1987-01-01

In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4β-phorbol, phorbol 12-tetradecanoate, phorbol 13-acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor-promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17β-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2-dioctanoylglycerol, was also found to have similar effects on the cells

Enhancement of protocatechuate decarboxylase activity for the effective production of muconate from lignin-related aromatic compounds.

Science.gov (United States)

Sonoki, Tomonori; Morooka, Miyuki; Sakamoto, Kimitoshi; Otsuka, Yuichiro; Nakamura, Masaya; Jellison, Jody; Goodell, Barry

2014-12-20

The decarboxylation reaction of protocatechuate has been described as a bottleneck and a rate-limiting step in cis,cis-muconate (ccMA) bioproduction from renewable feedstocks such as sugar. Because sugars are already in high demand in the development of many bio-based products, our work focuses on improving protocatechuate decarboxylase (Pdc) activity and ccMA production in particular, from lignin-related aromatic compounds. We previously had transformed an Escherichia coli strain using aroY, which had been used as a protocatechuate decarboxylase encoding gene from Klebsiella pneumoniae subsp. pneumoniae A170-40, and inserted other required genes from Pseudomonas putida KT2440, to allow the production of ccMA from vanillin. This recombinant strain produced ccMA from vanillin, however the Pdc reaction step remained a bottleneck during incubation. In the current study, we identify a way to increase protocatechuate decarboxylase activity in E. coli through enzyme production involving both aroY and kpdB; the latter which encodes for the B subunit of 4-hydroxybenzoate decarboxylase. This permits expression of Pdc activity at a level approximately 14-fold greater than the strain with aroY only. The expression level of AroY increased, apparently as a function of the co-expression of AroY and KpdB. Our results also imply that ccMA may inhibit vanillate demethylation, a reaction step that is rate limiting for efficient ccMA production from lignin-related aromatic compounds, so even though ccMA production may be enhanced, other challenges to overcome vanilate demethylation inhibition still remain.

Evolutionary Trails of Plant Group II Pyridoxal Phosphate-Dependent Decarboxylase Genes.

Science.gov (United States)

Kumar, Rahul

2016-01-01

Type II pyridoxal phosphate-dependent decarboxylase (PLP_deC) enzymes play important metabolic roles during nitrogen metabolism. Recent evolutionary profiling of these genes revealed a sharp expansion of histidine decarboxylase genes in the members of Solanaceae family. In spite of the high sequence homology shared by PLP_deC orthologs, these enzymes display remarkable differences in their substrate specificities. Currently, limited information is available on the gene repertoires and substrate specificities of PLP_deCs which renders their precise annotation challenging and offers technical challenges in the immediate identification and biochemical characterization of their full gene complements in plants. Herein, we explored their evolutionary trails in a comprehensive manner by taking advantage of high-throughput data accessibility and computational approaches. We discussed the premise that has enabled an improved reconstruction of their evolutionary lineage and evaluated the factors offering constraints in their rapid functional characterization, till date. We envisage that the synthesized information herein would act as a catalyst for the rapid exploration of their biochemical specificity and physiological roles in more plant species.

The Degradation of 14C-Glutamic Acid by L-Glutamic Acid Decarboxylase.

Science.gov (United States)

Dougherty, Charles M; Dayan, Jean

1982-01-01

Describes procedures and semi-micro reaction apparatus (carbon dioxide trap) to demonstrate how a particular enzyme (L-Glutamic acid decarboxylase) may be used to determine the site or sites of labeling in its substrate (carbon-14 labeled glutamic acid). Includes calculations, solutions, and reagents used. (Author/SK)

A coenzyme-independent decarboxylase/oxygenase cascade for the efficient synthesis of vanillin.

Science.gov (United States)

Furuya, Toshiki; Miura, Misa; Kino, Kuniki

2014-10-13

Vanillin is one of the most widely used flavor compounds in the world as well as a promising versatile building block. The biotechnological production of vanillin from plant-derived ferulic acid has attracted much attention as a new alternative to chemical synthesis. One limitation of the known metabolic pathway to vanillin is its requirement for expensive coenzymes. Here, we developed a novel route to vanillin from ferulic acid that does not require any coenzymes. This artificial pathway consists of a coenzyme-independent decarboxylase and a coenzyme-independent oxygenase. When Escherichia coli cells harboring the decarboxylase/oxygenase cascade were incubated with ferulic acid, the cells efficiently synthesized vanillin (8.0 mM, 1.2 g L(-1) ) via 4-vinylguaiacol in one pot, without the generation of any detectable aromatic by-products. The efficient method described here might be applicable to the synthesis of other high-value chemicals from plant-derived aromatics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

OpenAIRE

Alkan , Manal; Machavoine , François; Rignault , Rachel; Dam , Julie; Dy , Michel; Thieblemont , Nathalie

2015-01-01

International audience; Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC −/− m...

Overexpression, purification, crystallization and preliminary structural studies of p-coumaric acid decarboxylase from Lactobacillus plantarum

International Nuclear Information System (INIS)

Rodríguez, Héctor; Rivas, Blanca de las; Muñoz, Rosario; Mancheño, José M.

2007-01-01

The enzyme p-coumaric acid decarboxylase (PDC) from L. plantarum has been recombinantly expressed, purified and crystallized. The structure has been solved at 2.04 Å resolution by the molecular-replacement method. The substrate-inducible p-coumaric acid decarboxylase (PDC) from Lactobacillus plantarum has been overexpressed in Escherichia coli, purified and confirmed to possess decarboxylase activity. The recombinant His 6 -tagged enzyme was crystallized using the hanging-drop vapour-diffusion method from a solution containing 20%(w/v) PEG 4000, 12%(w/v) 2-propanol, 0.2 M sodium acetate, 0.1 M Tris–HCl pH 8.0 with 0.1 M barium chloride as an additive. Diffraction data were collected in-house to 2.04 Å resolution. Crystals belonged to the tetragonal space group P4 3 , with unit-cell parameters a = b = 43.15, c = 231.86 Å. The estimated Matthews coefficient was 2.36 Å 3 Da −1 , corresponding to 48% solvent content, which is consistent with the presence of two protein molecules in the asymmetric unit. The structure of PDC has been determined by the molecular-replacement method. Currently, the structure of PDC complexed with substrate analogues is in progress, with the aim of elucidating the structural basis of the catalytic mechanism

Overexpression, purification, crystallization and preliminary structural studies of p-coumaric acid decarboxylase from Lactobacillus plantarum

Energy Technology Data Exchange (ETDEWEB)

Rodríguez, Héctor; Rivas, Blanca de las; Muñoz, Rosario [Instituto de Fermentaciones Industriales, CSIC, Juan de la Cierva 3, 28006 Madrid (Spain); Mancheño, José M., E-mail: xjosemi@iqfr.csic.es [Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto Rocasolano, CSIC, Serrano 119, 28006 Madrid (Spain); Instituto de Fermentaciones Industriales, CSIC, Juan de la Cierva 3, 28006 Madrid (Spain)

2007-04-01

The enzyme p-coumaric acid decarboxylase (PDC) from L. plantarum has been recombinantly expressed, purified and crystallized. The structure has been solved at 2.04 Å resolution by the molecular-replacement method. The substrate-inducible p-coumaric acid decarboxylase (PDC) from Lactobacillus plantarum has been overexpressed in Escherichia coli, purified and confirmed to possess decarboxylase activity. The recombinant His{sub 6}-tagged enzyme was crystallized using the hanging-drop vapour-diffusion method from a solution containing 20%(w/v) PEG 4000, 12%(w/v) 2-propanol, 0.2 M sodium acetate, 0.1 M Tris–HCl pH 8.0 with 0.1 M barium chloride as an additive. Diffraction data were collected in-house to 2.04 Å resolution. Crystals belonged to the tetragonal space group P4{sub 3}, with unit-cell parameters a = b = 43.15, c = 231.86 Å. The estimated Matthews coefficient was 2.36 Å{sup 3} Da{sup −1}, corresponding to 48% solvent content, which is consistent with the presence of two protein molecules in the asymmetric unit. The structure of PDC has been determined by the molecular-replacement method. Currently, the structure of PDC complexed with substrate analogues is in progress, with the aim of elucidating the structural basis of the catalytic mechanism.

Pyridoxine Supplementation Improves the Activity of Recombinant Glutamate Decarboxylase and the Enzymatic Production of Gama-Aminobutyric Acid.

Directory of Open Access Journals (Sweden)

Yan Huang

Full Text Available Glutamate decarboxylase (GAD catalyzes the irreversible decarboxylation of L-glutamate to the valuable food supplement γ-aminobutyric acid (GABA. In this study, GAD from Escherichia coli K12, a pyridoxal phosphate (PLP-dependent enzyme, was overexpressed in E. coli. The GAD produced in media supplemented with 0.05 mM soluble vitamin B6 analog pyridoxine hydrochloride (GAD-V activity was 154.8 U mL-1, 1.8-fold higher than that of GAD obtained without supplementation (GAD-C. Purified GAD-V exhibited increased activity (193.4 U mg-1, 1.5-fold higher than that of GAD-C, superior thermostability (2.8-fold greater than that of GAD-C, and higher kcat/Km (1.6-fold higher than that of GAD-C. Under optimal conditions in reactions mixtures lacking added PLP, crude GAD-V converted 500 g L-1 monosodium glutamate (MSG to GABA with a yield of 100%, and 750 g L-1 MSG with a yield of 88.7%. These results establish the utility of pyridoxine supplementation and lay the foundation for large-scale enzymatic production of GABA.

Overexpression of pyruvate decarboxylase in the yeast Hansenula polymorpha results in increased ethanol yield in high-temperature fermentation of xylose.

Science.gov (United States)

Ishchuk, Olena P; Voronovsky, Andriy Y; Stasyk, Oleh V; Gayda, Galina Z; Gonchar, Mykhailo V; Abbas, Charles A; Sibirny, Andriy A

2008-11-01

Improvement of xylose fermentation is of great importance to the fuel ethanol industry. The nonconventional thermotolerant yeast Hansenula polymorpha naturally ferments xylose to ethanol at high temperatures (48-50 degrees C). Introduction of a mutation that impairs ethanol reutilization in H. polymorpha led to an increase in ethanol yield from xylose. The native and heterologous (Kluyveromyces lactis) PDC1 genes coding for pyruvate decarboxylase were expressed at high levels in H. polymorpha under the control of the strong constitutive promoter of the glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH). This resulted in increased pyruvate decarboxylase activity and improved ethanol production from xylose. The introduction of multiple copies of the H. polymorpha PDC1 gene driven by the strong constitutive promoter led to a 20-fold increase in pyruvate decarboxylase activity and up to a threefold elevation of ethanol production.

Swit_4259, an acetoacetate decarboxylase-like enzyme from Sphingomonas wittichii RW1

Energy Technology Data Exchange (ETDEWEB)

Mydy, Lisa S.; Mashhadi, Zahra; Knight, T. William; Fenske, Tyler; Hagemann, Trevor; Hoppe, Robert W.; Han, Lanlan; Miller, Todd R.; Schwabacher, Alan W.; Silvaggi, Nicholas R. (UW); (Vanderbilt)

2017-11-14

The Gram-negative bacteriumSphingomonas wittichiiRW1 is notable for its ability to metabolize a variety of aromatic hydrocarbons. Not surprisingly, theS. wittichiigenome contains a number of putative aromatic hydrocarbon-degrading gene clusters. One of these includes an enzyme of unknown function, Swit_4259, which belongs to the acetoacetate decarboxylase-like superfamily (ADCSF). Here, it is reported that Swit_4259 is a small (28.8 kDa) tetrameric ADCSF enzyme that, unlike the prototypical members of the superfamily, does not have acetoacetate decarboxylase activity. Structural characterization shows that the tertiary structure of Swit_4259 is nearly identical to that of the true decarboxylases, but there are important differences in the fine structure of the Swit_4259 active site that lead to a divergence in function. In addition, it is shown that while it is a poor substrate, Swit_4259 can catalyze the hydration of 2-oxo-hex-3-enedioate to yield 2-oxo-4-hydroxyhexanedioate. It is also demonstrated that Swit_4259 has pyruvate aldolase-dehydratase activity, a feature that is common to all of the family V ADCSF enzymes studied to date. The enzymatic activity, together with the genomic context, suggests that Swit_4259 may be a hydratase with a role in the metabolism of an as-yet-unknown hydrocarbon. These data have implications for engineering bioremediation pathways to degrade specific pollutants, as well as structure–function relationships within the ADCSF in general.

Novel protein–protein interaction between spermidine synthase and S-adenosylmethionine decarboxylase from Leishmania donovani

Energy Technology Data Exchange (ETDEWEB)

Mishra, Arjun K.; Agnihotri, Pragati; Srivastava, Vijay Kumar; Pratap, J. Venkatesh, E-mail: jvpratap@cdri.res.in

2015-01-09

Highlights: • L. donovani spermidine synthase and S-adenosylmethionine decarboxylase have been cloned and purified. • S-adenosylmethionine decarboxylase has autocatalytic property. • GST pull down assay shows the two proteins to form a metabolon. • Isothermal titration calorimetry shows that binding was exothermic having K{sub d} value of 0.4 μM. • Interaction confirmed by fluorescence spectroscopy and size exclusion chromatography. - Abstract: Polyamine biosynthesis pathway has long been considered an essential drug target for trypanosomatids including Leishmania. S-adenosylmethionine decarboxylase (AdoMetDc) and spermidine synthase (SpdSyn) are enzymes of this pathway that catalyze successive steps, with the product of the former, decarboxylated S-adenosylmethionine (dcSAM), acting as an aminopropyl donor for the latter enzyme. Here we have explored the possibility of and identified the protein–protein interaction between SpdSyn and AdoMetDc. The protein–protein interaction has been identified using GST pull down assay. Isothermal titration calorimetry reveals that the interaction is thermodynamically favorable. Fluorescence spectroscopy studies also confirms the interaction, with SpdSyn exhibiting a change in tertiary structure with increasing concentrations of AdoMetDc. Size exclusion chromatography suggests the presence of the complex as a hetero-oligomer. Taken together, these results suggest that the enzymes indeed form a heteromer. Computational analyses suggest that this complex differs significantly from the corresponding human complex, implying that this complex could be a better therapeutic target than the individual enzymes.

Benzoylformate analogues exhibit differential rate-determining steps in the benzoylformate decarboxylase reaction

International Nuclear Information System (INIS)

Garcia, G.A.; Weiss, P.M.; Cook, P.F.; Kenyon, G.L.; Cleland, W.W.

1987-01-01

Benzoylformate decarboxylase from Pseudomonas putida is a thiamine pyrophosphate (TPP)-dependent enzyme which converts benzoylformate to benzaldehyde and CO 2 . The rate-determining step(s) in the benzoylformate decarboxylase reaction for a series of substituted benzoylformates (p-CH 3 O, p-CH 3 , p-Cl, and m-F) were studied using solvent deuterium and 13 C kinetic isotope effects. The normal substrate was found to have two partially rate-determining steps; initial tetrahedral adduct formation (D 2 O-sensitive) and decarboxylation ( 13 C-sensitive). D 2 O and 13 C isotope effects indicate that electron-withdrawing substituents (p-Cl and m-F) remove the rate dependence upon decarboxylation such that only a D 2 O effect on (V/K) is observed. Conversely, electron-donating substituents increase the rate-dependence upon decarboxylation such that a larger 13 (V/K) is seen while the D 2 O effects on (V) and (V/K) are not dramatically different from those for benzoylformate. All of the data are consistent with substituent stabilization or destabilization of the carbanionic intermediate formed upon decarboxylation

Neurological disorders associated with glutamic acid decarboxylase antibodies: a Brazilian series

Directory of Open Access Journals (Sweden)

Maurício Fernandes

2012-09-01

Full Text Available Neurological disorders associated with glutamic acid decarboxylase (GAD antibodies are rare pleomorphic diseases of uncertain cause, of which stiff-person syndrome (SPS is the best-known. Here, we described nine consecutive cases of neurological disorders associated with anti-GAD, including nine patients with SPS and three cases with cerebellar ataxia. Additionally, four had hypothyroidism, three epilepsy, two diabetes mellitus and two axial myoclonus.

Effects of bis(guanylhydrazones) on the activity and expression of ornithine decarboxylase.

Science.gov (United States)

Nikula, P; Alhonen-Hongisto, L; Jänne, J

1985-01-01

Derivatives of glyoxal bis(guanylhydrazone) (GBG), such as methylglyoxal bis(guanylhydrazone) and ethylglyoxal bis(guanylhydrazone), are potent inhibitors of S-adenosylmethionine decarboxylase (EC 4.1.1.50), the key enzyme required for the synthesis of spermidine and spermine. These compounds, but not the parent compound, induce a massive accumulation of putrescine, partly by blocking the conversion of putrescine into spermidine, but also by strikingly stimulating ornithine decarboxylase (ODC; EC 4.1.1.17) activity. The mechanism of the stimulation of ODC activity and enhanced accumulation of the enzyme protein apparently involved a distinct stabilization of the enzyme against intracellular degradation. However, although the parent compound GBG also stabilized ODC, it powerfully inhibited the enzyme activity and the accumulation of immunoreactive protein in cultured L1210 leukaemia cells. Kinetic considerations indicated that, in addition to the stabilization, all three compounds, GBG in particular, inhibited the expression of ODC. It is unlikely that the decreased rate of synthesis of ODC was attributable to almost unaltered amounts of mRNA in drug-treated cells, thus supporting the view that especially GBG apparently depressed the expression of ODC at some post-transcriptional level. Images PMID:4062886

Crystallization and preliminary X-ray analysis of the inducible lysine decarboxylase from Escherichia coli

International Nuclear Information System (INIS)

Alexopoulos, Eftichia; Kanjee, Usheer; Snider, Jamie; Houry, Walid A.; Pai, Emil F.

2008-01-01

The structure of the decameric inducible lysine decarboxylase from E. coli was determined by SIRAS using a hexatantalum dodecabromide (Ta 6 Br 12 2+ ) derivative. Model building and refinement are under way. The decameric inducible lysine decarboxylase (LdcI) from Escherichia coli has been crystallized in space groups C2 and C222 1 ; the Ta 6 Br 12 2+ cluster was used to derivatize the C2 crystals. The method of single isomorphous replacement with anomalous scattering (SIRAS) as implemented in SHELXD was used to solve the Ta 6 Br 12 2+ -derivatized structure to 5 Å resolution. Many of the Ta 6 Br 12 2+ -binding sites had twofold and fivefold noncrystallographic symmetry. Taking advantage of this feature, phase modification was performed in DM. The electron-density map of LdcI displays many features in agreement with the low-resolution negative-stain electron-density map [Snider et al. (2006 ▶), J. Biol. Chem.281, 1532–1546

Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats

OpenAIRE

Brosnan, Margaret E.; Roebothan, Barbara V.; Hall, Douglas E.

1980-01-01

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicat...

DPD epitope-specific glutamic acid decarboxylase GAD)65 autoantibodies in children with Type 1 diabetes

Science.gov (United States)

To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes. We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical dat...

Antileishmanial activity of berenil and methylglyoxal bis (guanylhydrazone) and its correlation with S-adenosylmethionine decarboxylase and polyamines.

Science.gov (United States)

Mukhopadhyay, R; Madhubala, R

1995-01-01

Leishmania donovani S-adenosyl-L-methionine (AdoMet) decarboxylase was found to show a growth related pattern. Methylglyoxal bis (guanylhydrazone) (MGBG) and Berenil inhibited the growth of Leishmania donovani promastigotes (strain UR6) in a dose dependent manner. The concentrations of MGBG and Berenil required for 50% inhibition of rate of growth were 67 and 47 microM, respectively. The growth inhibition of MGBG was partially reversed by spermidine (100 microM) and spermine (100 microM). Berenil inhibition of promastigote growth was partially reversed by 100 microM spermidine whereas 100 microM spermine did not result in any reversal of growth. The reduction in parasitemia in vitro by these inhibitors was accompanied by inhibition of AdoMet decarboxylase activity and spermidine levels.

Crystal Structure and Substrate Specificity of Drosophila 3,4-Dihydroxyphenylalanine Decarboxylase

Energy Technology Data Exchange (ETDEWEB)

Han, Q.; Ding, H; Robinson, H; Christensen, B; Li, J

2010-01-01

3,4-Dihydroxyphenylalanine decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase, catalyzes the decarboxylation of a number of aromatic L-amino acids. Physiologically, DDC is responsible for the production of dopamine and serotonin through the decarboxylation of 3,4-dihydroxyphenylalanine and 5-hydroxytryptophan, respectively. In insects, both dopamine and serotonin serve as classical neurotransmitters, neuromodulators, or neurohormones, and dopamine is also involved in insect cuticle formation, eggshell hardening, and immune responses. In this study, we expressed a typical DDC enzyme from Drosophila melanogaster, critically analyzed its substrate specificity and biochemical properties, determined its crystal structure at 1.75 Angstrom resolution, and evaluated the roles residues T82 and H192 play in substrate binding and enzyme catalysis through site-directed mutagenesis of the enzyme. Our results establish that this DDC functions exclusively on the production of dopamine and serotonin, with no activity to tyrosine or tryptophan and catalyzes the formation of serotonin more efficiently than dopamine. The crystal structure of Drosophila DDC and the site-directed mutagenesis study of the enzyme demonstrate that T82 is involved in substrate binding and that H192 is used not only for substrate interaction, but for cofactor binding of drDDC as well. Through comparative analysis, the results also provide insight into the structure-function relationship of other insect DDC-like proteins.

Crystal structure and substrate specificity of Drosophila 3,4-dihydroxyphenylalanine decarboxylase.

Directory of Open Access Journals (Sweden)

Qian Han

2010-01-01

Full Text Available 3,4-Dihydroxyphenylalanine decarboxylase (DDC, also known as aromatic L-amino acid decarboxylase, catalyzes the decarboxylation of a number of aromatic L-amino acids. Physiologically, DDC is responsible for the production of dopamine and serotonin through the decarboxylation of 3,4-dihydroxyphenylalanine and 5-hydroxytryptophan, respectively. In insects, both dopamine and serotonin serve as classical neurotransmitters, neuromodulators, or neurohormones, and dopamine is also involved in insect cuticle formation, eggshell hardening, and immune responses.In this study, we expressed a typical DDC enzyme from Drosophila melanogaster, critically analyzed its substrate specificity and biochemical properties, determined its crystal structure at 1.75 Angstrom resolution, and evaluated the roles residues T82 and H192 play in substrate binding and enzyme catalysis through site-directed mutagenesis of the enzyme. Our results establish that this DDC functions exclusively on the production of dopamine and serotonin, with no activity to tyrosine or tryptophan and catalyzes the formation of serotonin more efficiently than dopamine.The crystal structure of Drosophila DDC and the site-directed mutagenesis study of the enzyme demonstrate that T82 is involved in substrate binding and that H192 is used not only for substrate interaction, but for cofactor binding of drDDC as well. Through comparative analysis, the results also provide insight into the structure-function relationship of other insect DDC-like proteins.

Requirement of a Functional Flavin Mononucleotide Prenyltransferase for the Activity of a Bacterial Decarboxylase in a Heterologous Muconic Acid Pathway in Saccharomyces cerevisiae.

Science.gov (United States)

Weber, Heike E; Gottardi, Manuela; Brückner, Christine; Oreb, Mislav; Boles, Eckhard; Tripp, Joanna

2017-05-15

Biotechnological production of cis , cis -muconic acid from renewable feedstocks is an environmentally sustainable alternative to conventional, petroleum-based methods. Even though a heterologous production pathway for cis , cis -muconic acid has already been established in the host organism Saccharomyces cerevisiae , the generation of industrially relevant amounts of cis , cis -muconic acid is hampered by the low activity of the bacterial protocatechuic acid (PCA) decarboxylase AroY isomeric subunit C iso (AroY-C iso ), leading to secretion of large amounts of the intermediate PCA into the medium. In the present study, we show that the activity of AroY-C iso in S. cerevisiae strongly depends on the strain background. We could demonstrate that the strain dependency is caused by the presence or absence of an intact genomic copy of PAD1 , which encodes a mitochondrial enzyme responsible for the biosynthesis of a prenylated form of the cofactor flavin mononucleotide (prFMN). The inactivity of AroY-C iso in strain CEN.PK2-1 could be overcome by plasmid-borne expression of Pad1 or its bacterial homologue AroY subunit B (AroY-B). Our data reveal that the two enzymes perform the same function in decarboxylation of PCA by AroY-C iso , although coexpression of Pad1 led to higher decarboxylase activity. Conversely, AroY-B can replace Pad1 in its function in decarboxylation of phenylacrylic acids by ferulic acid decarboxylase Fdc1. Targeting of the majority of AroY-B to mitochondria by fusion to a heterologous mitochondrial targeting signal did not improve decarboxylase activity of AroY-C iso , suggesting that mitochondrial localization has no major impact on cofactor biosynthesis. IMPORTANCE In Saccharomyces cerevisiae , the decarboxylation of protocatechuic acid (PCA) to catechol is the bottleneck reaction in the heterologous biosynthetic pathway for production of cis , cis -muconic acid, a valuable precursor for the production of bulk chemicals. In our work, we demonstrate

Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes

DEFF Research Database (Denmark)

Eising, Stefanie; Nilsson, Anita; Carstensen, Bendix

2011-01-01

A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes.......A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes....

Characterization of Phosphoenolpyruvate Carboxykinase from Pineapple Leaves Ananas comosus (L.) Merr. 1

Science.gov (United States)

Daley, Laurence S.; Ray, Thomas B.; Vines, H. Max; Black, Clanton C.

1977-01-01

Phosphoenolpyruvate carboxykinase has been partially purified from pineapple (Ananas comosus [L.]) leaves. Specific activities obtained show it to be a major activity in this tissue. Above 15 C, the respective activation energies for decarboxylation and carboxylation are 13 and 12 kcal/mol. Below 15 C, there are discontinuities in Arrhenius plots with an associated large increase in activation energy. The adenine nucleotides are preferred to other nucleotides as substrates. The apparent Km values in the carboxylation direction are: ADP 0.13 mm, HCO3- 3.4 mm, and phosphoenolpyruvate 5 mm. In the decarboxylation direction, the apparent Km values are: ATP 0.02 mm, ADP 0.05 mm, and oxaloacetate 0.4 mm. The decarboxylation activity had an almost equal velocity with either ADP or ATP. The pH optima are between 6.8 and 7. Inhibition of the carboxylation reaction by ATP, pyruvate, and carbonic anhydrase was demonstrated. Decarboxylase specific activities are over twice carboxylation activities. The data support a model in which phosphoenolpyruvate carboxykinase is of physiological significance only during the light period and then only as a decarboxylase. PMID:16659905

Characterization of Phosphoenolpyruvate Carboxykinase from Pineapple Leaves Ananas comosus (L.) Merr.

Science.gov (United States)

Daley, L S; Ray, T B; Vines, H M; Black, C C

1977-04-01

Phosphoenolpyruvate carboxykinase has been partially purified from pineapple (Ananas comosus [L.]) leaves. Specific activities obtained show it to be a major activity in this tissue. Above 15 C, the respective activation energies for decarboxylation and carboxylation are 13 and 12 kcal/mol. Below 15 C, there are discontinuities in Arrhenius plots with an associated large increase in activation energy. The adenine nucleotides are preferred to other nucleotides as substrates. The apparent Km values in the carboxylation direction are: ADP 0.13 mm, HCO(3) (-) 3.4 mm, and phosphoenolpyruvate 5 mm. In the decarboxylation direction, the apparent Km values are: ATP 0.02 mm, ADP 0.05 mm, and oxaloacetate 0.4 mm. The decarboxylation activity had an almost equal velocity with either ADP or ATP. The pH optima are between 6.8 and 7. Inhibition of the carboxylation reaction by ATP, pyruvate, and carbonic anhydrase was demonstrated. Decarboxylase specific activities are over twice carboxylation activities. The data support a model in which phosphoenolpyruvate carboxykinase is of physiological significance only during the light period and then only as a decarboxylase.

Identification of the orotidine-5'-monophosphate decarboxylase gene of the oleaginous yeast Rhodosporidium toruloides.

Science.gov (United States)

Yang, Fan; Zhang, Sufang; Tang, Wei; Zhao, Zongbao K

2008-09-01

Oleaginous yeast Rhodosporidium toruloides is an excellent microbial lipid producer of great industrial potential, yet there is no effective genetic tool for rationally engineering this microorganism. To develop a marker recycling system, the orotidine-5'-monophosphate (OMP) decarboxylase gene of R. toruloides (RtURA3) was isolated using methods of degenerate polymerase chain reaction (PCR) together with rapid amplification of cDNA ends. The results showed that RtURA3 contains four extrons and three introns, and that the encoded polypeptide holds a sequence of 279 amino acid residues with significant homology to those of OMP decarboxylases from other yeasts. A shuttle vector pYES2/CT-RtURA3 was constructed via site-specific insertion of RtURA3 into the commercial vector pYES2/CT. Transformation of the shuttle vector into Saccharomyces cerevisiae BY4741, a URA3-deficient yeast strain, ensured the viability of the strain on synthetic dextrose agar plate without uracil, suggesting that the isolated RtURA3 was functionally equivalent to the URA3 gene from S. cerevisiae.

In vivo trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors.

Science.gov (United States)

Bacchi, C J; Brun, R; Croft, S L; Alicea, K; Bühler, Y

1996-01-01

A series of novel aromatic derivatives based on the structure of methylglyoxal bis(guanylhydrazone) (MGBG) was examined for trypanocidal activities in human and veterinary trypanosomes of African origin. One agent, CGP 40215A, a bicyclic analog of MGBG which also resembles the diamidines diminazene (Berenil) and pentamidine, was curative of infections by 19 isolates of Trypanosoma brucei subspecies as well as a Trypanosoma congolense isolate. Several of these isolates were resistant to standard trypanocides. Curative doses were < or = 25 mg/kg of body weight/day for 3 days in these acute laboratory model infections. In addition, CGP 40215A also cured a model central nervous system infection in combination with the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine (DFMO; Ornidyl, eflornithine). Curative combinations were 14 days of oral 2% DFMO (approximately 5 g/kg/day) plus 5, 10, or 25 mg/kg/day for 3 or 7 days given by intraperitoneal injection or with a miniosmotic pump. Combinations were most effective if CGP 40215A was given in the second half or at the end of the DFMO regimen. MGBG has modest activity as an inhibitor of trypanosome S-adenosylmethionine decarboxylase (50% inhibitory concentration [IC50]. 130 microM), while CGP 40215A was a more active inhibitor (IC50, 20 microM). Preincubation of trypanosomes with CGP 40215A for 1 h caused a reduction in spermidine content (36%) and an increase in putrescine content (20%), indicating that one possible mechanism of its action may be inhibition of polyamine biosynthesis. PMID:8726018

Pyruvate Decarboxylase Activity Assay in situ of Different Industrial Yeast Strains

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Dorota Kręgiel

2009-01-01

Full Text Available Cytoplasmic pyruvate decarboxylase (PDC, EC 4.1.1.1 is one of the key enzymes of yeast fermentative metabolism. PDC is the first enzyme which, under anaerobic conditions, leads to decarboxylation of pyruvate with acetaldehyde as the end product. The aim of this study is to develop a suitable method for PDC activity assay in situ for different industrial yeast strains. Saccharomyces sp. and Debaryomyces sp. yeast strains grew in fermentative medium with 12 % of glucose. Enzymatic assay was conducted in cell suspension treated with digitonin as permeabilisation agent, and with sodium pyruvate as a substrate, at temperature of 30 °C. Metabolites of PDC pathway were detected using gas chromatographic (GC technique. Various parameters like type and molar concentration of the substrate, minimal effective mass fraction of digitonin, cell concentration, reaction time and effect of pyrazole (alcohol dehydrogenase inhibitor were monitored to optimize PDC enzymatic assay in situ. In the concentration range of yeast cells from 1⋅10^7 to 1⋅10^8 per mL, linear correlation between the produced acetaldehyde and cell density was noticed. Only pyruvate was the specific substrate for pyruvate decarboxylase. In the presence of 0.05 M sodium pyruvate and 0.05 % digitonin, the enzymatic reaction was linear up to 20 min of the assay. During incubation, there was no formation of ethanol and, therefore, pyrazole was not necessary for the assay.

Structural analysis of Bacillus pumilus phenolic acid decarboxylase, a lipocalin-fold enzyme

International Nuclear Information System (INIS)

Matte, Allan; Grosse, Stephan; Bergeron, Hélène; Abokitse, Kofi; Lau, Peter C. K.

2010-01-01

The crystal structure of phenolic acid decarboxylase from B. pumilus strain UI-670 has been determined and refined at 1.69 Å resolution. The enzyme is a dimer, with each subunit adopting a β-barrel structure belonging to the lipocalin fold. The decarboxylation of phenolic acids, including ferulic and p-coumaric acids, to their corresponding vinyl derivatives is of importance in the flavouring and polymer industries. Here, the crystal structure of phenolic acid decarboxylase (PAD) from Bacillus pumilus strain UI-670 is reported. The enzyme is a 161-residue polypeptide that forms dimers both in the crystal and in solution. The structure of PAD as determined by X-ray crystallography revealed a β-barrel structure and two α-helices, with a cleft formed at one edge of the barrel. The PAD structure resembles those of the lipocalin-fold proteins, which often bind hydrophobic ligands. Superposition of structurally related proteins bound to their cognate ligands shows that they and PAD bind their ligands in a conserved location within the β-barrel. Analysis of the residue-conservation pattern for PAD-related sequences mapped onto the PAD structure reveals that the conservation mainly includes residues found within the hydrophobic core of the protein, defining a common lipocalin-like fold for this enzyme family. A narrow cleft containing several conserved amino acids was observed as a structural feature and a potential ligand-binding site

Limbic encephalitis with antibodies to glutamic acid decarboxylase presenting with brainstem symptoms

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Faruk Incecik

2015-01-01

Full Text Available Limbic encephalitis (LE is a neurological syndrome that may present in association with cancer, infection, or as an isolate clinical condition often accompanying autoimmune disorders. LE associated with glutamic acid decarboxylase antibodies (anti-GAD is rare in children. Here, we characterized the clinical and laboratory features of a patient presenting with brainstem involvement with non-paraneoplastic LE associated with anti-GAD antibodies. In our patient, after plasma exchange, we determined a dramatic improvement of the neurological deficits.

The effect of different doses of epidermal growth factor on liver ornithine decarboxylase and Na-K ATPase activities in newborn rats.

Science.gov (United States)

Bilgihan, A; Turkozkan, N; Isman, F; Kilinc, M; Demirsoy, S

1998-08-01

1. Ornithine decarboxylase and Na-K ATPase activities were studied in rat livers that were treated with different doses of epidermal growth factor (EGF). 2. The ornithine decarboxylase activities were studied with spectrophotometry, and results were expressed as micromoles of putrescine per hour per milligram of protein. Na-K ATPase activities were studied on the basis of the principle of measuring the amount of inorganic phosphates released by the hydrolysis of ATP, and the results were expressed as micromoles of inorganic phosphate per hour per milligram of protein. 3. When compared with the controls, although the Na-K ATPase activities were decreased at low doses of EGF, their activities were found to be increased at high doses of EGF. On the other hand, there was a positive correlation between ornithine decarboxylase activities and EGF doses. 4. The results of this study suggest that, whereas the decrease in Na-K ATPase activities at low doses of EGF can be due to the utilization of the enzyme, the increase in Na-K ATPase activities at high doses of EGF can be attributed to its enhanced synthesis.

Glutamic acid decarboxylase 67 expression by a distinct population of mouse vestibular supporting cells.

Science.gov (United States)

Tavazzani, Elisa; Tritto, Simona; Spaiardi, Paolo; Botta, Laura; Manca, Marco; Prigioni, Ivo; Masetto, Sergio; Russo, Giancarlo

2014-01-01

The function of the enzyme glutamate decarboxylase (GAD) is to convert glutamate in γ-aminobutyric acid (GABA). Glutamate decarboxylase exists as two major isoforms, termed GAD65 and GAD67, that are usually expressed in GABA-containing neurons in the central nervous system. GAD65 has been proposed to be associated with GABA exocytosis whereas GAD67 with GABA metabolism. In the present immunofluorescence study, we have investigated the presence of the two GAD isoforms in the semicircular canal cristae of wild type and GAD67-GFP knock-in mice. While no evidence for GAD65 expression was found, GAD67 was detected in a distinct population of peripherally-located supporting cells, but not in hair cells or in centrally-located supporting cells. GABA, on the other hand, was found in all supporting cells. The present result indicate that only a discrete population of supporting cells use GAD67 to synthesize GABA. This is the first report of a marker that allows to distinguish two populations of supporting cells in the vestibular epithelium. On the other hand, the lack of GABA and GAD enzymes in hair cells excludes its involvement in afferent transmission.

Cognitive decline in a patient with anti-glutamic acid decarboxylase autoimmunity; case report

OpenAIRE

Takagi, Masahito; Yamasaki, Hiroshi; Endo, Keiko; Yamada, Tetsuya; Kaneko, Keizo; Oka, Yoshitomo; Mori, Etsuro

2011-01-01

Abstract Background Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for producing γ-aminobutyric acid, and it has been suggested that antibodies against GAD play a role in neurological conditions and type 1 diabetes. However, it is not known whether dementia appears as the sole neurological manifestation associated with anti-GAD antibodies in the central nervous system. Case presentation We describe the clinical, neuropsychological, and neuroradiological findings of a 73-year-ol...

Involvement of the ornithine decarboxylase gene in acid stress response in probiotic Lactobacillus delbrueckii UFV H2b20.

Science.gov (United States)

Ferreira, A B; Oliveira, M N V de; Freitas, F S; Paiva, A D; Alfenas-Zerbini, P; Silva, D F da; Queiroz, M V de; Borges, A C; Moraes, C A de

2015-01-01

Amino acid decarboxylation is important for the maintenance of intracellular pH under acid stress. This study aims to carry out phylogenetic and expression analysis by real-time PCR of two genes that encode proteins involved in ornithine decarboxylation in Lactobacillus delbrueckii UFV H2b20 exposed to acid stress. Sequencing and phylogeny analysis of genes encoding ornithine decarboxylase and amino acid permease in L. delbrueckii UFV H2b20 showed their high sequence identity (99%) and grouping with those of L. delbrueckii subsp. bulgaricus ATCC 11842. Exposure of L. delbrueckii UFV H2b20 cells in MRS pH 3.5 for 30 and 60 min caused a significant increase in expression of the gene encoding ornithine decarboxylase (up to 8.1 times higher when compared to the control treatment). Increased expression of the ornithine decarboxylase gene demonstrates its involvement in acid stress response in L. delbrueckii UFV H2b20, evidencing that the protein encoded by that gene could be involved in intracellular pH regulation. The results obtained show ornithine decarboxylation as a possible mechanism of adaptation to an acidic environmental condition, a desirable and necessary characteristic for probiotic cultures and certainly important to the survival and persistence of the L. delbrueckii UFV H2b20 in the human gastrointestinal tract.

An internal deletion in MTH1 enables growth on glucose of pyruvate-decarboxylase negative, non-fermentative Saccharomyces cerevisiae

NARCIS (Netherlands)

Oud, B.; Flores, C.L.; Gancedo, C.; Zhang, X.; Trueheart, J.; Daran, J.M.; Pronk, J.T.; Van Maris, A.J.A.

2012-01-01

Background Pyruvate-decarboxylase negative (Pdc-) strains of Saccharomyces cerevisiae combine the robustness and high glycolytic capacity of this yeast with the absence of alcoholic fermentation. This makes Pdc-S. cerevisiae an interesting platform for efficient conversion of glucose towards

Directed evolution of pyruvate decarboxylase-negative Saccharomyces cerevisiae, yielding a C2-independent, glucose-tolerant, and pyruvate-hyperproducing yeast

NARCIS (Netherlands)

A.J. van Maris; J.M. Geertman; A. Vermeulen; M.K. Groothuizen; A.A. Winkler; M.D. Piper; J.P. van Dijken; J.T. Pronk

2004-01-01

textabstractThe absence of alcoholic fermentation makes pyruvate decarboxylase-negative (Pdc(-)) strains of Saccharomyces cerevisiae an interesting platform for further metabolic engineering of central metabolism. However, Pdc(-) S. cerevisiae strains have two growth defects:

Polyamine regulation of ornithine decarboxylase and its antizyme in intestinal epithelial cells.

Science.gov (United States)

Yuan, Q; Ray, R M; Viar, M J; Johnson, L R

2001-01-01

Ornithine decarboxylase (ODC) is feedback regulated by polyamines. ODC antizyme mediates this process by forming a complex with ODC and enhancing its degradation. It has been reported that polyamines induce ODC antizyme and inhibit ODC activity. Since exogenous polyamines can be converted to each other after they are taken up into cells, we used an inhibitor of S-adenosylmethionine decarboxylase, diethylglyoxal bis(guanylhydrazone) (DEGBG), to block the synthesis of spermidine and spermine from putrescine and investigated the specific roles of individual polyamines in the regulation of ODC in intestinal epithelial crypt (IEC-6) cells. We found that putrescine, spermidine, and spermine inhibited ODC activity stimulated by serum to 85, 46, and 0% of control, respectively, in the presence of DEGBG. ODC activity increased in DEGBG-treated cells, despite high intracellular putrescine levels. Although exogenous spermidine and spermine reduced ODC activity of DEGBG-treated cells close to control levels, spermine was more effective than spermidine. Exogenous putrescine was much less effective in inducing antizyme than spermidine or spermine. High putrescine levels in DEGBG-treated cells did not induce ODC antizyme when intracellular spermidine and spermine levels were low. The decay of ODC activity and reduction of ODC protein levels were not accompanied by induction of antizyme in the presence of DEGBG. Our results indicate that spermine is the most, and putrescine the least, effective polyamine in regulating ODC activity, and upregulation of antizyme is not required for the degradation of ODC protein.

AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

OpenAIRE

N. V. Piven; L. N. Lukhverchyk; A. I. Burakovsky; N. V. Polegenkaya; M. V. Karpovich

2011-01-01

Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format) has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to g...

Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions.

Science.gov (United States)

Shih, De-Fen; Hsiao, Chung-Der; Min, Ming-Yuan; Lai, Wen-Sung; Yang, Chianne-Wen; Lee, Wang-Tso; Lee, Shyh-Jye

2013-01-01

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos). Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children.

Aromatic L-amino acid decarboxylase (AADC is crucial for brain development and motor functions.

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De-Fen Shih

Full Text Available Aromatic L-amino acid decarboxylase (AADC deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc, in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos. Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children.

Contribution of glutamate decarboxylase in Lactobacillus reuteri to acid resistance and persistence in sourdough fermentation.

Science.gov (United States)

Su, Marcia S; Schlicht, Sabine; Gänzle, Michael G

2011-08-30

Acid stress impacts the persistence of lactobacilli in industrial sourdough fermentations, and in intestinal ecosystems. However, the contribution of glutamate to acid resistance in lactobacilli has not been demonstrated experimentally, and evidence for the contribution of acid resistance to the competitiveness of lactobacilli in sourdough is lacking. It was therefore the aim of this study to investigate the ecological role of glutamate decarboxylase in L. reuteri. A gene coding for a putative glutamate decarboxylase, gadB, was identified in the genome of L. reuteri 100-23. Different from the organization of genetic loci coding for glutamate decarboxylase in other lactic acid bacteria, gadB was located adjacent to a putative glutaminase gene, gls3. An isogenic deletion mutant, L. reuteri ∆gadB, was generated by a double crossover method. L. reuteri 100-23 but not L. reuteri ∆gadB converted glutamate to γ-aminobutyrate (GABA) in phosphate butter (pH 2.5). In sourdough, both strains converted glutamine to glutamate but only L. reuteri 100-23 accumulated GABA. Glutamate addition to phosphate buffer, pH 2.5, improved survival of L. reuteri 100-23 100-fold. However, survival of L. reuteri ∆gadB remained essentially unchanged. The disruption of gadB did not affect growth of L. reuteri in mMRS or in sourdough. However, the wild type strain L. reuteri 100-23 displaced L. reuteri ∆gadB after 5 cycles of fermentation in back-slopped sourdough fermentations. The conversion of glutamate to GABA by L. reuteri 100-23 contributes to acid resistance and to competitiveness in industrial sourdough fermentations. The organization of the gene cluster for glutamate conversion, and the availability of amino acids in cereals imply that glutamine rather than glutamate functions as the substrate for GABA formation. The exceptional coupling of glutamine deamidation to glutamate decarboxylation in L. reuteri likely reflects adaptation to cereal substrates.

The function of glycine decarboxylase complex is optimized to maintain high photorespiratory flux via buffering of its reaction products

DEFF Research Database (Denmark)

Bykova, Natalia V; Møller, Ian Max; Gardeström, Per

2014-01-01

oxidase. We discuss here possible mechanisms of high photorespiratory flux maintenance in mitochondria and suggest that it is fulfilled under conditions where the concentrations of glycine decarboxylase reaction products NADH and CO2 achieve an equilibrium provided by malate dehydrogenase and carbonic...

Cloning of affecting pyruvate decarboxylase gene in the production bioethanol of agricultural waste in the E.coli bacteria

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Masome Zeinali

2016-09-01

Full Text Available Introduction: Ethanol made by a biomass is one of the useful strategies in terms of economic and environmental and as a clean and safe energy to replace fossil fuels considered and examined. Materials and methods: In this study, key enzyme in the production of ethanol (Pyruvate decarboxylase from Zymomonas mobilis bacteria was isolated and cloned at E. coli bacteria by freeze and thaw method. For gene cloning, we used specific primers of pdc and PCR reaction and then pdc gene isolated and pET 28a plasmid double digested with (Sal I and Xho I enzymes. Digestion Products were ligated by T4 DNA ligase in 16 °C for 16 hours. Results: Results of bacteria culture showed that a few colonies containing pET 28a plasmid could grow. Result of colony pcr of pdc gene with specific primers revealed 1700 bp bands in 1% agarose gel electrophoresis. The results of PCR with T7 promotor forward primer and pdc revers primer have proved the accurate direction of integration of pdc gene into plasmid and revealed 1885 bp band. Double digestion of recombinant plasmid with SalI and XhoI enzymes revealed same bands. Finally, RT showed the expected band of 1700 bp that implies the desired gene expression in the samples. Discussion and conclusion: Due to the increased production of ethanol via pyruvate decarboxylase gene cloning in expression plasmids with a strong promoter upstream of the cloning site can conclude that, pyruvate decarboxylase cloning as a key gene would be useful and according to beneficial properties of E. coli bacteria, transfering the gene to bacteria appears to be reasonable.

Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats.

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Gloria E Hoffman

Full Text Available A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC, would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

Effects of polyamine biosynthesis inhibitors on S-adenosylmethionine synthetase and S-adenosylmethionine decarboxylase activities in carrot cell cultures

Science.gov (United States)

S.C. Minocha; R. Minocha; A. Komamine

1991-01-01

Changes in the activites of S-adcnosylmethionine (SAM) synthetase (methionine adenosyltransferase, EC 2.5.1.6.) and SAM decarboxylase (EC 4.1.1.50) were studied in carrot (Daucus carota) cell cultures in response to 2,4-dichlorophenoxyacetic acid (2,4-D) and several inhibitors of polyamine biosynthesis. Activity of SAM synthetase increased...

Agdc1p - a Gallic Acid Decarboxylase Involved in the Degradation of Tannic Acid in the Yeast Blastobotrys (Arxula) adeninivorans.

Science.gov (United States)

Meier, Anna K; Worch, Sebastian; Böer, Erik; Hartmann, Anja; Mascher, Martin; Marzec, Marek; Scholz, Uwe; Riechen, Jan; Baronian, Kim; Schauer, Frieder; Bode, Rüdiger; Kunze, Gotthard

2017-01-01

Tannins and hydroxylated aromatic acids, such as gallic acid (3,4,5-trihydroxybenzoic acid), are plant secondary metabolites which protect plants against herbivores and plant-associated microorganisms. Some microbes, such as the yeast Arxula adeninivorans are resistant to these antimicrobial substances and are able to use tannins and gallic acid as carbon sources. In this study, the Arxula gallic acid decarboxylase (Agdc1p) which degrades gallic acid to pyrogallol was characterized and its function in tannin catabolism analyzed. The enzyme has a higher affinity for gallic acid (K m -0.7 ± 0.2 mM, k cat -42.0 ± 8.2 s -1 ) than to protocatechuic acid (3,4-dihydroxybenzoic acid) (K m -3.2 ± 0.2 mM, k cat -44.0 ± 3.2 s -1 ). Other hydroxylated aromatic acids, such as 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid are not gallic acid decarboxylase substrates. A. adeninivorans G1212/YRC102-AYNI1-AGDC1, which expresses the AGDC1 gene under the control of the strong nitrate inducible AYNI1 promoter achieved a maximum gallic acid decarboxylase activity of 1064.4 U/l and 97.5 U/g of dry cell weight in yeast grown in minimal medium with nitrate as nitrogen source and glucose as carbon source. In the same medium, gallic acid decarboxylase activity was not detected for the control strain G1212/YRC102 with AGDC1 expression under the control of the endogenous promoter. Gene expression analysis showed that AGDC1 is induced by gallic acid and protocatechuic acid. In contrast to G1212/YRC102-AYNI1-AGDC1 and G1212/YRC102, A. adeninivorans G1234 [Δ agdc1 ] is not able to grow on medium with gallic acid as carbon source but can grow in presence of protocatechuic acid. This confirms that Agdc1p plays an essential role in the tannic acid catabolism and could be useful in the production of catechol and cis,cis -muconic acid. However, the protocatechuic acid catabolism via Agdc1p to catechol seems to be

Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

International Nuclear Information System (INIS)

Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S.; Wada, H.; Horio, Y.

1990-01-01

The hepatic plasma membrane fatty acid-binding protein (h-FABP PM ) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP PM have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP PM reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of [ 3 H]oleate but not that of [ 35 S]sulfobromophthalein or [ 14 C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABP PM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP PM and mGOT are closely related

Study of pyruvate decarboxylase and thiamine kinase from brewer's yeast by SERS

Science.gov (United States)

Maskevich, Sergei A.; Chernikevich, Ivan P.; Gachko, Gennedy A.; Kivach, Leonid N.; Strekal, Nataliya D.

1993-06-01

The Surface Enhanced Raman Scattering (SERS) spectra of holopyruvate decarboxylase (PDC) and thiamine kinase (ThK) adsorbed on silver electrode were obtained. In contrast to the Raman, the SERS spectrum of PDC contained no modes of tryptophan residues, it indicates a removal of this moiety from the surface. In the SERS spectrum of ThK the bands belonging to ligands bound to the protein were observed. A correlation between the SERS signal intensity and the enzymatic activity of the ThK separate fraction and found. The influence of amino acids on SERS spectra of thiamine (Th) was studied to determine the possible composition on microsurrounding of coenzyme.

Plutonium solubilities

International Nuclear Information System (INIS)

Puigdomnech, I.; Bruno, J.

1991-02-01

Thermochemical data has been selected for plutonium oxide, hydroxide, carbonate and phosphate equilibria. Equilibrium constants have been evaluated in the temperature range 0 to 300 degrees C at a pressure of 1 bar to T≤100 degrees C and at the steam saturated pressure at higher temperatures. Measured solubilities of plutonium that are reported in the literature for laboratory experiments have been collected. Solubility data on oxides, hydroxides, carbonates and phosphates have been selected. No solubility data were found at temperatures higher than 60 degrees C. The literature solubility data have been compared with plutonium solubilities calculated with the EQ3/6 geochemical modelling programs, using the selected thermodynamic data for plutonium. (authors)

A comparative study of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels in the saliva of diabetic and normal patients.

Science.gov (United States)

Verma, M; Metgud, R; Madhusudan, A S; Verma, N; Saxena, M; Soni, A

2014-10-01

Diabetes has been reported to affect salivary glands adversely in humans and experimental models. Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) are salivary enzymes that also are widely distributed in animal tissues. We determined GOT and GPT levels in saliva samples of 100 type 1 and 30 type 2 diabetic patients using reflectance spectrophotometry and compared them to 30 age and sex matched healthy controls. Statistically significant differences were observed in the mean values of GOT and GPT in type 1 diabetics compared to type 2 and control groups. Significantly higher GOT levels were found in the 1-20 year age group of type 1 diabetics. Our findings suggest that salivary gland damage is due to the same immunological attack that affects pancreatic β cells and results in type 1 diabetes.

Influence of ornithine decarboxylase antizymes and antizyme inhibitors on agmatine uptake by mammalian cells.

Science.gov (United States)

Ramos-Molina, Bruno; López-Contreras, Andrés J; Lambertos, Ana; Dardonville, Christophe; Cremades, Asunción; Peñafiel, Rafael

2015-05-01

Agmatine (4-aminobutylguanidine), a dicationic molecule at physiological pH, exerts relevant modulatory actions at many different molecular target sites in mammalian cells, having been suggested that the administration of this compound may have therapeutic interest. Several plasma membrane transporters have been implicated in agmatine uptake by mammalian cells. Here we report that in kidney-derived COS-7 cell line, at physiological agmatine levels, the general polyamine transporter participates in the plasma membrane translocation of agmatine, with an apparent Km of 44 ± 7 µM and Vmax of 17.3 ± 3.3 nmol h(-1) mg(-1) protein, but that at elevated concentrations, agmatine can be also taken up by other transport systems. In the first case, the physiological polyamines (putrescine, spermidine and spermine), several diguanidines and bis(2-aminoimidazolines) and the polyamine transport inhibitor AMXT-1501 markedly decreased agmatine uptake. In cells transfected with any of the three ornithine decarboxylase antizymes (AZ1, AZ2 and AZ3), agmatine uptake was dramatically reduced. On the contrary, transfection with antizyme inhibitors (AZIN1 and AZIN2) markedly increased the transport of agmatine. Furthermore, whereas putrescine uptake was significantly decreased in cells transfected with ornithine decarboxylase (ODC), the accumulation of agmatine was stimulated, suggesting a trans-activating effect of intracellular putrescine on agmatine uptake. All these results indicate that ODC and its regulatory proteins (antizymes and antizyme inhibitors) may influence agmatine homeostasis in mammalian tissues.

An endosymbiont positively modulates ornithine decarboxylase in host trypanosomatids

International Nuclear Information System (INIS)

Frossard, Mariana Lins; Seabra, Sergio Henrique; Matta, Renato Augusto da; Souza, Wanderley de; Garcia de Mello, Fernando; Motta, Maria Cristina Machado

2006-01-01

Summary: Some trypanosomatids, such as Crithidia deanei, are endosymbiont-containing species. Aposymbiotic strains are obtained after antibiotic treatment, revealing interesting aspects of this symbiotic association. Ornithine decarboxylase (ODC) promotes polyamine biosynthesis and contributes to cell proliferation. Here, we show that ODC activity is higher in endosymbiont-bearing trypanosomatids than in aposymbiotic cells, but isolated endosymbionts did not display this enzyme activity. Intriguingly, expressed levels of ODC were similar in both strains, suggesting that ODC is positively modulated in endosymbiont-bearing cells. When the aposymbiotic strain was grown in conditioned medium, obtained after cultivation of the endosymbiont-bearing strain, cellular proliferation as well as ODC activity and localization were similar to that observed in the endosymbiont-containing trypanosomatids. Furthermore, dialyzed-heated medium and trypsin treatment reduced ODC activity of the aposymbiont strain. Taken together, these data indicate that the endosymbiont can enhance the protozoan ODC activity by providing factors of protein nature, which increase the host polyamine metabolism

Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain

International Nuclear Information System (INIS)

Nilsson, Tatjana; Bogdanovic, Nenad; Volkman, Inga; Winblad, Bengt; Folkesson, Ronnie; Benedikz, Eirikur

2006-01-01

The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD) brains. In frontal cortex and hippocampus of control cases, the most pronounced ODC immunoreactivity was found in the nucleus. In possible and definite AD the immunoreactivity had shifted to the cytoplasm. In cerebellum of control cases, ODC staining was found in a small portion of Purkinje cells, mostly in the nucleus. In AD, both possible and definite, the number of stained Purkinje cells increased significantly and immunoreactivity was shifted to the cytoplasm, even though it was still prominent in the nucleus. In conclusion, our study reveals an early shift of the ODC immunoreactivity in AD from the nuclear compartment towards the cytoplasm

Agdc1p – a Gallic Acid Decarboxylase Involved in the Degradation of Tannic Acid in the Yeast Blastobotrys (Arxula adeninivorans

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Anna K. Meier

2017-09-01

Full Text Available Tannins and hydroxylated aromatic acids, such as gallic acid (3,4,5-trihydroxybenzoic acid, are plant secondary metabolites which protect plants against herbivores and plant-associated microorganisms. Some microbes, such as the yeast Arxula adeninivorans are resistant to these antimicrobial substances and are able to use tannins and gallic acid as carbon sources. In this study, the Arxula gallic acid decarboxylase (Agdc1p which degrades gallic acid to pyrogallol was characterized and its function in tannin catabolism analyzed. The enzyme has a higher affinity for gallic acid (Km −0.7 ± 0.2 mM, kcat −42.0 ± 8.2 s−1 than to protocatechuic acid (3,4-dihydroxybenzoic acid (Km −3.2 ± 0.2 mM, kcat −44.0 ± 3.2 s−1. Other hydroxylated aromatic acids, such as 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid are not gallic acid decarboxylase substrates. A. adeninivorans G1212/YRC102-AYNI1-AGDC1, which expresses the AGDC1 gene under the control of the strong nitrate inducible AYNI1 promoter achieved a maximum gallic acid decarboxylase activity of 1064.4 U/l and 97.5 U/g of dry cell weight in yeast grown in minimal medium with nitrate as nitrogen source and glucose as carbon source. In the same medium, gallic acid decarboxylase activity was not detected for the control strain G1212/YRC102 with AGDC1 expression under the control of the endogenous promoter. Gene expression analysis showed that AGDC1 is induced by gallic acid and protocatechuic acid. In contrast to G1212/YRC102-AYNI1-AGDC1 and G1212/YRC102, A. adeninivorans G1234 [Δagdc1] is not able to grow on medium with gallic acid as carbon source but can grow in presence of protocatechuic acid. This confirms that Agdc1p plays an essential role in the tannic acid catabolism and could be useful in the production of catechol and cis,cis-muconic acid. However, the protocatechuic acid catabolism via Agdc1p to

Agdc1p – a Gallic Acid Decarboxylase Involved in the Degradation of Tannic Acid in the Yeast Blastobotrys (Arxula) adeninivorans

Science.gov (United States)

Meier, Anna K.; Worch, Sebastian; Böer, Erik; Hartmann, Anja; Mascher, Martin; Marzec, Marek; Scholz, Uwe; Riechen, Jan; Baronian, Kim; Schauer, Frieder; Bode, Rüdiger; Kunze, Gotthard

2017-01-01

Tannins and hydroxylated aromatic acids, such as gallic acid (3,4,5-trihydroxybenzoic acid), are plant secondary metabolites which protect plants against herbivores and plant-associated microorganisms. Some microbes, such as the yeast Arxula adeninivorans are resistant to these antimicrobial substances and are able to use tannins and gallic acid as carbon sources. In this study, the Arxula gallic acid decarboxylase (Agdc1p) which degrades gallic acid to pyrogallol was characterized and its function in tannin catabolism analyzed. The enzyme has a higher affinity for gallic acid (Km −0.7 ± 0.2 mM, kcat −42.0 ± 8.2 s−1) than to protocatechuic acid (3,4-dihydroxybenzoic acid) (Km −3.2 ± 0.2 mM, kcat −44.0 ± 3.2 s−1). Other hydroxylated aromatic acids, such as 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid are not gallic acid decarboxylase substrates. A. adeninivorans G1212/YRC102-AYNI1-AGDC1, which expresses the AGDC1 gene under the control of the strong nitrate inducible AYNI1 promoter achieved a maximum gallic acid decarboxylase activity of 1064.4 U/l and 97.5 U/g of dry cell weight in yeast grown in minimal medium with nitrate as nitrogen source and glucose as carbon source. In the same medium, gallic acid decarboxylase activity was not detected for the control strain G1212/YRC102 with AGDC1 expression under the control of the endogenous promoter. Gene expression analysis showed that AGDC1 is induced by gallic acid and protocatechuic acid. In contrast to G1212/YRC102-AYNI1-AGDC1 and G1212/YRC102, A. adeninivorans G1234 [Δagdc1] is not able to grow on medium with gallic acid as carbon source but can grow in presence of protocatechuic acid. This confirms that Agdc1p plays an essential role in the tannic acid catabolism and could be useful in the production of catechol and cis,cis-muconic acid. However, the protocatechuic acid catabolism via Agdc1p to catechol seems to be

Local anesthetics inhibit induction of ornithine decarboxylase by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.

OpenAIRE

Yuspa, S H; Lichti, U; Ben, T

1980-01-01

The induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity in mouse epidermal cells in vivo and in vitro occurs rapidly after exposure to the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). This induction has characteristics of a cell surface receptor-mediated process. Local anesthetics modify a variety of cellular responses mediated by membrane receptors. When cultured mouse epidermal cells were exposed to the local anesthetics lidocaine, tetracaine...

Recombinant thermoactive phosphoenolpyruvate carboxylase (PEPC) from Thermosynechococcus elongatus and its coupling with mesophilic/thermophilic bacterial carbonic anhydrases (CAs) for the conversion of CO2 to oxaloacetate.

Science.gov (United States)

Del Prete, Sonia; De Luca, Viviana; Capasso, Clemente; Supuran, Claudiu T; Carginale, Vincenzo

2016-01-15

With the continuous increase of atmospheric CO2 in the last decades, efficient methods for carbon capture, sequestration, and utilization are urgently required. The possibility of converting CO2 into useful chemicals could be a good strategy to both decreasing the CO2 concentration and for achieving an efficient exploitation of this cheap carbon source. Recently, several single- and multi-enzyme systems for the catalytic conversion of CO2 mainly to bicarbonate have been implemented. In order to design and construct a catalytic system for the conversion of CO2 to organic molecules, we implemented an in vitro multienzyme system using mesophilic and thermophilic enzymes. The system, in fact, was constituted by a recombinant phosphoenolpyruvate carboxylase (PEPC) from the thermophilic cyanobacterium Thermosynechococcus elongatus, in combination with mesophilic/thermophilic bacterial carbonic anhydrases (CAs), for converting CO2 into oxaloacetate, a compound of potential utility in industrial processes. The catalytic procedure is in two steps: the conversion of CO2 into bicarbonate by CA, followed by the carboxylation of phosphoenolpyruvate with bicarbonate, catalyzed by PEPC, with formation of oxaloacetate (OAA). All tested CAs, belonging to α-, β-, and γ-CA classes, were able to increase OAA production compared to procedures when only PEPC was used. Interestingly, the efficiency of the CAs tested in OAA production was in good agreement with the kinetic parameters for the CO2 hydration reaction of these enzymes. This PEPC also revealed to be thermoactive and thermostable, and when coupled with the extremely thermostable CA from Sulphurhydrogenibium azorense (SazCA) the production of OAA was achieved even if the two enzymes were exposed to temperatures up to 60 °C, suggesting a possible role of the two coupled enzymes in biotechnological processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inhibition of S-adenosylmethionine decarboxylase and diamine oxidase activities by analogues of methylglyoxal bis(guanylhydrazone) and their cellular uptake during lymphocyte activation.

Science.gov (United States)

Jänne, J; Morris, D R

1984-03-15

Several congeners of methylglyoxal bis(guanylhydrazone) were tested for their ability to inhibit eukaryotic putrescine-activated S-adenosylmethionine decarboxylase (EC 4.1.1.50) and intestinal diamine oxidase (EC 1.4.3.6). All the compounds tested, namely methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone), dimethylglyoxal bis(guanylhydrazone) and the di-N"-methyl derivative of methylglyoxal bis(guanylhydrazone), were strong inhibitors of both yeast and mouse liver adenosylmethionine decarboxylase activity in vitro. The enzyme from both sources was most powerfully inhibited by ethylglyoxal bis(guanylhydrazone). All the diguanidines likewise inhibited diamine oxidase activity in vitro. The maximum intracellular concentrations of the ethyl and dimethylated analogues achieved in activated lymphocytes were only about one-fifth of that of the parent compound. However, both derivatives appeared to utilize the polyamine-carrier system, as indicated by competition experiments with spermidine.

Human Monoclonal Islet Cell Antibodies From a Patient with Insulin- Dependent Diabetes Mellitus Reveal Glutamate Decarboxylase as the Target Antigen

Science.gov (United States)

Richter, Wiltrud; Endl, Josef; Eiermann, Thomas H.; Brandt, Michael; Kientsch-Engel, Rosemarie; Thivolet, Charles; Jungfer, Herbert; Scherbaum, Werner A.

1992-09-01

The autoimmune phenomena associated with destruction of the β cell in pancreatic islets and development of type 1 (insulin-dependent) diabetes mellitus (IDDM) include circulating islet cell antibodies. We have immortalized peripheral blood lymphocytes from prediabetic individuals and patients with newly diagnosed IDDM by Epstein-Barr virus transformation. IgG-positive cells were selected by anti-human IgG-coupled magnetic beads and expanded in cell culture. Supernatants were screened for cytoplasmic islet cell antibodies using the conventional indirect immunofluorescence test on cryostat sections of human pancreas. Six islet cell-specific B-cell lines, originating from a patient with newly diagnosed IDDM, could be stabilized on a monoclonal level. All six monoclonal islet cell antibodies (MICA 1-6) were of the IgG class. None of the MICA reacted with human thyroid, adrenal gland, anterior pituitary, liver, lung, stomach, and intestine tissues but all six reacted with pancreatic islets of different mammalian species and, in addition, with neurons of rat cerebellar cortex. MICA 1-6 were shown to recognize four distinct antigenic epitopes in islets. Islet cell antibody-positive diabetic sera but not normal human sera blocked the binding of the monoclonal antibodies to their target epitopes. Immunoprecipitation of 35S-labeled human islet cell extracts revealed that a protein of identical size to the enzyme glutamate decarboxylase (EC 4.1.1.15) was a target of all MICA. Furthermore, antigen immunotrapped by the MICA from brain homogenates showed glutamate decarboxylase enzyme activity. MICA 1-6 therefore reveal glutamate decarboxylase as the predominant target antigen of cytoplasmic islet cell autoantibodies in a patient with newly diagnosed IDDM.

DOPA Decarboxylase Modulates Tau Toxicity.

Science.gov (United States)

Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

2018-03-01

The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

Energy Technology Data Exchange (ETDEWEB)

Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S. (Mount Sinai School of Medicine, New York, NY (USA)); Wada, H.; Horio, Y. (Univ. of Osaka (Japan))

1990-05-01

The hepatic plasma membrane fatty acid-binding protein (h-FABP{sub PM}) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP{sub PM} have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP{sub PM} reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of ({sup 3}H)oleate but not that of ({sup 35}S)sulfobromophthalein or ({sup 14}C)taurocholate. The inhibition of oleate uptake produced by anti-h-FABP{sub PM} can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP{sub PM} and mGOT are closely related.

Crystallization and preliminary crystallographic analysis of orotidine 5′-monophosphate decarboxylase from the human malaria parasite Plasmodium falciparum

International Nuclear Information System (INIS)

Krungkrai, Sudaratana R.; Tokuoka, Keiji; Kusakari, Yukiko; Inoue, Tsuyoshi; Adachi, Hiroaki; Matsumura, Hiroyoshi; Takano, Kazufumi; Murakami, Satoshi; Mori, Yusuke; Kai, Yasushi; Krungkrai, Jerapan; Horii, Toshihiro

2006-01-01

Orotidine 5′-monophosphate decarboxylase of human malaria parasite P. falciparum was crystallized by the seeding method in a hanging drop using PEG 3000 as a precipitant. A complete set of diffraction data from a native crystal was collected to 2.7 Å resolution at 100 K using synchrotron radiation. Orotidine 5′-monophosphate (OMP) decarboxylase (OMPDC; EC 4.1.1.23) catalyzes the final step in the de novo synthesis of uridine 5′-monophosphate (UMP) and defects in the enzyme are lethal in the malaria parasite Plasmodium falciparum. Active recombinant P. falciparum OMPDC (PfOMPDC) was crystallized by the seeding method in a hanging drop using PEG 3000 as a precipitant. A complete set of diffraction data from a native crystal was collected to 2.7 Å resolution at 100 K using synchrotron radiation at the Swiss Light Source. The crystal exhibits trigonal symmetry (space group R3), with hexagonal unit-cell parameters a = b = 201.81, c = 44.03 Å. With a dimer in the asymmetric unit, the solvent content is 46% (V M = 2.3 Å 3 Da −1 )

Issues concerning the determination of solubility products of sparingly soluble crystalline solids. Solubility of HfO2(cr)

International Nuclear Information System (INIS)

Rai, Dhanpat; Kitamura, Akira; Rosso, Kevin M.; Sasaki, Takayuki; Kobayashi, Taishi

2016-01-01

Solubility studies were conducted with HfO 2 (cr) solid as a function HCl and ionic strength ranging from 2.0 to 0.004 mol kg -1 . These studies involved (1) using two different amounts of the solid phase, (2) acid washing the bulk solid phase, (3) preheating the solid phase to 1400 C, and (4) heating amorphous HfO 2 (am) suspensions to 90 C to ascertain whether the HfO 2 (am) converts to HfO 2 (cr) and to determine the solubility from the oversaturation direction. Based on the results of these treatments it is concluded that the HfO 2 (cr) contains a small fraction of less crystalline, but not amorphous, material [HfO 2 (lcr)] and this, rather than the HfO 2 (cr), is the solubility-controlling phase in the range of experimental variables investigated in this study. The solubility data are interpreted using both the Pitzer and SIT models and they provide log 10 K 0 values of -(59.75±0.35) and -(59.48±0.41), respectively, for the solubility product of HfO 2 (lcr)[HfO 2 (lcr) + 2H 2 O ↔ Hf 4+ + 4OH - ]. The log 10 of the solubility product of HfO 2 (cr) is estimated to be < -63. The observation of a small fraction of less crystalline higher solubility material is consistent with the general picture that mineral surfaces are often structurally and/or compositionally imperfect leading to a higher solubility than the bulk crystalline solid. This study stresses the urgent need, during interpretation of solubility data, of taking precautions to make certain that the observed solubility behavior for sparingly-soluble solids is assigned to the proper solid phase.

Structural basis of enzymatic activity for the ferulic acid decarboxylase (FADase from Enterobacter sp. Px6-4.

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Wen Gu

Full Text Available Microbial ferulic acid decarboxylase (FADase catalyzes the transformation of ferulic acid to 4-hydroxy-3-methoxystyrene (4-vinylguaiacol via non-oxidative decarboxylation. Here we report the crystal structures of the Enterobacter sp. Px6-4 FADase and the enzyme in complex with substrate analogues. Our analyses revealed that FADase possessed a half-opened bottom β-barrel with the catalytic pocket located between the middle of the core β-barrel and the helical bottom. Its structure shared a high degree of similarity with members of the phenolic acid decarboxylase (PAD superfamily. Structural analysis revealed that FADase catalyzed reactions by an "open-closed" mechanism involving a pocket of 8 × 8 × 15 Å dimension on the surface of the enzyme. The active pocket could directly contact the solvent and allow the substrate to enter when induced by substrate analogues. Site-directed mutagenesis showed that the E134A mutation decreased the enzyme activity by more than 60%, and Y21A and Y27A mutations abolished the enzyme activity completely. The combined structural and mutagenesis results suggest that during decarboxylation of ferulic acid by FADase, Trp25 and Tyr27 are required for the entering and proper orientation of the substrate while Glu134 and Asn23 participate in proton transfer.

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

Science.gov (United States)

De Luca, Maria; Roshina, Nataliya V; Geiger-Thornsberry, Gretchen L; Lyman, Richard F; Pasyukova, Elena G; Mackay, Trudy F C

2003-08-01

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

Molecular cloning and expression of gene encoding aromatic amino acid decarboxylase in 'Vidal blanc' grape berries.

Science.gov (United States)

Pan, Qiu-Hong; Chen, Fang; Zhu, Bao-Qing; Ma, Li-Yan; Li, Li; Li, Jing-Ming

2012-04-01

The pleasantly fruity and floral 2-phenylethanol are a dominant aroma compound in post-ripening 'Vidal blanc' grapes. However, to date little has been reported about its synthetic pathway in grapevine. In the present study, a full-length cDNA of VvAADC (encoding aromatic amino acid decarboxylase) was firstly cloned from the berries of 'Vidal blanc', an interspecific hybrid variety of Vitis vinifera × Vitis riparia. This sequence encodes a complete open reading frame of 482 amino acids with a calculated molecular mass of 54 kDa and isoelectric point value (pI) of 5.73. The amino acid sequence deduced shared about 79% identity with that of aromatic L: -amino acid decarboxylases (AADCs) from tomato. Real-time PCR analysis indicated that VvAADC transcript abundance presented a small peak at 110 days after full bloom and then a continuous increase at the berry post-ripening stage, which was consistent with the accumulation of 2-phenylethanol, but did not correspond to the trends of two potential intermediates, phenethylamine and 2-phenylacetaldehyde. Furthermore, phenylalanine still exhibited a continuous increase even in post-ripening period. It is thus suggested that 2-phenylethanol biosynthetic pathway mediated by AADC exists in grape berries, but it has possibly little contribution to a considerable accumulation of 2-phenylethanol in post-ripening 'Vidal blanc' grapes.

Acid Evolution of Escherichia coli K-12 Eliminates Amino Acid Decarboxylases and Reregulates Catabolism.

Science.gov (United States)

He, Amanda; Penix, Stephanie R; Basting, Preston J; Griffith, Jessie M; Creamer, Kaitlin E; Camperchioli, Dominic; Clark, Michelle W; Gonzales, Alexandra S; Chávez Erazo, Jorge Sebastian; George, Nadja S; Bhagwat, Arvind A; Slonczewski, Joan L

2017-06-15

Acid-adapted strains of Escherichia coli K-12 W3110 were obtained by serial culture in medium buffered at pH 4.6 (M. M. Harden, A. He, K. Creamer, M. W. Clark, I. Hamdallah, K. A. Martinez, R. L. Kresslein, S. P. Bush, and J. L. Slonczewski, Appl Environ Microbiol 81:1932-1941, 2015, https://doi.org/10.1128/AEM.03494-14). Revised genomic analysis of these strains revealed insertion sequence (IS)-driven insertions and deletions that knocked out regulators CadC (acid induction of lysine decarboxylase), GadX (acid induction of glutamate decarboxylase), and FNR (anaerobic regulator). Each acid-evolved strain showed loss of one or more amino acid decarboxylase systems, which normally help neutralize external acid (pH 5 to 6) and increase survival in extreme acid (pH 2). Strains from populations B11, H9, and F11 had an IS 5 insertion or IS-mediated deletion in cadC , while population B11 had a point mutation affecting the arginine activator adiY The cadC and adiY mutants failed to neutralize acid in the presence of exogenous lysine or arginine. In strain B11-1, reversion of an rpoC (RNA polymerase) mutation partly restored arginine-dependent neutralization. All eight strains showed deletion or downregulation of the Gad acid fitness island. Strains with the Gad deletion lost the ability to produce GABA (gamma-aminobutyric acid) and failed to survive extreme acid. Transcriptome sequencing (RNA-seq) of strain B11-1 showed upregulated genes for catabolism of diverse substrates but downregulated acid stress genes (the biofilm regulator ariR , yhiM , and Gad). Other strains showed downregulation of H 2 consumption mediated by hydrogenases ( hya and hyb ) which release acid. Strains F9-2 and F9-3 had a deletion of fnr and showed downregulation of FNR-dependent genes ( dmsABC , frdABCD , hybABO , nikABCDE , and nrfAC ). Overall, strains that had evolved in buffered acid showed loss or downregulation of systems that neutralize unbuffered acid and showed altered regulation of

Structures of the N47A and E109Q mutant proteins of pyruvoyl-dependent arginine decarboxylase from Methanococcus jannaschii

International Nuclear Information System (INIS)

Soriano, Erika V.; McCloskey, Diane E.; Kinsland, Cynthia; Pegg, Anthony E.; Ealick, Steven E.

2008-01-01

The crystal structures of two arginine decarboxylase mutant proteins provide insights into the mechanisms of pyruvoyl-group formation and the decarboxylation reaction. Pyruvoyl-dependent arginine decarboxylase (PvlArgDC) catalyzes the first step of the polyamine-biosynthetic pathway in plants and some archaebacteria. The pyruvoyl group of PvlArgDC is generated by an internal autoserinolysis reaction at an absolutely conserved serine residue in the proenzyme, resulting in two polypeptide chains. Based on the native structure of PvlArgDC from Methanococcus jannaschii, the conserved residues Asn47 and Glu109 were proposed to be involved in the decarboxylation and autoprocessing reactions. N47A and E109Q mutant proteins were prepared and the three-dimensional structure of each protein was determined at 2.0 Å resolution. The N47A and E109Q mutant proteins showed reduced decarboxylation activity compared with the wild-type PvlArgDC. These residues may also be important for the autoprocessing reaction, which utilizes a mechanism similar to that of the decarboxylation reaction

Issues concerning the determination of solubility products of sparingly soluble crystalline solids. Solubility of HfO{sub 2}(cr)

Energy Technology Data Exchange (ETDEWEB)

Rai, Dhanpat [Rai Enviro-Chem, LLC, Yachats, OR (United States); Kitamura, Akira [Japan Atomic Energy Agency, Ibaraki (Japan); Rosso, Kevin M. [Pacific Northwest National Laboratory, Richland, WA (United States); Sasaki, Takayuki; Kobayashi, Taishi [Kyoto Univ. (Japan)

2016-11-01

Solubility studies were conducted with HfO{sub 2}(cr) solid as a function HCl and ionic strength ranging from 2.0 to 0.004 mol kg{sup -1}. These studies involved (1) using two different amounts of the solid phase, (2) acid washing the bulk solid phase, (3) preheating the solid phase to 1400 C, and (4) heating amorphous HfO{sub 2}(am) suspensions to 90 C to ascertain whether the HfO{sub 2}(am) converts to HfO{sub 2}(cr) and to determine the solubility from the oversaturation direction. Based on the results of these treatments it is concluded that the HfO{sub 2}(cr) contains a small fraction of less crystalline, but not amorphous, material [HfO{sub 2}(lcr)] and this, rather than the HfO{sub 2}(cr), is the solubility-controlling phase in the range of experimental variables investigated in this study. The solubility data are interpreted using both the Pitzer and SIT models and they provide log{sub 10} K{sup 0} values of -(59.75±0.35) and -(59.48±0.41), respectively, for the solubility product of HfO{sub 2}(lcr)[HfO{sub 2}(lcr) + 2H{sub 2}O ↔ Hf{sup 4+} + 4OH{sup -}]. The log{sub 10} of the solubility product of HfO{sub 2}(cr) is estimated to be < -63. The observation of a small fraction of less crystalline higher solubility material is consistent with the general picture that mineral surfaces are often structurally and/or compositionally imperfect leading to a higher solubility than the bulk crystalline solid. This study stresses the urgent need, during interpretation of solubility data, of taking precautions to make certain that the observed solubility behavior for sparingly-soluble solids is assigned to the proper solid phase.

A porphodimethene chemical inhibitor of uroporphyrinogen decarboxylase.

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Kenneth W Yip

Full Text Available Uroporphyrinogen decarboxylase (UROD catalyzes the conversion of uroporphyrinogen to coproporphyrinogen during heme biosynthesis. This enzyme was recently identified as a potential anticancer target; its inhibition leads to an increase in reactive oxygen species, likely mediated by the Fenton reaction, thereby decreasing cancer cell viability and working in cooperation with radiation and/or cisplatin. Because there is no known chemical UROD inhibitor suitable for use in translational studies, we aimed to design, synthesize, and characterize such a compound. Initial in silico-based design and docking analyses identified a potential porphyrin analogue that was subsequently synthesized. This species, a porphodimethene (named PI-16, was found to inhibit UROD in an enzymatic assay (IC50 = 9.9 µM, but did not affect porphobilinogen deaminase (at 62.5 µM, thereby exhibiting specificity. In cellular assays, PI-16 reduced the viability of FaDu and ME-180 cancer cells with half maximal effective concentrations of 22.7 µM and 26.9 µM, respectively, and only minimally affected normal oral epithelial (NOE cells. PI-16 also combined effectively with radiation and cisplatin, with potent synergy being observed in the case of cisplatin in FaDu cells (Chou-Talalay combination index <1. This work presents the first known synthetic UROD inhibitor, and sets the foundation for the design, synthesis, and characterization of higher affinity and more effective UROD inhibitors.

A novel expression platform for the production of diabetes-associated autoantigen human glutamic acid decarboxylase (hGAD65

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Maxwell Denis

2008-11-01

Full Text Available Abstract Background Human glutamic acid decarboxylase 65 (hGAD65 is a key autoantigen in type 1 diabetes, having much potential as an important marker for the prediction and diagnosis of type 1 diabetes, and for the development of novel antigen-specific therapies for the treatment of type 1 diabetes. However, recombinant production of hGAD65 using conventional bacterial or mammalian cell culture-based expression systems or nuclear transformed plants is limited by low yield and low efficiency. Chloroplast transformation of the unicellular eukaryotic alga Chlamydomonas reinhardtii may offer a potential solution. Results A DNA cassette encoding full-length hGAD65, under the control of the C. reinhardtii chloroplast rbcL promoter and 5'- and 3'-UTRs, was constructed and introduced into the chloroplast genome of C. reinhardtii by particle bombardment. Integration of hGAD65 DNA into the algal chloroplast genome was confirmed by PCR. Transcriptional expression of hGAD65 was demonstrated by RT-PCR. Immunoblotting verified the expression and accumulation of the recombinant protein. The antigenicity of algal-derived hGAD65 was demonstrated with its immunoreactivity to diabetic sera by ELISA and by its ability to induce proliferation of spleen cells from NOD mice. Recombinant hGAD65 accumulated in transgenic algae, accounts for approximately 0.25–0.3% of its total soluble protein. Conclusion Our results demonstrate the potential value of C. reinhardtii chloroplasts as a novel platform for rapid mass production of immunologically active hGAD65. This demonstration opens the future possibility for using algal chloroplasts as novel bioreactors for the production of many other biologically active mammalian therapeutic proteins.

Gas solubilities widespread applications

CERN Document Server

Gerrard, William

1980-01-01

Gas Solubilities: Widespread Applications discusses several topics concerning the various applications of gas solubilities. The first chapter of the book reviews Henr's law, while the second chapter covers the effect of temperature on gas solubility. The third chapter discusses the various gases used by Horiuti, and the following chapters evaluate the data on sulfur dioxide, chlorine data, and solubility data for hydrogen sulfide. Chapter 7 concerns itself with solubility of radon, thoron, and actinon. Chapter 8 tackles the solubilities of diborane and the gaseous hydrides of groups IV, V, and

Urtica dioica Effect on Malonyl-CoA Decarboxylase

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Qujeq

2014-09-01

Full Text Available Background The malonyl-CoA decarboxylase (MCD, EC.4.1.1.9 enzyme regulates malonyl-CoA levels. The effect of aerial parts extracts of Urtica dioica (UD on MCD is poorly understood. Objectives The present experiment was undertaken to evaluate the effect of UD aerial parts extracts on MCD level. Materials and Methods In this experimental study, two groups of rats were used: normal and hyperglycemic group. Then UD aerial parts extracts (5 mg /500 µL administrated to the hyperglycemic group of rats and finally, the MCD and insulin levels were measured in both groups. Results Interestingly, we observed that the UD aerial parts extracts powder caused a significant (P < 0.05 increase in insulin level during the experiment, from the base level of 0.36 ± 0.07 μg/L to the peak value of 0.52 ± 0.15 μg/L. Also, it caused a significant (P < 0.05 decrease in MCD level, from the base level of 29.68 ±1.29 pg/mL to the bottom value of 22.12 ± 2.41 pg/mL. Conclusions The results of the present study indicate that UD aerial part extracts would decrease MCD level in hyperglycemic rats.

Harmonization of Glutamic Acid Decarboxylase and Islet Antigen-2 Autoantibody Assays for National Institute of Diabetes and Digestive and Kidney Diseases Consortia

OpenAIRE

Bonifacio, Ezio; Yu, Liping; Williams, Alastair K.; Eisenbarth, George S.; Bingley, Polly J.; Marcovina, Santica M.; Adler, Kerstin; Ziegler, Anette G.; Mueller, Patricia W.; Schatz, Desmond A.; Krischer, Jeffrey P.; Steffes, Michael W.; Akolkar, Beena

2010-01-01

Background/Rationale: Autoantibodies to islet antigen-2 (IA-2A) and glutamic acid decarboxylase (GADA) are markers for diagnosis, screening, and measuring outcomes in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consortia studies. A harmonization program was established to increase comparability of results within and among these studies.

Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.

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Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

2016-03-29

γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage.

Role of ornithine decarboxylase in breast cancer

Institute of Scientific and Technical Information of China (English)

Wensheng Deng; Xian Jiang; Yu Mei; Jingzhong Sun; Rong Ma; Xianxi Liu; Hui Sun; Hui Tian; Xueying Sun

2008-01-01

Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis that decarboxylates ornithine to putrescine, has become a promising target for cancer research. The aim of this study is to investigate the role of ODC in breast cancer. We detected expression of ODC in breast cancer tissues and four breast cancer cell lines, and transfected breast cancer cells with an adenoviral vector carrying antisense ODC (rAd-ODC/Ex3as) and examined their growth and migration.ODC was overexpressed in breast cancer tissues and cell lines compared with non-tumor tissues and normal breast epithelial celis,and there was a positive correlation between the level of ODC mRNA and the staging of tumors.The expression of ODC correlated with cyclin D1,a cell cycle protein,in synchronized breast cancer MDA-MB-231 cells.Gene transfection of rAd-ODC/Ex3as markedly down-regulated expression Of ODC and cyclin D1,resulting in suppression of proliferation and cell cycle arrest at G0-G1 phase,and the inhibifion of colony formation,an anchorage-independent growth pattern,and the migratory ability of MDA-MB-231 cells.rAd-ODC/Ex3as also markedly reduced the concentration of putrescine,but not spermidine or spermine,in MDA-MB-231 cells.The results suggested that the ODC gene might act as aprognostic factor for breast cancer and it could be a promising therapeutic target.

Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence.

Science.gov (United States)

Ma, Jennie Z; Beuten, Joke; Payne, Thomas J; Dupont, Randolph T; Elston, Robert C; Li, Ming D

2005-06-15

DOPA decarboxylase (DDC; also known as L-amino acid decarboxylase; AADC) is involved in the synthesis of dopamine, norepinephrine and serotonin. Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, the DDC gene is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND). Further, this gene is located within the 7p11 region that showed a 'suggestive linkage' to ND in our previous genome-wide scan in the Framingham Heart Study population. In the present study, we tested eight single nucleotide polymorphisms (SNPs) within DDC for association with ND, which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerstrom test for ND (FTND) score, in a total of 2037 smokers and non-smokers from 602 nuclear families of African- or European-American (AA or EA, respectively) ancestry. Association analysis for individual SNPs using the PBAT-GEE program indicated that SNP rs921451 was significantly associated with two of the three adjusted ND measures in the EA sample (P=0.01-0.04). Haplotype-based association analysis revealed a protective T-G-T-G haplotype for rs921451-rs3735273-rs1451371-rs2060762 in the AA sample, which was significantly associated with all three adjusted ND measures after correction for multiple testing (min Z=-2.78, P=0.006 for HSI). In contrast, we found a high-risk T-G-T-G haplotype for a different SNP combination in the EA sample, rs921451-rs3735273-rs1451371-rs3757472, which showed a significant association after Bonferroni correction with the SQ and FTND score (max Z=2.73, P=0.005 for FTND). In summary, our findings provide the first evidence for the involvement of DDC in the susceptibility to ND and, further, reveal the racial specificity of its impact.

Diethylglyoxal bis(guanylhydrazone): a novel highly potent inhibitor of S-adenosylmethionine decarboxylase with promising properties for potential chemotherapeutic use.

Science.gov (United States)

Elo, H; Mutikainen, I; Alhonen-Hongisto, L; Laine, R; Jänne, J

1988-07-01

Diethylglyoxal bis(guanylhydrazone) (DEGBG), a novel analog of the antileukemic agent methylglyoxal bis(guanylhydrazone) (MGBG) was synthesized. It was found to be the most powerful inhibitor of yeast S-adenosylmethionine decarboxylase (AdoMetDC) so far studied (Ki approx. 9 nM). This property, together with the finding that the compound is a weaker inhibitor of intestinal diamine oxidase than are MGBG and its glyoxal, ethylglyoxal and ethylmethylglyoxal analogs, makes the compound a promising candidate as a polyamine antimetabolite for chemotherapy studies. DEGBG was also found to potentiate the antiproliferative effect of the ornithine decarboxylase inhibitor alpha-difluoromethyl ornithine against mouse L1210 leukemia cells in vitro. DEGBG increased several-fold the intracellular putrescine concentration of cultured L1210 cells, just as MGBG and its ethylglyoxal analog are known to do. The results strongly suggest that DEGBG is worth further studies. Combined with previous studies, they also made possible the construction of some empirical rules concerning the structure-activity relationships of bis(guanylhydrazone) type inhibitors of AdoMetDC. The identity of DEGBG was confirmed by a single-crystal X-ray analysis and by 1H- and 13C-NMR spectroscopy. It consisted of the same isomer as MGBG and several of its analogs are known to consist of.

Diagnostic accuracy of the anti-glutamic acid decarboxylase antibody in type 1 diabetes mellitus: Comparison between radioimmunoassay and enzyme-linked immunosorbent assay.

Science.gov (United States)

Murata, Takashi; Tsuzaki, Kokoro; Nirengi, Shinsuke; Watanabe, Tomokazu; Mizutani, Yukako; Okada, Hayami; Tsukamoto, Masami; Odori, Shinji; Nakagawachi, Reiko; Kawaguchi, Yaeko; Yoshioka, Fumi; Yamada, Kazunori; Shimatsu, Akira; Kotani, Kazuhiko; Satoh-Asahara, Noriko; Sakane, Naoki

2017-07-01

The distributer of the anti-glutamic acid decarboxylase antibody assay kit using radioimmunoassay (RIA) recently announced its discontinuation, and proposed an alternative kit using enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to investigate the diagnostic values of the anti-glutamic acid decarboxylase antibody by RIA and ELISA among type 1 diabetes mellitus patients and control participants. A total of 79 type 1 diabetes mellitus patients and 79 age-matched controls were enrolled and assessed using RIA and ELISA. Sensitivity, specificity, positive predictive values and negative predictive values were calculated for cut-off values (RIA = 1.5 U/mL and ELISA = 5.0 U/mL, respectively). Kappa coefficients were used to test for agreements between the RIA and ELISA methods regarding the diagnosis of type 1 diabetes mellitus. The sensitivity, specificity, positive predictive values, and negative predictive values for diagnosing type 1 diabetes mellitus were 57.0, 97.5, 95.7, and 69.4% by RIA, and 60.8, 100.0, 100.0 and 71.8% by ELISA, respectively. The diagnosis of type 1 diabetes mellitus using the RIA and ELISA methods showed substantial agreement with the kappa values of 0.74 for all participants, and of 0.64 for the acute type; however, there was moderate agreement with the kappa value of 0.56 for the slowly progressive type. The present study suggests that both anti-glutamic acid decarboxylase antibody by RIA and ELISA was useful for diagnosing type 1 diabetes mellitus. However, in the slowly progressive type, the degree of agreement of these two kits was poorer compared with those in all participants or in the acute type. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Measurement of activity for S-adenosylmethionine decarboxylase using radioisotope 14C

International Nuclear Information System (INIS)

Ko, Kyong Cheol; Park, Sang Hyun; Kamio, Yoshiyuku

2007-01-01

Polyamines are essential for normal cell growth and have important physiological function. They are polycationic compounds that are present in all biological materials. Also, they have been implicated in a wide variety of biological reactions. Generally, putrescine and spermidine are contained high amount in prokaryote, but spermidine and spermine are in eukaryote, respectively. However, S. ruminantium cells contain the polyamins such as spermidine and spermine. Addition of an aminopropyl group to putrescine conducts to the synthesis of spermidine. Aminopropyl group is derived from the dcSAM, a decarboxylation of S-adenosylmethionine, through action of S-adenosylmethionine decarboxylase (SAMDC). We suggested that S. ruminantium has a different pathway compare with prokaryote for polyamine synthesis. Assay for SAMDC activity was used 14 C labeled substrate. Key enzyme in the biosynthesis of polyamines, SAMDC, was purified from S. ruminantium and characterized. The enzyme was purified about 1,259-fold to electrophoretic homogeneity with a specific activity of 1.89×10 -5 kat kg'- 1 of protein

Structural Characterization of the Molecular Events during a Slow Substrate-Product Transition in Orotidine 5'-Monophosphate Decarboxylase

Energy Technology Data Exchange (ETDEWEB)

Fujihashi, Masahiro; Wei, Lianhu; Kotra, Lakshmi P; Pai, Emil F; (TGRI); (Toronto); (Kyoto)

2009-04-06

Crystal structures of substrate-product complexes of Methanobacterium thermoautotrophicum orotidine 5'-monophosphate decarboxylase, obtained at various steps in its catalysis of the unusual transformation of 6-cyano-uridine 5'-monophosphate (UMP) into barbituric acid ribosyl monophosphate, show that the cyano substituent of the substrate, when bound to the active site, is first bent significantly from the plane of the pyrimidine ring and then replaced by an oxygen atom. Although the K72A and D70A/K72A mutants are either catalytically impaired or even completely inactive, they still display bending of the C6 substituent. Interestingly, high-resolution structures of the D70A and D75N mutants revealed a covalent bond between C6 of UMP and the Lys72 side chain after the -CN moiety's release. The same covalent bond was observed when the native enzyme was incubated with 6-azido-UMP and 6-iodo-UMP; in contrast, the K72A mutant transformed 6-iodo-UMP to barbituric acid ribosyl 5'-monophosphate. These results demonstrate that, given a suitable environment, native orotidine 5'-monophosphate decarboxylase and several of its mutants are not restricted to the physiologically relevant decarboxylation; they are able to catalyze even nucleophilic substitution reactions but consistently maintain distortion on the C6 substituent as an important feature of catalysis.

Redox Cycling, pH Dependence, and Ligand Effects of Mn(III) in Oxalate Decarboxylase from Bacillus subtilis.

Science.gov (United States)

Twahir, Umar T; Ozarowski, Andrew; Angerhofer, Alexander

2016-11-29

This contribution describes electron paramagnetic resonance (EPR) experiments on Mn(III) in oxalate decarboxylase of Bacillus subtilis, an interesting enzyme that catalyzes the redox-neutral dissociation of oxalate into formate and carbon dioxide. Chemical redox cycling provides strong evidence that both Mn centers can be oxidized, although the N-terminal Mn(II) appears to have the lower reduction potential and is most likely the carrier of the +3 oxidation state under moderate oxidative conditions, in agreement with the general view that it represents the active site. Significantly, Mn(III) was observed in untreated OxDC in succinate and acetate buffers, while it could not be directly observed in citrate buffer. Quantitative analysis showed that up to 16% of the EPR-visible Mn is in the +3 oxidation state at low pH in the presence of succinate buffer. The fine structure and hyperfine structure parameters of Mn(III) are affected by small carboxylate ligands that can enter the active site and have been recorded for formate, acetate, and succinate. The results from a previous report [Zhu, W., et al. (2016) Biochemistry 55, 429-434] could therefore be reinterpreted as evidence of formate-bound Mn(III) after the enzyme is allowed to turn over oxalate. The pH dependence of the Mn(III) EPR signal compares very well with that of enzymatic activity, providing strong evidence that the catalytic reaction of oxalate decarboxylase is driven by Mn(III), which is generated in the presence of dioxygen.

Neptunium (IV) oxalate solubility

International Nuclear Information System (INIS)

Luerkens, D.W.

1983-07-01

The equilibrium solubility of neptunium (IV) oxalate in nitric/oxalic acid solutions was determined at 22 0 C, 45 0 C, and 60 0 C. The concentrations of nitric/oxalic acid solutions represented a wide range of free oxalate ion concentration. A mathematical solubility model was developed which is based on the formation of the known complexes of neptunium (IV) oxalate. the solubility model uses a simplified concentration parameter which is proportional to the free oxalate ion concentration. The solubility model can be used to estimate the equilibrium solubility of neptunium (IV) oxalate over a wide range of oxalic and nitric acid concentrations at each temperature

Uranium solubility and solubility controls in selected Needle's Eye groundwaters

International Nuclear Information System (INIS)

Falck, W.E.; Hooker, P.J.

1991-01-01

The solubility control of uranium in selected groundwater samples from the cliff and sediments at the Needle's Eye natural analogue site is investigated using the speciation code PHREEQE and the CHEMVAL thermodynamic database (release 3). Alkali-earth bearing uranyl carbonate secondary minerals are likely to exert influence on the solubility . Other candidates are UO 2 and arsenates, depending on the prevailing redox conditions. In the absence of literature data, solubility products for important arsenates have been estimated from analogy with other arsenates and phosphates. Phosphates themselves are unlikely to exert control owing to their comparatively high solubilities. The influence of seawater flooding into the sediments is also discussed. The importance of uranyl arsenates in the retardation of uranium in shallow sediments has been demonstrated in theory, but there are some significant gaps in the thermodynamic databases used. (author)

Enhancement of the catalytic activity of ferulic acid decarboxylase from Enterobacter sp. Px6-4 through random and site-directed mutagenesis.

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Lee, Hyunji; Park, Jiyoung; Jung, Chaewon; Han, Dongfei; Seo, Jiyoung; Ahn, Joong-Hoon; Chong, Youhoon; Hur, Hor-Gil

2015-11-01

The enzyme ferulic acid decarboxylase (FADase) from Enterobacter sp. Px6-4 catalyzes the decarboxylation reaction of lignin monomers and phenolic compounds such as p-coumaric acid, caffeic acid, and ferulic acid into their corresponding 4-vinyl derivatives, that is, 4-vinylphenol, 4-vinylcatechol, and 4-vinylguaiacol, respectively. Among various ferulic acid decarboxylase enzymes, we chose the FADase from Enterobacter sp. Px6-4, whose crystal structure is known, and produced mutants to enhance its catalytic activity by random and site-directed mutagenesis. After three rounds of sequential mutations, FADase(F95L/D112N/V151I) showed approximately 34-fold higher catalytic activity than wild-type for the production of 4-vinylguaiacol from ferulic acid. Docking analyses suggested that the increased activity of FADase(F95L/D112N/V151I) could be due to formation of compact active site compared with that of the wild-type FADase. Considering the amount of phenolic compounds such as lignin monomers in the biomass components, successfully bioengineered FADase(F95L/D112N/V151I) from Enterobacter sp. Px6-4 could provide an ecofriendly biocatalytic tool for producing diverse styrene derivatives from biomass.

Crystal Structures of Apo and Liganded 4-Oxalocrotonate Decarboxylase Uncover a Structural Basis for the Metal-Assisted Decarboxylation of a Vinylogous β-Keto Acid.

Science.gov (United States)

Guimarães, Samuel L; Coitinho, Juliana B; Costa, Débora M A; Araújo, Simara S; Whitman, Christian P; Nagem, Ronaldo A P

2016-05-10

The enzymes in the catechol meta-fission pathway have been studied for more than 50 years in several species of bacteria capable of degrading a number of aromatic compounds. In a related pathway, naphthalene, a toxic polycyclic aromatic hydrocarbon, is fully degraded to intermediates of the tricarboxylic acid cycle by the soil bacteria Pseudomonas putida G7. In this organism, the 83 kb NAH7 plasmid carries several genes involved in this biotransformation process. One enzyme in this route, NahK, a 4-oxalocrotonate decarboxylase (4-OD), converts 2-oxo-3-hexenedioate to 2-hydroxy-2,4-pentadienoate using Mg(2+) as a cofactor. Efforts to study how 4-OD catalyzes this decarboxylation have been hampered because 4-OD is present in a complex with vinylpyruvate hydratase (VPH), which is the next enzyme in the same pathway. For the first time, a monomeric, stable, and active 4-OD has been expressed and purified in the absence of VPH. Crystal structures for NahK in the apo form and bonded with five substrate analogues were obtained using two distinct crystallization conditions. Analysis of the crystal structures implicates a lid domain in substrate binding and suggests roles for specific residues in a proposed reaction mechanism. In addition, we assign a possible function for the NahK N-terminal domain, which differs from most of the other members of the fumarylacetoacetate hydrolase superfamily. Although the structural basis for metal-dependent β-keto acid decarboxylases has been reported, this is the first structural report for that of a vinylogous β-keto acid decarboxylase and the first crystal structure of a 4-OD.

Hydrogen solubility measurements of analyzed tall oil fractions and a solubility model

International Nuclear Information System (INIS)

Uusi-Kyyny, Petri; Pakkanen, Minna; Linnekoski, Juha; Alopaeus, Ville

2017-01-01

Highlights: • Hydrogen solubility was measured in four tall oil fractions between 373 and 597 K. • Continuous flow synthetic isothermal and isobaric method was used. • A Henry’s law model was developed for the distilled tall oil fractions. • The complex composition of the samples was analyzed and is presented. - Abstract: Knowledge of hydrogen solubility in tall oil fractions is important for designing hydrotreatment processes of these complex nonedible biobased materials. Unfortunately measurements of hydrogen solubility into these fractions are missing in the literature. This work reports hydrogen solubility measured in four tall oil fractions between 373 and 597 K and at pressures from 5 to 10 MPa. Three of the fractions were distilled tall oil fractions their resin acids contents are respectively 2, 20 and 23 in mass-%. Additionally one fraction was a crude tall oil (CTO) sample containing sterols as the main neutral fraction. Measurements were performed using a continuous flow synthetic isothermal and isobaric method based on the visual observation of the bubble point. Composition of the flow was changed step-wise for the bubble point composition determination. We assume that the tall oil fractions did not react during measurements, based on the composition analysis performed before and after the measurements. Additionally the densities of the fractions were measured at atmospheric pressure from 293.15 to 323.15 K. A Henry’s law model was developed for the distilled tall oil fractions describing the solubility with an absolute average deviation of 2.1%. Inputs of the solubility model are temperature, total pressure and the density of the oil at 323.15 K. The solubility of hydrogen in the CTO sample can be described with the developed model with an absolute average deviation of 3.4%. The solubility of hydrogen increases both with increasing pressure and/or increasing temperature. The more dense fractions of the tall oil exhibit lower hydrogen

Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

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Manal Alkan

2015-01-01

Full Text Available Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD mouse model. To this end, we used mice (inactivated knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC−/− mice decreased the incidence of diabetes in relation to their wild-type counterpart. Whereas the proportion of regulatory T and myeloid-derived suppressive cells was similar in both strains, histamine deficiency was associated with increased levels of immature macrophages, as compared with wild-type NOD mice. Concerning the cytokine pattern, we found a decrease in circulating IL-12 and IFN-γ in HDC−/− mice, while IL-6 or leptin remained unchanged, suggesting that histamine primarily modulates the inflammatory environment. Paradoxically, exogenous histamine given to NOD HDC−/− mice provided also protection against T1D. Our study supports the notion that histamine is involved in the pathogenesis of diabetes, thus providing additional evidence for its role in the regulation of the immune response.

L-Dopa decarboxylase expression profile in human cancer cells.

Science.gov (United States)

Chalatsa, Ioanna; Nikolouzou, Eleftheria; Fragoulis, Emmanuel G; Vassilacopoulou, Dido

2011-02-01

L-Dopa decarboxylase (DDC) catalyses the decarboxylation of L-Dopa. It has been shown that the DDC gene undergoes alternative splicing within its 5'-untranslated region (UTR), in a tissue-specific manner, generating identical protein products. The employment of two alternative 5'UTRs is thought to be responsible for tissue-specific expression of the human DDC mRNA. In this study, we focused on the investigation of the nature of the mRNA expression in human cell lines of neural and non-neural origin. Our results show the expression of a neural-type DDC mRNA splice variant, lacking exon 3 in all cell lines studied. Co-expression of the full length non-neural DDC mRNA and the neural-type DDC splice variant lacking exon 3 was detected in all cell lines. The alternative DDC protein isoform, Alt-DDC, was detected in SH-SY5Y and HeLa cells. Our findings suggest that the human DDC gene undergoes complex processing, leading to the formation of multiple mRNA isoforms. The study of the significance of this phenomenon of multiple DDC mRNA isoforms could provide us with new information leading to the elucidation of the complex biological pathways that the human enzyme is involved in.

Reactions of Ferrous Coproheme Decarboxylase (HemQ) with O2 and H2O2 Yield Ferric Heme b.

Science.gov (United States)

Streit, Bennett R; Celis, Arianna I; Shisler, Krista; Rodgers, Kenton R; Lukat-Rodgers, Gudrun S; DuBois, Jennifer L

2017-01-10

A recently discovered pathway for the biosynthesis of heme b ends in an unusual reaction catalyzed by coproheme decarboxylase (HemQ), where the Fe(II)-containing coproheme acts as both substrate and cofactor. Because both O 2 and H 2 O 2 are available as cellular oxidants, pathways for the reaction involving either can be proposed. Analysis of reaction kinetics and products showed that, under aerobic conditions, the ferrous coproheme-decarboxylase complex is rapidly and selectively oxidized by O 2 to the ferric state. The subsequent second-order reaction between the ferric complex and H 2 O 2 is slow, pH-dependent, and further decelerated by D 2 O 2 (average kinetic isotope effect of 2.2). The observation of rapid reactivity with peracetic acid suggested the possible involvement of Compound I (ferryl porphyrin cation radical), consistent with coproheme and harderoheme reduction potentials in the range of heme proteins that heterolytically cleave H 2 O 2 . Resonance Raman spectroscopy nonetheless indicated a remarkably weak Fe-His interaction; how the active site structure may support heterolytic H 2 O 2 cleavage is therefore unclear. From a cellular perspective, the use of H 2 O 2 as an oxidant in a catalase-positive organism is intriguing, as is the unusual generation of heme b in the Fe(III) rather than Fe(II) state as the end product of heme synthesis.

Autoantibodies against voltage-gated potassium channel and glutamic acid decarboxylase in psychosis: A systematic review, meta-analysis, and case series.

OpenAIRE

Grain, Rosemary; Lally, John; Stubbs, Brendon; Malik, Steffi; LeMince, Anne; Nicholson, Timothy R; Murray, Robin M; Gaughran, Fiona

2017-01-01

Antibodies to the voltage-gated potassium channel (VGKC) complex and glutamic acid decarboxylase (GAD) have been reported in some cases of psychosis. We conducted the first systematic review and meta-analysis to investigate their prevalence in people with psychosis and report a case series of VGKC-complex antibodies in refractory psychosis. Only five studies presenting prevalence rates of VGKC seropositivity in psychosis were identified, in addition to our case series, with an overall prevale...

Pure Phase Solubility Limits: LANL

International Nuclear Information System (INIS)

C. Stockman

2001-01-01

The natural and engineered system at Yucca Mountain (YM) defines the site-specific conditions under which one must determine to what extent the engineered and the natural geochemical barriers will prevent the release of radioactive material from the repository. Most important mechanisms for retention or enhancement of radionuclide transport include precipitation or co-precipitation of radionuclide-bearing solid phases (solubility limits), complexation in solution, sorption onto surfaces, colloid formation, and diffusion. There may be many scenarios that could affect the near-field environment, creating chemical conditions more aggressive than the conditions presented by the unperturbed system (such as pH changes beyond the range of 6 to 9 or significant changes in the ionic strength of infiltrated waters). For an extended period of time, the near-field water composition may be quite different and more extreme in pH, ionic strength, and CO 2 partial pressure (or carbonate concentration) than waters at some distance from the repository. Reducing conditions, high pH (up to 11), and low carbonate concentration may be present in the near-field after reaction of infiltrating groundwater with engineered barrier systems, such as cementitious materials. In the far-field, conditions are controlled by the rock-mass buffer providing a near-neutral, oxidizing, low-ionic-strength environment that controls radionuclide solubility limits and sorption capacities. There is the need for characterization of variable chemical conditions that affect solubility, speciation, and sorption reactions. Modeling of the groundwater chemistry is required and leads to an understanding of solubility and speciation of the important radionuclides. Because experimental studies cannot be performed under the numerous potential chemical conditions, solubility limitations must rely on geochemical modeling of the radionuclide's chemistry. Fundamental thermodynamic properties, such as solubility products

Pure Phase Solubility Limits: LANL

Energy Technology Data Exchange (ETDEWEB)

C. Stockman

2001-01-26

The natural and engineered system at Yucca Mountain (YM) defines the site-specific conditions under which one must determine to what extent the engineered and the natural geochemical barriers will prevent the release of radioactive material from the repository. Most important mechanisms for retention or enhancement of radionuclide transport include precipitation or co-precipitation of radionuclide-bearing solid phases (solubility limits), complexation in solution, sorption onto surfaces, colloid formation, and diffusion. There may be many scenarios that could affect the near-field environment, creating chemical conditions more aggressive than the conditions presented by the unperturbed system (such as pH changes beyond the range of 6 to 9 or significant changes in the ionic strength of infiltrated waters). For an extended period of time, the near-field water composition may be quite different and more extreme in pH, ionic strength, and CO{sub 2} partial pressure (or carbonate concentration) than waters at some distance from the repository. Reducing conditions, high pH (up to 11), and low carbonate concentration may be present in the near-field after reaction of infiltrating groundwater with engineered barrier systems, such as cementitious materials. In the far-field, conditions are controlled by the rock-mass buffer providing a near-neutral, oxidizing, low-ionic-strength environment that controls radionuclide solubility limits and sorption capacities. There is the need for characterization of variable chemical conditions that affect solubility, speciation, and sorption reactions. Modeling of the groundwater chemistry is required and leads to an understanding of solubility and speciation of the important radionuclides. Because experimental studies cannot be performed under the numerous potential chemical conditions, solubility limitations must rely on geochemical modeling of the radionuclide's chemistry. Fundamental thermodynamic properties, such as solubility

4-Amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) exerts in vitro growth inhibitory effects that are not only related to S-adenosylmethionine decarboxylase (SAMdc) inhibition

NARCIS (Netherlands)

Dorhout, B; Odink, MFG; deHoog, E; Kingma, AW; vanderVeer, E; Muskiet, FAJ

1997-01-01

The competitive S-adenosylmethionine decarboxylase (SAMdc; EC 4.1.1.50) inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) inhibits growth more effectively than the irreversible SAMdc inhibitor 5'-{[(Z)-4-amino-2-butenyl]methylamino}-5'-deoxyadenosine (AbeAdo), while having similar

Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.

Science.gov (United States)

Williams, Brianna B; Van Benschoten, Andrew H; Cimermancic, Peter; Donia, Mohamed S; Zimmermann, Michael; Taketani, Mao; Ishihara, Atsushi; Kashyap, Purna C; Fraser, James S; Fischbach, Michael A

2014-10-08

Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the β-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare among bacteria more broadly, analysis of the Human Microbiome Project data demonstrate that at least 10% of the human population harbors at least one bacterium encoding a tryptophan decarboxylase in their gut community. Our results uncover a previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and suggests a potential direct mechanism by which gut microbiota can influence host physiology, including behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of cyclodextrin complexation on the aqueous solubility and solubility/dose ratio of praziquantel.

Science.gov (United States)

Maragos, Stratos; Archontaki, Helen; Macheras, Panos; Valsami, Georgia

2009-01-01

Praziquantel (PZQ), the primary drug of choice in the treatment of schistosomiasis, is a highly lipophilic drug that possesses high permeability and low aqueous solubility and is, therefore, classified as a Class II drug according to the Biopharmaceutics Classification System (BCS). In this work, beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were used in order to determine whether increasing the aqueous solubility of a drug by complexation with CDs, a BCS-Class II compound like PZQ could behave as BCS-Class I (highly soluble/highly permeable) drug. Phase solubility and the kneading and lyophilization techniques were used for inclusion complex preparation; solubility was determined by UV spectroscopy. The ability of the water soluble polymer polyvinylpyrolidone (PVP) to increase the complexation and solubilization efficiency of beta-CD and HP-beta-CD for PZQ was examined. Results showed significant improvement of PZQ solubility in the presence of both cyclodextrins but no additional effect in the presence of PVP. The solubility/dose ratios values of PZQ-cyclodextrin complexes calculated considering the low (150 mg) and the high dose (600 mg) of PZQ, used in practice, indicate that PZQ complexation with CDs may result in drug dosage forms that would behave as a BCS-Class I depending on the administered dose.

Oral formulation strategies to improve solubility of poorly water-soluble drugs.

Science.gov (United States)

Singh, Abhishek; Worku, Zelalem Ayenew; Van den Mooter, Guy

2011-10-01

In the past two decades, there has been a spiraling increase in the complexity and specificity of drug-receptor targets. It is possible to design drugs for these diverse targets with advances in combinatorial chemistry and high throughput screening. Unfortunately, but not entirely unexpectedly, these advances have been accompanied by an increase in the structural complexity and a decrease in the solubility of the active pharmaceutical ingredient. Therefore, the importance of formulation strategies to improve the solubility of poorly water-soluble drugs is inevitable, thus making it crucial to understand and explore the recent trends. Drug delivery systems (DDS), such as solid dispersions, soluble complexes, self-emulsifying drug delivery systems (SEDDS), nanocrystals and mesoporous inorganic carriers, are discussed briefly in this review, along with examples of marketed products. This article provides the reader with a concise overview of currently relevant formulation strategies and proposes anticipated future trends. Today, the pharmaceutical industry has at its disposal a series of reliable and scalable formulation strategies for poorly soluble drugs. However, due to a lack of understanding of the basic physical chemistry behind these strategies, formulation development is still driven by trial and error.

Effects of methylglyoxal bis(guanylhydrazone) and two phenylated analogues on S-adenosylmethionine decarboxylase activity from Eimeria stiedai (Apicomplexa).

Science.gov (United States)

San-Martín Núñez, B; Alunda, J M; Balaña-Fouce, R; Ordóñez Escudero, D

1987-01-01

1. Activity of S-adenosylmethionine decarboxylase, one of the rate-limiting enzymes of polyamine biosynthesis, was determined in oocysts of Eimeria stiedai, a coccidian parasite of the rabbit. 2. Several properties of the enzyme were compared to the mammalian enzyme. It showed considerably less substrate affinity than the analog enzyme from the rabbit. 3. The E. stiedai enzyme showed a low sensitivity to methylglyoxal bis(guanylhydrazone), a frequently used inhibitor of the enzyme in mammals, and two phenylated derivatives. 4. Results with the inhibitors are discussed in view of their potential use in chemotherapy.

The solubility-permeability interplay and its implications in formulation design and development for poorly soluble drugs.

Science.gov (United States)

Dahan, Arik; Miller, Jonathan M

2012-06-01

While each of the two key parameters of oral drug absorption, the solubility and the permeability, has been comprehensively studied separately, the relationship and interplay between the two have been largely ignored. For instance, when formulating a low-solubility drug using various solubilization techniques: what are we doing to the apparent permeability when we increase the solubility? Permeability is equal to the drug's diffusion coefficient through the membrane times the membrane/aqueous partition coefficient divided by the membrane thickness. The direct correlation between the intestinal permeability and the membrane/aqueous partitioning, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggests that the solubility and the permeability are closely associated, exhibiting a certain interplay between them, and the current view of treating the one irrespectively of the other may not be sufficient. In this paper, we describe the research that has been done thus far, and present new data, to shed light on this solubility-permeability interplay. It has been shown that decreased apparent permeability accompanies the solubility increase when using different solubilization methods. Overall, the weight of the evidence indicates that the solubility-permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility enhancement that the formulation enables may be misleading with regards to predicting the resulting absorption, and hence, the solubility-permeability interplay must be taken into account to strike the optimal solubility-permeability balance, in order to maximize the overall absorption.

A Dopa Decarboxylase Modulating the Immune Response of Scallop Chlamys farreri

Science.gov (United States)

Zhou, Zhi; Yang, Jialong; Wang, Lingling; Zhang, Huan; Gao, Yang; Shi, Xiaowei; Wang, Mengqiang; Kong, Pengfei; Qiu, Limei; Song, Linsheng

2011-01-01

Background Dopa decarboxylase (DDC) is a pyridoxal 5-phosphate (PLP)-dependent enzyme that catalyzes the decarboxylation of L-Dopa to dopamine, and involved in complex neuroendocrine-immune regulatory network. The function for DDC in the immunomodulation remains unclear in invertebrate. Methodology The full-length cDNA encoding DDC (designated CfDDC) was cloned from mollusc scallop Chlamys farreri. It contained an open reading frame encoding a polypeptide of 560 amino acids. The CfDDC mRNA transcripts could be detected in all the tested tissues, including the immune tissues haemocytes and hepatopancreas. After scallops were treated with LPS stimulation, the mRNA expression level of CfDDC in haemocytes increased significantly (5.5-fold, PDDC inhibitor methyldopa, the ROS level in haemocytes of scallops was decreased significantly to 0.41-fold (PDDC in scallop, modulated the immune responses such as haemocytes encapsulation as well as the ROS level through its catalytic activity, functioning as an indispensable immunomodulating enzyme in the neuroendocrine-immune regulatory network of mollusc. PMID:21533240

Inhibition of S-adenosylmethionine decarboxylase and diamine oxidase activities by analogues of methylglyoxal bis(guanylhydrazone) and their cellular uptake during lymphocyte activation.

OpenAIRE

Jänne, J; Morris, D R

1984-01-01

Several congeners of methylglyoxal bis(guanylhydrazone) were tested for their ability to inhibit eukaryotic putrescine-activated S-adenosylmethionine decarboxylase (EC 4.1.1.50) and intestinal diamine oxidase (EC 1.4.3.6). All the compounds tested, namely methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone), dimethylglyoxal bis(guanylhydrazone) and the di-N"-methyl derivative of methylglyoxal bis(guanylhydrazone), were strong inhibitors of both yeast and mouse liver adenosylm...

Head-To-Head Comparison of Different Solubility-Enabling Formulations of Etoposide and Their Consequent Solubility-Permeability Interplay.

Science.gov (United States)

Beig, Avital; Miller, Jonathan M; Lindley, David; Carr, Robert A; Zocharski, Philip; Agbaria, Riad; Dahan, Arik

2015-09-01

The purpose of this study was to conduct a head-to-head comparison of different solubility-enabling formulations, and their consequent solubility-permeability interplay. The low-solubility anticancer drug etoposide was formulated in several strengths of four solubility-enabling formulations: hydroxypropyl-β-cyclodextrin, the cosolvent polyethylene glycol 400 (PEG-400), the surfactant sodium lauryl sulfate, and an amorphous solid dispersion formulation. The ability of these formulations to increase the solubility of etoposide was investigated, followed by permeability studies using the parallel artificial membrane permeability assay (PAMPA) and examination of the consequent solubility-permeability interplay. All formulations significantly increased etoposide's apparent solubility. The cyclodextrin-, surfactant-, and cosolvent-based formulations resulted in a concomitant decreased permeability that could be modeled directly from the proportional increase in the apparent solubility. On the contrary, etoposide permeability remained constant when using the ASD formulation, irrespective of the increased apparent solubility provided by the formulation. In conclusion, supersaturation resulting from the amorphous form overcomes the solubility-permeability tradeoff associated with other formulation techniques. Accounting for the solubility-permeability interplay may allow to develop better solubility-enabling formulations, thereby maximizing the overall absorption of lipophilic orally administered drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Indomethacin solubility estimation in 1,4-dioxane + water mixtures by the extended hildebrand solubility approach

Directory of Open Access Journals (Sweden)

Miller A Ruidiaz

2011-09-01

Full Text Available Extended Hildebrand Solubility Approach (EHSA was successfully applied to evaluate the solubility of Indomethacin in 1,4-dioxane + water mixtures at 298.15 K. An acceptable correlation-performance of EHSA was found by using a regular polynomial model in order four of the W interaction parameter vs. solubility parameter of the mixtures (overall deviation was 8.9%. Although the mean deviation obtained was similar to that obtained directly by means of an empiric regression of the experimental solubility vs. mixtures solubility parameters, the advantages of EHSA are evident because it requires physicochemical properties easily available for drugs.

Solubility behavior and biopharmaceutical classification of novel high-solubility ciprofloxacin and norfloxacin pharmaceutical derivatives.

Science.gov (United States)

Breda, Susana A; Jimenez-Kairuz, Alvaro F; Manzo, Ruben H; Olivera, María E

2009-04-17

The hydrochlorides of the 1:3 aluminum:norfloxacin and aluminum:ciprofloxacin complexes were characterized according to the Biopharmaceutics Classification System (BCS) premises in comparison with their parent compounds. The pH-solubility profiles of the complexes were experimentally determined at 25 and 37 degrees C in the range of pH 1-8 and compared to that of uncomplexed norfloxacin and ciprofloxacin. Both complexes are clearly more soluble than the antibiotics themselves, even at the lowest solubility pHs. The increase in solubility was ascribed to the species controlling solubility, which were analyzed in the solid phases at equilibrium at selected pHs. Additionally, permeability was set as low, based on data reported in the scientific literature regarding oral bioavailability, intestinal and cell cultures permeabilities and also considering the influence of stoichiometric amounts of aluminum. The complexes fulfill the BCS criterion to be classified as class 3 compounds (high solubility/low permeability). Instead, the active pharmaceutical ingredients (APIs) currently used in solid dosage forms, norfloxacin and ciprofloxacin hydrochloride, proved to be BCS class 4 (low solubility/low permeability). The solubility improvement turns the complexes as potential biowaiver candidates from the scientific point of view and may be a good way for developing more dose-efficient formulations. An immediate release tablet showing very rapid dissolution was obtained. Its dissolution profile was compared to that of the commercial ciprofloxacin hydrochloride tablets allowing to dissolution of the complete dose at a critical pH such as 6.8.

Mevalonate 5-diphosphate mediates ATP binding to the mevalonate diphosphate decarboxylase from the bacterial pathogen Enterococcus faecalis

Energy Technology Data Exchange (ETDEWEB)

Chen, Chun-Liang; Mermoud, James C.; Paul, Lake N.; Steussy, Calvin Nicklaus; Stauffacher, Cynthia V. (Purdue)

2017-10-12

The mevalonate pathway produces isopentenyl diphosphate (IPP), a building block for polyisoprenoid synthesis, and is a crucial pathway for growth of the human bacterial pathogen Enterococcus faecalis. The final enzyme in this pathway, mevalonate diphosphate decarboxylase (MDD), acts on mevalonate diphosphate (MVAPP) to produce IPP while consuming ATP. This essential enzyme has been suggested as a therapeutic target for the treatment of drug-resistant bacterial infections. Here, we report functional and structural studies on the mevalonate diphosphate decarboxylase from E. faecalis (MDDEF). The MDDEF crystal structure in complex with ATP (MDDEF–ATP) revealed that the phosphate-binding loop (amino acids 97–105) is not involved in ATP binding and that the phosphate tail of ATP in this structure is in an outward-facing position pointing away from the active site. This suggested that binding of MDDEF to MVAPP is necessary to guide ATP into a catalytically favorable position. Enzymology experiments show that the MDDEF performs a sequential ordered bi-substrate reaction with MVAPP as the first substrate, consistent with the isothermal titration calorimetry (ITC) experiments. On the basis of ITC results, we propose that this initial prerequisite binding of MVAPP enhances ATP binding. In summary, our findings reveal a substrate-induced substrate-binding event that occurs during the MDDEF-catalyzed reaction. The disengagement of the phosphate-binding loop concomitant with the alternative ATP-binding configuration may provide the structural basis for antimicrobial design against these pathogenic enterococci.

Expression of the Aspergillus terreus itaconic acid biosynthesis cluster in Aspergillus niger.

Science.gov (United States)

van der Straat, Laura; Vernooij, Marloes; Lammers, Marieke; van den Berg, Willy; Schonewille, Tom; Cordewener, Jan; van der Meer, Ingrid; Koops, Andries; de Graaff, Leo H

2014-01-17

Aspergillus terreus is a natural producer of itaconic acid and is currently used to produce itaconic acid on an industrial scale. The metabolic process for itaconic acid biosynthesis is very similar to the production of citric acid in Aspergillus niger. However, a key enzyme in A. niger, cis-aconitate decarboxylase, is missing. The introduction of the A. terreus cadA gene in A. niger exploits the high level of citric acid production (over 200 g per liter) and theoretically can lead to production levels of over 135 g per liter of itaconic acid in A. niger. Given the potential for higher production levels in A. niger, production of itaconic acid in this host was investigated. Expression of Aspergillus terreus cis-aconitate decarboxylase in Aspergillus niger resulted in the production of a low concentration (0.05 g/L) of itaconic acid. Overexpression of codon-optimized genes for cis-aconitate decarboxylase, a mitochondrial transporter and a plasma membrane transporter in an oxaloacetate hydrolase and glucose oxidase deficient A. niger strain led to highly increased yields and itaconic acid production titers. At these higher production titers, the effect of the mitochondrial and plasma membrane transporters was much more pronounced, with levels being 5-8 times higher than previously described. Itaconic acid can be produced in A. niger by the introduction of the A. terreus cis-aconitate decarboxylase encoding cadA gene. This results in a low itaconic acid production level, which can be increased by codon-optimization of the cadA gene for A. niger. A second crucial requirement for efficient production of itaconic acid is the expression of the A. terreus mttA gene, encoding a putative mitochondrial transporter. Expression of this transporter results in a twenty-fold increase in the secretion of itaconic acid. Expression of the A. terreus itaconic acid cluster consisting of the cadA gene, the mttA gene and the mfsA gene results in A. niger strains that produce over

Argon solubility in liquid steel

NARCIS (Netherlands)

Boom, R; Dankert, O; Van Veen, A; Kamperman, AA

2000-01-01

Experiments have been performed to establish the solubility of argon in liquid interstitial-free steel. The solubility appears to be lower than 0.1 at ppb, The results are in line with argon solubilities reported in the literature on liquid iron. Semiempirical theories and calculations based on the

Autoantibodies against voltage-gated potassium channel (VGKC) and glutamic acid decarboxylase (GAD) in psychosis: A systematic review, meta-analysis and case series.

OpenAIRE

Lally*, John; Grain*, Rosemary; Stubbs, Brendon; Malik, Steffi; LeMince, Anne; Nicholson, Timothy RJ; Murray, Robin MacGregor; Gaughran, Fiona Patricia

2017-01-01

Antibodies to the voltage-gated potassium channel (VGKC) complex and glutamic acid decarboxylase (GAD) have been reported in some cases of psychosis. We conducted the first systematic review and meta-analysis to investigate their prevalence in people with psychosis and report a case series of VGKC-complex antibodies in refractory psychosis. Only five studies presenting prevalence rates of VGKC seropositivity in psychosis were identified, in addition to our case series, with an overall prevale...

Students’ misconceptions on solubility equilibrium

Science.gov (United States)

Setiowati, H.; Utomo, S. B.; Ashadi

2018-05-01

This study investigated the students’ misconceptions of the solubility equilibrium. The participants of the study consisted of 164 students who were in the science class of second year high school. Instrument used is two-tier diagnostic test consisting of 15 items. Responses were marked and coded into four categories: understanding, misconception, understand little without misconception, and not understanding. Semi-structured interviews were carried out with 45 students according to their written responses which reflected different perspectives, to obtain a more elaborated source of data. Data collected from multiple methods were analyzed qualitatively and quantitatively. Based on the data analysis showed that the students misconceptions in all areas in solubility equilibrium. They had more misconceptions such as in the relation of solubility and solubility product, common-ion effect and pH in solubility, and precipitation concept.

Renal ornithine decarboxylase activity, polyamines, and compensatory renal hypertrophy in the rat

International Nuclear Information System (INIS)

Humphreys, M.H.; Etheredge, S.B.; Lin, Shanyan; Ribstein, J.; Marton, L.J.

1988-01-01

The authors determined the role of ornithine decarboxylase (ODC) in compensatory renal hypertrophy (CRH) by relating renal ODC activity and polyamine content to kidney size, expressed as a percent of body weight, 1 wk after unilateral nephrectomy (UN). In normal rats, renal ODC activity increased after UN; 1 wk later the remaining kidney weight had increased. Renal concentration of putrescine, the product of ODC's decarboxylation of ornithine, was increased 3, 8, and 48 h after UN, but concentrations of polyamines synthesized later in the pathway, spermidine and spermine, were not appreciably affected. Pretreatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC inhibited both base-line renal ODC activity and putrescine concentration as well as increases stimulated by UN, although concentrations of spermidine and spermine were not decreased. In hypophysectomized rats, both increased renal ODC activity and CRH occurred as well, indicating that these two consequences of UN do not require intact pituitary function. Thus stimulation of renal ODC activity and putrescine content do not appear critical to the process of CRH after UN

Pyruvate decarboxylase provides growing pollen tubes with a competitive advantage in petunia.

Science.gov (United States)

Gass, Nathalie; Glagotskaia, Tatiana; Mellema, Stefan; Stuurman, Jeroen; Barone, Mario; Mandel, Therese; Roessner-Tunali, Ute; Kuhlemeier, Cris

2005-08-01

Rapid pollen tube growth places unique demands on energy production and biosynthetic capacity. The aim of this work is to understand how primary metabolism meets the demands of such rapid growth. Aerobically grown pollen produce ethanol in large quantities. The ethanolic fermentation pathway consists of two committed enzymes: pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH). Because adh mutations do not affect male gametophyte function, the obvious question is why pollen synthesize an abundant enzyme if they could do just as well without. Using transposon tagging in Petunia hybrida, we isolated a null mutant in pollen-specific Pdc2. Growth of the mutant pollen tubes through the style is reduced, and the mutant allele shows reduced transmission through the male, when in competition with wild-type pollen. We propose that not ADH but rather PDC is the critical enzyme in a novel, pollen-specific pathway. This pathway serves to bypass pyruvate dehydrogenase enzymes and thereby maintain biosynthetic capacity and energy production under the unique conditions prevailing during pollen-pistil interaction.

Insights on ornithine decarboxylase silencing as a potential strategy for targeting retinoblastoma.

Science.gov (United States)

Muthukumaran, Sivashanmugam; Bhuvanasundar, Renganathan; Umashankar, Vetrivel; Sulochana, K N

2018-02-01

Ornithine Decarboxylase (ODC) is a key enzyme involved in polyamine synthesis and is reported to be up regulated in several cancers. However, the effect of ODC gene silencing in retinoblastoma is to be understood for utilization in therapeutic applications. Hence, in this study, a novel siRNA (small interference RNA) targeting ODC was designed and validated in Human Y79 retinoblastoma cells for its effects on intracellular polyamine levels, Matrix Metalloproteinase 2 & 9 activity and Cell cycle. The designed siRNA showed efficient silencing of ODC mRNA expression and protein levels in Y79 cells. It also showed significant reduction of intracellular polyamine levels and altered levels of oncogenic LIN28b expression. By this study, a regulatory loop is proposed, wherein, ODC silencing in Y79 cells to result in decreased polyamine levels, thereby, leading to altered protein levels of Lin28b, MMP-2 and MMP-9, which falls in line with earlier studies in neuroblastoma. Thus, by this study, we propose ODC silencing as a prospective strategy for targeting retinoblastoma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Measurement of activity for S-adenosylmethionine decarboxylase using radioisotope {sup 14}C

Energy Technology Data Exchange (ETDEWEB)

Ko, Kyong Cheol; Park, Sang Hyun [Radiation Research Center for Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Kamio, Yoshiyuku [Division of Bioscience and Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University (Japan)

2007-05-15

Polyamines are essential for normal cell growth and have important physiological function. They are polycationic compounds that are present in all biological materials. Also, they have been implicated in a wide variety of biological reactions. Generally, putrescine and spermidine are contained high amount in prokaryote, but spermidine and spermine are in eukaryote, respectively. However, S. ruminantium cells contain the polyamins such as spermidine and spermine. Addition of an aminopropyl group to putrescine conducts to the synthesis of spermidine. Aminopropyl group is derived from the dcSAM, a decarboxylation of S-adenosylmethionine, through action of S-adenosylmethionine decarboxylase (SAMDC). We suggested that S. ruminantium has a different pathway compare with prokaryote for polyamine synthesis. Assay for SAMDC activity was used {sup 14}C labeled substrate. Key enzyme in the biosynthesis of polyamines, SAMDC, was purified from S. ruminantium and characterized. The enzyme was purified about 1,259-fold to electrophoretic homogeneity with a specific activity of 1.89×10{sup -5} kat kg'-{sup 1} of protein.

Construction of an Unstable Ring-X Chromosome Bearing the Autosomal Dopa Decarboxylase Gene in Drosophila melanogaster and Analysis of Ddc Mosaics

OpenAIRE

Gailey, Donald A.; Bordne, Deborah L.; Vallés, Ana Maria; Hall, Jeffrey C.; White, Kalpana

1987-01-01

An unstable Ring-X chromosome, Ddc+- Ring-X carrying a cloned Dopa decarboxylase (Ddc) encoding segment was constructed. The construction involved a double recombination event between the unstable Ring-X, R(1)wvC and a Rod-X chromosome which contained a P-element mediated Ddc + insert. The resulting Ddc+-Ring-X chromosome behaves similarly to the parent chromosome with respect to somatic instability. The Ddc+-Ring-X chromosome was used to generate Ddc mosaics. Analyses of Ddc mosaics reveal...

Trypanosoma cruzi has not lost its S-adenosylmethionine decarboxylase: characterization of the gene and the encoded enzyme.

Science.gov (United States)

Persson, K; Aslund, L; Grahn, B; Hanke, J; Heby, O

1998-01-01

All attempts to identify ornithine decarboxylase in the human pathogen Trypanosoma cruzi have failed. The parasites have instead been assumed to depend on putrescine uptake and S-adenosylmethionine decarboxylase (AdoMetDC) for their synthesis of the polyamines spermidine and spermine. We have now identified the gene encoding AdoMetDC in T. cruzi by PCR cloning, with degenerate primers corresponding to conserved amino acid sequences in AdoMetDC proteins of other trypanosomatids. The amplified DNA fragment was used as a probe to isolate the complete AdoMetDC gene from a T. cruzi genomic library. The AdoMetDC gene was located on chromosomes with a size of approx. 1.4 Mbp, and contained a coding region of 1110 bp, specifying a sequence of 370 amino acid residues. The protein showed a sequence identity of only 25% with human AdoMetDC, the major differences being additional amino acids present in the terminal regions of the T. cruzi enzyme. As expected, a higher sequence identity (68-72%) was found in comparison with trypanosomatid AdoMetDCs. When the coding region was expressed in Escherichia coli, the recombinant protein underwent autocatalytic cleavage, generating a 33-34 kDa alpha subunit and a 9 kDa beta subunit. The encoded protein catalysed the decarboxylation of AdoMet (Km 0.21 mM) and was stimulated by putrescine but inhibited by the polyamines, weakly by spermidine and strongly by spermine. Methylglyoxal-bis(guanylhydrazone) (MGBG), a potent inhibitor of human AdoMetDC, was a poor inhibitor of the T. cruzi enzyme. This differential sensitivity to MGBG suggests that the two enzymes are sufficiently different to warrant the search for compounds that might interfere with the progression of Chagas' disease by selectively inhibiting T. cruzi AdoMetDC. PMID:9677309

The Solubility Parameters of Ionic Liquids

Science.gov (United States)

Marciniak, Andrzej

2010-01-01

The Hildebrand’s solubility parameters have been calculated for 18 ionic liquids from the inverse gas chromatography measurements of the activity coefficients at infinite dilution. Retention data were used for the calculation. The solubility parameters are helpful for the prediction of the solubility in the binary solvent mixtures. From the solubility parameters, the standard enthalpies of vaporization of ionic liquids were estimated. PMID:20559495

The Solubility Parameters of Ionic Liquids

Directory of Open Access Journals (Sweden)

Andrzej Marciniak

2010-04-01

Full Text Available The Hildebrand’s solubility parameters have been calculated for 18 ionic liquids from the inverse gas chromatography measurements of the activity coefficients at infinite dilution. Retention data were used for the calculation. The solubility parameters are helpful for the prediction of the solubility in the binary solvent mixtures. From the solubility parameters, the standard enthalpies of vaporization of ionic liquids were estimated.

Solubility of sparingly soluble drug derivatives of anthranilic acid.

Science.gov (United States)

Domańska, Urszula; Pobudkowska, Aneta; Pelczarska, Aleksandra

2011-03-24

This work is a continuation of our systematic study of the solubility of pharmaceuticals (Pharms). All substances here are derivatives of anthranilic acid, and have an anti-inflammatory direction of action (niflumic acid, flufenamic acid, and diclofenac sodium). The basic thermal properties of pure Pharms, i.e., melting and glass-transition temperatures as well as the enthalpy of melting, have been measured with the differential scanning microcalorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The equilibrium mole fraction solubilities of three pharmaceuticals were measured in a range of temperatures from 285 to 355 K in three important solvents for Pharm investigations: water, ethanol, and 1-octanol using a dynamic method and spectroscopic UV-vis method. The experimental solubility data have been correlated by means of the commonly known G(E) equation: the NRTL, with the assumption that the systems studied here have revealed simple eutectic mixtures. pK(a) precise measurement values have been investigated with the Bates-Schwarzenbach spectrophotometric method. © 2011 American Chemical Society

Prediction of the solubility in lipidic solvent mixture: Investigation of the modeling approach and thermodynamic analysis of solubility.

Science.gov (United States)

Patel, Shruti V; Patel, Sarsvatkumar

2015-09-18

Self-micro emulsifying drug delivery system (SMEDDS) is one of the methods to improve solubility and bioavailability of poorly soluble drug(s). The knowledge of the solubility of pharmaceuticals in pure lipidic solvents and solvent mixtures is crucial for designing the SMEDDS of poorly soluble drug substances. Since, experiments are very time consuming, a model, which allows for solubility predictions in solvent mixtures based on less experimental data is desirable for efficiency. Solvents employed were Labrafil® M1944CS and Labrasol® as lipidic solvents; Capryol-90®, Capryol-PGMC® and Tween®-80 as surfactants; Transcutol® and PEG-400 as co-solvents. Solubilities of both drugs were determined in single solvent systems at temperature (T) range of 283-333K. In present study, we investigated the applicability of the thermodynamic model to understand the solubility behavior of drugs in the lipiodic solvents. By using the Van't Hoff and general solubility theory, the thermodynamic functions like Gibbs free energy, enthalpy and entropy of solution, mixing and solvation for drug in single and mixed solvents were understood. The thermodynamic parameters were understood in the framework of drug-solvent interaction based on their chemical similarity and dissimilarity. Clotrimazole and Fluconazole were used as active ingredients whose solubility was measured in single solvent as a function of temperature and the data obtained were used to derive mathematical models which can predict solubility in multi-component solvent mixtures. Model dependent parameters for each drug were calculated at each temperature. The experimental solubility data of solute in mixed solvent system were measured experimentally and further correlated with the calculates values obtained from exponent model and log-linear model of Yalkowsky. The good correlation was observed between experimental solubility and predicted solubility. Copyright © 2015 Elsevier B.V. All rights reserved.

Solubility of Carbon in Nanocrystalline -Iron

OpenAIRE

Alexander Kirchner; Bernd Kieback

2012-01-01

A thermodynamic model for nanocrystalline interstitial alloys is presented. The equilibrium solid solubility of carbon in -iron is calculated for given grain size. Inside the strained nanograins local variation of the carbon content is predicted. Due to the nonlinear relation between strain and solubility, the averaged solubility in the grain interior increases with decreasing grain size. The majority of the global solubility enhancement is due to grain boundary enrichment however. Therefor...

Intrinsic solubility estimation and pH-solubility behavior of cosalane (NSC 658586), an extremely hydrophobic diprotic acid.

Science.gov (United States)

Venkatesh, S; Li, J; Xu, Y; Vishnuvajjala, R; Anderson, B D

1996-10-01

The selection of cosalane (NSC 658586) by the National Cancer Institute for further development as a potential drug candidate for the treatment of AIDS led to the exploration of the solubility behavior of this extremely hydrophobic drug, which has an intrinsic solubility (S0 approaching 1 ng/ml. This study describes attempts to reliably measure the intrinsic solubility of cosalane and examine its pH-solubility behavior. S0 was estimated by 5 different strategies: (a) direct determination in an aqueous suspension: (b) facilitated dissolution; (c) estimation from the octanol/water partition coefficient and octanol solubility (d) application of an empirical equation based on melting point and partition coefficient; and (e) estimation from the hydrocarbon solubility and functional group contributions for transfer from hydrocarbon to water. S0 estimates using these five methods varied over a 5 x 107-fold range Method (a) yielded the highest values, two-orders of magnitude greater than those obtained by method (b) (facilitated dissolution. 1.4 +/- 0.5 ng/ml). Method (c) gave a value 20-fold higher while that from method (d) was in fair agreement with that from facilitated dissolution. Method (e) yielded a value several orders-of-magnitude lower than other methods. A molecular dynamics simulation suggests that folded conformations not accounted for by group contributions may reduce cosalane's effective hydrophobicity. Ionic equilibria calculations for this weak diprotic acid suggested a 100-fold increase in solubility per pH unit increase. The pH-solubility profile of cosalane at 25 degrees C agreed closely with theory. These studies highlight the difficulty in determining solubility of very poorly soluble compounds and the possible advantage of the facilitated dissolution method. The diprotic nature of cosalane enabled a solubility enhancement of > 107-fold by simple pH adjustment.

On the americium oxalate solubility

International Nuclear Information System (INIS)

Zakolupin, S.A.; Korablin, Eh.V.

1977-01-01

The americium oxalate solubility at different nitric (0.0-1 M) and oxalic (0.0-0.4 M) acid concentrations was investigated in the temperature range from 14 to 60 deg C. The dependence of americium oxalate solubility on the oxalic acid concentration was determined. Increasing oxalic acid concentration was found to reduce the americium oxalate solubility. The dependence of americium oxalate solubility on the oxalic acid concentration was noted to be a minimum at low acidity (0.1-0.3 M nitric acid). This is most likely due to Am(C 2 O 4 ) + , Am(C 2 O 4 ) 2 - and Am(C 2 O 4 ) 3 3- complex ion formation which have different unstability constants. On the basis of the data obtained, a preliminary estimate was carried out for the product of americium oxalate solubility in nitric acid medium (10 -29 -10 -31 ) and of the one in water (6.4x10 -20 )

Solubilities of uranium for TILA-99

International Nuclear Information System (INIS)

Ollila, K.; Ahonen, L.

1998-11-01

This report presents the evaluation of the uranium solubilities in the reference waters of TILA-99. The behaviour of uranium has been discussed separately in the near-field and far-field conditions. The bentonite/groundwater interactions have been considered in the compositions of the fresh and saline near-field reference waters. The far-field groundwaters' compositions include fresh, brackish, saline and very saline, almost brine-type compositions. The pH and redox conditions, as the main parameters affecting the solubilities, are considered. A literature study was made in order to obtain information on the recent dissolution and leaching experiments of UO 2 and spent fuel. The latest literature includes studies on UO 2 solubility under anoxic conditions, in which the methods for simulating the reducing conditions of deep groundwater have been improved. Studies on natural uraninite and its alteration products give a valuable insight into the long-term behaviour of spent fuel. Also the solubility equilibria for some relevant poorly known uranium minerals have been determined. The solubilities of the selected solubility-limiting phases were calculated using the geochemical code, EQ3/6. The NEA database for uranium was the basis for the modelling. The recently extended and updated SR '97 database was used for comparison. The solubility products for uranophane were taken from the latest literature. The recommended values for solubilities were given after a comparison between the calculated solubilities, experimental information and measured concentrations in natural groundwaters. The experiments include several UO 2 dissolution studies in synthetic groundwaters with compositions close to the reference groundwaters. (author)

Solubilities of uranium for TILA-99

Energy Technology Data Exchange (ETDEWEB)

Ollila, K. [VTT Chemical Technology, Espoo (Finland); Ahonen, L. [Geological Survey of Finland, Espoo (Finland)

1998-11-01

This report presents the evaluation of the uranium solubilities in the reference waters of TILA-99. The behaviour of uranium has been discussed separately in the near-field and far-field conditions. The bentonite/groundwater interactions have been considered in the compositions of the fresh and saline near-field reference waters. The far-field groundwaters` compositions include fresh, brackish, saline and very saline, almost brine-type compositions. The pH and redox conditions, as the main parameters affecting the solubilities, are considered. A literature study was made in order to obtain information on the recent dissolution and leaching experiments of UO{sub 2} and spent fuel. The latest literature includes studies on UO{sub 2} solubility under anoxic conditions, in which the methods for simulating the reducing conditions of deep groundwater have been improved. Studies on natural uraninite and its alteration products give a valuable insight into the long-term behaviour of spent fuel. Also the solubility equilibria for some relevant poorly known uranium minerals have been determined. The solubilities of the selected solubility-limiting phases were calculated using the geochemical code, EQ3/6. The NEA database for uranium was the basis for the modelling. The recently extended and updated SR `97 database was used for comparison. The solubility products for uranophane were taken from the latest literature. The recommended values for solubilities were given after a comparison between the calculated solubilities, experimental information and measured concentrations in natural groundwaters. The experiments include several UO{sub 2} dissolution studies in synthetic groundwaters with compositions close to the reference groundwaters. (author) 81 refs.

The effects of disordered structure on the solubility and dissolution rates of some hydrophilic, sparingly soluble drugs.

Science.gov (United States)

Mosharraf, M; Sebhatu, T; Nyström, C

1999-01-15

The effects of experimental design on the apparent solubility of two sparingly soluble hydrophilic compounds (barium sulphate and calcium carbonate) were studied in this paper. The apparent solubility appeared to be primarily dependent on the amount of solute added to the solvent in each experiment, increasing with increased amounts. This effect seems to be due to the existence of a peripheral disordered layer. However physico-chemical methods used in the present study were not able to unambiguously verify the existence of any disorder in the solid state structure of the drugs. At higher proportions of solute to solvent, the solubility reached a plateau corresponding to the solubility of the disordered or amorphous molecular form of the material. Milling the powders caused the plateau to be reached at lower proportions of solute to solvent, since this further disordered the surface of the drug particles. It was also found that the apparent solubility of the drugs tested decreased after storage at high relative humidities. A model for describing the effects of a disordered surface layer of varying thickness and continuity on the solubility of a substance is presented. This model may be used as a method for detection of minute amount of disorder, where no other technique is capable of detecting the disordered structure. It is suggested that recrystallisation of the material occurs via slow solid-state transition at the surface of the drug particle; this would slowly reduce the apparent solubility of the substance at the plateau level to the thermodynamically stable value. A biphasic dissolution rate profile was obtained. The solubility of the disordered surface of the particles appeared to be the rate-determining factor during the initial dissolution phase, while the solubility of the crystalline core was the rate-determining factor during the final slower phase.

Determination of radionuclide solubility limits to be used in SR 97. Uncertainties associated to calculated solubilities

Energy Technology Data Exchange (ETDEWEB)

Bruno, J.; Cera, E.; Duro, L.; Jordana, S. [QuantiSci S.L., Barcelona (Spain); Pablo, J. de [DEQ-UPC, Barcelona (Spain); Savage, D. [QuantiSci Ltd., Henley-on-Thames (United Kingdom)

1997-12-01

The thermochemical behaviour of 24 critical radionuclides for the forthcoming SR97 PA exercise is discussed. The available databases are reviewed and updated with new data and an extended database for aqueous and solid species of the radionuclides of interest is proposed. We have calculated solubility limits for the radionuclides of interest under different groundwater compositions. A sensitivity analysis of the calculated solubilities with the composition of the groundwater is presented. Besides selecting the most likely solubility limiting phases, in this work we have used coprecipitation approaches in order to calculate more realistic solubility limits for minor radionuclides, such as Ra, Am and Cm. The comparison between the calculated solubilities and the concentrations measured in relevant natural systems (NA) and in spent fuel leaching experiments helps to assess the validity of the methodology used and to derive source term concentrations for the radionuclides studied. The uncertainties associated to the solubilities of the main radionuclides involved in the spent nuclear fuel have also been discussed in this work. The variability of the groundwater chemistry; redox conditions and temperature of the system have been considered the main factors affecting the solubilities. In this case, a sensitivity analysis has been performed in order to study solubility changes as a function of these parameters. The uncertainties have been calculated by including the values found in a major extent in typical granitic groundwaters. The results obtained from this analysis indicate that there are some radionuclides which are not affected by these parameters, i.e. Ag, Cm, Ho, Nb, Ni, Np, Pu, Se, Sm, Sn, Sr, Tc and U

Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate.

Science.gov (United States)

Yousaf, Abid Mehmood; Mustapha, Omer; Kim, Dong Wuk; Kim, Dong Shik; Kim, Kyeong Soo; Jin, Sung Giu; Yong, Chul Soon; Youn, Yu Seok; Oh, Yu-Kyoung; Kim, Jong Oh; Choi, Han-Gon

2016-01-01

The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate. Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP) and Labrafil(®) M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion. All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1:4:0.5 resulted in a particle size of water-soluble fenofibrate.

Retrograde curves of solidus and solubility

International Nuclear Information System (INIS)

Vasil'ev, M.V.

1979-01-01

The investigation was concerned with the constitutional diagrams of the eutectic type with ''retrograde solidus'' and ''retrograde solubility curve'' which must be considered as diagrams with degenerate monotectic transformation. The solidus and the solubility curves form a retrograde curve with a common retrograde point representing the solubility maximum. The two branches of the Aetrograde curve can be described with the aid of two similar equations. Presented are corresponding equations for the Cd-Zn system and shown is the possibility of predicting the run of the solubility curve

Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes.

Science.gov (United States)

Khawaja, Ayaz M; Vines, Brannon L; Miller, David W; Szaflarski, Jerzy P; Amara, Amy W

2016-03-01

Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs.

Interlaboratory validation of small-scale solubility and dissolution measurements of poorly water-soluble drugs

DEFF Research Database (Denmark)

Andersson, Sara B. E.; Alvebratt, Caroline; Bevernage, Jan

2016-01-01

The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at m...

MRI findings in glutamic acid decarboxylase associated autoimmune epilepsy

Energy Technology Data Exchange (ETDEWEB)

Fredriksen, Jason R.; Carr, Carrie M.; Koeller, Kelly K.; Verdoorn, Jared T.; Kotsenas, Amy L. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Gadoth, Avi; Pittock, Sean J. [Mayo Clinic, Department of Neurology, Rochester, MN (United States)

2018-03-15

Glutamic acid decarboxylase (GAD65) has been implicated in a number of autoimmune-associated neurologic syndromes, including autoimmune epilepsy. This study categorizes the spectrum of MRI findings in patients with a clinical diagnosis of autoimmune epilepsy and elevated serum GAD65 autoantibodies. An institutional database search identified patients with elevated serum GAD65 antibodies and a clinical diagnosis of autoimmune epilepsy who had undergone brain MRI. Imaging studies were reviewed by three board-certified neuroradiologists and one neuroradiology fellow. Studies were evaluated for cortical/subcortical and hippocampal signal abnormality, cerebellar and cerebral volume loss, mesial temporal sclerosis, and parenchymal/leptomeningeal enhancement. The electronic medical record was reviewed for relevant clinical information and laboratory markers. A study cohort of 19 patients was identified. The majority of patients were female (84%), with a mean age of onset of 27 years. Serum GAD65 titers ranged from 33 to 4415 nmol/L (normal < 0.02 nmol/L). The most common presentation was medically intractable, complex partial seizures with temporal lobe onset. Parenchymal atrophy was the most common imaging finding (47%), with a subset of patients demonstrating cortical/subcortical parenchymal T2 hyperintensity (37%) or abnormal hippocampal signal (26%). No patients demonstrated abnormal parenchymal/leptomeningeal enhancement. The most common MRI finding in GAD65-associated autoimmune epilepsy is disproportionate parenchymal atrophy for age, often associated with abnormal cortical/subcortical T2 hyperintensities. Hippocampal abnormalities are seen in a minority of patients. This constellation of findings in a patient with medically intractable epilepsy should raise the possibility of GAD65 autoimmunity. (orig.)

Solubility limits of importance to leaching

International Nuclear Information System (INIS)

Ogard, A.; Bentley, G.; Bryant, E.; Duffy, C.; Grisham, J.; Norris, E.; Orth, C.; Thomas, K.

1981-01-01

The solubilities of some radionuclides, especially rare earths and actinides, may be an important and controlling factor in leaching of waste forms. These solubilities should be measured accurately as a function of pH and not as a part of a multicomponent system. Individual solubilities should be measured as a function of temperature to determine if a kinetic effect is being observed in the data. A negative temperature coefficient of solubility for actinides and rare earths in water would have important consequences for nuclear reactor safety and for the management of nuclear wastes

Uranyl Oxalate Solubility

Energy Technology Data Exchange (ETDEWEB)

Leturcq, G.; Costenoble, S.; Grandjean, S. [CEA Marcoule DEN/DRCP/SCPS/LCA - BP17171 - 30207 Bagnols sur Ceze cedex (France)

2008-07-01

The solubility of uranyl oxalate was determined at ambient temperature by precipitation in oxalic-nitric solutions, using an initial uranyl concentration of 0.1 mol/L. Oxalic concentration varied from 0.075 to 0.3 mol/L while nitric concentration ranged between 0.75 and 3 mol/L. Dissolution tests, using complementary oxalic-nitric media, were carried out for 550 hours in order to study the kinetic to reach thermodynamic equilibrium. Similar solubility values were reached by dissolution and precipitation. Using the results, it was possible to draw the solubility surface versus oxalic and nitric concentrations and to determine both the apparent solubility constant of UO{sub 2}C{sub 2}O{sub 4}, 3H{sub 2}O (Ks) and the apparent formation constant of the first uranyl-oxalate complex UO{sub 2}C{sub 2}O{sub 4} (log {beta}1), for ionic strengths varying between 1 and 3 mol/L. Ks and log {beta}1 values were found to vary from 1.9 10{sup -8} to 9.2 10{sup -9} and from 5.95 to 6.06, respectively, when ionic strength varied from 1 to 3 mol/L. A second model may fit our data obtained at an ionic strength of 3 mol/L suggesting as reported by Moskvin et al. (1959) that no complexes are formed for [H{sup +}] at 3 M. The Ks value would then be 1.3 10{sup -8}. (authors)

Solubility behavior of narcotic analgesics in aqueous media: solubilities and dissociation constants of morphine, fentanyl, and sufentanil.

Science.gov (United States)

Roy, S D; Flynn, G L

1989-02-01

The pH dependence of the aqueous solubility of morphine, fentanyl, and sufentanil was investigated at 35 degrees C. Dissociation constants and corresponding pKa' values of the drugs were obtained from measured free-base solubilities (determined at high pH's) and the concentrations of saturated solutions at intermediate pH's. Morphine, fentanyl, and sufentanil exhibited pKa' values of 8.08, 8.99, and 8.51, respectively. Over the pH range of 5 to 12.5 the apparent solubilities are determined by the intrinsic solubility of the free base plus the concentration of ionized drug necessary to satisfy the dissociation equilibrium at a given pH. Consequently, the drug concentrations of saturated aqueous solutions fall off precipitously as the pH is raised and ionization is suppressed. Further, at low pH's the aqueous solubility of morphine increased in a linear fashion with increases in the molar strength of citric acid which was added to acidify the medium, suggesting the formation of a soluble morphine-citrate complex.

Solubility studies of Np(IV)

International Nuclear Information System (INIS)

Zhang Yingjie; Yao Jun; Jiao Haiyang; Ren Lihong; Zhou Duo; Fan Xianhua

2001-01-01

The solubility of Np(IV) in simulated underground water and redistilled water has been measured with the variations of pH(6-12) and storage time (0-100 d) in the presence of reductant (Na 2 S 2 O 4 , metallic Fe). All experiments are performed in a low oxygen concentration glove box containing high purity Ar(99.99%), with an oxygen content of less than 5 x 10 -6 mol/mol. Experimental results show that the variation of pH in solution has little effect on the solubility of Np(IV) in the two kinds of water; the measured solubility of Np(IV) is affected by the composition of solution; with Na 2 S 2 O 4 as a reductant, the solubility of Np(IV) in simulated underground water is (9.23 +- 0.48) x 10 -10 mol/L, and that in redistilled water is (8.31 +- 0.35) x 10 -10 mol/L; with metallic Fe as a reductant, the solubility of Np(IV) in simulated underground water is (1.85 +- 0.56) x 10 -9 mol/L, and that in redistilled water is (1.48 +- 0.66) x 10 -9 mol/L

Solubility of Nd in brine

International Nuclear Information System (INIS)

Khalili, F.I.; Symeopoulos, V.; Chen, J.F.; Choppin, G.R.

1994-01-01

The solubility of Nd(III) has been measured at 23±3 C in a synthetic brine at pcH 6.4, 8.4, 10.4 and 12.4. The brine consisted predominantly of (Na+K)Cl and MgCl 2 with an ionic strength of 7.8 M (9.4 m) a solid compound of Nd(III) at each pcH was assigned from X-ray diffraction patterns. The log values of the experimental solubilities decrease fomr -3 at pcH 6.4 to -5.8 at pcH 8.4; at pcH 10.4 and 12.4 the solubility was below the detection limit of -7.5. The experimental solubility does not follow closely the variation with pcH estimated from modeling of the species in solution in equilibrium with the Nd solid using S.I.T. (orig.)

Thermodynamic approach to improving solubility prediction of co-crystals in comparison with individual poorly soluble components

International Nuclear Information System (INIS)

Perlovich, German L.

2014-01-01

Highlights: • Thermodynamic approach for solubility improvement of co-crystal was developed. • The graphical technique for estimation of co-crystal solubility was elaborated. • Hydration enthalpies of some drugs and amino acids were calculated. • Applicability/operability of the approach was exemplified by some drugs and amino acids. - Abstract: A novel thermodynamic approach to compare poorly soluble components (active pharmaceutical ingredient (API)) both in co-crystals and individual compounds was developed. An algorithm of choosing potential co-crystals with improved solubility characteristics on the basis of the known solvation/hydration API and co-former enthalpies is described. The applicability and operability of the algorithm were tested exemplified by some drugs and amino acids

The DOPA decarboxylase (DDC) gene is associated with alerting attention.

Science.gov (United States)

Zhu, Bi; Chen, Chuansheng; Moyzis, Robert K; Dong, Qi; Chen, Chunhui; He, Qinghua; Li, Jin; Li, Jun; Lei, Xuemei; Lin, Chongde

2013-06-03

DOPA decarboxylase (DDC) is involved in the synthesis of dopamine, norepinephrine and serotonin. It has been suggested that genes involved in the dopamine, norepinephrine, and cholinergic systems play an essential role in the efficiency of human attention networks. Attention refers to the cognitive process of obtaining and maintaining the alert state, orienting to sensory events, and regulating the conflicts of thoughts and behavior. The present study tested seven single nucleotide polymorphisms (SNPs) within the DDC gene for association with attention, which was assessed by the Attention Network Test to detect three networks of attention, including alerting, orienting, and executive attention, in a healthy Han Chinese sample (N=451). Association analysis for individual SNPs indicated that four of the seven SNPs (rs3887825, rs7786398, rs10499695, and rs6969081) were significantly associated with alerting attention. Haplotype-based association analysis revealed that alerting was associated with the haplotype G-A-T for SNPs rs7786398-rs10499695-rs6969081. These associations remained significant after correcting for multiple testing by max(T) permutation. No association was found for orienting and executive attention. This study provides the first evidence for the involvement of the DDC gene in alerting attention. A better understanding of the genetic basis of distinct attention networks would allow us to develop more effective diagnosis, treatment, and prevention of deficient or underdeveloped alerting attention as well as its related prevalent neuropsychiatric disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Antibacterial activity of oregano and sage plant extracts against decarboxylase-positive enterococci isolated from rabbit meat

Directory of Open Access Journals (Sweden)

Ľubica Chrastinová

2013-02-01

Full Text Available The effect of plant extracts (sage, oregano against decarboxylase-positive enterococci from rabbit back limb meat  was reported in this study. Oregano plant extract inhibited the growth of all 34 tested enterococci (the inhibitory zones: 12 to 45 mm. The growth of the majority of strains  (n=23 was inhibited by oregano plant extract (the high size inhibitory zones (higher than 25 mm. The growth of 11 strains  was inhibited by oregano extract reaching medium size inhibitory zones (10 to 25mm. The most sensitive strain to oregano extract was E. faecium M7bA (45 mm. Sage extract was less active against tested enterococci (n=16  reaching lower inhibitory zones (up to 10 mm. doi:10.5219/239 Normal 0 21 false false false SK X-NONE X-NONE

Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain

DEFF Research Database (Denmark)

Zhang, Yiming; Liu, Guodong; Engqvist, Martin K. M.

2015-01-01

Background: A Saccharomyces cerevisiae strain carrying deletions in all three pyruvate decarboxylase (PDC) genes (also called Pdc negative yeast) represents a non-ethanol producing platform strain for the production of pyruvate derived biochemicals. However, it cannot grow on glucose as the sole...... DNA sequencing. Among these genetic changes, 4 genes were found to carry point mutations in at least two of the evolved strains: MTH1 encoding a negative regulator of the glucose-sensing signal transduction pathway, HXT2 encoding a hexose transporter, CIT1 encoding a mitochondrial citrate synthase...... further increased the maximum specific growth rate to 0.069 h-1. Conclusions: In this study, possible evolving mechanisms of Pdc negative strains on glucose were investigated by genome sequencing and reverse engineering. The non-synonymous mutations in MTH1 alleviated the glucose repression by repressing...

Oxaloacetate-to-malate conversion by mineral photoelectrochemistry: implications for the viability of the reductive tricarboxylic acid cycle in prebiotic chemistry

Science.gov (United States)

Guzman, Marcelo I.; Martin, Scot T.

2008-10-01

The carboxylic acids produced by the reductive tricarboxylic acid (rTCA) cycle are possibly a biosynthetic core of initial life, although several steps such as the reductive kinetics of oxaloacetate (OAA) to malate (MA) are problematic by conventional chemical routes. In this context, we studied the kinetics of this reaction as promoted by ZnS mineral photoelectrochemistry. The quantum efficiency φMA of MA production from the photoelectrochemical reduction of OAA followed φMA=0.13 [OAA] (2.1×10-3+[OAA])-1 and was independent of temperature (5 to 50°C). To evaluate the importance of this forward rate under a prebiotic scenario, we also studied the temperature-dependent rate of the backward thermal decarboxylation of OAA to pyruvate (PA), which followed an Arrhenius behavior as log (k-2)=11.74 4956/T, where k-2 is in units of s-1. These measured rates were employed in conjunction with the indirectly estimated carboxylation rate of PA to OAA to assess the possible importance of mineral photoelectrochemistry in the conversion of OAA to MA under several scenarios of prebiotic conditions on early Earth. As an example, our analysis shows that there is 90% efficiency with a forward velocity of 3 yr/cycle for the OAA→MA step of the rTCA cycle at 280 K. Efficiency and velocity both decrease for increasing temperature. These results suggest high viability for mineral photoelectrochemistry as an enzyme-free engine to drive the rTCA cycle through the early aeons of early Earth, at least for the investigated OAA→MA step.

Cortical Gene Expression After a Conditional Knockout of 67 kDa Glutamic Acid Decarboxylase in Parvalbumin Neurons.

Science.gov (United States)

Georgiev, Danko; Yoshihara, Toru; Kawabata, Rika; Matsubara, Takurou; Tsubomoto, Makoto; Minabe, Yoshio; Lewis, David A; Hashimoto, Takanori

2016-07-01

In the cortex of subjects with schizophrenia, expression of glutamic acid decarboxylase 67 (GAD67), the enzyme primarily responsible for cortical GABA synthesis, is reduced in the subset of GABA neurons that express parvalbumin (PV). This GAD67 deficit is accompanied by lower cortical levels of other GABA-associated transcripts, including GABA transporter-1, PV, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B, somatostatin, GABAA receptor α1 subunit, and KCNS3 potassium channel subunit mRNAs. In contrast, messenger RNA (mRNA) levels for glutamic acid decarboxylase 65 (GAD65), another enzyme for GABA synthesis, are not altered. We tested the hypothesis that this pattern of GABA-associated transcript levels is secondary to the GAD67 deficit in PV neurons by analyzing cortical levels of these GABA-associated mRNAs in mice with a PV neuron-specific GAD67 knockout. Using in situ hybridization, we found that none of the examined GABA-associated transcripts had lower cortical expression in the knockout mice. In contrast, PV, BDNF, KCNS3, and GAD65 mRNA levels were higher in the homozygous mice. In addition, our behavioral test battery failed to detect a change in sensorimotor gating or working memory, although the homozygous mice exhibited increased spontaneous activities. These findings suggest that reduced GAD67 expression in PV neurons is not an upstream cause of the lower levels of GABA-associated transcripts, or of the characteristic behaviors, in schizophrenia. In PV neuron-specific GAD67 knockout mice, increased levels of PV, BDNF, and KCNS3 mRNAs might be the consequence of increased neuronal activity secondary to lower GABA synthesis, whereas increased GAD65 mRNA might represent a compensatory response to increase GABA synthesis. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Solubility database for TILA-99

Energy Technology Data Exchange (ETDEWEB)

Vuorinen, U.; Carlsson, T. [VTT Chemical Technology, Espoo (Finland); Kulmala, S.; Hakanen, M. [Helsinki Univ. (Finland). Lab. of Radiochemistry; Ahonen, L. [Geological Survey of Finland, Espoo (Finland)

1998-11-01

The safety assessment of spent fuel disposal requires solubility values for several elements estimated in Finnish disposal conditions. In Finland four sites (Haestholmen, Kivetty, Olkiluoto and Romuvaara) are investigated for the disposal of spent fuel. Haestholmen and OLkiluoto are onshore sites, while Kivetty and Romuvaara are inland sites. Based on groundwater analysis and classification according to salinity at the planned disposal depth mainly fresh groundwater is encountered at Kivetty and Romuvaara, while brackish and saline water-types are met at Haestholmen and Olkiluoto. Very saline, almost brine-type water ({approx}70 g/l) has been found in the deepest parts of the investigated bedrock at one of the sites (Olkiluoto). The reference waters and conditions were chosen according to the water-types. The considered reference conditions incorporated both the near- and far-field, and both oxidizing and reducing conditions were considered. In the reference conditions, the changes in solubilities were also estimated as caused by possible variations in the pH, carbonate content and redox conditions. Uranium, which is the main component of spent fuel is dealt with in a separate report presenting the solubility of uranium and spent fuel dissolution. In this work the solubilities of all the other elements of concern (Am, Cu, Nb, Np, Pa, Pd, Pu, Ra, Se, Sn, Tc, Zr, Cm, Ni, Sr, Th, C, Cl, Cs, Fe, Ho, I, and Sm) in the safety assessment are considered. Some discussion on the corrosion of the spent fuel canister is also presented. For the estimation of solubilities of the elements in question, literature data was collected that mainly comprised experimentally measured concentrations. The sources used were spent fuel experiments, concentrations measured in solubility measurements, natural concentrations and concentrations from natural analogue sites (especially Palmottu and Hyrkkoelae in Finland) as well as the concentrations measured at the Finnish investigation sites

Solubility database for TILA-99

International Nuclear Information System (INIS)

Vuorinen, U.; Carlsson, T.; Kulmala, S.; Hakanen, M.

1998-11-01

The safety assessment of spent fuel disposal requires solubility values for several elements estimated in Finnish disposal conditions. In Finland four sites (Haestholmen, Kivetty, Olkiluoto and Romuvaara) are investigated for the disposal of spent fuel. Haestholmen and OLkiluoto are onshore sites, while Kivetty and Romuvaara are inland sites. Based on groundwater analysis and classification according to salinity at the planned disposal depth mainly fresh groundwater is encountered at Kivetty and Romuvaara, while brackish and saline water-types are met at Haestholmen and Olkiluoto. Very saline, almost brine-type water (∼70 g/l) has been found in the deepest parts of the investigated bedrock at one of the sites (Olkiluoto). The reference waters and conditions were chosen according to the water-types. The considered reference conditions incorporated both the near- and far-field, and both oxidizing and reducing conditions were considered. In the reference conditions, the changes in solubilities were also estimated as caused by possible variations in the pH, carbonate content and redox conditions. Uranium, which is the main component of spent fuel is dealt with in a separate report presenting the solubility of uranium and spent fuel dissolution. In this work the solubilities of all the other elements of concern (Am, Cu, Nb, Np, Pa, Pd, Pu, Ra, Se, Sn, Tc, Zr, Cm, Ni, Sr, Th, C, Cl, Cs, Fe, Ho, I, and Sm) in the safety assessment are considered. Some discussion on the corrosion of the spent fuel canister is also presented. For the estimation of solubilities of the elements in question, literature data was collected that mainly comprised experimentally measured concentrations. The sources used were spent fuel experiments, concentrations measured in solubility measurements, natural concentrations and concentrations from natural analogue sites (especially Palmottu and Hyrkkoelae in Finland) as well as the concentrations measured at the Finnish investigation sites. The

Overview of milling techniques for improving the solubility of poorly water-soluble drugs

Directory of Open Access Journals (Sweden)

Zhi Hui Loh

2015-07-01

Full Text Available Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a “top–down” approach in the production of fine particles. Fine drug particulates are especially desired in formulations designed for parenteral, respiratory and transdermal use. Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents, often to enhance processability or solubility especially for drugs with limited aqueous solubility. The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size, specific surface area and shape of the drug particles as well as milling-induced amorphization and/or structural disordering of the drug crystal (mechanochemical activation. Technology advancements in milling now enable the production of drug micro- and nano-particles on a commercial scale with relative ease. This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs. Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.

Noble gases solubility in water

International Nuclear Information System (INIS)

Crovetto, Rosa; Fernandez Prini, Roberto.

1980-07-01

The available experimental data of solubility of noble gases in water for temperatures smaller than 330 0 C have been critically surveyed. Due to the unique structure of the solvent, the solubility of noble gases in water decreases with temperature passing through a temperature of minimum solubility which is different for each gas, and then increases at higher temperatures. As aresult of the analysis of the experimental data and of the features of the solute-solvent interaction, a generalized equation is proposed which enables thecalculation of Henry's coefficient at different temperatures for all noble gases. (author) [es

Solubility of xenon in amino-acid solutions. II. Nine less-soluble amino acids

Science.gov (United States)

Kennan, Richard P.; Himm, Jeffrey F.; Pollack, Gerald L.

1988-05-01

Ostwald solubility (L) of xenon gas, as the radioisotope 133Xe, has been measured as a function of solute concentration, at 25.0 °C, in aqueous solutions of nine amino acids. The amino-acid concentrations investigated covered much of their solubility ranges in water, viz., asparagine monohydrate (0-0.19 M), cysteine (0-1.16 M), glutamine (0-0.22 M), histidine (0-0.26 M), isoleucine (0-0.19 M), methionine (0-0.22 M), serine (0-0.38 M), threonine (0-1.4 M), and valine (0-0.34 M). We have previously reported solubility results for aqueous solutions of six other, generally more soluble, amino acids (alanine, arginine, glycine, hydroxyproline, lysine, and proline), of sucrose and sodium chloride. In general, L decreases approximately linearly with increasing solute concentration in these solutions. If we postulate that the observed decreases in gas solubility are due to hydration, the results under some assumptions can be used to calculate hydration numbers (H), i.e., the number of H2O molecules associated with each amino-acid solute molecule. The average values of hydration number (H¯) obtained at 25.0 °C are 15.3±1.5 for asparagine, 6.8±0.3 for cysteine, 11.5±1.1 for glutamine, 7.3±0.7 for histidine, 5.9±0.4 for isoleucine, 10.6±0.8 for methionine, 11.2±1.3 for serine, 7.7± 1.0 for threonine, and 6.6±0.6 for valine. We have also measured the temperature dependence of solubility L(T) from 5-40 °C for arginine, glycine, and proline, and obtained hydration numbers H¯(T) in this range. Between 25-40 °C, arginine has an H¯ near zero. This may be evidence for an attractive interaction between xenon and arginine molecules in aqueous solution.

Ultraviolet radiation induction of ornithine decarboxylase in rat keratinocytes

International Nuclear Information System (INIS)

Rosen, C.F.; Gajic, D.; Drucker, D.J.

1990-01-01

UV radiation plays an important role in the induction of cutaneous malignancy, including basal cell and squamous cell carcinomas and malignant melanoma. In addition to its effects on DNA damage and repair mechanisms, UV radiation has been shown to modulate the expression of specific genes, altering the levels of their mRNAs and the synthesis of their corresponding proteins. In order to gain further information about the molecular effects of UV radiation, we have studied the regulation of ornithine decarboxylase (ODC) gene expression in response to UVB radiation. ODC is the rate-limiting enzyme in polyamine biosynthesis, is involved in growth and differentiation, and has been implicated in carcinogenesis. Keratinocytes grown in culture were either sham-irradiated or exposed to increasing doses of UVB (1-5 mJ/cm2). Northern blot analysis of keratinocyte RNA under basal conditions demonstrated the presence of two ODC mRNA transcripts. Increasing exposure to UVB resulted in a dose-dependent increase in the levels of both ODC mRNA transcripts. The induction of ODC gene expression following UVB was noted 2 h after UVB exposure, and ODC mRNA levels continued to increase up to 24 h after UVB exposure. The UVB-induced increase in ODC gene expression was not serum dependent, despite the ability of serum alone to induce ODC gene expression. The mRNA transcripts for actin and hexosaminidase A were not induced after UVB exposure. These studies show that the UVB-induced increase in ODC activity is due, at least in part, to an increase in ODC gene expression and they provide a useful model for the analysis of the molecular effects of UVB radiation

Ultraviolet radiation induction of ornithine decarboxylase in rat keratinocytes

Energy Technology Data Exchange (ETDEWEB)

Rosen, C.F.; Gajic, D.; Drucker, D.J. (Women' s College Hospital, Toronto, Ontario (Canada))

1990-05-01

UV radiation plays an important role in the induction of cutaneous malignancy, including basal cell and squamous cell carcinomas and malignant melanoma. In addition to its effects on DNA damage and repair mechanisms, UV radiation has been shown to modulate the expression of specific genes, altering the levels of their mRNAs and the synthesis of their corresponding proteins. In order to gain further information about the molecular effects of UV radiation, we have studied the regulation of ornithine decarboxylase (ODC) gene expression in response to UVB radiation. ODC is the rate-limiting enzyme in polyamine biosynthesis, is involved in growth and differentiation, and has been implicated in carcinogenesis. Keratinocytes grown in culture were either sham-irradiated or exposed to increasing doses of UVB (1-5 mJ/cm2). Northern blot analysis of keratinocyte RNA under basal conditions demonstrated the presence of two ODC mRNA transcripts. Increasing exposure to UVB resulted in a dose-dependent increase in the levels of both ODC mRNA transcripts. The induction of ODC gene expression following UVB was noted 2 h after UVB exposure, and ODC mRNA levels continued to increase up to 24 h after UVB exposure. The UVB-induced increase in ODC gene expression was not serum dependent, despite the ability of serum alone to induce ODC gene expression. The mRNA transcripts for actin and hexosaminidase A were not induced after UVB exposure. These studies show that the UVB-induced increase in ODC activity is due, at least in part, to an increase in ODC gene expression and they provide a useful model for the analysis of the molecular effects of UVB radiation.

Isoform expression in the multiple soluble malate dehydrogenase of Hoplias malabaricus (Erythrinidae, Characiformes

Directory of Open Access Journals (Sweden)

M. R. Aquino-Silva

Full Text Available Kinetic properties and thermal stabilities of Hoplias malabaricus liver and skeletal muscle unfractionated malate dehydrogenase (MDH, EC 1.1.1.37 and its isolated isoforms were analyzed to further study the possible sMDH-A* locus duplication evolved from a recent tandem duplication. Both A (A1 and A2 and B isoforms had similar optima pH (7.5-8.0. While Hoplias A isoform could not be characterized as thermostable, B could as thermolabile. A isoforms differed from B isoform in having higher Km values for oxaloacetate. The possibly duplicated A2 isoform showed higher substrate affinity than the A1. Hoplias duplicated A isoforms may influence the direction of carbon flow between glycolisis and gluconeogenesis.

Isoform expression in the multiple soluble malate dehydrogenase of Hoplias malabaricus (Erythrinidae, Characiformes

Directory of Open Access Journals (Sweden)

Aquino-Silva M. R.

2003-01-01

Full Text Available Kinetic properties and thermal stabilities of Hoplias malabaricus liver and skeletal muscle unfractionated malate dehydrogenase (MDH, EC 1.1.1.37 and its isolated isoforms were analyzed to further study the possible sMDH-A* locus duplication evolved from a recent tandem duplication. Both A (A1 and A2 and B isoforms had similar optima pH (7.5-8.0. While Hoplias A isoform could not be characterized as thermostable, B could as thermolabile. A isoforms differed from B isoform in having higher Km values for oxaloacetate. The possibly duplicated A2 isoform showed higher substrate affinity than the A1. Hoplias duplicated A isoforms may influence the direction of carbon flow between glycolisis and gluconeogenesis.

Uroporphyrinogen decarboxylase is a radiosensitizing target for head and neck cancer.

Science.gov (United States)

Ito, Emma; Yue, Shijun; Moriyama, Eduardo H; Hui, Angela B; Kim, Inki; Shi, Wei; Alajez, Nehad M; Bhogal, Nirmal; Li, Guohua; Datti, Alessandro; Schimmer, Aaron D; Wilson, Brian C; Liu, Peter P; Durocher, Daniel; Neel, Benjamin G; O'Sullivan, Brian; Cummings, Bernard; Bristow, Rob; Wrana, Jeff; Liu, Fei-Fei

2011-01-26

Head and neck cancer (HNC) is the eighth most common malignancy worldwide, comprising a diverse group of cancers affecting the head and neck region. Despite advances in therapeutic options over the last few decades, treatment toxicities and overall clinical outcomes have remained disappointing, thereby underscoring a need to develop novel therapeutic approaches in HNC treatment. Uroporphyrinogen decarboxylase (UROD), a key regulator of heme biosynthesis, was identified from an RNA interference-based high-throughput screen as a tumor-selective radiosensitizing target for HNC. UROD knockdown plus radiation induced caspase-mediated apoptosis and cell cycle arrest in HNC cells in vitro and suppressed the in vivo tumor-forming capacity of HNC cells, as well as delayed the growth of established tumor xenografts in mice. This radiosensitization appeared to be mediated by alterations in iron homeostasis and increased production of reactive oxygen species, resulting in enhanced tumor oxidative stress. Moreover, UROD was significantly overexpressed in HNC patient biopsies. Lower preradiation UROD mRNA expression correlated with improved disease-free survival, suggesting that UROD could potentially be used to predict radiation response. UROD down-regulation also radiosensitized several different models of human cancer, as well as sensitized tumors to chemotherapeutic agents, including 5-fluorouracil, cisplatin, and paclitaxel. Thus, our study has revealed UROD as a potent tumor-selective sensitizer for both radiation and chemotherapy, with potential relevance to many human malignancies.

Benchmarking pKa prediction methods for Lys115 in acetoacetate decarboxylase.

Science.gov (United States)

Liu, Yuli; Patel, Anand H G; Burger, Steven K; Ayers, Paul W

2017-05-01

Three different pK a prediction methods were used to calculate the pK a of Lys115 in acetoacetate decarboxylase (AADase): the empirical method PROPKA, the multiconformation continuum electrostatics (MCCE) method, and the molecular dynamics/thermodynamic integration (MD/TI) method with implicit solvent. As expected, accurate pK a prediction of Lys115 depends on the protonation patterns of other ionizable groups, especially the nearby Glu76. However, since the prediction methods do not explicitly sample the protonation patterns of nearby residues, this must be done manually. When Glu76 is deprotonated, all three methods give an incorrect pK a value for Lys115. If protonated, Glu76 is used in an MD/TI calculation, the pK a of Lys115 is predicted to be 5.3, which agrees well with the experimental value of 5.9. This result agrees with previous site-directed mutagenesis studies, where the mutation of Glu76 (negative charge when deprotonated) to Gln (neutral) causes no change in K m , suggesting that Glu76 has no effect on the pK a shift of Lys115. Thus, we postulate that the pK a of Glu76 is also shifted so that Glu76 is protonated (neutral) in AADase. Graphical abstract Simulated abundances of protonated species as pH is varied.

Determination of soluble protein contents from RVNRL

International Nuclear Information System (INIS)

Wan Manshol Wan Zin; Nurulhuda Othman

1996-01-01

This project was carried out to determine the soluble protein contents on RVNRL film vulcanisates, with respect to the RVNRL storage time, gamma irradiation dose absorbed by the latex and the effect of different leaching time and leaching conditions. These three factors are important in the hope to determine the best possible mean of minimizing the soluble protein contents in products made from RVNRL. Within the nine months storage period employed in the study, the results show that, the longer the storage period the less the soluble protein extracted from the film samples. Gamma irradiation dose absorbed by the samples, between 5.3 kGy to 25.2 kGy seems to influence the soluble protein contents of the RVNRL films vulcanisates. The higher the dose the more was the soluble protein extracted from the film samples. At an absorbed dose of 5.3 kGy and 25.2 kGy, the soluble contents were 0. 198 mg/ml and 0.247 mg/ml respectively. At a fixed leaching temperature, the soluble proteins increases with leaching time and at a fixed leaching time, the soluble proteins increases with leaching temperature. ne highest extractable protein contents was determined at a leaching time of 10 minutes and leaching temperature of 90'C The protein analysis were done by using Modified Lowry Method

Overcoming the solubility limit with solubility-enhancement tags: successful applications in biomolecular NMR studies

International Nuclear Information System (INIS)

Zhou Pei; Wagner, Gerhard

2010-01-01

Although the rapid progress of NMR technology has significantly expanded the range of NMR-trackable systems, preparation of NMR-suitable samples that are highly soluble and stable remains a bottleneck for studies of many biological systems. The application of solubility-enhancement tags (SETs) has been highly effective in overcoming solubility and sample stability issues and has enabled structural studies of important biological systems previously deemed unapproachable by solution NMR techniques. In this review, we provide a brief survey of the development and successful applications of the SET strategy in biomolecular NMR. We also comment on the criteria for choosing optimal SETs, such as for differently charged target proteins, and recent new developments on NMR-invisible SETs.

Solubility of Tc(IV) oxides

International Nuclear Information System (INIS)

Liu, D.J.; Fan, X.H.

2005-01-01

Full text of publication follows: The deep geological disposal of the high level radioactive wastes is expected to be a safer disposal method in most countries. The long-lived fission product 99 Tc is present in large quantities in nuclear wastes and its chemical behavior in aqueous solution is of considerable interest. Under the reducing conditions, expected to exist in a deep geological repository, it is generally predicted that technetium will be present as TcO 2 .nH 2 O. The solubility of Tc(IV) is used as a source term in performance assessment of radioactive waste repository. Technetium oxide was prepared by reduction of a technetate solution with Sn 2+ . The solubility of Tc(IV) oxide has been determined in simulated groundwater and re-distilled water under aerobic and anaerobic conditions. The effects of pH and CO 3 2- concentration of solution on solubility of Tc(IV) oxide were studied. The concentration of total technetium and Tc(IV) species in the solutions were periodically determined by separating the oxidized and reduced technetium species using a solvent extraction procedure and counting the beta activity of the 99 Tc with a liquid scintillation counter. The experimental results show that the rate of oxidation of Tc(IV) in simulated groundwater and re-distilled water is about (1.49∼1.86) x 10 -9 mol/(L.d) under aerobic conditions, but Tc(IV) in simulated groundwater and re-distilled water is not oxidized under anaerobic conditions. Under aerobic or anaerobic conditions the solubility of Tc(IV) oxide in simulated groundwater and re-distilled water is equal on the whole after centrifugation or ultrafiltration. The solubility of Tc(IV) oxide decreases with the increase of pH at pH 10 and is pH independent in the range 2 -8 to 10 -9 mol/L at 2 3 2- concentration. These data could be used to estimate the Tc(IV) solubility for cases where solubility limits transport of technetium in reducing environments of high-level waste repositories. (authors)

Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments

DEFF Research Database (Denmark)

Madsen, Cecilie Maria; Feng, Kung-I; Leithead, Andrew

2018-01-01

The composition of the human intestinal fluids varies both intra- and inter-individually. This will influence the solubility of orally administered drug compounds, and hence, the absorption and efficacy of compounds displaying solubility limited absorption. The purpose of this study was to assess...... studies feasible compared to single SIF solubility studies. Applying this DoE approach will lead to a better understanding of the impact of intestinal fluid composition on the solubility of a given drug compound....

Evolution of Substrate Specificity within a Diverse Family of [beta/alpha]-Barrel-fold Basic Amino Acid Decarboxylases X-ray Structure Determination of Enzymes with Specificity for L-Arginine and Carboxynorspermidine

Energy Technology Data Exchange (ETDEWEB)

Deng, Xiaoyi; Lee, Jeongmi; Michael, Anthony J.; Tomchick, Diana R.; Goldsmith, Elizabeth J.; Phillips, Margaret A. (Sungkyunkwan); (UTSMC)

2010-08-26

Pyridoxal 5{prime}-phosphate (PLP)-dependent basic amino acid decarboxylases from the {beta}/{alpha}-barrel-fold class (group IV) exist in most organisms and catalyze the decarboxylation of diverse substrates, essential for polyamine and lysine biosynthesis. Herein we describe the first x-ray structure determination of bacterial biosynthetic arginine decarboxylase (ADC) and carboxynorspermidine decarboxylase (CANSDC) to 2.3- and 2.0-{angstrom} resolution, solved as product complexes with agmatine and norspermidine. Despite low overall sequence identity, the monomeric and dimeric structures are similar to other enzymes in the family, with the active sites formed between the {beta}/{alpha}-barrel domain of one subunit and the {beta}-barrel of the other. ADC contains both a unique interdomain insertion (4-helical bundle) and a C-terminal extension (3-helical bundle) and it packs as a tetramer in the asymmetric unit with the insertions forming part of the dimer and tetramer interfaces. Analytical ultracentrifugation studies confirmed that the ADC solution structure is a tetramer. Specificity for different basic amino acids appears to arise primarily from changes in the position of, and amino acid replacements in, a helix in the {beta}-barrel domain we refer to as the 'specificity helix.' Additionally, in CANSDC a key acidic residue that interacts with the distal amino group of other substrates is replaced by Leu{sup 314}, which interacts with the aliphatic portion of norspermidine. Neither product, agmatine in ADC nor norspermidine in CANSDC, form a Schiff base to pyridoxal 5{prime}-phosphate, suggesting that the product complexes may promote product release by slowing the back reaction. These studies provide insight into the structural basis for the evolution of novel function within a common structural-fold.

pH-metric solubility. 3. Dissolution titration template method for solubility determination.

Science.gov (United States)

Avdeef, A; Berger, C M

2001-12-01

The main objective of this study was to develop an effective potentiometric saturation titration protocol for determining the aqueous intrinsic solubility and the solubility-pH profile of ionizable molecules, with the specific aim of overcoming incomplete dissolution conditions, while attempting to shorten the data collection time. A modern theory of dissolution kinetics (an extension of the Noyes-Whitney approach) was applied to acid-base titration experiments. A thermodynamic method was developed, based on a three-component model, to calculate interfacial, diffusion-layer, and bulk-water reactant concentrations in saturated solutions of ionizable compounds perturbed by additions of acid/base titrant, leading to partial dissolution of the solid material. Ten commercial drugs (cimetidine, diltiazem hydrochloride, enalapril maleate, metoprolol tartrate, nadolol, propoxyphene hydrochloride, quinine hydrochloride, terfenadine, trovafloxacin mesylate, and benzoic acid) were chosen to illustrate the new titration methodology. It was shown that the new method is about 10 times faster in determining equilibrium solubility constants, compared to the traditional saturation shake-flask methods.

Sibutramine characterization and solubility, a theoretical study

Science.gov (United States)

Aceves-Hernández, Juan M.; Nicolás Vázquez, Inés; Hinojosa-Torres, Jaime; Penieres Carrillo, Guillermo; Arroyo Razo, Gabriel; Miranda Ruvalcaba, René

2013-04-01

Solubility data from sibutramine (SBA) in a family of alcohols were obtained at different temperatures. Sibutramine was characterized by using thermal analysis and X-ray diffraction technique. Solubility data were obtained by the saturation method. The van't Hoff equation was used to obtain the theoretical solubility values and the ideal solvent activity coefficient. No polymorphic phenomena were found from the X-ray diffraction analysis, even though this compound is a racemic mixture of (+) and (-) enantiomers. Theoretical calculations showed that the polarisable continuum model was able to reproduce the solubility and stability of sibutramine molecule in gas phase, water and a family of alcohols at B3LYP/6-311++G (d,p) level of theory. Dielectric constant, dipolar moment and solubility in water values as physical parameters were used in those theoretical calculations for explaining that behavior. Experimental and theoretical results were compared and good agreement was obtained. Sibutramine solubility increased from methanol to 1-octanol in theoretical and experimental results.

Ideal gas solubilities and solubility selectivities in a binary mixture of room-temperature ionic liquids.

Science.gov (United States)

Finotello, Alexia; Bara, Jason E; Narayan, Suguna; Camper, Dean; Noble, Richard D

2008-02-28

This study focuses on the solubility behaviors of CO2, CH4, and N2 gases in binary mixtures of imidazolium-based room-temperature ionic liquids (RTILs) using 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2mim][Tf2N]) and 1-ethyl-3-methylimidazolium tetrafluoroborate ([C2mim][BF4]) at 40 degrees C and low pressures (approximately 1 atm). The mixtures tested were 0, 25, 50, 75, 90, 95, and 100 mol % [C2mim][BF4] in [C2mim][Tf2N]. Results show that regular solution theory (RST) can be used to describe the gas solubility and selectivity behaviors in RTIL mixtures using an average mixture solubility parameter or an average measured mixture molar volume. Interestingly, the solubility selectivity, defined as the ratio of gas mole fractions in the RTIL mixture, of CO2 with N2 or CH4 in pure [C2mim][BF4] can be enhanced by adding 5 mol % [C2mim][Tf2N].

Ornithine decarboxylase regulates the activity and localization of rhoA via polyamination

International Nuclear Information System (INIS)

Maekitie, Laura T.; Kanerva, Kristiina; Andersson, Leif C.

2009-01-01

Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis. Polyamines and ODC are connected to cell proliferation and transformation. Resting cells display a low ODC activity while normal, proliferating cells display fluctuations in ODC activity that coincide with changes in the actin cytoskeleton during the cell cycle. Cancerous cells display constitutively elevated ODC activity. Overexpression of ODC in NIH 3T3 fibroblasts induces a transformed phenotype. The cytoskeletal rearrangements during cytokinesis and cell transformation are intimately coupled to the ODC activity but the molecular mechanisms have remained elusive. In this study we investigated how ODC and polyamines influence the organization of the cytoskeleton. Given that the small G-proteins of the rho family are key modulators of the actin cytoskeleton, we investigated the molecular interactions of rhoA with ODC and polyamines. Our results show that transglutaminase-catalyzed polyamination of rhoA regulates its activity. The polyamination status of rhoA crucially influences the progress of the cell cycle as well as the rate of transformation of rat fibroblasts infected with temperature-sensitive v-src. We also show that ODC influences the intracellular distribution of rhoA. These findings provide novel insights into the mechanisms by which ODC and polyamines regulate the dynamics of the cytoskeleton during cell proliferation and transformation

Solubility of carbohydrates in heavy water.

Science.gov (United States)

Cardoso, Marcus V C; Carvalho, Larissa V C; Sabadini, Edvaldo

2012-05-15

The solubility of several mono-(glucose and xylose), di-(sucrose and maltose), tri-(raffinose) and cyclic (α-cyclodextrin) saccharides in H(2)O and in D(2)O were measured over a range of temperatures. The solution enthalpies for the different carbohydrates in the two solvents were determined using the vant' Hoff equation and the values in D(2)O are presented here for the first time. Our findings indicate that the replacement of H(2)O by D(2)O remarkably decreases the solubilities of the less soluble carbohydrates, such as maltose, raffinose and α-cyclodextrin. On the other hand, the more soluble saccharides, glucose, xylose, and sucrose, are practically insensitive to the H/D replacement in water. Copyright © 2012 Elsevier Ltd. All rights reserved.

Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate

Directory of Open Access Journals (Sweden)

Yousaf AM

2016-01-01

Full Text Available Abid Mehmood Yousaf,1,2 Omer Mustapha,1 Dong Wuk Kim,1 Dong Shik Kim,1 Kyeong Soo Kim,1 Sung Giu Jin,1 Chul Soon Yong,3 Yu Seok Youn,4 Yu-Kyoung Oh,5 Jong Oh Kim,3 Han-Gon Choi1 1College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea; 2Faculty of Pharmacy, University of Central Punjab, Johar, Lahore, Pakistan; 3College of Pharmacy, Yeungnam University, Gyongsan, North Gyeongsang, 4School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi, 5College of Pharmacy, Seoul National University, Seoul, South Korea Purpose: The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate.Methods: Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP and Labrafil® M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion.Results: All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1

Water-soluble dietary fibers and cardiovascular disease.

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Theuwissen, Elke; Mensink, Ronald P

2008-05-23

One well-established way to reduce the risk of developing cardiovascular disease (CVD) is to lower serum LDL cholesterol levels by reducing saturated fat intake. However, the importance of other dietary approaches, such as increasing the intake of water-soluble dietary fibers is increasingly recognized. Well-controlled intervention studies have now shown that four major water-soluble fiber types-beta-glucan, psyllium, pectin and guar gum-effectively lower serum LDL cholesterol concentrations, without affecting HDL cholesterol or triacylglycerol concentrations. It is estimated that for each additional gram of water-soluble fiber in the diet serum total and LDL cholesterol concentrations decrease by -0.028 mmol/L and -0.029 mmol/L, respectively. Despite large differences in molecular structure, no major differences existed between the different types of water-soluble fiber, suggesting a common underlying mechanism. In this respect, it is most likely that water-soluble fibers lower the (re)absorption of in particular bile acids. As a result hepatic conversion of cholesterol into bile acids increases, which will ultimately lead to increased LDL uptake by the liver. Additionally, epidemiological studies suggest that a diet high in water-soluble fiber is inversely associated with the risk of CVD. These findings underlie current dietary recommendations to increase water-soluble fiber intake.

Transport of soluble species in backfill and rock

International Nuclear Information System (INIS)

Chambre, P.L.; Lee, W.W.L.; Light, W.B.; Pigford, T.H.

1992-03-01

In this report we study the release and transport of soluble species from spent nuclear fuel. By soluble species we mean a fraction of certain fission product species. Our previously developed methods for calculating release rates of solubility-limited species need to be revised for these soluble species. Here we provide methods of calculating release rates of soluble species directly into rock and into backfill and then into rock. Section 2 gives a brief discussion of the physics of fission products dissolution from U0 2 spent fuel. Section 3 presents the mathematics for calculating release rates of soluble species into backfill and then into rock. The calculation of release rates directly into rock is a special case. Section 4 presents numerical illustrations of the analytic results

Solubility limits on radionuclide dissolution

Energy Technology Data Exchange (ETDEWEB)

Kerrisk, J.F.

1984-12-31

This paper examines the effects of solubility in limiting dissolution rates of a number of important radionuclides from spent fuel and high-level waste. Two simple dissolution models were used for calculations that would be characteristics of a Yucca Mountain repository. A saturation-limited dissolution model, in which the water flowing through the repository is assumed to be saturated with each waste element, is very conservative in that it overestimates dissolution rates. A diffusion-limited dissolution model, in which element-dissolution rates are limited by diffusion of waste elements into water flowing past the waste, is more realistic, but it is subject to some uncertainty at this time. Dissolution rates of some elements (Pu, Am, Sn, Th, Zr, Sm) are always limited by solubility. Dissolution rates of other elements (Cs, Tc, Np, Sr, C, I) are never solubility limited; their release would be limited by dissolution of the bulk waste form. Still other elements (U, Cm, Ni, Ra) show solubility-limited dissolution under some conditions. 9 references, 3 tables.

Hydrogen solubility in austenite of Fe-Ni-Cr alloys

International Nuclear Information System (INIS)

Zhirnova, V.V.; Mogutnov, B.M.; Tomilin, I.A.

1981-01-01

Hydrogen solubility in Fe-Ni-Cr alloys at 600-1000 deg C is determined. Hydrogen solubility in ternary alloys can not be predicted on the basis of the data on its solubility in binary Fe-Ni, Fe-Cr alloys. Chromium and nickel effect on hydrogen solubility in iron is insignificant in comparison with the effect of these elements on carbon or nitrogen solubility [ru

Glutamate decarboxylase immunoreactivity and gamma-[3H] aminobutyric acid accumulation within the same neurons in dissociated cell cultures of cerebral cortex

International Nuclear Information System (INIS)

Neale, E.A.; Oertel, W.H.; Bowers, L.M.; Weise, V.K.

1983-01-01

In order to evaluate the reliability of high affinity [ 3 H]GABA accumulation as a marker for GABAergic neurons, murine cerebral cortical neurons were studied in dissociated cell culture. Cultures which had been incubated in [ 3 H]GABA were stained immunohistochemically for the GABA-synthesizing enzyme, glutamate decarboxylase, fixed with paraformaldehyde, and subsequently processed for radioautography. In mature cultures, there was an 84 to 94% correlation between the presence of the enzyme and [ 3 H]GABA uptake within the same cortical neurons. These data provide direct evidence that those neurons which synthesize GABA are the same neurons which are labeled by high affinity [ 3 H]GABA uptake

Carcinogenicity assessment of water-soluble nickel compounds.

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Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

2009-01-01

IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

Solubility study of Tc(IV) oxides

International Nuclear Information System (INIS)

Liu, D.J.; Fan, X.H.

2005-01-01

The deep geological disposal of the high level radioactive wastes is expected to be a safer disposal method in most countries. The long-lived fission product 99 Tc is present in large quantities in nuclear wastes and its chemical behavior in aqueous solution is of considerable interest. Under oxidizing conditions technetium exists as the anionic species TcO 4 - whereas under the reducing conditions, expected to exist in a deep geological repository, it is generally predicted that technetium will be present as TcO 2 ·nH 2 O. Hence, the mobility of Tc(IV) in reducing groundwater may be limited by the solubility of TcO 2 ·nH 2 O under these conditions. Due to this fact it is important to investigate the solubility of TcO 2 ·nH 2 O. The solubility determines the release of radionuclides from waste form and is used as a source term in radionuclide migration analysis in performance assessment of radioactive waste repository. Technetium oxide was prepared by reduction of a technetate solution with Sn 2 + . The solubility of Tc(IV) oxide has been determined in simulated groundwater and redistilled water under aerobic and anaerobic conditions. The effects of pH and CO 3 2- concentration of solution on solubility of Tc(IV) oxide were studied. The concentration of total technetium and Tc(IV) species in the solutions were periodically determined by separating the oxidized and reduced technetium species using a solvent extraction procedure and counting the beta activity of the 99 Tc with a liquid scintillation counter. The experimental results show that the rate of oxidation of Tc(IV) in simulated groundwater and redistilled water is about (1.49-1.86) x 10 -9 mol/(L·d) under aerobic conditions, but Tc(IV) in simulated groundwater and redistilled water is not oxidized under anaerobic conditions. Under aerobic or anaerobic conditions the solubility of Tc(IV) oxide in simulated groundwater and redistilled water is equal on the whole after centrifugation or ultrafiltration. The

Solubility of cefoxitin acid in different solvent systems

International Nuclear Information System (INIS)

Yuan, Fuhong; Wang, Yongli; Xiao, Liping; Huang, Qiaoyin; Xu, Jinchao; Jiang, Chen; Hao, Hongxun

2016-01-01

Highlights: • The solubility of cefoxitin acid in different solvent systems was measured. • Three models were used to correlate the solubility data. • The dissolution enthalpy of the dissolution process was calculated. - Abstract: Cefoxitin acid is one kind of important pharmaceutical intermediate. Its solubility is crucial for designing and optimizing the crystallization processes. In this work, the solubility of cefoxitin acid in organic solvents (methanol, acetonitrile, ethanol, isopropanol, n-propanol and ethyl acetate), water and water-methanol mixtures was measured spectrophotometrically using a shake-flask method within the temperature range 278.15–303.15 K. PXRD data and the Karl Fischer method were used to verify the crystal form stability of cefoxitin acid in the solubility measuring process. The melting points, the enthalpy and entropy of fusion were estimated. Results showed that the solubility of cefoxitin acid increases with the increasing temperature in all tested solvents in this work, and the solubility of cefoxitin acid increases with the increasing methanol concentration in water-methanol mixtures. The experimental solubility values were well correlated using the modified Apelblat equation, NRTL model and CNIBS/R-K model. An equation proposed by Williamson was adopted to calculate the molar enthalpy during the dissolution process.

Active intestinal drug absorption and the solubility-permeability interplay.

Science.gov (United States)

Porat, Daniel; Dahan, Arik

2018-02-15

The solubility-permeability interplay deals with the question: what is the concomitant effect on the drug's apparent permeability when increasing the apparent solubility with a solubility-enabling formulation? The solubility and the permeability are closely related, exhibit certain interplay between them, and ongoing research throughout the past decade shows that treating the one irrespectively of the other may be insufficient. The aim of this article is to provide an overview of the current knowledge on the solubility-permeability interplay when using solubility-enabling formulations for oral lipophilic drugs, highlighting active permeability aspects. A solubility-enabling formulation may affect the permeability in opposite directions; the passive permeability may decrease as a result of the apparent solubility increase, according to the solubility-permeability tradeoff, but at the same time, certain components of the formulation may inhibit/saturate efflux transporters (when relevant), resulting in significant apparent permeability increase. In these cases, excipients with both solubilizing and e.g. P-gp inhibitory properties may lead to concomitant increase of both the solubility and the permeability. Intelligent development of such formulation will account for the simultaneous effects of the excipients' nature/concentrations on the two arms composing the overall permeability: the passive and the active arms. Overall, thorough mechanistic understanding of the various factors involved in the solubility-permeability interplay may allow developing better solubility-enabling formulations, thereby exploiting the advantages analyzed in this article, offering oral delivery solution even for BCS class IV drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Study of solubility of some metal cyclohexane carbonates

International Nuclear Information System (INIS)

Niyazov, A.N.; Amanov, K.B.; Trapeznikova, V.F.; Kul'maksimov, A.; Kolosova, N.

1978-01-01

The solubility of calcium, magnesium, strontium, barium, cabalt, copper and aluminium cyclohexane, carbonates (CHC) in water has been studied at 25 deg C. The salt solubility has been calculated according to the metal ion concentration in saturated solutions. It has been established, that the cobalt and rare earth cyclohexane carbonates are relatively very soluble in water and have solubility products of SP > 1x10 -5 . The solubility of CHC of multivalent metals increases with the decrease of pH values. Each salt has some ''limiting'' pH value of a solution, below which it decomposes completely and can not exist in a solution in the form of solid phase

Simultaneous silencing of two arginine decarboxylase genes alters development in Arabidopsis

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Diana eSánchez-Rangel

2016-03-01

Full Text Available Polyamines (PAs are small aliphatic polycations that are found ubiquitously in all organisms. In plants, PAs are involved in diverse biological processes such as growth, development, and stress responses. In Arabidopsis thaliana, the arginine decarboxylase enzymes (ADC1 and 2 catalyze the first step of PA biosynthesis. For a better understanding of PA biological functions, mutants in PA biosynthesis have been generated; however, the double adc1/adc2 mutant is not viable in A. thaliana. In this study, we generated non-lethal A. thaliana lines through an artificial microRNA that simultaneously silenced the two ADC genes (amiR:ADC. The generated transgenic lines (amiR:ADC-L1 and -L2 showed reduced AtADC1 and AtADC2 transcript levels. For further analyses the amiR:ADC-L2 line was selected. We found that the amiR:ADC-L2 line showed a significant decrease of their PA levels. The co-silencing revealed a stunted growth in A. thaliana seedlings, plantlets and delay in its flowering rate; these phenotypes were reverted with PA treatment. In addition, amiR:ADC-L2 plants displayed two seed phenotypes, such as yellow and brownish seeds. The yellow mutant seeds were smaller than adc1, adc2 mutants and wild type seeds; however, the brownish were the smallest seeds with arrested embryos at the torpedo stage. These data reinforce the importance of PA homeostasis in the plant development processes.

Hydrothermal solubility of uraninite. Final technical report

International Nuclear Information System (INIS)

Parks, G.A.; Pohl, D.C.

1985-01-01

Experimental measurements of the solubility of UO 2 from 100 to 300 0 C under 500 bars H 2 , in NaCl solutions at pH from 1 to 8 do not agree with solubilities calculated using existing thermodynamic databases. For pH 2 (hyd) has precipitated and is controlling solubility. For pH > 8, solubilities at all temperatures are much lower than predicted, suggesting that the U(OH)/sub delta/ - complex is much weaker than predicted. Extrapolated to 25 0 C, high pH solubility agrees within experimental error with the upper limit suggested by Ryan and Rai (1983). In the pH range 2 to 6, solubilities are up to three orders of magnitude lower than predicted for temperatures exceeding 200 0 C and up to two orders higher than predicted at lower temperatures. pH dependence in this region is negligible suggesting that U(OH) 4 (aq) predominates, thus the stability of this species is higher than presently estimated at low temperatures, but the enthalpy of solution is smaller. A low maximum observed near pH approx. =3 is presently unexplained. 40 refs., 16 figs., 12 tabs

Biotic and abiotic stress tolerance in transgenic tomatoes by constitutive expression of S-adenosylmethionine decarboxylase gene.

Science.gov (United States)

Hazarika, Pranjal; Rajam, Manchikatla Venkat

2011-04-01

Recent findings have implicated the role of polyamines (putrescine, spermidine and spermine) in stress tolerance. Therefore, the present work was carried out with the goal of generating transgenic tomato plants with human S-adenosylmethionine decarboxylase (samdc) gene, a key gene involved in biosynthesis of polyamines, viz. spermidine and spermine and evaluating the transgenic plants for tolerance to both biotic and abiotic stresses. Several putative transgenic tomato plants with normal phenotype were obtained, and the transgene integration and expression was validated by PCR, Southern blot analysis and RT-PCR analysis, respectively. The transgenic plants exhibited high levels of polyamines as compared to the untransformed control plants. They also showed increased resistance against two important fungal pathogens of tomato, the wilt causing Fusarium oxysporum and the early blight causing Alternaria solani and tolerance to multiple abiotic stresses such as salinity, drought, cold and high temperature. These results suggest that engineering polyamine accumulation can confer tolerance to both biotic and abiotic stresses in plants.

Syndromic intellectual disability: a new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant.

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Graziano, Claudio; Wischmeijer, Anita; Pippucci, Tommaso; Fusco, Carlo; Diquigiovanni, Chiara; Nõukas, Margit; Sauk, Martin; Kurg, Ants; Rivieri, Francesca; Blau, Nenad; Hoffmann, Georg F; Chaubey, Alka; Schwartz, Charles E; Romeo, Giovanni; Bonora, Elena; Garavelli, Livia; Seri, Marco

2015-04-01

The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution. Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities. Copyright © 2015 Elsevier B.V. All rights reserved.

Cloning and characterization of the ddc homolog encoding L-2,4-diaminobutyrate decarboxylase in Enterobacter aerogenes.

Science.gov (United States)

Yamamoto, S; Mutoh, N; Tsuzuki, D; Ikai, H; Nakao, H; Shinoda, S; Narimatsu, S; Miyoshi, S I

2000-05-01

L-2,4-diaminobutyrate decarboxylase (DABA DC) catalyzes the formation of 1,3-diaminopropane (DAP) from DABA. In the present study, the ddc gene encoding DABA DC from Enterobacter aerogenes ATCC 13048 was cloned and characterized. Determination of the nucleotide sequence revealed an open reading frame of 1470 bp encoding a 53659-Da protein of 490 amino acids, whose deduced NH2-terminal sequence was identical to that of purified DABA DC from E. aerogenes. The deduced amino acid sequence was highly similar to those of Acinetobacter baumannii and Haemophilus influenzae DABA DCs encoded by the ddc genes. The lysine-307 of the E. aerogenes DABA DC was identified as the pyridoxal 5'-phosphate binding residue by site-directed mutagenesis. Furthermore, PCR analysis revealed the distribution of E. aerogenes ddc homologs in some other species of Enterobacteriaceae. Such a relatively wide occurrence of the ddc homologs implies biological significance of DABA DC and its product DAP.

Diagnosing solubility limitations – the example of hydrate formation

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Joerg Berghausen

2014-07-01

Full Text Available Solubility is regarded as one of the key challenges in many drug discovery projects. Thus, it’s essential to support the lead finding and optimization efforts by appropriate solubility data. In silico solubility prediction remains challenging and therefore a screening assay is used as a first filter, followed by selected follow-up assays to reveal what causes the low solubility of a specific compound or chemotype. Results from diagnosing the underlying reason for solubility limitation are discussed. As lipophilicity and crystal lattice forces are regarded as main contributors to limiting solubility, changes in solid state are important to be recognized. Solubility limitation by various factors will be presented and the impact of the solid-state is exemplified by compounds that are able to form hydrates.

Serum Soluble Corin is Decreased in Stroke.

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Peng, Hao; Zhu, Fangfang; Shi, Jijun; Han, Xiujie; Zhou, Dan; Liu, Yan; Zhi, Zhongwen; Zhang, Fuding; Shen, Yun; Ma, Juanjuan; Song, Yulin; Hu, Weidong

2015-07-01

Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke. © 2015 American Heart Association, Inc.

Combined Use of α‐Difluoromethylornithine and an Inhibitor of S‐Adenosylmethionine Decarboxylase in Mice Bearing P388 Leukemia or Lewis Lung Carcinoma

Science.gov (United States)

Nakaike, Shiro; Kashiwagi, Keiko; Terao, Kiyoshi; Iio, Kokoro

1988-01-01

The antitumor and antimetastatic effects of α‐difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, combined with an inhibitor of S‐adenosylmethionine decarboxylase, either methylglyoxal bis(guanylhydrazone) (MGBG) or ethylglyoxal bis(guanylhydrazone) (EGBG), were studied in mice bearing P388 leukemia or Lewis lung carcinoma. Although EGBG is a more specific inhibitor of polyamine biosynthesis than the widely used MGBG, the antitumor effect of the DFMO‐EGBG combination on P388 leukemia‐bearing mice was less than that of the DFMO‐MGBG combination. The prolongation of survival time by the DFMOC1000 mg/kg)‐MGBG(25 mg/kg) combination was 2.65‐fold, while that of the DFMO(1000 mg/kg)‐EGBG(50 mg/kg) combination was 1.34‐fold. When mice were fed a polyamine‐deficient diet, stronger antitumor effects were exerted; the prolongation of survival time by the DFMO‐MGBG and the DFMO‐EGBG combinations was 2.89‐fold and 2.03‐fold, respectively. The antitumor effect of combined use of the two polyamine antimetabolites with mice on normal and polyamine‐deficient diets correlated with a decrease of polyamine charge contents in the tumor cells. The above in vivo results were confirmed clearly in the KB cell culture system. The antimetastatic activity of DFMO on Lewis lung carcinoma‐bearing mice was strengthened by the addition of MGBG or EGBG. The antimetastatic activity of the DFMO‐MGBG or DFMO‐EGBG combination did not parallel the polyamine charge contents in the primary tumor and blood. PMID:3133338

Solubility and degradation of paracetamol in subcritical water

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Emire Zuhal

2017-01-01

Full Text Available In this study, solubility and degradation of paracetamol were examined using subcritical water. Effect of temperature and static time was investigated during solubility process in subcritical water at constant pressure (50 bar. Experimental results show that temperature and static time have crucial effect on the degradation and solubility rates. Maximum mole fraction for solubility of paracetamol was obtained at 403 K as (14.68 ± 0.74×103. Approximation model for solubility of paracetamol was proposed. O2 and H2O2 were used in degradation process of paracetamol. Maximum degradation rate was found as 68.66 ± 1.05 and 100 ± 0.00 % using O2 and H2O2, respectively.

Solubility of hydrogen in bio-oil compounds

International Nuclear Information System (INIS)

Qureshi, Muhammad Saad; Touronen, Jouni; Uusi-Kyyny, Petri; Richon, Dominique; Alopaeus, Ville

2016-01-01

Highlights: • Solubility of Hydrogen was measured in bio-oil compounds in the at temperatures from 342 to 473 K and pressures up to 16 MPa. • Phase equilibrium data were acquired using a visualization enabled continuous flow synthetic apparatus. • The measured solubility is modeled with Peng-Robinson EoS. - Abstract: The knowledge of accurate hydrogen solubility values in bio-oil compounds is essential for the design and optimization of hydroprocesses relevant to biofuel industry. This work reports the solubility of hydrogen in three industrially relevant bio-oil compounds (allyl alcohol, furan, and eugenol) at temperatures from 342 to 473 K and pressures up to 16 MPa. Phase equilibrium data were acquired using a continuous flow synthetic method. The method is based on the visual observation of the bubble point using a high resolution camera. The measured solubility is modeled with Peng-Robinson EoS with classical van der Waals one fluid mixing rules.

The Relationship among Tyrosine Decarboxylase and Agmatine Deiminase Pathways in Enterococcus faecalis

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Marta Perez

2017-11-01

Full Text Available Enterococci are considered mainly responsible for the undesirable accumulation of the biogenic amines tyramine and putrescine in cheeses. The biosynthesis of tyramine and putrescine has been described as a species trait in Enterococcus faecalis. Tyramine is formed by the decarboxylation of the amino acid tyrosine, by the tyrosine decarboxylase (TDC route encoded in the tdc cluster. Putrescine is formed from agmatine by the agmatine deiminase (AGDI pathway encoded in the agdi cluster. These biosynthesis routes have been independently studied, tyrosine and agmatine transcriptionally regulate the tdc and agdi clusters. The objective of the present work is to study the possible co-regulation among TDC and AGDI pathways in E. faecalis. In the presence of agmatine, a positive correlation between putrescine biosynthesis and the tyrosine concentration was found. Transcriptome studies showed that tyrosine induces the transcription of putrescine biosynthesis genes and up-regulates pathways involved in cell growth. The tyrosine modulation over AGDI route was not observed in the mutant Δtdc strain. Fluorescence analyses using gfp as reporter protein revealed PaguB (the promoter of agdi catabolic genes was induced by tyrosine in the wild-type but not in the mutant strain, confirming that tdc cluster was involved in the tyrosine induction of putrescine biosynthesis. This study also suggests that AguR (the transcriptional regulator of agdi was implicated in interaction among the two clusters.

Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction.

Science.gov (United States)

Brownfoot, Fiona C; Hastie, Roxanne; Hannan, Natalie J; Cannon, Ping; Tuohey, Laura; Parry, Laura J; Senadheera, Sevvandi; Illanes, Sebastian E; Kaitu'u-Lino, Tu'uhevaha J; Tong, Stephen

2016-03-01

Preeclampsia is associated with placental ischemia/hypoxia and secretion of soluble fms-like tyrosine kinase 1 and soluble endoglin into the maternal circulation. This causes widespread endothelial dysfunction that manifests clinically as hypertension and multisystem organ injury. Recently, small molecule inhibitors of hypoxic inducible factor 1α have been found to reduce soluble fms-like tyrosine kinase 1 and soluble endoglin secretion. However, their safety profile in pregnancy is unknown. Metformin is safe in pregnancy and is also reported to inhibit hypoxic inducible factor 1α by reducing mitochondrial electron transport chain activity. The purposes of this study were to determine (1) the effects of metformin on placental soluble fms-like tyrosine kinase 1 and soluble endoglin secretion, (2) to investigate whether the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion are regulated through the mitochondrial electron transport chain, and (3) to examine its effects on endothelial dysfunction, maternal blood vessel vasodilation, and angiogenesis. We performed functional (in vitro and ex vivo) experiments using primary human tissues to examine the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from placenta, endothelial cells, and placental villous explants. We used succinate, mitochondrial complex II substrate, to examine whether the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion were mediated through the mitochondria. We also isolated mitochondria from preterm preeclamptic placentas and gestationally matched control subjects and measured mitochondrial electron transport chain activity using kinetic spectrophotometric assays. Endothelial cells or whole maternal vessels were incubated with metformin to determine whether it rescued endothelial dysfunction induced by either tumor necrosis factor-α (to endothelial cells) or placenta villous

The solubility of palladium(II) bis-dimethylglyoximate

International Nuclear Information System (INIS)

Maghzian, R.

1978-01-01

The solubility of palladium(II) bis-dimethylglyoximate in different solutions has been determined. Values obtained for the solubility of the palladium complex are tabulated. The solubility is the lowest in water, ammonium acetate and a 25% acetone-water mixture. It is highest in dilute HCl and acetone but precipitation from aqueous acetone should be satisfactory for most purposes if the acetone content of the solvent is roughly less than 50% by volume. The solubility in dilute HCl reflects the concern by previous workers for losses in precipitation from mineral acid. In general, however, the losses are unlikely to be significant unless the quantity of palladium to be precipitated and weighed is small. (T.G.)

Biochemical evaluation of a parsley tyrosine decarboxylase results in a novel 4-hydroxyphenylacetaldehyde synthase enzyme.

Science.gov (United States)

Torrens-Spence, Michael P; Gillaspy, Glenda; Zhao, Bingyu; Harich, Kim; White, Robert H; Li, Jianyong

2012-02-10

Plant aromatic amino acid decarboxylases (AAADs) are effectively indistinguishable from plant aromatic acetaldehyde syntheses (AASs) through primary sequence comparison. Spectroscopic analyses of several characterized AASs and AAADs were performed to look for absorbance spectral identifiers. Although this limited survey proved inconclusive, the resulting work enabled the reevaluation of several characterized plant AAS and AAAD enzymes. Upon completion, a previously reported parsley AAAD protein was demonstrated to have AAS activity. Substrate specificity tests demonstrate that this novel AAS enzyme has a unique substrate specificity towards tyrosine (km 0.46mM) and dopa (km 1.40mM). Metabolite analysis established the abundance of tyrosine and absence of dopa in parsley extracts. Such analysis indicates that tyrosine is likely to be the sole physiological substrate. The resulting information suggests that this gene is responsible for the in vivo production of 4-hydroxyphenylacetaldehyde (4-HPAA). This is the first reported case of an AAS enzyme utilizing tyrosine as a primary substrate and the first report of a single enzyme capable of producing 4-HPAA from tyrosine. Copyright © 2012 Elsevier Inc. All rights reserved.

Functional Characterization of Waterlogging and Heat Stresses Tolerance Gene Pyruvate decarboxylase 2 from Actinidia deliciosa

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Hui-Ting Luo

2017-11-01

Full Text Available A previous report showed that both Pyruvate decarboxylase (PDC genes were significantly upregulated in kiwifruit after waterlogging treatment using Illumina sequencing technology, and that the kiwifruit AdPDC1 gene was required during waterlogging, but might not be required during other environmental stresses. Here, the function of another PDC gene, named AdPDC2, was analyzed. The expression of the AdPDC2 gene was determined using qRT-PCR, and the results showed that the expression levels of AdPDC2 in the reproductive organs were much higher than those in the nutritive organs. Waterlogging, NaCl, and heat could induce the expression of AdPDC2. Overexpression of kiwifruit AdPDC2 in transgenic Arabidopsis enhanced resistance to waterlogging and heat stresses in five-week-old seedlings, but could not enhance resistance to NaCl and mannitol stresses at the seed germination stage and in early seedlings. These results suggested that the kiwifruit AdPDC2 gene may play an important role in waterlogging resistance and heat stresses in kiwifruit.

Solubility and physical properties of sugars in pressurized water

International Nuclear Information System (INIS)

Saldaña, Marleny D.A.; Alvarez, Víctor H.; Haldar, Anupam

2012-01-01

Highlights: ► Sugar solubility in pressurized water and density at high pressures were measured. ► Glucose solubility was higher than that of lactose as predicted by their σ-profiles. ► Sugar aqueous solubility decreased with an increase in pressure from 15 to 120 bar. ► Aqueous glucose molecular packing shows high sensitivity to pressure. ► The COSMO-SAC model qualitatively predicted the sugar solubility data. - Abstract: In this study, the solubility, density, and refractive index of glucose and lactose in water as a function of temperature were measured. For solubility of sugars in pressurized water, experimental data were obtained at pressures of (15 to 120) bar and temperatures of (373 to 433) K using a dynamic flow high pressure system. Density data for aqueous sugar solutions were obtained at pressures of (1 to 300) bar and temperatures of (298 to 343) K. The refractive index of aqueous sugar solutions was obtained at 293 K and atmospheric pressure. Activity coefficient models, Van Laar and the Conductor-like Screening Model-Segment Activity Coefficient (COSMO-SAC), were used to fit and predict the experimental solubility data, respectively. The results obtained showed that the solubility of both sugars in pressurized water increase with an increase in temperature. However, with the increase of pressure from 15 bar to 120 bar, the solubility of both sugars in pressurized water decreased. The Van Laar model fit the experimental aqueous solubility data with deviations lower than 13 and 53% for glucose and lactose, respectively. The COSMO-SAC model predicted qualitatively the aqueous solubility of these sugars.

Dual Activity of Hydroxypropyl-β-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol.

Science.gov (United States)

Zoghbi, Abdelmoumin; Geng, Tianjiao; Wang, Bo

2017-11-01

Carvedilol (CAR) is a non-selective α and β blocker categorized as class II drug with low water solubility. Several recent studies have investigated ways to overcome this problem. The aim of the present study was to combine two of these methods: the inclusion complex using hydroxypropyl-β-cyclodextrin (HPβCD) with solid dispersion using two carriers: Poloxamer 188 (PLX) and Polyvinylpyrrolidone K-30 (PVP) to enhance the solubility, bioavailability, and the stability of CAR. Kneading method was used to prepare CAR-HPβCD inclusion complex (KD). The action of different carriers separately and in combination on Carvedilol solubility was investigated in three series. CAR-carrier and KD-carrier solid dispersions were prepared by solvent evaporation method. In vitro dissolution test was conducted in three different media: double-distilled water (DDW), simulative gastric fluid (SGF), and PBS pH 6.8 (PBS). The interactions between CAR, HPβCD, and different carriers were explored by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), and differential scanning colorimetry (DSC). The results showed higher solubility of CAR in KD-PVP solid dispersions up to 70, 25, and 22 fold compared to pure CAR in DDW, SGF, and PBS, respectively. DSC and XRD analyses indicated an improved degree of transformation of CAR in KD-PVP solid dispersion from crystalline to amorphous state. This study provides a new successful combination of two polymers with the dual action of HPβCD and PLX/PVP on water solubility and bioavailability of CAR.

Effect of Cyclodextrin Complexation on the Aqueous Solubility and Solubility/Dose Ratio of Praziquantel

OpenAIRE

Maragos, Stratos; Archontaki, Helen; Macheras, Panos; Valsami, Georgia

2009-01-01

Praziquantel (PZQ), the primary drug of choice in the treatment of schistosomiasis, is a highly lipophilic drug that possesses high permeability and low aqueous solubility and is, therefore, classified as a Class II drug according to the Biopharmaceutics Classification System (BCS). In this work, β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were used in order to determine whether increasing the aqueous solubility of a drug by complexation with CDs, a BCS-Class II compound ...

Research on solubility characteristics of gaseous methyl iodide

International Nuclear Information System (INIS)

Zhou Yanmin; Sun Zhongning; Gu Haifeng; Wang Junlong

2014-01-01

With the deionized water as the absorbent, the solubility characteristics of the gaseous methyl iodide were studied under different temperature and pressure conditions, using a dynamic measuring method. The results show that within the range of experiment parameters, namely temperature is below 80℃ and pressure is lower than 0.3 MPa, the physical dissolution process of gaseous methyl iodide in water obeys Henry's law. The solubility coefficient under different temperature and pressure conditions was calculated based on the measurement results. Further research indicates that at atmospheric pressure, the solubility coefficient of methyl iodide in water decreases exponentially with the increase of temperature. While the pressure changes from 0.1 MPa to 0.3 MPa with equal interval, the solubility coefficient also increases linearly. The variation of the solubility coefficient with temperature under different pressure conditions all decreases exponentially. An equation is given to calculate the solubility coefficient of methyl iodide under different pressure and temperature conditions. (authors)

Uranium solubility and speciation in ground water

International Nuclear Information System (INIS)

Ollila, K.

1985-04-01

The purpose of this study has been to assess the solubility and possible species of uranium in groundwater at the disposal conditions of spent fuel. The effects of radiolysis and bentonite are considered. The assessment is based on the theoretical calculations found in the literature. The Finnish experimental results are included. The conservative estimate for uranium solubility under the oxidizing conditions caused by alpha radiolysis is based on the oxidation of uranium to the U(VI) state and formation of carbonate complex. For the groundwater with the typical carbonate content of 275 mg/l and the high carbonate content of 485 mg/l due to bentonite, the solubility values of 360 mg u/l and 950 mg U/l, are obtained, respectively. The experimental results predict considerably lower values, 0.5-20 mg U/l. The solubility of uranium under the undisturbed reducing conditions may be calculated based on the hydrolysis, carbonate complexation and redox reactions. The results vary considerably depending on the thermodynamic data used. The wide ranges of the most important groundwater parameters are seen in the solubility values. The experimental results show the same trends. As a conservative value for the solubility in reducing groundwater 50-500 μg U/l is estimated. (author)

S-adenosylmethionine decarboxylase inhibitors: new aryl and heteroaryl analogues of methylglyoxal bis(guanylhydrazone).

Science.gov (United States)

Stanek, J; Caravatti, G; Capraro, H G; Furet, P; Mett, H; Schneider, P; Regenass, U

1993-01-08

A series of 3-acylbenzamidine (amidino)hydrazones 7a-h, the corresponding (hetero)aromatic congeners 7i-p, and 3,3'-bis-amidino-biaryls 25a-e were synthesized. The hydrazones 7a-p were prepared by conversion of the corresponding acyl nitriles 1a,c-d,i,n-p to the imido esters 3a,c-d,i and the amidines 5a,c-d,h-i, followed by a reaction with aminoguanidine, or vice versa. Similarly, the biaryl 3,3'-dinitriles 23a-e were converted, via the imino esters 24a-c or the imino thioesters 27d-e, to the diamidines 25a-e. These new products are conformationally constrained analogues of methylglyoxal bis(guanylhydrazone) (MGBG). They are up to 100 times more potent as inhibitors of rat liver S-adenosylmethionine decarboxylase (SMDC) and generally less potent inhibitors of rat small intestine diamine oxidase (DAO) than MGBG. Some of these SAMDC inhibitors, e.g., compounds 7a, 7e, 7i, 25a, and 25d, have shown antiproliferative effects against T24 human bladder carcinoma cells. These products, whose structure-activity relationships are discussed, are of interest as potential anticancer agents and drugs for the treatment of protozoal and Pneumocystis carinii infections.

Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer.

Science.gov (United States)

Avgeris, Margaritis; Koutalellis, Georgios; Fragoulis, Emmanuel G; Scorilas, Andreas

2008-10-01

L-Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP). Total RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene. DDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (pDDC expression has significant discriminatory value between CaP and BPH (pDDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p=0.022) as well as in advanced stage patients (p=0.032). Our data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer.

Evaluation of Brachypodium distachyon L-Tyrosine Decarboxylase Using L-Tyrosine Over-Producing Saccharomyces cerevisiae.

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Shuhei Noda

Full Text Available To demonstrate that herbaceous biomass is a versatile gene resource, we focused on the model plant Brachypodium distachyon, and screened the B. distachyon for homologs of tyrosine decarboxylase (TDC, which is involved in the modification of aromatic compounds. A total of 5 candidate genes were identified in cDNA libraries of B. distachyon and were introduced into Saccharomyces cerevisiae to evaluate TDC expression and tyramine production. It is suggested that two TDCs encoded in the transcripts Bradi2g51120.1 and Bradi2g51170.1 have L-tyrosine decarboxylation activity. Bradi2g51170.1 was introduced into the L-tyrosine over-producing strain of S. cerevisiae that was constructed by the introduction of mutant genes that promote deregulated feedback inhibition. The amount of tyramine produced by the resulting transformant was 6.6-fold higher (approximately 200 mg/L than the control strain, indicating that B. distachyon TDC effectively converts L-tyrosine to tyramine. Our results suggest that B. distachyon possesses enzymes that are capable of modifying aromatic residues, and that S. cerevisiae is a suitable host for the production of L-tyrosine derivatives.

Glutamic acid decarboxylase 67 expression by a distinct population of mouse vestibular supporting cells

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Giancarlo eRusso

2014-12-01

Full Text Available The function of the enzyme glutamate decarboxylase (GAD is to convert glutamate in -aminobutyric acid (GABA.GAD exists as two major isoforms, termed GAD65 and GAD67,.that are usually expressed in GABA-containing neurons in the central nervous system. GAD65 has been proposed to be associated with GABA exocytosis whereas GAD67 with GABA metabolism. In the present immunofluorescence study, we have investigated the presence of the two GAD isoforms in the semicircular canal cristae of wild type and GAD67-GFP knock-in mice. While no evidence for GAD65 expression was found, GAD67 was detected in a distinct population of peripherally-located supporting cells, but not in hair cells or in centrally-located supporting cells. GABA, on the other hand, was found in all supporting cells. The present result indicate that only a discrete population of supporting cells use GAD67 to synthesize GABA. This is the first report of a marker that allows to distinguish two populations of supporting cells in the vestibular epithelium. On the other hand, the lack of GABA and GAD enzymes in hair cells excludes its involvement in afferent transmission.

Dry season aerosol iron solubility in tropical northern Australia

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V. H. L. Winton

2016-10-01

Full Text Available Marine nitrogen fixation is co-limited by the supply of iron (Fe and phosphorus in large regions of the global ocean. The deposition of soluble aerosol Fe can initiate nitrogen fixation and trigger toxic algal blooms in nitrate-poor tropical waters. We present dry season soluble Fe data from the Savannah Fires in the Early Dry Season (SAFIRED campaign in northern Australia that reflects coincident dust and biomass burning sources of soluble aerosol Fe. The mean soluble and total aerosol Fe concentrations were 40 and 500 ng m−3 respectively. Our results show that while biomass burning species may not be a direct source of soluble Fe, biomass burning may substantially enhance the solubility of mineral dust. We observed fractional Fe solubility up to 12 % in mixed aerosols. Thus, Fe in dust may be more soluble in the tropics compared to higher latitudes due to higher concentrations of biomass-burning-derived reactive organic species in the atmosphere. In addition, biomass-burning-derived particles can act as a surface for aerosol Fe to bind during atmospheric transport and subsequently be released to the ocean upon deposition. As the aerosol loading is dominated by biomass burning emissions over the tropical waters in the dry season, additions of biomass-burning-derived soluble Fe could have harmful consequences for initiating nitrogen-fixing toxic algal blooms. Future research is required to quantify biomass-burning-derived particle sources of soluble Fe over tropical waters.

Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase.

Science.gov (United States)

Burbaeva, G Sh; Boksha, I S; Tereshkina, E B; Savushkina, O K; Prokhorova, T A; Vorobyeva, E A

2014-10-01

Enzymes of glutamate and GABA metabolism in postmortem cerebellum from patients with Alzheimer's disease (AD) have not been comprehensively studied. The present work reports results of original comparative study on levels of phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase isoenzymes (GAD65/67) in autopsied cerebellum samples from AD patients and matched controls (13 cases in each group) as well as summarizes published evidence for altered levels of PAG and GAD65/67 in AD brain. Altered (decreased) levels of these enzymes and changes in links between amounts of these enzymes and other glutamate-metabolizing enzymes (such as glutamate dehydrogenase and glutamine synthetase-like protein) in AD cerebella suggest significantly impaired glutamate and GABA metabolism in this brain region, which was previously regarded as not substantially involved in AD pathogenesis.

A systematic evaluation of solubility enhancing excipients to enable the generation of permeability data for poorly soluble compounds in Caco-2 model.

Science.gov (United States)

Shah, Devang; Paruchury, Sundeep; Matta, Muralikrishna; Chowan, Gajendra; Subramanian, Murali; Saxena, Ajay; Soars, Matthew G; Herbst, John; Haskell, Roy; Marathe, Punit; Mandlekar, Sandhya

2014-01-01

The study presented here identified and utilized a panel of solubility enhancing excipients to enable the generation of flux data in the Human colon carcinoma (Caco-2) system for compounds with poor solubility. Solubility enhancing excipients Dimethyl acetamide (DMA) 1 % v/v, polyethylene glycol (PEG) 400 1% v/v, povidone 1% w/v, poloxamer 188 2.5% w/v and bovine serum albumin (BSA) 4% w/v did not compromise Caco-2 monolayer integrity as assessed by trans-epithelial resistance measurement (TEER) and Lucifer yellow (LY) permeation. Further, these excipients did not affect P-glycoprotein (P-gp) mediated bidirectional transport of digoxin, permeabilities of high (propranolol) or low permeability (atenolol) compounds, and were found to be inert to Breast cancer resistant protein (BCRP) mediated transport of cladribine. This approach was validated further using poorly soluble tool compounds, atazanavir (poloxamer 188 2.5% w/v) and cyclosporine A (BSA 4% w/v) and also applied to new chemical entity (NCE) BMS-A in BSA 4% w/v, for which Caco-2 data could not be generated using the traditional methodology due to poor solubility (solubility of atazanavir by >8 fold whereas BSA 4% w/v increased the solubility of cyclosporine A and BMS-A by >2-4 fold thereby enabling permeability as well as efflux liability estimation in the Caco-2 model with reasonable recovery values. To conclude, addition of excipients such as poloxamer 188 2.5% w/v and BSA 4% w/v to HBSS leads to a significant improvement in the solubility of the poorly soluble compounds resulting in enhanced recoveries without modulating transporter-mediated efflux, expanding the applicability of Caco-2 assays to poorly soluble compounds.

Nanosuspension Technology for Solubilizing Poorly Soluble Drugs

OpenAIRE

Deoli Mukesh

2012-01-01

Poor water solubility for many drugs and drug candidates remains a major obstacle to their development and clinical application. It is estimated that around 40% of drugs in the pipeline cannot be delivered through the preferred route or in some cases, at all owing to poor water solubility. Conventional formulations to improve solubility suffer from low bioavailability and poor pharmacokinetics, with some carriers rendering systemic toxicities (e.g. Cremophor1 EL). To date, nanoscale systems f...

Solubility of pllutonium in alkaline salt solutions

International Nuclear Information System (INIS)

Hobbs, D.T.; Edwards, T.B.

1993-01-01

Plutonium solubility data from several studies have been evaluated. For each data set, a predictive model has been developed where appropriate. In addition, a statistical model and corresponding prediction intervals for plutonium solubility as a quadratic function of the hydroxide concentration have been developed. Because of the wide range of solution compositions, the solubility of plutonium can vary by as much as three orders of magnitude for any given hydroxide concentration and still remain within the prediction interval. Any nuclear safety assessments that depend on the maximum amount of plutonium dissolved in alkaline salt solutions should use concentrations at least as great as the upper prediction limits developed in this study. To increase the confidence in the prediction model, it is recommended that additional solubility tests be conducted at low hydroxide concentrations and with all of the other solution components involved. To validate the model for application to actual waste solutions, it is recommended that the plutonium solubilities in actual waste solutions be determined and compared to the values predicted by the quadratic model

Enhancing the solubility and bioavailability of poorly water-soluble drugs using supercritical antisolvent (SAS) process.

Science.gov (United States)

Abuzar, Sharif Md; Hyun, Sang-Min; Kim, Jun-Hee; Park, Hee Jun; Kim, Min-Soo; Park, Jeong-Sook; Hwang, Sung-Joo

2018-03-01

Poor water solubility and poor bioavailability are problems with many pharmaceuticals. Increasing surface area by micronization is an effective strategy to overcome these problems, but conventional techniques often utilize solvents and harsh processing, which restricts their use. Newer, green technologies, such as supercritical fluid (SCF)-assisted particle formation, can produce solvent-free products under relatively mild conditions, offering many advantages over conventional methods. The antisolvent properties of the SCFs used for microparticle and nanoparticle formation have generated great interest in recent years, because the kinetics of the precipitation process and morphologies of the particles can be accurately controlled. The characteristics of the supercritical antisolvent (SAS) technique make it an ideal tool for enhancing the solubility and bioavailability of poorly water-soluble drugs. This review article focuses on SCFs and their properties, as well as the fundamentals of overcoming poorly water-soluble drug properties by micronization, crystal morphology control, and formation of composite solid dispersion nanoparticles with polymers and/or surfactants. This article also presents an overview of the main aspects of the SAS-assisted particle precipitation process, its mechanism, and parameters, as well as our own experiences, recent advances, and trends in development. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

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Sonam Choudhary

2017-05-01

Full Text Available Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.

L-dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer.

Science.gov (United States)

Koutalellis, Georgios; Stravodimos, Konstantinos; Avgeris, Margaritis; Mavridis, Konstantinos; Scorilas, Andreas; Lazaris, Andreas; Constantinides, Constantinos

2012-09-01

What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL. DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination

pH-metric solubility. 2: correlation between the acid-base titration and the saturation shake-flask solubility-pH methods.

Science.gov (United States)

Avdeef, A; Berger, C M; Brownell, C

2000-01-01

The objective of this study was to compare the results of a normal saturation shake-flask method to a new potentiometric acid-base titration method for determining the intrinsic solubility and the solubility-pH profiles of ionizable molecules, and to report the solubility constants determined by the latter technique. The solubility-pH profiles of twelve generic drugs (atenolol, diclofenac.Na, famotidine, flurbiprofen, furosemide, hydrochlorothiazide, ibuprofen, ketoprofen, labetolol.HCl, naproxen, phenytoin, and propranolol.HCl), with solubilities spanning over six orders of magnitude, were determined both by the new pH-metric method and by a traditional approach (24 hr shaking of saturated solutions, followed by filtration, then HPLC assaying with UV detection). The 212 separate saturation shake-flask solubility measurements and those derived from 65 potentiometric titrations agreed well. The analysis produced the correlation equation: log(1/S)titration = -0.063(+/- 0.032) + 1.025(+/- 0.011) log(1/S)shake-flask, s = 0.20, r2 = 0.978. The potentiometrically-derived intrinsic solubilities of the drugs were: atenolol 13.5 mg/mL, diclofenac.Na 0.82 microg/mL, famotidine 1.1 mg/ mL, flurbiprofen 10.6 microg/mL, furosemide 5.9 microg/mL, hydrochlorothiazide 0.70 mg/mL, ibuprofen 49 microg/mL, ketoprofen 118 microg/mL, labetolol.HCl 128 microg/mL, naproxen 14 microg/mL, phenytoin 19 microg/mL, and propranolol.HCl 70 microg/mL. The new potentiometric method was shown to be reliable for determining the solubility-pH profiles of uncharged ionizable drug substances. Its speed compared to conventional equilibrium measurements, its sound theoretical basis, its ability to generate the full solubility-pH profile from a single titration, and its dynamic range (currently estimated to be seven orders of magnitude) make the new pH-metric method an attractive addition to traditional approaches used by preformulation and development scientists. It may be useful even to discovery

The clinical significance of detecting serum glutamic acid decarboxylase antibody (GAD), C-peptide and insulin in diabetics

International Nuclear Information System (INIS)

Zheng Tingliang; Zhang Jinchi; Yao Yingfei; Chen Linxing; Huang Hua

2005-01-01

Objective: To explore the clinical significance of detecting serum glutamic acid decarboxylase (GAD) antibody, C-peptide (CP) and insulin (INS) in the classification of diabetic patients. Methods: Serum GAD antibody, CP and INS concentration were determined with RIA in 27 patients with type 1 diabetes mellitus (DM1) and 49 patients with type 2 diabetes mellitus (DM2). Sugar-electrode-method was used to detect the concentrations of fasting plasma glucose (FPG) in these patients. Results: The positive rate of GAD antibody in DM1 patients (66.7%) were significantly higher than that in DM2 group (8.2%) (P<0.01), The levels of CP and INS were lower in DM1 group than those in DM2 group as well (P<0.01). Conclusion: GAD antibody is a valuable marker to predict the impairment of β-cell GAD antibody levels, together with CP /FPG and INS/FPG ratios, might be useful in determining the type of DM and guiding the therapy. (authors)

Water Soluble Polymers for Pharmaceutical Applications

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Veeran Gowda Kadajji

2011-11-01

Full Text Available Advances in polymer science have led to the development of novel drug delivery systems. Some polymers are obtained from natural resources and then chemically modified for various applications, while others are chemically synthesized and used. A large number of natural and synthetic polymers are available. In the present paper, only water soluble polymers are described. They have been explained in two categories (1 synthetic and (2 natural. Drug polymer conjugates, block copolymers, hydrogels and other water soluble drug polymer complexes have also been explained. The general properties and applications of different water soluble polymers in the formulation of different dosage forms, novel delivery systems and biomedical applications will be discussed.

Solubility of actinides and surrogates in nuclear glasses

International Nuclear Information System (INIS)

Lopez, Ch.

2003-01-01

The nuclear wastes are currently incorporated in borosilicate glass matrices. The resulting glass must be perfectly homogeneous. The work discussed here is a study of actinide (thorium and plutonium) solubility in borosilicate glass, undertaken to assess the extent of actinide solubility in the glass and to understand the mechanisms controlling actinide solubilization. Glass specimens containing; actinide surrogates were used to prepare and optimize the fabrication of radioactive glass samples. These preliminary studies revealed that actinide Surrogates solubility in the glass was enhanced by controlling the processing temperature, the dissolution kinetic of the surrogate precursors, the glass composition and the oxidizing versus reducing conditions. The actinide solubility was investigated in the borosilicate glass. The evolution of thorium solubility in borosilicate glass was determined for temperatures ranging from 1200 deg C to 1400 deg C.Borosilicate glass specimens containing plutonium were fabricated. The experimental result showed that the plutonium solubility limit ranged from 1 to 2.5 wt% PuO 2 at 1200 deg C. A structural approach based on the determination of the local structure around actinides and their surrogates by EXAFS spectroscopy was used to determine their structural role in the glass and the nature of their bonding with the vitreous network. This approach revealed a correlation between the length of these bonds and the solubility of the actinides and their surrogates. (author)

Solubility limited radionuclide transport through geologic media

International Nuclear Information System (INIS)

Muraoka, Susumu; Iwamoto, Fumio; Pigford, T.H.

1980-11-01

Prior analyses for the migration of radionuclides neglect solubility limits of resolved radionuclide in geologic media. But actually some of the actinides may appear in chemical forms of very low solubility. In the present report we have proposed the migration model with no decay parents in which concentration of radionuclide is limited in concentration of solubility in ground water. In addition, the analytical solutions of the space-time-dependent concentration are presented in the case of step release, band release and exponential release. (author)

Molecular Thermodynamic Modeling of Mixed Solvent Solubility

DEFF Research Database (Denmark)

Ellegaard, Martin Dela; Abildskov, Jens; O’Connell, John P.

2010-01-01

A method based on statistical mechanical fluctuation solution theory for composition derivatives of activity coefficients is employed for estimating dilute solubilities of 11 solid pharmaceutical solutes in nearly 70 mixed aqueous and nonaqueous solvent systems. The solvent mixtures range from...... nearly ideal to strongly nonideal. The database covers a temperature range from 293 to 323 K. Comparisons with available data and other existing solubility methods show that the method successfully describes a variety of observed mixed solvent solubility behaviors using solute−solvent parameters from...

Solubility Products of M(II) - Carbonates

International Nuclear Information System (INIS)

Grauer, Rolf; Berner, Urs

1999-01-01

Many solubility data for M(II) carbonates commonly compiled in tables are contradictory and sometimes obviously wrong. The quality of such data has been evaluated based on the original publications and reliable solubility constants have been selected for the carbonates of Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb with the help of cross-comparisons. (author)

Biochemical identification of residues that discriminate between 3,4-dihydroxyphenylalanine decarboxylase and 3,4-dihydroxyphenylacetaldehyde synthase-mediated reactions.

Science.gov (United States)

Liang, Jing; Han, Qian; Ding, Haizhen; Li, Jianyong

2017-12-01

In available insect genomes, there are several L-3,4-dihydroxyphenylalanine (L-dopa) decarboxylase (DDC)-like or aromatic amino acid decarboxylase (AAAD) sequences. This contrasts to those of mammals whose genomes contain only one DDC. Our previous experiments established that two DDC-like proteins from Drosophila actually mediate a complicated decarboxylation-oxidative deamination process of dopa in the presence of oxygen, leading to the formation of 3,4-dihydroxyphenylacetaldehyde (DHPA), CO 2 , NH 3, and H 2 O 2 . This contrasts to the typical DDC-catalyzed reaction, which produces CO 2 and dopamine. These DDC-like proteins were arbitrarily named DHPA synthases based on their critical role in insect soft cuticle formation. Establishment of reactions catalyzed by these AAAD-like proteins solved a puzzle that perplexed researchers for years, but to tell a true DHPA synthase from a DDC in the insect AAAD family remains problematic due to high sequence similarity. In this study, we performed extensive structural and biochemical comparisons between DHPA synthase and DDC. These comparisons identified several target residues potentially dictating DDC-catalyzed and DHPA synthase-catalyzed reactions, respectively. Comparison of DHPA synthase homology models with crystal structures of typical DDC proteins, particularly residues in the active sites, provided further insights for the roles these identified target residues play. Subsequent site-directed mutagenesis of the tentative target residues and activity evaluations of their corresponding mutants determined that active site His192 and Asn192 are essential signature residues for DDC- and DHPA synthase-catalyzed reactions, respectively. Oxygen is required in DHPA synthase-mediated process and this oxidizing agent is reduced to H 2 O 2 in the process. Biochemical assessment established that H 2 O 2 , formed in DHPA synthase-mediated process, can be reused as oxidizing agent and this active oxygen species is reduced to H 2

Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs.

Science.gov (United States)

Lukyanov, Anatoly N; Torchilin, Vladimir P

2004-05-07

Polymeric micelles have a whole set of unique characteristics, which make them very promising drug carriers, in particular, for poorly soluble drugs. Our review article focuses on micelles prepared from conjugates of water-soluble polymers, such as polyethylene glycol (PEG) or polyvinyl pyrrolidone (PVP), with phospholipids or long-chain fatty acids. The preparation of micelles from certain polymer-lipid conjugates and the loading of these micelles with various poorly soluble anticancer agents are discussed. The data on the characterization of micellar preparations in terms of their morphology, stability, longevity in circulation, and ability to spontaneously accumulate in experimental tumors via the enhanced permeability and retention (EPR) effect are presented. The review also considers the preparation of targeted immunomicelles with specific antibodies attached to their surface. Available in vivo results on the efficiency of anticancer drugs incorporated into plain micelles and immunomicelles in animal models are also discussed.

Solubility of lithium deuteride in liquid lithium

International Nuclear Information System (INIS)

Veleckis, E.; Yonco, R.M.; Maroni, V.A.

1977-01-01

The solubility of LiD in liquid lithium between the eutectic and monotectic temperatures was measured using a direct sampling method. Solubilities were found to range from 0.0154 mol.% LiD at 199 0 C to 3.32 mol.% LiD at 498 0 C. The data were used in the derivation of an expression for the activity coefficient of LiD as a function of temperature and composition and an equation relating deuteride solubility and temperature, thus defining the liquidus curve. Similar equations were also derived for the Li-LiH system using the existing solubility data. Extrapolation of the liquidus curves yielded the eutectic concentrations (0.040 mol.% LiH and 0.035 mol.% LiD) and the freezing point depressions (0.23 0 C for Li-LiH and 0.20 0 C for Li-LiD) at the eutectic point. The results are compared with the literature data for hydrogen and deuterium. The implications of the relatively high solubility of hydrogen isotopes in lithium just above the melting point are discussed with respect to the cold trapping of tritium in fusion reactor blankets. (Auth.)

Thorium oxalate solubility and morphology

International Nuclear Information System (INIS)

Monson, P.R. Jr.; Hall, R.

1981-10-01

Thorium was used as a stand-in for studying the solubility and precipitation of neptunium and plutonium oxalates. Thorium oxalate solubility was determined over a range of 0.001 to 10.0 in the concentration parameter [H 2 C 2 O 4 ]/[HNO 3 ] 2 . Morphology of thorium oxide made from the oxalate precipitates was characterized by scanning electron microscopy. The different morphologies found for oxalate-lean and oxalate-rich precipitations were in agreement with predictions based on precipitation theory

The amorphous solid dispersion of the poorly soluble ABT-102 forms nano/microparticulate structures in aqueous medium: impact on solubility

Directory of Open Access Journals (Sweden)

Frank KJ

2012-11-01

Full Text Available Kerstin J Frank,1,3 Ulrich Westedt,2 Karin M Rosenblatt,2 Peter Hölig,2 Jörg Rosenberg,2 Markus Mägerlein,2 Gert Fricker,3 Martin Brandl11Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark; 2Abbott GmbH and Co. KG, Ludwigshafen, Germany; 3Department of Pharmaceutical Technology, University of Heidelberg, Heidelberg, GermanyAbstract: Amorphous solid dispersions (ASDs are a promising formulation approach for poorly soluble active pharmaceutical ingredients (APIs, because they ideally enhance both dissolution rate and solubility. However, the mechanism behind this is not understood in detail. In the present study, we investigated the supramolecular and the nano/microparticulate structures that emerge spontaneously upon dispersion of an ASD in aqueous medium and elucidated their influence on solubility. The ASD, prepared by hot melt extrusion, contained the poorly soluble ABT-102 (solubility in buffer, 0.05 µg/mL, a hydrophilic polymer, and three surfactants. The apparent solubility of ABT-102 from the ASD-formulation was enhanced up to 200 times in comparison to crystalline ABT-102. At the same time, the molecular solubility, as assessed by inverse equilibrium dialysis, was enhanced two times. Asymmetrical flow field-flow fractionation in combination with a multiangle light-scattering detector, an ultraviolet detector, and a refractometer enabled us to separate and identify the various supramolecular assemblies that were present in the aqueous dispersions of the API-free ASD (placebo and of binary/ternary blends of the ingredients. Thus, the supramolecular assemblies with a molar mass between 20,000 and 90,000 could be assigned to the polyvinylpyrrolidone/vinyl acetate 64, while two other kinds of assemblies were assigned to different surfactant assemblies (micelles. The amount of ABT-102 remaining associated with each of the assemblies upon fractionation was quantified offline with high

Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa

Science.gov (United States)

McCurtain, Jennifer L.; Gilbertsen, Adam J.; Kalstabakken, Kyle A.; Williams, Bryan J.

2018-01-01

A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled 13C5,15N4-agmatine (synthesized by decarboxylation of uniformly labeled 13C6,15N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,l,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1 % (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients. PMID:25957842

Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa.

Science.gov (United States)

Dalluge, Joseph J; McCurtain, Jennifer L; Gilbertsen, Adam J; Kalstabakken, Kyle A; Williams, Bryan J

2015-07-01

A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled (13)C5,(15)N4-agmatine (synthesized by decarboxylation of uniformly labeled (13)C6,(15)N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1% (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients.

Tetraphenylborate Solubility in High Ionic Strength Salt Solutions

International Nuclear Information System (INIS)

Serkiz, S.M.; Ginn, J.D.; Jurgensen, A.R.

1998-04-01

Solubility of sodium and potassium salts of the tetraphenylborate ion (TPB) in simulated Savannah River Site High Level Waste was investigated. Data generated from this study allow more accurate predictions of TPB solubility at the In-Tank Precipitation (ITP) facility. Because previous research showed large deviations in the observed solubility of TPB salts when compared with model predictions, additional data were generated to better understand the solubility of TPB in more complex systems of high ionic strength and those containing both potassium and sodium. These data allow evaluation of the ability of current models to accurately predict equilibrium TPB concentrations over the range of experimental conditions investigated in this study

Analysis of chemical concepts as the basic of virtual laboratory development and process science skills in solubility and solubility product subject

Science.gov (United States)

Syafrina, R.; Rohman, I.; Yuliani, G.

2018-05-01

This study aims to analyze the concept characteristics of solubility and solubility products that will serve as the basis for the development of virtual laboratory and students' science process skills. Characteristics of the analyzed concepts include concept definitions, concept attributes, and types of concepts. The concept analysis method uses concept analysis according to Herron. The results of the concept analysis show that there are twelve chemical concepts that become the prerequisite concept before studying the solubility and solubility and five core concepts that students must understand in the solubility and Solubility product. As many as 58.3% of the definitions of the concepts contained in high school textbooks support students' science process skills, the rest of the definition of the concept is memorized. Concept attributes that meet three levels of chemical representation and can be poured into a virtual laboratory have a percentage of 66.6%. Type of concept, 83.3% is a concept based on principle; and 16.6% concepts that state the process. Meanwhile, the science process skills that can be developed based on concept analysis are the ability to observe, calculate, measure, predict, interpret, hypothesize, apply, classify, and inference.

Solubility and stability of inorganic carbonates

International Nuclear Information System (INIS)

Taylor, P.

1987-01-01

The chemistry of inorganic carbonates is reviewed, with emphasis on solubility and hydrolytic stability, in order to identify candidate waste forms for immobilization and disposal of 14 C. At present, CaCO 3 and BaCO 3 are the two most widely favoured wasted forms, primarily because they are the products of proven CO 2 -scrubbing technology. However, they have relatively high solubilities in non-alkaline solutions, necessitating care in selecting and assessing an appropriate disposal environment. Three compounds with better solubility characteristics in near-neutral waters are identified: bismutite, (BiO) 2 CO 3 ; hydrocerussite, Pb 3 (OH) 2 (CO 3 ) 2 ; and rhodochrosite, MnCO 3 . Some of the limitations of each of these alternative waste forms are discussed

Differential retinoic acid inhibition of ornithine decarboxylase induction by 12-O-tetradecanoylphorbol-13-acetate and by germicidal ultraviolet light

International Nuclear Information System (INIS)

Lichti, U.; Patterson, E.; Hennings, H.; Yuspa, S.H.

1981-01-01

Several retinoids including retinoic acid effectively inhibit phorbol ester-mediated tumor promotion and ornithine decarboxylase (ODC) induction in mouse epidermis. To understand better the possible cellular site of action of retinoids, the inhibitory action of retinoic acid on the induction of ODC was compared for two distinctly different inducers, namely, 12-O-tetradecanoylphorbol-13-acetate (TPA) and germicidal ultraviolet light (uv), in primary mouse epidermal cell cultures. It was found that the induction of ODC by TPA is almost completely prevented by retinoic acid while the induction by uv is only moderately inhibited. The differential inhibition of enzyme induction cannot be accounted for by selective retinoid inhibition of DNA, RNA, or protein synthesis either alone or in concert with TPA or uv. These agents possibly act at transcription or translation, both of which are required for ODC induction by TPA or uv

Water-soluble resorcin[4]arene based cavitands

NARCIS (Netherlands)

Grote gansey, M.H.B.; Grote Gansey, Marcel H.B.; Bakker, Frank K.G.; Feiters, Martinus C.; Geurts, Hubertus P.M.; Verboom, Willem; Reinhoudt, David

1998-01-01

Water-soluble resorcin[4]arene based cavitands were obtained in good yields by reaction of bromomethylcavitands with pyridine. Their solubility was determined by conductometry. The behaviour in water depends on the alkyl chain length; the methylcavitand does not aggregate, whereas the pentyl- and

Ability of m-chloroperoxybenzoic acid to induce the ornithine decarboxylase marker of skin tumor promotion and inhibition of this response by gallotannins, oligomeric proanthocyanidins, and their monomeric units in mouse epidermis in Vivo

Science.gov (United States)

Guilan Chen; Elisabeth M. Perchellet; Xiao Mei Gao; Steven W. Newell; richard W. Hemingway; Vittorio Bottari; Jean-Pierre Perchellet

1995-01-01

m-Chloroperoxybenzoic acid (CPBA) was tested for its ability to induce the ornithine decarboxylase (ODC) marker of skin tumor promotion. In contrast to benzoyl peroxide, dicumyl peroxide, and 2-butanol peroxide, 5 mg of CPBA applied twice at a 72-h interval induce ODC activity at least as much as 3 ug of 12-O-tetradecanoylphorbol-13-acetate (TPA). ODC induction peaks...

Determination of water-soluble vitamins using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium salts.

Science.gov (United States)

Tsukatani, Tadayuki; Suenaga, Hikaru; Ishiyama, Munetaka; Ezoe, Takatoshi; Matsumoto, Kiyoshi

2011-07-15

A method for the determination of water-soluble vitamins using a colorimetric microbial viability assay based on the reduction of the tetrazolium salt {2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8)} via 2-methyl-1,4-napthoquinone (NQ) was developed. Measurement conditions were optimized for the microbiological determination of water-soluble vitamins, such as vitamin B(6), biotin, folic acid, niacin, and pantothenic acid, using microorganisms that have a water-soluble vitamin requirement. A linear relationship between absorbance and water-soluble vitamin concentration was obtained. The proposed method was applied to determine the concentration of vitamin B(6) in various foodstuffs. There was good agreement between vitamin B(6) concentrations determined after 24h using the WST-8 colorimetric method and those obtained after 48h using a conventional method. The results suggest that the WST-8 colorimetric assay is a useful method for the rapid determination of water-soluble vitamins in a 96-well microtiter plate. Copyright © 2011 Elsevier Ltd. All rights reserved.

Respiratory carcinogenicity assessment of soluble nickel compounds.

Science.gov (United States)

Oller, Adriana R

2002-10-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

Ornithine decarboxylase and extracellular polyamines regulate microvascular sprouting and actin cytoskeleton dynamics in endothelial cells

International Nuclear Information System (INIS)

Kucharzewska, Paulina; Welch, Johanna E.; Svensson, Katrin J.; Belting, Mattias

2010-01-01

The polyamines are essential for cancer cell proliferation during tumorigenesis. Targeted inhibition of ornithine decarboxylase (ODC), i.e. a key enzyme of polyamine biosynthesis, by α-difluoromethylornithine (DFMO) has shown anti-neoplastic activity in various experimental models. This activity has mainly been attributed to the anti-proliferative effect of DFMO in cancer cells. Here, we provide evidence that unperturbed ODC activity is a requirement for proper microvessel sprouting ex vivo as well as the migration of primary human endothelial cells. DFMO-mediated ODC inhibition was reversed by extracellular polyamine supplementation, showing that anti-angiogenic effects of DFMO were specifically related to polyamine levels. ODC inhibition was associated with an abnormal morphology of the actin cytoskeleton during cell spreading and migration. Moreover, our data suggest that de-regulated actin cytoskeleton dynamics in DFMO treated endothelial cells may be related to constitutive activation of the small GTPase CDC42, i.e. a well-known regulator of cell motility and actin cytoskeleton remodeling. These insights into the potential role of polyamines in angiogenesis should stimulate further studies testing the combined anti-tumor effect of polyamine inhibition and established anti-angiogenic therapies in vivo.

40 CFR Table 7 to Subpart Vvvvvv... - Partially Soluble HAP

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 14 2010-07-01 2010-07-01 false Partially Soluble HAP 7 Table 7 to... Pt. 63, Subpt. VVVVVV, Table 7 Table 7 to Subpart VVVVVV of Part 63—Partially Soluble HAP As required... partially soluble HAP listed in the following table. Partially soluble HAP name CAS No. 1. 1,1,1...

Enhanced Iron Solubility at Low pH in Global Aerosols

Directory of Open Access Journals (Sweden)

Ellery D. Ingall

2018-05-01

Full Text Available The composition and oxidation state of aerosol iron were examined using synchrotron-based iron near-edge X-ray absorption spectroscopy. By combining synchrotron-based techniques with water leachate analysis, impacts of oxidation state and mineralogy on aerosol iron solubility were assessed for samples taken from multiple locations in the Southern and the Atlantic Oceans; and also from Noida (India, Bermuda, and the Eastern Mediterranean (Crete. These sampling locations capture iron-containing aerosols from different source regions with varying marine, mineral dust, and anthropogenic influences. Across all locations, pH had the dominating influence on aerosol iron solubility. When aerosol samples were approximately neutral pH, iron solubility was on average 3.4%; when samples were below pH 4, the iron solubility increased to 35%. This observed aerosol iron solubility profile is consistent with thermodynamic predictions for the solubility of Fe(III oxides, the major iron containing phase in the aerosol samples. Source regions and transport paths were also important factors affecting iron solubility, as samples originating from or passing over populated regions tended to contain more soluble iron. Although the acidity appears to affect aerosol iron solubility globally, a direct relationship for all samples is confounded by factors such as anthropogenic influence, aerosol buffer capacity, mineralogy and physical processes.

Solubility Part 1

NARCIS (Netherlands)

Tantra, Ratna; Bolea, Eduardo; Bouwmeester, H.; Rey-Castro, Carlos; David, C.A.A.; Dogné, Jean Michel; Laborda, Francisco; Laloy, Julie; Robinson, Kenneth N.; Undas, A.K.; Zande, van der M.

2016-01-01

This chapter gives an overview of different methods that can potentially be used to determine the solubility of nanomaterials. In general, the methods presented can be broadly divided into four categories: separation methods, methods to quantify free ions, methods to quantify total dissolved

Molybdenum solubility in aluminium nitrate solutions

Energy Technology Data Exchange (ETDEWEB)

Heres, X.; Sans, D.; Bertrand, M.; Eysseric, C. [CEA, Centre de Marcoule, Nuclear Energy Division, DRCP, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Brackx, E.; Domenger, R.; Excoffier, E. [CEA, Centre de Marcoule, Nuclear Energy Division, DTEC, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Valery, J.F. [AREVA-NC, DOR/RDP, Paris - La Defense (France)

2016-07-01

For over 60 years, research reactors (RR or RTR for research testing reactors) have been used as neutron sources for research, radioisotope production ({sup 99}Mo/{sup 99m}Tc), nuclear medicine, materials characterization, etc... Currently, over 240 of these reactors are in operation in 56 countries. They are simpler than power reactors and operate at lower temperature (cooled to below 100 C. degrees). The fuel assemblies are typically plates or cylinders of uranium alloy and aluminium (U-Al) coated with pure aluminium. These fuels can be processed in AREVA La Hague plant after batch dissolution in concentrated nitric acid and mixing with UOX fuel streams. The aim of this study is to accurately measure the solubility of molybdenum in nitric acid solution containing high concentrations of aluminium. The higher the molybdenum solubility is, the more flexible reprocessing operations are, especially when the spent fuels contain high amounts of molybdenum. To be most representative of the dissolution process, uranium-molybdenum alloy and molybdenum metal powder were dissolved in solutions of aluminium nitrate at the nominal dissolution temperature. The experiments showed complete dissolution of metallic elements after 30 minutes long stirring, even if molybdenum metal was added in excess. After an induction period, a slow precipitation of molybdic acid occurs for about 15 hours. The data obtained show the molybdenum solubility decreases with increasing aluminium concentration. The solubility law follows an exponential relation around 40 g/L of aluminium with a high determination coefficient. Molybdenum solubility is not impacted by the presence of gadolinium, or by an increasing concentration of uranium. (authors)

Nucleotide variation at the dopa decarboxylase (Ddc) gene in natural populations of Drosophila melanogaster.

Science.gov (United States)

Tatarenkov, Andrey; Ayala, Francisco J

2007-08-01

We studied nucleotide sequence variation at the gene coding for dopa decarboxylase (Ddc) in seven populations of Drosophila melanogaster. Strength and pattern of linkage disequilibrium are somewhat distinct in the extensively sampled Spanish and Raleigh populations. In the Spanish population, a few sites are in strong positive association, whereas a large number of sites in the Raleigh population are associated nonrandomly but the association is not strong. Linkage disequilibrium analysis shows presence of two groups of haplotypes in the populations, each of which is fairly diverged, suggesting epistasis or inversion polymorphism. There is evidence of two forms of natural selection acting on Ddc. The McDonald-Kreitman test indicates a deficit of fixed amino acid differences between D. melanogaster and D. simulans, which may be due to negative selection. An excess of derived alleles at high frequency, significant according to the H-test, is consistent with the effect of hitchhiking. The hitchhiking may have been caused by directional selection downstream of the locus studied, as suggested by a gradual decrease of the polymorphism-to-divergence ratio. Altogether, the Ddc locus exhibits a complicated pattern of variation apparently due to several evolutionary forces. Such a complex pattern may be a result of an unusually high density of functionally important genes.

Residual nilpotence and residual solubility of groups

International Nuclear Information System (INIS)

Mikhailov, R V

2005-01-01

The properties of the residual nilpotence and the residual solubility of groups are studied. The main objects under investigation are the class of residually nilpotent groups such that each central extension of these groups is also residually nilpotent and the class of residually soluble groups such that each Abelian extension of these groups is residually soluble. Various examples of groups not belonging to these classes are constructed by homological methods and methods of the theory of modules over group rings. Several applications of the theory under consideration are presented and problems concerning the residual nilpotence of one-relator groups are considered.

Radionuclide solubilities at elevated temperatures. A literature study

International Nuclear Information System (INIS)

Carlsson, T.; Vuorinen, U.

1997-07-01

This literature study contains experimental data and modelling data collected in order to illustrate how temperature affects radionuclide solubilities under conditions similar to those expected in the vicinity of a planned repository for spent nuclear fuel. The elements considered were Ni, Se, Zr, Tc, Pd, Sn, Ra, Th, Pa, U, Np, Pu and Am. The temperatures of main interest are restricted to the interval between room temperature and 100 deg C. The study showed that the literature on radionuclide solubility at temperatures above room temperature is scarce. Therefore, also work that refers to conditions slightly varying from the expected repository conditions has been considered. A minor modelling exercise was done in this study in order to show the effect of temperature on the solubilities of Ni, Np and U under various conditions. The results from the literature survey and our modelling demonstrate the complexity of groundwater systems and the difficulty in finding simple and general relationships between temperature and radionuclide solubilities. Often an increase in temperature (below 100 deg C) leads to a reduction of the radionuclide solubility or leaves it roughly unchanged. However, examples are also found where the rise in temperature increases the radionuclide solubility by several orders of magnitude. (orig.)

Radionuclide solubilities at elevated temperatures. A literature study

Energy Technology Data Exchange (ETDEWEB)

Carlsson, T.; Vuorinen, U. [Technical Research Centre of Finland, Espoo (Finland)

1997-07-01

This literature study contains experimental data and modelling data collected in order to illustrate how temperature affects radionuclide solubilities under conditions similar to those expected in the vicinity of a planned repository for spent nuclear fuel. The elements considered were Ni, Se, Zr, Tc, Pd, Sn, Ra, Th, Pa, U, Np, Pu and Am. The temperatures of main interest are restricted to the interval between room temperature and 100 deg C. The study showed that the literature on radionuclide solubility at temperatures above room temperature is scarce. Therefore, also work that refers to conditions slightly varying from the expected repository conditions has been considered. A minor modelling exercise was done in this study in order to show the effect of temperature on the solubilities of Ni, Np and U under various conditions. The results from the literature survey and our modelling demonstrate the complexity of groundwater systems and the difficulty in finding simple and general relationships between temperature and radionuclide solubilities. Often an increase in temperature (below 100 deg C) leads to a reduction of the radionuclide solubility or leaves it roughly unchanged. However, examples are also found where the rise in temperature increases the radionuclide solubility by several orders of magnitude. (orig.). 54 refs.

Feasibility study of SMART core with soluble boron

International Nuclear Information System (INIS)

Kim, Kang Seog; Lee, Chung Chan; Zee, Sung Quun

2000-11-01

The excess reactivity of SMART core without soluble boron is effectively controlled by 49 CEDM. We suggest another method to control the core excess reactivity using both the checkerboard type of 25 CEDM and soluble boron and perform a feasibility calculation. The soluble boron operation is categorized into the on-line and the off-line mechanisms. The former is to successively control the boron concentration according to the excess reactivity during operation and the latter is to add and change some soluble boron during refueling and repairing. Since the on-line soluble boron control system of SMART is conceptually identical to that of the commercial pressurized water reactor, we did not perform the analysis. Since the soluble boron in the complete off-line system increases the moderator temperature coefficient, the reactivity defect between hot and cold moderator temperature is decreased. However, the decrease of the reactivity is not big to satisfy the core reactivity limits. When using 25 CEDM, the possible mechanism is to control the excess reactivity by both control rod and on-line boron control mechanism between cold and hot zero power and by only control rod at hot full power. We selected the loading pattern satisfying the requirement in the view of nuclear design

In vitro dynamic solubility test: influence of various parameters.

Science.gov (United States)

Thélohan, S; de Meringo, A

1994-10-01

This article discusses the dissolution of mineral fibers in simulated physiological fluids (SPF), and the parameters that affect the solubility measurement in a dynamic test where an SPF runs through a cell containing fibers (Scholze and Conradt test). Solutions simulate either the extracellular fluid (pH 7.6) or the intracellular fluid (pH 4.5). The fibers have various chemical compositions and are either continuously drawn or processed as wool. The fiber solubility is determined by the amount of SiO2 (and occasionally other ions) released in the solution. Results are stated as percentage of the initial silica content released or as dissolution rate v in nm/day. The reproducibility of the test is higher with the less soluble fibers (10% solubility), than with highly soluble fibers (20% solubility). The influence of test parameters, including SPF, test duration, and surface area/volume (SA/V), has been studied. The pH and the inorganic buffer salts have a major influence: industrial glasswool composition is soluble at pH 7.6 but not at pH 4.5. The opposite is true for rock- (basalt) wool composition. For slightly soluble fibers, the dissolution rate v remains constant with time, whereas for highly soluble fibers, the dissolution rate decreases rapidly. The dissolution rates believed to occur are v1, initial dissolution rate, and v2, dissolution rate of the residual fibers. The SA of fibers varies with the mass of the fibers tested, or with the fiber diameter at equal mass. Volume, V, is the chosen flow rate. An increase in the SA/V ratio leads to a decrease in the dissolution rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of aqueous solubility of TODGA using group contribution method

International Nuclear Information System (INIS)

Balasubramonian, S.; Kumar, Shekhar; Sampath, M.; Sivakumar, D.; Kamachi Mudali, U.

2017-01-01

The aqueous solubility of N, N, N', N'-tetraoctyl-3-oxapentanediamide normally referred as TODGA is experimentally measured. The aqueous solubility was also predicted using Marrero and Gani group contribution method. The modification of original Marrero and Gani method was proposed to accurately predict TODGA solubility. The predicted solubility of TODGA using original Marrero and Gani method, Modified Marrero and Gani method and UNIFAC Model was compared. The predicted solubility of TODGA using modified Marrero and Gani method is 0.0237 g/l against the experimentally measured value of 0.0226 g/l. (author)

On nitrogen solubility in water

International Nuclear Information System (INIS)

Kalajda, Yu.A.; Katkov, Yu.D.; Kuznetsov, V.A.; Lastovtsev, A.Yu.; Lastochkin, A.P.; Susoev, V.S.

1980-01-01

Presented are the results of experimental investigations on nitrogen solubility in water under 0-15 MPa pressure, at the temperature of 100-340 deg C and nitrogen concentration of 0-5000 n.ml. N 2 /kg H 2 O. Empiric equations are derived and a diagram of nitrogen solubility in water is developed on the basis of the experimental data, as well as critically evaluated published data. The investigation results can be used in analyzing water-gas regime of a primary heat carrier in stream-generating plants with water-water reactors

A framework for API solubility modelling

DEFF Research Database (Denmark)

Conte, Elisa; Gani, Rafiqul; Crafts, Peter

. In addition, most of the models are not predictive and requires experimental data for the calculation of the needed parameters. This work aims at developing an efficient framework for the solubility modelling of Active Pharmaceutical Ingredients (API) in water and organic solvents. With this framework......-SAFT) are used for solubility calculations when the needed interaction parameters or experimental data are available. The CI-UNIFAC is instead used when the previous models lack interaction parameters or when solubility data are not available. A new GC+ model for APIs solvent selection based...... on the hydrophobicity, hydrophilicity and polarity information of the API and solvent is also developed, for performing fast solvent selection and screening. Eventually, all the previous developments are integrated in a framework for their efficient and integrated use. Two case studies are presented: the first...

The solubility of metals in Pb-17Li liquid alloy

International Nuclear Information System (INIS)

Borgstedt, H.U.; Feuerstein, H.

1992-01-01

The solubility data of iron in the eutectic alloy Pb-17Li which were evaluated from corrosion tests in a turbulent flow of the molten alloy are discussed in the frame of solubilities of the transition metals in liquid lead. It is shown that the solubility of iron in the alloy is close to that in lead. This is also the fact for several other alloying elements of steels. A comparison of all known data shows that they are in agreement with generally shown trends for the solubility of the transition metals in low melting metals. These trends indicate comparably high solubilities of nickel and manganese in the liquid metals, lower saturation concentration of vanadium, chromium, iron, and cobalt, and extremely low solubility of molybdenum. (orig.)

Solubility Study of Curatives in Various Rubbers

NARCIS (Netherlands)

Guo, R.; Talma, Auke; Datta, Rabin; Dierkes, Wilma K.; Noordermeer, Jacobus W.M.

2008-01-01

The previous works on solubility of curatives in rubbers were mainly carried out in natural rubber. Not too much information available on dissimilar rubbers and this is important because most of the compounds today are blends of dissimilar rubbers. Although solubility can be expected to certain

Characterization of soluble protein BCP 11/24 from bovine corneal epithelium, different from the principal soluble protein BCP 54

NARCIS (Netherlands)

Bakker, C.; Pasmans, S.; Verhagen, C.; van Haren, M.; van der Gaag, R.; Hoekzema, R.

1992-01-01

The water-soluble fraction of bovine corneal epithelium was analysed by polyacrylamide gel electrophoresis in the presence of SDS (SDS-PAGE). Next to the principal soluble protein BCP 54, which has recently been identified as a corneal aldehyde dehydrogenase (ALDH), another abundant protein was

Progress in the research of neptunium solubility

International Nuclear Information System (INIS)

Jiang Tao; Liu Yongye; Yao Jun

2012-01-01

237 Np is considered a possible long-term potential threat for environment, because of its long half-life, high toxicity and its mobile nature under aerobic conditions due to the high chemical stability of its pentavalent state. Therefore 237 Np is considered as one of high-level radioactive waste and need to be disposed in deep geologic disposal repository. The dissolution behavior is an important aspect of migration research. The solubility is considered very important for high level waste geological disposal safety and environmental evaluation. The solubility determines the maximum concentration of the discharge, and then it is initial concentration of the radionuclides migration to the environment. The solubility impact directly on radionuclides migration in host rock, and can be used to predict the concentration and speciation of radionuclides in groundwater around disposal sites many years later. This paper focused on research results of the solubility, some proposals for Np dissolution chemistry research were also been suggested. (authors)

On barium oxide solubility in barium-containing chloride melts

International Nuclear Information System (INIS)

Nikolaeva, Elena V.; Zakiryanova, Irina D.; Bovet, Andrey L.; Korzun, Iraida V.

2016-01-01

Oxide solubility in chloride melts depends on temperature and composition of molten solvent. The solubility of barium oxide in the solvents with barium chloride content is essentially higher than that in molten alkali chlorides. Spectral data demonstrate the existence of oxychloride ionic groupings in such melts. This work presents the results of the BaO solubility in two molten BaCl 2 -NaCl systems with different barium chloride content. The received data together with earlier published results revealed the main regularities of BaO solubility in molten BaO-BaCl 2 -MCl systems.

The solubilities and solubility products of zirconium hydroxide and oxide after aging at 278, 313, and 333 K

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Taishi; Uemura, Takuya; Sasaki, Takayuki; Takagi, Ikuji [Kyoto Univ. (Japan). Dept. of Nuclear Engineering; Moriyama, Hirotake [Kyoto Univ. (Japan). Research Reactor Inst.

2016-07-01

The solubilities of zirconium hydroxide and oxide after aging at 278, 313, and 333 K were measured at 278, 298, 313, and 333 K in the pH{sub c} range of 0.3-7 in a 0.5 M ionic strength solution of NaClO{sub 4} and HClO{sub 4}. Size distributions of the colloidal species were investigated by ultrafiltration using membranes with different pore sizes, and the solid phases were examined by X-ray diffraction. The apparent solubility of zirconium amorphous hydroxide (Zr(OH){sub 4}(am)), prepared by the oversaturation method, decreased with increasing aging temperature (T{sub a}), and the size distributions obtained after aging at elevated temperatures indicated the growth of the colloidal species. We, therefore, suggested that agglomeration of the colloidal species and dehydration and crystallization of Zr(OH){sub 4}(am) as the solubility-limiting solid phase occurred over the course of aging at elevated temperatures. For sample solutions of the crystalline oxide (ZrO{sub 2}(cr)), the aging temperature had no significant effect on the solubility, but the solubility data at lower temperatures were found to be slightly higher than those at higher temperatures, implying a small fraction of the amorphous components. In the analysis of different solid phases (Zr(OH){sub 4}(s,T{sub a}), T{sub a} = 278, 313, and 333 K) depending on the aging temperatures, the solubility products (K{sub sp}, T{sub a}) were determined at different measurement temperatures, and the enthalpy change (Δ{sub r}H {sup circle}) for Zr{sup 4+} 4OH{sup -} <=> Zr(OH){sub 4}(s,T{sub a}) was calculated using the van't Hoff equation. The solid-phase-transformation process at elevated temperatures was also analyzed based on the obtained K{sub sp}, T{sub a} and Δ{sub r}H {sup circle} values.

Three new hydrochlorothiazide cocrystals: Structural analyses and solubility studies

Science.gov (United States)

Ranjan, Subham; Devarapalli, Ramesh; Kundu, Sudeshna; Vangala, Venu R.; Ghosh, Animesh; Reddy, C. Malla

2017-04-01

Hydrochlorothiazide (HCT) is a diuretic BCS class IV drug with poor aqueous solubility and low permeability leading to poor oral absorption. The present work explores the cocrystallization technique to enhance the aqueous solubility of HCT. Three new cocrystals of HCT with water soluble coformers phenazine (PHEN), 4-dimethylaminopyridine (DMAP) and picolinamide (PICA) were prepared successfully by solution crystallization method and characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), fourier transform -infraredspectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Structural characterization revealed that the cocrystals with PHEN, DMAP and PICA exists in P21/n, P21/c and P21/n space groups, respectively. The improved solubility of HCT-DMAP (4 fold) and HCT-PHEN (1.4 fold) cocrystals whereas decreased solubility of HCT-PICA (0.5 fold) as compared to the free drug were determined after 4 h in phosphate buffer, pH 7.4, at 25 °C by using shaking flask method. HCT-DMAP showed a significant increase in solubility than all previously reported cocrystals of HCT suggest the role of a coformer. The study demonstrates that the selection of coformer could have pronounced impact on the physicochemical properties of HCT and cocrystallization can be a promising approach to improve aqueous solubility of drugs.

Solubility of Meloxicam in Mixed Solvent Systems | Babu | Ethiopian ...

African Journals Online (AJOL)

The solubility of meloxicam is higher in phosphate buffer (pH 7.4) compared to water, probably due to ionization of the drug. The solubility of meloxicam is marginally enhanced in surfactant systems (Tween 80 and Brij 35) at concentrations higher than cmc, proving the micellar solubilization. Meloxicam solubility studies in ...

Solubility of inorganic salts in pure ionic liquids

International Nuclear Information System (INIS)

Pereiro, A.B.; Araújo, J.M.M.; Oliveira, F.S.; Esperança, J.M.S.S.; Canongia Lopes, J.N.; Marrucho, I.M.; Rebelo, L.P.N.

2012-01-01

Highlights: ► We report the solubility of different conventional salts in several ionic liquids. ► The solubility was initially screened using a visual detection method. ► The most promising mixtures were quantitatively re-measured using an ATR–FTIR. - Abstract: The solubility of different conventional salts in several room-temperature ionic liquids – containing ammonium, phosphonium or imidazolium cations combined with acetate, sulfate, sulfonate, thiocyanate, chloride, tetracyano-borate, tris(pentafluoroethyl)trifluoro-phosphate, L-lactate, bis(trifluoromethylsulfonyl)imide or trifluoromethylsulfonate anions – were screened using a visual detection method. The most promising mixtures were then re-measured using an ATR–FTIR (Attenuated Total Reflection Fourier Transform Infra Red) spectroscopy technique in order to accurately and quantitatively determine the corresponding solubility at 298.15 K.

Measurement and correlation of solubility of carbon dioxide in triglycerides

International Nuclear Information System (INIS)

Howlader, Md Shamim; French, William Todd; Toghiani, Hossein; Hartenbower, Ben; Pearson, Larry; DuBien, Janice; Rai, Neeraj

2017-01-01

Graphical abstract: Comparison of experimental results with correlation for solubility of CO 2 in triglycerides as a function pressure at two different temperatures of 289.15 and 303.15 K, respectively. - Highlights: • New pressure drop gas apparatus was developed to determine the solubility of gases in liquids. • Solubility of CO 2 in triglycerides was measured at different temperatures and pressures. • Experimental solubility data were correlated using three thermodynamic models. • Enthalpy, entropy and Gibbs energy of dissolution for CO 2 -triglyceride were determined. - Abstract: A new pressure drop solubility gas apparatus was developed to determine the solubility of carbon dioxide in canola oil, a triglyceride consisting primarily of oleic, linoleic, and alpha linoleic acid radicals. Solubility of CO 2 in triglycerides was determined at different temperatures (283.2–303.2 K) and pressures (600–2450 kPa). It was found that the solubility of CO 2 in triglycerides is higher than that of pure water because triglycerides lack strong hydrogen bond networks that exist in liquid water at the ambient conditions. The experimental solubility was correlated using Krichevsky–Kasarnovsky (KK), Mather-Jou (MJ), and Carvalho-Coutinho (CC) correlations. We find that KK and MJ equations can predict the solubility with higher accuracy. The enthalpy and entropy of absorption of CO 2 were calculated using the van’t Hoff plot and were found to be −7.165 kJ.mol −1 , and −28.791 J.mol −1 .K −1 , respectively.

Thermodynamic data development using the solubility method (Joint research)

International Nuclear Information System (INIS)

Rai, Dhanpat; Yui, Mikazu

2013-05-01

The solubility method is one of the most powerful tools to obtain reliable thermodynamic data for 1) solubility products of discrete solids and double salts, 2) complexation constants for various ligands, 3) development of data in a wide range of pH values, 4) evaluation of data for metals that form very insoluble solids (e.g. tetravalent actinides), 5) determining solubility-controlling solids in different types of wastes and 6) elevated temperatures for redox sensitive systems. This document is focused on describing various aspects of obtaining thermodynamic data using the solubility method. This manuscript deals with various aspects of conducting solubility studies, including selecting the study topic, modeling to define important variables, selecting the range of variables and experimental parameters, anticipating results, general equipment requirements, conducting experiments, and interpreting experimental data. (author)

Solubility of corrosion products in high temperature water

International Nuclear Information System (INIS)

Srinivasan, M.P.; Narasimhan, S.V.

1995-01-01

A short review of solubility of corrosion products at high temperature in either neutral or alkaline water as encountered in BWR, PHWR and PWR primary coolant reactor circuits is presented in this report. Based on the available literature, various experimental techniques involved in the study of the solubility, theory for fitting the solubility data to the thermodynamic model and discussion of the published results with a scope for future work have been brought out. (author). 17 refs., 7 figs

The Hildebrand solubility parameters of ionic liquids-part 2.

Science.gov (United States)

Marciniak, Andrzej

2011-01-01

The Hildebrand solubility parameters have been calculated for eight ionic liquids. Retention data from the inverse gas chromatography measurements of the activity coefficients at infinite dilution were used for the calculation. From the solubility parameters, the enthalpies of vaporization of ionic liquids were estimated. Results are compared with solubility parameters estimated by different methods.

Lower glutamic acid decarboxylase 65-kDa isoform messenger RNA and protein levels in the prefrontal cortex in schizoaffective disorder but not schizophrenia.

Science.gov (United States)

Glausier, Jill R; Kimoto, Sohei; Fish, Kenneth N; Lewis, David A

2015-01-15

Altered gamma-aminobutyric acid (GABA) signaling in the prefrontal cortex (PFC) has been associated with cognitive dysfunction in patients with schizophrenia and schizoaffective disorder. Levels of the GABA-synthesizing enzyme glutamic acid decarboxylase 67-kDa isoform (GAD67) in the PFC have been consistently reported to be lower in patients with these disorders, but the status of the second GABA-synthesizing enzyme, glutamic acid decarboxylase 65-kDa isoform (GAD65), remains unclear. GAD65 messenger RNA (mRNA) levels were quantified in PFC area 9 by quantitative polymerase chain reaction from 62 subjects with schizophrenia or schizoaffective disorder and 62 matched healthy comparison subjects. In a subset of subject pairs, GAD65 relative protein levels were quantified by confocal immunofluorescence microscopy. Mean GAD65 mRNA levels were 13.6% lower in subjects with schizoaffective disorder but did not differ in subjects with schizophrenia relative to their matched healthy comparison subjects. In the subjects with schizoaffective disorder, mean GAD65 protein levels were 19.4% lower and were correlated with GAD65 mRNA levels. Lower GAD65 mRNA and protein levels within subjects with schizoaffective disorder were not attributable to factors commonly comorbid with the diagnosis. In concert with previous studies, these findings suggest that schizoaffective disorder is associated with lower levels of both GAD65 and GAD67 mRNA and protein in the PFC, whereas subjects with schizophrenia have lower mean levels of only GAD67 mRNA and protein. Because cognitive function is generally better preserved in patients with schizoaffective disorder relative to patients with schizophrenia, these findings may support an interpretation that GAD65 downregulation provides a homeostatic response complementary to GAD67 downregulation that serves to reduce inhibition in the face of lower PFC network activity. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc

Sensitivity analysis of uranium solubility under strongly oxidizing conditions

International Nuclear Information System (INIS)

Liu, L.; Neretnieks, I.

1999-01-01

To evaluate the effect of geochemical conditions in the repository on the solubility of uranium under strongly oxidizing conditions, a mathematical model has been developed to determine the solubility, by utilizing a set of nonlinear algebraic equations to describe the chemical equilibria in the groundwater environment. The model takes into account the predominant precipitation-dissolution reactions, hydrolysis reactions and complexation reactions that may occur under strongly oxidizing conditions. The model also includes the solubility-limiting solids induced by the presence of carbonate, phosphate, silicate, calcium, and sodium in the groundwater. The thermodynamic equilibrium constants used in the solubility calculations are essentially taken from the NEA Thermochemical Data Base of Uranium, with some modification and some uranium minerals added, such as soddyite, rutherfordite, uranophane, uranyl orthophosphate, and becquerelite. By applying this model, the sensitivities of uranium solubility to variations in the concentrations of various groundwater component species are systematically investigated. The results show that the total analytical concentrations of carbonate, phosphate, silicate, and calcium in deep groundwater play the most important role in determining the solubility of uranium under strongly oxidizing conditions

Soluble L-selectin levels predict survival in sepsis

DEFF Research Database (Denmark)

Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

2002-01-01

To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis.......To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis....

Scoring function to predict solubility mutagenesis

Directory of Open Access Journals (Sweden)

Deutsch Christopher

2010-10-01

Full Text Available Abstract Background Mutagenesis is commonly used to engineer proteins with desirable properties not present in the wild type (WT protein, such as increased or decreased stability, reactivity, or solubility. Experimentalists often have to choose a small subset of mutations from a large number of candidates to obtain the desired change, and computational techniques are invaluable to make the choices. While several such methods have been proposed to predict stability and reactivity mutagenesis, solubility has not received much attention. Results We use concepts from computational geometry to define a three body scoring function that predicts the change in protein solubility due to mutations. The scoring function captures both sequence and structure information. By exploring the literature, we have assembled a substantial database of 137 single- and multiple-point solubility mutations. Our database is the largest such collection with structural information known so far. We optimize the scoring function using linear programming (LP methods to derive its weights based on training. Starting with default values of 1, we find weights in the range [0,2] so that predictions of increase or decrease in solubility are optimized. We compare the LP method to the standard machine learning techniques of support vector machines (SVM and the Lasso. Using statistics for leave-one-out (LOO, 10-fold, and 3-fold cross validations (CV for training and prediction, we demonstrate that the LP method performs the best overall. For the LOOCV, the LP method has an overall accuracy of 81%. Availability Executables of programs, tables of weights, and datasets of mutants are available from the following web page: http://www.wsu.edu/~kbala/OptSolMut.html.

Hansen Solubility Parameters for Octahedral Oligomeric Silsesquioxanes

Science.gov (United States)

2012-08-28

1997, 80, 386-&. 5. Hansen, C. M. The three-dimensional solubility parameter -- key to paint component affinities I. J. Paint Technol. 1967, 39, 104...Chai, J.; Zhang, Q. X.; Han, D. X.; Niu, L. Synthesis and Application of Widely Soluble Graphene Sheets. Langmuir 2010, 26, 12314-12320. 12. Hansen, C

A Colorful Solubility Exercise for Organic Chemistry

Science.gov (United States)

Shugrue, Christopher R.; Mentzen, Hans H., II; Linton, Brian R.

2015-01-01

A discovery chemistry laboratory has been developed for the introductory organic chemistry student to investigate the concepts of polarity, miscibility, solubility, and density. The simple procedure takes advantage of the solubility of two colored dyes in a series of solvents or solvent mixtures, and the diffusion of colors can be easily…

The Hildebrand Solubility Parameters of Ionic Liquids—Part 2

Science.gov (United States)

Marciniak, Andrzej

2011-01-01

The Hildebrand solubility parameters have been calculated for eight ionic liquids. Retention data from the inverse gas chromatography measurements of the activity coefficients at infinite dilution were used for the calculation. From the solubility parameters, the enthalpies of vaporization of ionic liquids were estimated. Results are compared with solubility parameters estimated by different methods. PMID:21747694

The Hildebrand Solubility Parameters of Ionic Liquids—Part 2

Directory of Open Access Journals (Sweden)

Andrzej Marciniak

2011-06-01

Full Text Available The Hildebrand solubility parameters have been calculated for eight ionic liquids. Retention data from the inverse gas chromatography measurements of the activity coefficients at infinite dilution were used for the calculation. From the solubility parameters, the enthalpies of vaporization of ionic liquids were estimated. Results are compared with solubility parameters estimated by different methods.

Exposure of Atlantic salmon parr (Salmo salar) to a combination of resin acids and a water soluble fraction of diesel fuel oil: A model to investigate the chemical causes of pigmented salmon syndrome

International Nuclear Information System (INIS)

Croce, B.; Scottish Environmental Protection Agency, Aberdeen; Stagg, R.M.

1997-01-01

Pigmented salmon syndrome is a pollutant-induced hemolytic anemia and hyperbilirubinemia. As part of an investigation of this condition, S2 Atlantic salmon parr (Salmo salar) were exposed to a diesel fuel oil, water soluble fraction (WSF) in combination with a mixture of three resin acids (isopimaric, dehydroabietic, and abietic acids) in a continuous-flow freshwater system. The total nominal concentrations of resin acids in the exposure tanks were 10, 50, and 100 microg/L; the diesel WSF was generated in situ and provided a mean hydrocarbon concentration of 2.0 ± 0.1 mg/L (n = 12) during the 9-d exposure period. Exposure to the diesel WSF alone depressed liver bilirubin UDP-glucuronosyl transferase (UDPGT) activity and induced phenol UDPGT activity. Exposure to the diesel WSF in the absence or presence of resin acids induced liver cytochrome P4501A and increased the concentrations in the plasma of the enzymes lactate dehydrogenase, alkaline phosphatase, and glutamic oxaloacetic transaminase. The combined exposure to diesel WSF with either 50 or 100 microg/L total resin acid caused significant elevations in the concentrations of bilirubin in the plasma and many of these fish had yellow pigmentation on the ventral surface and around the gill arches. The results demonstrate that exposure to combinations of two groups of contaminants can result in the manifestation of toxic effects not apparent from exposure to either of these chemicals in isolation

X-radiation effect on soluble proteins of gastric mucosa

International Nuclear Information System (INIS)

Sukhomlinov, B.F.; Chajka, Ya.P.; Fedorovich, A.N.

1979-01-01

Using the method of electrophoresis in agar gel soluble proteins of gastric mucosa of rats were separated into 11 fractions. Proteins posessing a proteolytic (pH 1.8) and lipase (pH 7.4) activity were localized within the second and third prealbumin fractions. Soluble proteins of gastric mucosa contain glyco- and lipoproteid complexes. Exposure of rats to 1000 R of X-rays induces quantitative redistribution within the electrophoretic spectrum of soluble proteins and a considerable disturbance of the proteolytic activity of total soluble proteins throughout the entire period of observation (from 10 min to 72h)

Soluble Molecularly Imprinted Nanorods for Homogeneous Molecular Recognition

Directory of Open Access Journals (Sweden)

Rongning Liang

2018-03-01

Full Text Available Nowadays, it is still difficult for molecularly imprinted polymers (MIPs to achieve homogeneous recognition since they cannot be easily dissolved in organic or aqueous phase. To address this issue, soluble molecularly imprinted nanorods have been synthesized by using soluble polyaniline doped with a functionalized organic protonic acid as the polymer matrix. By employing 1-naphthoic acid as a model, the proposed imprinted nanorods exhibit an excellent solubility and good homogeneous recognition ability. The imprinting factor for the soluble imprinted nanoroads is 6.8. The equilibrium dissociation constant and the apparent maximum number of the proposed imprinted nanorods are 248.5 μM and 22.1 μmol/g, respectively. We believe that such imprinted nanorods may provide an appealing substitute for natural receptors in homogeneous recognition related fields.

Soluble Molecularly Imprinted Nanorods for Homogeneous Molecular Recognition

Science.gov (United States)

Liang, Rongning; Wang, Tiantian; Zhang, Huan; Yao, Ruiqing; Qin, Wei

2018-03-01

Nowadays, it is still difficult for molecularly imprinted polymer (MIPs) to achieve homogeneous recognition since they cannot be easily dissolved in organic or aqueous phase. To address this issue, soluble molecularly imprinted nanorods have been synthesized by using soluble polyaniline doped with a functionalized organic protonic acid as the polymer matrix. By employing 1-naphthoic acid as a model, the proposed imprinted nanorods exhibit an excellent solubility and good homogeneous recognition ability. The imprinting factor for the soluble imprinted nanoroads is 6.8. The equilibrium dissociation constant and the apparent maximum number of the proposed imprinted nanorods are 248.5 μM and 22.1 μmol/g, respectively. We believe that such imprinted nanorods may provide an appealing substitute for natural receptors in homogeneous recognition related fields.

Review on theoretical calculation of the magnetite solubility

International Nuclear Information System (INIS)

Kim, Myongjin; Kim, Hongpyo

2013-01-01

FAC is influenced by many factors such as water chemistry (temperature, pH, dissolved oxygen (D. O.) in a solution, and etc.), chemical composition of carbon steel, and fluid dynamics. Magnetite is formed at the inner surface of carbon steel, and protects the integrity of pipes from the damage. The magnetite has a stable state at each equilibrium condition, so that it can be dissolved into the fluid under conditions that satisfy the equilibrium state. The iron solubility can be calculated by considering the reaction equilibrium constants for prediction of a change in the magnetite layer. In the present work, studies on the magnetite solubility were reviewed for the theoretical calculation of magnetite, and iron solubility data were compared to find the proper solubility values of each study

Association of the −243A>G, +61450C>A Polymorphisms of the Glutamate Decarboxylase 2 (GAD2) Gene with Obesity and Insu¬lin Level in North Indian Population

OpenAIRE

Jai PRAKASH; Balraj MITTAL; Shally AWASTHI; Neena SRIVASTAVA

2016-01-01

Background: Obesity associated with type 2 diabetes, and hypertension increased mortality and morbidity. Glutamate decarboxylase 2 (GAD2) gene is associated with obesity and it regulate food intake and insulin level. We investigated the association of GAD-2gene −243A>G (rs2236418) and +61450C>A (rs992990) polymorphisms with obesity and related phenotypes.Methods: Insulin, glucose and lipid levels were estimated using standard protocols. All subjects were genotyped (PCR-RFLP) method.Resu...

Soluble Non-ammonia Nitrogen in Ruminal and Omasal Digesta of Korean Native Steers Supplemented with Soluble Proteins

Directory of Open Access Journals (Sweden)

C. W. Choi

2012-09-01

Full Text Available An experiment was conducted to study the effect of soluble protein supplements on concentration of soluble non-ammonia nitrogen (SNAN in the liquid phase of ruminal (RD and omasal digesta (OD of Korean native steers, and to investigate diurnal pattern in SNAN concentration in RD and OD. Three ruminally cannulated Korean native steers in a 3×3 Latin square design consumed a basal diet of rice straw and corn-based concentrate (control, and that supplemented (kg/d DM basis with intact casein (0.24; IC or acid hydrolyzed casein (0.46; AHC. Ruminal digesta was sampled using a vacuum pump, whereas OD was collected using an omasal sampling system at 2.0 h intervals after a morning feeding. The SNAN fractions (free amino acid (AA, peptide and soluble protein in RD and OD were assessed using the ninhydrin assay. Concentrations of free AA and total SNAN in RD were significantly (p<0.05 lower than those in OD. Although free AA concentration was relatively high, mean peptide was quantitatively the most important fraction of total SNAN in both RD and OD, indicating that degradation of peptide to AA rather than hydrolysis of soluble protein to peptide or deamination may be the most limiting step in rumen proteolysis of Korean native steers. Diurnal variation in peptide concentration in OD for the soluble protein supplemented diets during the feeding cycle peaked 2 h post-feeding and decreased thereafter whereas that for the control was relatively constant during the entire feeding cycle. Diurnal variation in peptide concentration was rather similar between RD and OD.

Mesomere-derived glutamate decarboxylase-expressing blastocoelar mesenchyme cells of sea urchin larvae

Directory of Open Access Journals (Sweden)

Hideki Katow

2013-12-01

The ontogenetic origin of blastocoelar glutamate decarboxylase (GAD-expressing cells (GADCs in larvae of the sea urchin Hemicentrotus pulcherrimus was elucidated. Whole-mount in situ hybridisation (WISH detected transcription of the gene that encodes GAD in H. pulcherrimus (Hp-gad in unfertilised eggs and all blastomeres in morulae. However, at and after the swimming blastula stage, the transcript accumulation was particularly prominent in clumps of ectodermal cells throughout the embryonic surface. During the gastrula stage, the transcripts also accumulated in the endomesoderm and certain blastocoelar cells. Consistent with the increasing number of Hp-gad transcribing cells, immunoblot analysis indicated that the relative abundance of Hp-Gad increased considerably from the early gastrula stage until the prism stage. The expression pattern of GADCs determined by immunohistochemistry was identical to the pattern of Hp-gad transcript accumulation determined using WISH. In early gastrulae, GADCs formed blastocoelar cell aggregates around the blastopore with primary mesenchyme cells. The increase in the number of blastocoelar GADCs was inversely proportional to the number of ectodermal GADCs ranging from a few percent of total GADCs in early gastrulae to 80% in late prism larvae; this depended on ingression of ectodermal GADCs into the blastocoel. Some of the blastocoelar GADCs were fluorescein-positive in the larvae that developed from the 16-cell stage chimeric embryos; these comprised fluorescein-labeled mesomeres and unlabelled macromeres and micromeres. Our finding indicates that some of the blastocoelar GADCs are derived from the mesomeres and thus they are the new group of mesenchyme cells, the tertiary mesenchyme cells.

SITE-94. Radionuclide solubilities for SITE-94

Energy Technology Data Exchange (ETDEWEB)

Arthur, R.; Apted, M. [QuantiSci, Denver, CO (United States)

1996-12-01

In this report, solubility constraints are evaluated on radioelement source-term concentrations supporting the SITE-94 performance assessment. Solubility models are based on heterogeneous-equilibrium, mass- and charge-balance constraints incorporated into the EQ3/6 geochemical software package, which is used to calculate the aqueous speciation behavior and solubilities of U, Th, Pu, Np, Am, Ni, Ra, Se, Sn, Sr, Tc and Zr in site groundwaters and near-field solutions. The chemical evolution of the near field is approximated using EQ3/6 in terms of limiting conditions at equilibrium, or steady state, in three closed systems representing fully saturated bentonite, Fe{sup o} corrosion products of the canister, and spent fuel. The calculations consider both low-temperature (15 deg C) and high-temperature (80 deg C) conditions in the near field, and the existence of either reducing or strongly oxidizing conditions in each of the bentonite, canister, and spent-fuel barriers. Heterogeneities in site characteristics are evaluated through consideration of a range of initial groundwaters and their interactions with engineered barriers. Aqueous speciation models for many radioelements are constrained by thermodynamic data that are estimated with varying degrees of accuracy. An important question, however, is how accurate do these models need to be for purposes of estimating source-term concentrations? For example, it is unrealistic to expect a high degree of accuracy in speciation models if such models predict solubilities that are below the analytical detection limit for a given radioelement. From a practical standpoint, such models are irrelevant if calculated solubilities cannot be tested by direct comparison to experimental data. In the absence of models that are both accurate and relevant for conditions of interest, the detection limit could define a pragmatic upper limit on radioelement solubility 56 refs, 25 tabs, 10 figs

SITE-94. Radionuclide solubilities for SITE-94

International Nuclear Information System (INIS)

Arthur, R.; Apted, M.

1996-12-01

In this report, solubility constraints are evaluated on radioelement source-term concentrations supporting the SITE-94 performance assessment. Solubility models are based on heterogeneous-equilibrium, mass- and charge-balance constraints incorporated into the EQ3/6 geochemical software package, which is used to calculate the aqueous speciation behavior and solubilities of U, Th, Pu, Np, Am, Ni, Ra, Se, Sn, Sr, Tc and Zr in site groundwaters and near-field solutions. The chemical evolution of the near field is approximated using EQ3/6 in terms of limiting conditions at equilibrium, or steady state, in three closed systems representing fully saturated bentonite, Fe o corrosion products of the canister, and spent fuel. The calculations consider both low-temperature (15 deg C) and high-temperature (80 deg C) conditions in the near field, and the existence of either reducing or strongly oxidizing conditions in each of the bentonite, canister, and spent-fuel barriers. Heterogeneities in site characteristics are evaluated through consideration of a range of initial groundwaters and their interactions with engineered barriers. Aqueous speciation models for many radioelements are constrained by thermodynamic data that are estimated with varying degrees of accuracy. An important question, however, is how accurate do these models need to be for purposes of estimating source-term concentrations? For example, it is unrealistic to expect a high degree of accuracy in speciation models if such models predict solubilities that are below the analytical detection limit for a given radioelement. From a practical standpoint, such models are irrelevant if calculated solubilities cannot be tested by direct comparison to experimental data. In the absence of models that are both accurate and relevant for conditions of interest, the detection limit could define a pragmatic upper limit on radioelement solubility

Iron solubility in highly boron-doped silicon

International Nuclear Information System (INIS)

McHugo, S.A.; McDonald, R.J.; Smith, A.R.; Hurley, D.L.; Weber, E.R.

1998-01-01

We have directly measured the solubility of iron in high and low boron-doped silicon using instrumental neutron activation analysis. Iron solubilities were measured at 800, 900, 1000, and 1100thinsp degree C in silicon doped with either 1.5x10 19 or 6.5x10 14 thinspboronthinspatoms/cm 3 . We have measured a greater iron solubility in high boron-doped silicon as compared to low boron-doped silicon, however, the degree of enhancement is lower than anticipated at temperatures >800thinsp degree C. The decreased enhancement is explained by a shift in the iron donor energy level towards the valence band at elevated temperatures. Based on this data, we have calculated the position of the iron donor level in the silicon band gap at elevated temperatures. We incorporate the iron energy level shift in calculations of iron solubility in silicon over a wide range of temperatures and boron-doping levels, providing a means to accurately predict iron segregation between high and low boron-doped silicon. copyright 1998 American Institute of Physics

Soluble CD163

DEFF Research Database (Denmark)

Møller, Holger J

2012-01-01

CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function o...

New and highly sensitive assay for L-5-hydroxytryptophan decarboxylase activity by high-performance liquid chromatography-voltammetry.

Science.gov (United States)

Rahman, M K; Nagatsu, T; Kato, T

1980-12-12

This paper describes a new, inexpensive and highly sensitive assay for aromatic L-amino acid decarboxylase (AADC) activity, using L-5-hydroxytryptophan (L-5-HTP) as substrate, in rat and human brains and serum by high-performance liquid chromatography (HPLC) with voltammetric detection. L-5-HTP was used as substrate and D-5-HTP for the blank. After isolating serotonin (5-HT) formed enzymatically from L-5-HTP on a small Amberlite CG-50 column, the 5-HT was eluted with hydrochloric acid and assayed by HPLC with a voltammetric detector. N-Methyldopamine was added to each incubation mixture as an internal standard. This method is sensitive enough to measure 5-HT, formed by the enzyme, 100 fmol to 140 pmol or more. An advantage of this method is that one can incubate the enzyme for longer time (up to 150 min), as compared with AADC assay using L-DOPA as substrate, resulting in a very high sensitivity. By using this new method, AADC activity was discovered in rat serum.

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

Directory of Open Access Journals (Sweden)

Jing Lin

2017-12-01

Full Text Available Self-renewing tumor-initiating cells (TICs are thought to be responsible for tumor recurrence and chemo-resistance. Glycine decarboxylase, encoded by the GLDC gene, is reported to be overexpressed in TIC-enriched primary non-small-cell lung carcinoma (NSCLC. GLDC is a component of the mitochondrial glycine cleavage system, and its high expression is required for growth and tumorigenic capacity. Currently, there are no therapeutic agents against GLDC. As a therapeutic strategy, we have designed and tested splicing-modulating steric hindrance antisense oligonucleotides (shAONs that efficiently induce exon skipping (half maximal inhibitory concentration [IC50] at 3.5–7 nM, disrupt the open reading frame (ORF of GLDC transcript (predisposing it for nonsense-mediated decay, halt cell proliferation, and prevent colony formation in both A549 cells and TIC-enriched NSCLC tumor sphere cells (TS32. One candidate shAON causes 60% inhibition of tumor growth in mice transplanted with TS32. Thus, our shAONs candidates can effectively inhibit the expression of NSCLC-associated metabolic enzyme GLDC and may have promising therapeutic implications.

Solubilities of boric acid in heavy water

International Nuclear Information System (INIS)

Nakai, Shigetsugu; Aoi, Hideki; Hayashi, Ken-ichi; Katoh, Taizo; Watanabe, Takashi.

1988-01-01

A gravimetric analysis using meta-boric acid (HBO 2 or DBO 2 ) as a weighing form has been developed for solubility measurement. The method gave satisfactory results in preliminary measurement of solubilities of boric acid in light water. By using this method, the solubilities of 10 B enriched D 3 BO 3 in heavy water were measured. The results are as follows; 2.67 (7deg C), 3.52 (15deg C), 5.70 (30deg C), 8.87 (50deg C) and 12.92 (70deg C) w/o, respectively. These values are about 10% lower than those in light water. Thermodynamical consideration based on the data shows that boric acid is the water structure breaker. (author)

Solubility Products of M(II) - Carbonates

Energy Technology Data Exchange (ETDEWEB)

Grauer, Rolf; Berner, Urs [ed.

1999-01-01

Many solubility data for M(II) carbonates commonly compiled in tables are contradictory and sometimes obviously wrong. The quality of such data has been evaluated based on the original publications and reliable solubility constants have been selected for the carbonates of Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb with the help of cross-comparisons. (author) translated from a PSI internal report written in German in 1994 (TM-44-94-05). 5 figs., 1 tab., 68 refs.

Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes.

Science.gov (United States)

Ali, Md Ashraf; Kataoka, Noriko; Ranneh, Abdul-Hackam; Iwao, Yasunori; Noguchi, Shuji; Oka, Toshihiko; Itai, Shigeru

2017-01-01

Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI- and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, -13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, -12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NI-loaded and blank cubosomes existed in the cubic space group Im3̄m. The lattice parameters of the SPI- and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI- and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.

Solubility of iron in liquid lead

International Nuclear Information System (INIS)

Ali-Khan, I.

1981-01-01

The use of liquid lead in high temperature chemical and metallurgical processes is well known. The structural materials applied for the containment of these processes are either iron base alloys or possess iron as an alloying element. Besides that, lead itself is alloyed in some steels to achieve some very useful properties. For understanding the effect of liquid lead in such structural materials, it is important to determine the solubility of iron in liquid lead which would also be indicative of the stability of these alloys. At the institute of reactor materials of KFA Juelich, investigations have been conducted to determine the solubility of iron in liquid lead up to a temperature of about 1000 0 C. In this presentation the data concerning the solubility of iron in liquid lead are brought up to date and discussed including the results of our previous investigations. (orig.)

pH-potentiometric determination of solubility of barely soluble organic extracting agents in water and aqueous solutions of neutral salts

International Nuclear Information System (INIS)

Pavlovskaya, E.M.; Charykov, A.K.; Tikhomirov, V.I.

1977-01-01

A pH-potentiometric method has been used to estimate the solubility of chloroform, benzene and nitrobenzene in water. The desalting effect is studied of alkali metal chlorides on chloroform solubility to establish the following phenomenological series of alkali metal cations by their desalting action: Li + + + + + . The non-conformity of chloroform solubility values in water-isoactive solutions of different salts is indicative of the high specificity of desalting processes with respect to the chemical nature of the desalting cation. Salt effects also essentially depend on the chemical nature of the desalted substance, particularly on its acid-base properties

Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid.

Science.gov (United States)

Yuvaraja, K; Khanam, Jasmina

2014-08-05

Aim of the present work is to enhance aqueous solubility of carvedilol (CV) by solid dispersion technique using wide variety of carriers such as: β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD), tartaric acid (TA), polyvinyl pyrrolidone K-30 (PVP K-30) and poloxamer-407 (PLX-407). Various products of 'CV-solid dispersion' had been studied extensively in various pH conditions to check enhancement of solubility and dissolution characteristics of carvedilol. Any physical change upon interaction between CV and carriers was confirmed by instrumental analysis: XRD, DSC, FTIR and SEM. Negative change of Gibb's free energy and complexation constants (Kc, 75-240M(-1), for cyclodextrins and 1111-20,365M(-1), for PVP K-30 and PLX-407) were the evidence of stable nature of the binding between CV and carriers. 'Solubility enhancement factor' of ionized-CV was found high enough (340 times) with HPβCD in presence of TA. TA increases the binding efficiency of cyclodextrin and changing the pH of microenvironment in dissolution medium. In addition, ionization process was used to increase the apparent intrinsic solubility of drug. In vitro, dissolution time of CV was remarkably reduced in the solid dispersion system compared to that of pure drug. This may be attributed to increased wettability, dispersing ability and transformation of crystalline state of drug to amorphous one. Copyright © 2014 Elsevier B.V. All rights reserved.

Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells.

Science.gov (United States)

Persson, H; Pelto-Huikko, M; Metsis, M; Söder, O; Brene, S; Skog, S; Hökfelt, T; Ritzén, E M

1990-09-01

The gene encoding glutamic acid decarboxylase (GAD), the key enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid, is shown to be expressed in the testis of several different species. Nucleotide sequence analysis of a cDNA clone isolated from the human testis confirmed the presence of GAD mRNA in the testis. The major GAD mRNA in the testis was 2.5 kilobases. Smaller amounts of a 3.7-kilobase mRNA with the same size as GAD mRNA in the brain was also detected in the testis. In situ hybridization using a GAD-specific probe revealed GAD mRNA expressing spermatocytes and spermatids located in the middle part of rat seminiferous tubules. Studies on the ontogeny of GAD mRNA expression showed low levels of GAD mRNA in testes of prepubertal rats, with increasing levels as sexual maturation is reached, compatible with GAD mRNA expression in germ cells. In agreement with this, fractionation of cells from the rat seminiferous epithelium followed by Northern (RNA) blot analysis showed the highest levels of GAD mRNA associated with spermatocytes and spermatids. Evidence for the presence of GAD protein in the rat testis was obtained from the demonstration of GAD-like immunoreactivity in seminiferous tubules, predominantly at a position where spermatids and spermatozoa are found. Furthermore, GAD-like immunoreactivity was seen in the midpiece of ejaculated human spermatozoa, the part that is responsible for generating energy for spermatozoan motility.

Influence of milling process on efavirenz solubility

Directory of Open Access Journals (Sweden)

Erizal Zaini

2017-01-01

Full Text Available Introduction: The aim of this study was to investigate the influence of the milling process on the solubility of efavirenz. Materials and Methods: Milling process was done using Nanomilling for 30, 60, and 180 min. Intact and milled efavirenz were characterized by powder X-ray diffraction, scanning electron microscopy (SEM, spectroscopy infrared (IR, differential scanning calorimetry (DSC, and solubility test. Results: The X-ray diffractogram showed a decline on peak intensity of milled efavirenz compared to intact efavirenz. The SEM graph depicted the change from crystalline to amorphous habit after milling process. The IR spectrum showed there was no difference between intact and milled efavirenz. Thermal analysis which performed by DSC showed a reduction on endothermic peak after milling process which related to decreasing of crystallinity. Solubility test of intact and milled efavirenz was conducted in distilled water free CO2with 0.25% sodium lauryl sulfate media and measured using high-performance liquid chromatography method with acetonitrile: distilled water (80:20 as mobile phases. The solubility was significantly increased (P < 0.05 after milling processes, which the intact efavirenz was 27.12 ± 2.05, while the milled efavirenz for 30, 60, and 180 min were 75.53 ± 1.59, 82.34 ± 1.23, and 104.75 ± 0.96 μg/mL, respectively. Conclusions: Based on the results, the solubility of efavirenz improved after milling process.

Hydrogen solubility in FLiNaK mixed with titanium powder

International Nuclear Information System (INIS)

Yagi, Juro; Sagara, Akio; Watanabe, Takashi; Tanaka, Teruya; Takayama, Sadatsugu; Muroga, Takeo

2015-01-01

Highlights: • The hydrogen solubility in a FLiNaK mixed with Ti powder was investigated. • A significant increase in hydrogen solubility was observed. • Controlling the purity of the molten salt was found to be one of the key issues. • A vanadium alloy would be compatible with the Ti powder/molten salt mixture. - Abstract: The hydrogen solubility in a FLiNaK molten salt mixed with Ti powder was investigated. A hydrogen-soluble metal powder mixed with a molten salt can increase the effective hydrogen solubility of the molten salt, which is currently a major disadvantage of molten salts. A significant increase in hydrogen solubility was observed, even with a mass fraction of Ti powder of only 0.1 wt%. The increase of hydrogen solubility was so large that a vanadium alloy would be compatible with the Ti powder/molten salt mixture, unlike typical molten salts that result in an unacceptably large tritium inventory in the vanadium alloy. In addition, contamination of the Ti powder by oxidation suppressed the hydrogen uptake and release capability. Controlling the purity of the molten salt was found to be one of the key issues for the metal powder mixture concept.

Solubility and dissolution improvement of ketoprofen by emulsification ionic gelation

Science.gov (United States)

Rachmaniar, Revika; Tristiyanti, Deby; Hamdani, Syarif; Afifah

2018-02-01

Ketoprofen or [2-(3-benzoylphenyl) propionic acid] is non-steroidal anti-inflammatory (NSAID) and an analgesic which has high permeability and low solubility. The purpose of this work was to improve the solubility and dissolution of poorly water-soluble ketoprofen prepared by emulsification ionic gelation method and utilizing polymer (chitosan) and cross linker (tripolyphosphate, TPP) for particles formulation. The results show that increasing pH value of TPP, higher solubility and dissolution of as-prepared ketoprofen-chitosan was obtained. The solubility in water of ketoprofen-chitosan with pH 6 for TPP increased 2.71-fold compared to untreated ketoprofen. While the dissolution of ketoprofen-chitosan with pH 6 of TPP in simulated gastric fluid without enzyme (0.1 N HCl), pH 4.5 buffer and simulated intestinal fluid without enzyme (phosphate buffer pH 6.8) was increased 1.9-fold, 1.6-fold and 1.2-fold compared to untreated ketoprofen for dissolution time of 30 minutes, respectively. It could be concluded that chitosan and TPP in the emulsification ionic gelation method for ketoprofen preparation effectively increases solubility and dissolution of poorly water-soluble ketoprofen.

Hydrodistillation-adsorption method for the isolation of water-soluble, non-soluble and high volatile compounds from plant materials.

Science.gov (United States)

Mastelić, J; Jerković, I; Blazević, I; Radonić, A; Krstulović, L

2008-08-15

Proposed method of hydrodistillation-adsorption (HDA) on activated carbon and hydrodistillation (HD) with solvent trap were compared for the isolation of water-soluble, non-soluble and high volatile compounds, such as acids, monoterpenes, isothiocyanates and others from carob (Certonia siliqua L.), rosemary (Rosmarinus officinalis L.) and rocket (Eruca sativa L.). Isolated volatiles were analyzed by GC and GC/MS. The main advantages of HDA method over ubiquitous HD method were higher yields of volatile compounds and their simultaneous separation in three fractions that enabled more detail analyses. This method is particularly suitable for the isolation and analysis of the plant volatiles with high amounts of water-soluble compounds. In distinction from previously published adsorption of remaining volatile compounds from distillation water on activated carbon, this method offers simultaneous hydrodistillation and adsorption in the same apparatus.

Preliminary considerations concerning actinide solubilities

International Nuclear Information System (INIS)

Newton, T.W.; Bayhurst, B.P.; Daniels, W.R.; Erdal, B.R.; Ogard, A.E.

1980-01-01

Work at the Los Alamos Scientific Laboratory on the fundamental solution chemistry of the actinides has thus far been confined to preliminary considerations of the problems involved in developing an understanding of the precipitation and dissolution behavior of actinide compounds under environmental conditions. Attempts have been made to calculate solubility as a function of Eh and pH using the appropriate thermodynamic data; results have been presented in terms of contour maps showing lines of constant solubility as a function of Eh and pH. Possible methods of control of the redox potential of rock-groundwater systems by the use of Eh buffers (redox couples) is presented

Transcriptional response to deletion of the phosphatidylserine decarboxylase Psd1p in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Gsell, Martina; Mascher, Gerald; Schuiki, Irmgard; Ploier, Birgit; Hrastnik, Claudia; Daum, Günther

2013-01-01

In the yeast, Saccharomyces cerevisiae, the synthesis of the essential phospholipid phosphatidylethanolamine (PE) is accomplished by a network of reactions which comprises four different pathways. The enzyme contributing most to PE formation is the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) which catalyzes conversion of phosphatidylserine (PS) to PE. To study the genome wide effect of an unbalanced cellular and mitochondrial PE level and in particular the contribution of Psd1p to this depletion we performed a DNA microarray analysis with a ∆psd1 deletion mutant. This approach revealed that 54 yeast genes were significantly up-regulated in the absence of PSD1 compared to wild type. Surprisingly, marked down-regulation of genes was not observed. A number of different cellular processes in different subcellular compartments were affected in a ∆psd1 mutant. Deletion mutants bearing defects in all 54 candidate genes, respectively, were analyzed for their growth phenotype and their phospholipid profile. Only three mutants, namely ∆gpm2, ∆gph1 and ∆rsb1, were affected in one of these parameters. The possible link of these mutations to PE deficiency and PSD1 deletion is discussed.

Histidine decarboxylase knockout mice, a genetic model of Tourette syndrome, show repetitive grooming after induced fear.

Science.gov (United States)

Xu, Meiyu; Li, Lina; Ohtsu, Hiroshi; Pittenger, Christopher

2015-05-19

Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene histidine decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d-amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48h after it had been paired with a shock. During the 30min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ornithine decarboxylase activity in rat organs and tissues under artificial hypobiosis.

Science.gov (United States)

Aksyonova, G E; Logvinovich, O S; Fialkovskaya, L A; Afanasyev, V N; Ignat'ev, D A; Kolomiytseva, I K

2010-09-01

The influence of hypothermia-hypoxia-hypercapnia on ornithine decarboxylase (ODC, EC 4.1.1.17) activities in rat organs and tissues and also on the thymocyte distribution throughout the cell cycle stages was studied. The state of artificial hypobiosis in rats on decrease in the body temperature to 14.4-18.0°C during 3.0-3.5 h was accompanied by drops in the ODC activities in the neocortex and liver by 50-60% and in rapidly proliferating tissues (thymus, spleen, and small intestine mucosa) by 80% of the control value. In kidneys the ODC activity raised to 200% of the control level. Twenty-four hours after termination of the cooling and replacing the rats under the standard conditions, the ODC activities in the neocortex, liver, kidneys, spleen, and intestinal mucosa returned to the control values, but remained decreased in the thymus. Forty-eight hours later the ODC activities in the thymus and spleen exceeded the normal level. The distribution of thymocytes throughout the cell cycle stages did not change in rats in the state of hypothermia (hypobiosis); 24 and 48 h after termination of the cooling the fraction of thymocytes in the S stage was decreased and the fraction of the cells in the G(0)+G(1) stage was increased. The normal distribution of thymocytes throughout the cell cycle stages recovered in 72 h. Thus, in the thymus the diminution of the ODC activity preceded the suppression of the cell proliferation rate. The tissue-specific changes in the ODC activity are suggested to reflect adaptive changes in the functional and proliferative activities of organs and tissues during the development of hypobiosis under conditions of hypothermia-hypoxia-hypercapnia.

Catalytic properties of the archaeal S-adenosylmethionine decarboxylase from Methanococcus jannaschii.

Science.gov (United States)

Lu, Zichun J; Markham, George D

2004-01-02

S-Adenosylmethionine decarboxylase (AdoMetDC) is a pyruvoyl cofactor-dependent enzyme that participates in polyamine biosynthesis. AdoMetDC from the Archaea Methanococcus jannaschii is a prototype for a recently discovered class that is not homologous to the eucaryotic enzymes or to a distinct group of microbial enzymes. M. jannaschii AdoMetDC has a Km of 95 microm and the turnover number (kcat) of 0.0075 s(-1) at pH 7.5 and 22 degrees C. The turnover number increased approximately 38-fold at a more physiological temperature of 80 degrees C. AdoMetDC was inactivated by treatment with the imine reductant NaCNBH3 only in the presence of substrate. Mass spectrometry of the inactivated protein showed modification solely of the pyruvoyl-containing subunit, with a mass increase corresponding to reduction of a Schiff base adduct with decarboxylated AdoMet. The presteady state time course of the AdoMetDC reaction revealed a burst of product formation; thus, a step after CO2 formation is rate-limiting in turnover. Comparable D2O kinetic isotope effects of were seen on the first turnover (1.9) and on kcat/Km (1.6); there was not a significant D2O isotope effect on kcat, suggesting that product release is rate-limiting in turnover. The pH dependence of the steady state rate showed participation of acid and basic groups with pK values of 5.3 and 8.2 for kcat and 6.5 and 8.3 for kcat/Km, respectively. The competitive inhibitor methylglyoxal bis(guanylhydrazone) binds at a single site per (alphabeta) heterodimer. UV spectroscopic studies show that methylglyoxal bis(guanylhydrazone) binds as the dication with a 23 microm dissociation constant. Studies with substrate analogs show a high specificity for AdoMet.

Research activities for measurement of hydrogen solubility in LiPb

International Nuclear Information System (INIS)

Katayama, K.; Edao, Y.; Fukada, S.

2014-01-01

Research activities for measurement of hydrogen solubility in LiPb has been conducted under the U.S.-Japan TITAN collaboration program at STAR facility in Idaho National Laboratory. The solubility test using a quartz crucible has been tried at 300degC but the crack had been caused at about 15 hours after temperature reached 300degC. This is caused by chemical reaction of LLE and SiO_2. Hydrogen solubility and apparent diffusivity has been estimated from data obtained by solubility tests using alumina crucible by fitting method assuming one dimensional diffusion. The estimated solubility in the range from 300degC to 500degC is close to Reiter's one. However, the value of solubility increased sharply at 600degC. This seemed to be caused by chemical reaction of LLE and Al_2O_3. The estimated diffusivity was two orders of magnitude larger than literature data. This large difference may be due to natural convection of LLE in the alumina crucible. (author)

Total and soluble oxalate content of some Indian spices.

Science.gov (United States)

Ghosh Das, Sumana; Savage, G P

2012-06-01

Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.

Synthesis gas solubility in Fischer-Tropsch slurry: Final report

Energy Technology Data Exchange (ETDEWEB)

Chao, K.C.; Lin, H.M.

1988-01-01

The objective is to investigate the phase equilibrium behavior of synthesis gases and products in a Fischer-Tropsch slurry reactor. A semi-flow apparatus has been designed and constructed for this purpose. Measurements have been made for hydrogen, cabon monoxide, methane, ethane, ethylene, and carbon dioxide in a heavy n-paraffin at temperatures from 100 to 300)degree)C and pressures 10 to 50 atm. Three n-paraffin waxes: n-eicosane (n-C/sub 20/), n-octacosane )n-C/sub 28/), and n-hexatriacontane (n-C/sub 36/), were studied to model the industrial wax. Solubility of synthesis gas mixtures of H/sub 2/ and CO in n-C/sub 28/ was also determined at two temperatures (200 and 300)degree)C) for each of three gas compositions (40.01, 50.01, and 66.64 mol%) of hydrogen). Measurements were extended to investigate the gas solubility in two industrial Fischer-Tropsch waxes: Mobilwax and SASOL wax. Observed solubility increases in the order: H/sub 2/, CO, CH/sub 4/, CO/sub 2/, C/sub 2/H/sub 4/, C/sub 2/H/sub 6/, at a given temperature pressure, and in the same solvent. Solubility increases with increasing pressure for all the gases. Lighter gases H/sub 2/ and CO show increased solubility with increasing temperature, while the heavier gases CO/sub 2/, ethane, and ethylene show decreased solubility with increasing temperature. The solubility of methane, the intermediate gas, changes little with temperature, and shows a shallow minimum at about 200)degrees)C or somewhat above. Henry's constant and partial molal volume of the gas solute at infinite dilution are determinedfrom the gas solubility data. A correlation is developed from the experimental data in the form on an equation of state. A computer program has been prepared to implement the correlation. 19 refs., 66 figs., 39 tabs.

Development of solid lipid nanoparticles for enhanced solubility of poorly soluble drugs

DEFF Research Database (Denmark)

Potta, Sriharsha Gupta; Minemi, Sriharsha; Nukala, Ravi Kumar

2010-01-01

Cyclosporine (CyA) solid lipid nanoparticles were prepared by using a solvent free high pressure homogenization process. CyA was incorporated into SLNs that consisted of stearic acid, trilaurin or tripalmitin lipid solid cores in order to enhance drug solubility. The process was conducted...

Aspartate beta-decarboxylase from Alcaligenes faecalis: carbon-13 kinetic isotope effect and deuterium exchange experiments

International Nuclear Information System (INIS)

Rosenberg, R.M.; O'Leary, M.H.

1985-01-01

The authors have measured the 13 C kinetic isotope effect at pH 4.0, 5.0, 6.0, and 6.5 and in D 2 O at pH 5.0 and the rate of D-H exchange of the alpha and beta protons of aspartic acid in D 2 O at pH 5.0 for the reaction catalyzed by the enzyme aspartate beta-decarboxylase from Alcaligenes faecalis. The 13 C kinetic isotope effect, with a value of 1.0099 +/- 0.0002 at pH 5.0, is less than the intrinsic isotope effect for the decarboxylation step, indicating that the decarboxylation step is not entirely rate limiting. The authors have been able to estimate probable values of the relative free energies of the transition states of the enzymatic reaction up to and including the decarboxylation step from the 13 C kinetic isotope effect and the rate of D-H exchange of alpha-H. The pH dependence of the kinetic isotope effect reflects the pKa of the pyridine nitrogen of the coenzyme pyridoxal 5'-phosphate but not that of the imine nitrogen. A mechanism is proposed for the exchange of aspartate beta-H that is consistent with the stereochemistry suggested earlier

Aluminum Solubility in Complex Electrolytes - 13011

Energy Technology Data Exchange (ETDEWEB)

Agnew, S.F. [Columbia Energy and Environmental Services, Inc., 1806 Terminal Dr., Richland, WA 99354 (United States); Johnston, C.T. [Dept. of Crop, Soil, and Environmental Sciences, Purdue University, West Lafayette, IN 47907 (United States)

2013-07-01

Predicting aluminum solubility for Hanford and Savannah River waste liquids is very important for their disposition. It is a key mission goal at each Site to leach as much aluminum as practical from sludges in order to minimize the amount of vitrified high level waste. And it is correspondingly important to assure that any soluble aluminum does not precipitate during subsequent decontamination of the liquid leachates with ion exchange. This report shows a very simple and yet thermodynamic model for aluminum solubility that is consistent with a wide range of Al liquors, from simple mixtures of hydroxide and aluminate to over 300 Hanford concentrates and to a set of 19 Bayer liquors for temperatures from 20-100 deg. C. This dimer-dS{sub mix} (DDS) model incorporates an ideal entropy of mixing along with previous reports for the Al dimer, water activities, gibbsite, and bayerite thermodynamics. We expect this model will have broad application for nuclear wastes as well as the Bayer gibbsite process industry. (authors)

Solubility of ocular therapeutic agents in self-emulsifying oils. I. Self-emulsifying oils for ocular drug delivery: solubility of indomethacin, aciclovir and hydrocortisone.

Science.gov (United States)

Czajkowska-Kośnik, Anna; Sznitowska, Małgorzata

2009-01-01

Self-emulsifying drug delivery systems (SEDDS) were prepared by dissolving Cremophor EL, Tween 20, Tween 80 and Span 80 (1% or 5%) in oils (Miglyol 812 or castor oil). Solubilities of three ophthalmic drugs, namely aciclovir, hydrocortisone and indomethacin were determined in these systems. In addition, the effect of a small amount of water (0.5% and 2%) on solubilization properties of the systems was estimated. Of the three substances, indomethacin showed the best solubility in Miglyol while aciclovir was practically insoluble in this oil. The surfactants usually increased drug solubility in the oily phase. Only Tween 20 was found to decrease the solubility of aciclovir and hydrocortisone in Miglyol. Addition of a small amount of water to the oil/surfactant system increased solubility of hydrocortisone, but not of indomethacin. The results of the current study may be utilized to design a suitable composition of SEDDS and allow continuation of research on this type of drug carriers.

The solubility of carbon in low-nitrogen liquid lithium

International Nuclear Information System (INIS)

Yonco, R.M.; Homa, M.I.

1986-01-01

The solubility of carbon in liquid lithium containing 0 C and compared with the solubility in lithium containing proportional 2600 wppm nitrogen in that same temperature range. A direct sampling method was employed in which filtered samples of the saturated solution were taken at randomly selected temperatures. The entire sample was analyzed for carbon by the acetylene evolution method. The analytical method was examined critically and it was found that (1) all of the carbon in solution, including carbon introduced as lithium cyanamide is detected and (2) ethylene and ethane must also be measured and included with the acetylene to get complete recovery of the carbon content of the sample. The solubility of carbon in low-nitrogen lithium can be expressed by the equations ln S=6.731-8617T -1 and log Ssup(*)=7.459-3740T -1 , where S is the mole percent Li 2 C 2 and Ssup(*) is in weight parts per million carbon. The presence of proportional 2600 wppm nitrogen does not affect the solubility of carbon in lithium at temperatures above proportional 350 0 C, but at lower temperatures it increased the solubility by as much as an order of magnitude compared to the solubility in low-nitrogen lithium. (orig.)

Solubilities of some gases in four immidazolium-based ionic liquids

International Nuclear Information System (INIS)

Afzal, Waheed; Liu, Xiangyang; Prausnitz, John M.

2013-01-01

Graphical abstract: Experimental apparatus based on the synthetic-volumetric method for measuring solubilities of gases in liquids. Highlights: • We constructed an apparatus for measuring solubilities of sparingly-soluble gases. • We measured solubilities of five gases in four immidazolium-based ionic liquids. • We calculated Henry’s constants for gases in the ionic liquids studied in this work. -- Abstract: The synthetic-volumetric method is used for rapidly measuring solubilities of sparingly-soluble gases in monoethylene glycol and in four ionic liquids. Known molar quantities of solute and solvent are charged into an equilibrium vessel. Measured quantities at equilibrium include: temperature, pressure, quantities of fluids, and volumes of the gas and liquid phases in the equilibrium vessel. These measurements enable calculation of equilibrium compositions using material balances. No sampling or chemical analyses are required. Solubilities are reported for carbon dioxide, krypton, oxygen, and hydrogen in monoethylene glycol, l-n-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4], l-n-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6], 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [EMIM][Tf 2 N], or 1-ethyl-3-methylimidazolium acetate [EMIM][AC]. Solubilities were measured over the temperature range (298 to 355) K and for pressures up to about 7 MPa using two different pieces of equipment, both based on the volumetric method: a low-pressure glass apparatus and a high-pressure stainless-steel apparatus. Special emphasis is given to experimental reliability to assure consistent data

Characterization of glutamate decarboxylase from Lactobacillus plantarum and its C-terminal function for the pH dependence of activity.

Science.gov (United States)

Shin, Sun-Mi; Kim, Hana; Joo, Yunhye; Lee, Sang-Jae; Lee, Yong-Jik; Lee, Sang Jun; Lee, Dong-Woo

2014-12-17

The gadB gene encoding glutamate decarboxylase (GAD) from Lactobacillus plantarum was cloned and expressed in Escherichia coli. The recombinant enzyme exhibited maximal activity at 40 °C and pH 5.0. The 3D model structure of L. plantarum GAD proposed that its C-terminal region (Ile454-Thr468) may play an important role in the pH dependence of catalysis. Accordingly, C-terminally truncated (Δ3 and Δ11 residues) mutants were generated and their enzyme activities compared with that of the wild-type enzyme at different pH values. Unlike the wild-type GAD, the mutants showed pronounced catalytic activity in a broad pH range of 4.0-8.0, suggesting that the C-terminal region is involved in the pH dependence of GAD activity. Therefore, this study may provide effective target regions for engineering pH dependence of GAD activity, thereby meeting industrial demands for the production of γ-aminobutyrate in a broad range of pH values.

Involvement of a putative substrate binding site in the biogenesis and assembly of phosphatidylserine decarboxylase 1 from Saccharomyces cerevisiae.

Science.gov (United States)

Di Bartolomeo, Francesca; Doan, Kim Nguyen; Athenstaedt, Karin; Becker, Thomas; Daum, Günther

2017-07-01

In the yeast Saccharomyces cerevisiae, the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) produces the largest amount of cellular phosphatidylethanolamine (PE). Psd1p is synthesized as a larger precursor on cytosolic ribosomes and then imported into mitochondria in a three-step processing event leading to the formation of an α-subunit and a β-subunit. The α-subunit harbors a highly conserved motif, which was proposed to be involved in phosphatidylserine (PS) binding. Here, we present a molecular analysis of this consensus motif for the function of Psd1p by using Psd1p variants bearing either deletions or point mutations in this region. Our data show that mutations in this motif affect processing and stability of Psd1p, and consequently the enzyme's activity. Thus, we conclude that this consensus motif is essential for structural integrity and processing of Psd1p. Copyright © 2017 Elsevier B.V. All rights reserved.

Solubility of heavy metals added to MSW

International Nuclear Information System (INIS)

Lo, H.M.; Lin, K.C.; Liu, M.H.; Pai, T.Z.; Lin, C.Y.; Liu, W.F.; Fang, G.C.; Lu, C.; Chiang, C.F.; Wang, S.C.; Chen, P.H.; Chen, J.K.; Chiu, H.Y.; Wu, K.C.

2009-01-01

This paper aims to investigate the six heavy metal levels (Cd, Cr, Cu, Pb, Ni and Zn) in municipal solid waste (MSW) at different pHs. It intends to provide the baseline information of metals solubility in MSW co-disposed or co-digested with MSW incinerator ashes in landfill or anaerobic bioreactors or heavy metals contaminated in anaerobic digesters. One milliliter (equal to 1 mg) of each metal was added to the 100 ml MSW and the batch reactor test was carried out. The results showed that higher HNO 3 and NaOH were consumed at extreme pH of 1 and 13 compared to those from pH 2 to 11 due to the comparably higher buffer capacity. Pb was found to have the least soluble level, highest metal adsorption (%) and highest partitioning K d (l g -1 ) between pH 3 and 12. In contrast, Ni showed the highest soluble level, lowest metal adsorption (%) and lowest K d (l g -1 ) between pH 4 and 12. Except Ni and Cr, other four metals seemed to show the amphibious properties as comparative higher solubility was found in the acidic and basic conditions

Solubility of heavy metals added to MSW

Energy Technology Data Exchange (ETDEWEB)

Lo, H.M. [Department of Environmental Engineering and Management, Chaoyang University of Technology, 168 Gifong E. Road, Wufong, Taichung County 41349, Taiwan (China)], E-mail: hmlo@cyut.edu.tw; Lin, K.C. [Department of Occupational Safety and Health, Chung Shan Medical University, 110, Sec. 1, Jiangguo N. Rd., Taichung 402, Taiwan (China); Liu, M.H.; Pai, T.Z. [Department of Environmental Engineering and Management, Chaoyang University of Technology, 168 Gifong E. Road, Wufong, Taichung County 41349, Taiwan (China); Lin, C.Y. [Department of Soil and Water Conservation, Chung Hsing University, 250 Kuokuang Road, Taichung 402, Taiwan (China); Liu, W.F. [Department of Electronical Engineering, Feng Chia University, 100 Wenhwa Road, Taichung 407, Taiwan (China); Fang, G.C. [Department of Environmental Engineering, Hungkuang University, 34 Chung-Chie Road, Sha Lu, Taichung 433, Taiwan (China); Lu, C. [Department of Environmental Engineering, Chung Hsing University, 250 Kuokuang Road, Taichung 402, Taiwan (China); Chiang, C.F. [Department of Health Risk Management, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan (China); Wang, S.C.; Chen, P.H.; Chen, J.K.; Chiu, H.Y.; Wu, K.C. [Department of Environmental Engineering and Management, Chaoyang University of Technology, 168 Gifong E. Road, Wufong, Taichung County 41349, Taiwan (China)

2009-01-15

This paper aims to investigate the six heavy metal levels (Cd, Cr, Cu, Pb, Ni and Zn) in municipal solid waste (MSW) at different pHs. It intends to provide the baseline information of metals solubility in MSW co-disposed or co-digested with MSW incinerator ashes in landfill or anaerobic bioreactors or heavy metals contaminated in anaerobic digesters. One milliliter (equal to 1 mg) of each metal was added to the 100 ml MSW and the batch reactor test was carried out. The results showed that higher HNO{sub 3} and NaOH were consumed at extreme pH of 1 and 13 compared to those from pH 2 to 11 due to the comparably higher buffer capacity. Pb was found to have the least soluble level, highest metal adsorption (%) and highest partitioning K{sub d} (l g{sup -1}) between pH 3 and 12. In contrast, Ni showed the highest soluble level, lowest metal adsorption (%) and lowest K{sub d} (l g{sup -1}) between pH 4 and 12. Except Ni and Cr, other four metals seemed to show the amphibious properties as comparative higher solubility was found in the acidic and basic conditions.

Dietary fiber content influences soluble carbohydrate levels in ruminal fluids.

Science.gov (United States)

Pinder, R S; Patterson, J A; O'Bryan, C A; Crandall, P G; Ricke, S C

2012-01-01

The soluble carbohydrate concentration of ruminal fluid, as affected by dietary forage content (DFC) and/or ruminally undegradable intake protein content (UIPC), was determined. Four ruminally cannulated steers, in a 4 × 4 Latin square design, were offered diets containing high (75 % of DM) or low (25 % of DM) DFC and high (6 % of DM) or low (5 % of DM) UIPC, in a 2 × 2 factorial arrangement. Zinc-treated SBM was the primary UIP source. Soluble hexose concentration (145.1 μM) in ruminal fluid (RF) of steers fed low DFC diets exhibited a higher trend (P = 0.08) than that (124.5 μM) of steers fed high DFC diets. UIPC did not modulate (P = 0.54) ruminal soluble hexose concentrations. Regardless of diet, soluble hexose concentration declined immediately after feeding and did not rise until 3 h after feeding (P ruminal fluid could not be determined. However, unsubstituted xylose and arabinose were excluded. These data indicate that: (i) soluble carbohydrate concentrations remain in ruminal fluid during digestion and fermentation; (ii) slight diurnal changes began after feeding; (iii) DFC influences the soluble carbohydrate concentration in RF; and (iv) UIPC of these diets does not affect the soluble carbohydrate concentration of RF.

Solubility of β-carotene in ethanol- and triolein-modified CO2

International Nuclear Information System (INIS)

Araus, Karina A.; Canales, Roberto I.; Valle, Jose M. del; Fuente, Juan C. de la

2011-01-01

Highlights: → We measure solubility of β-carotene in pure CO 2 , and with ethanol and triolein as co-solvents. → We model the solubility of β-carotene in pure CO 2 , and with co-solvents. → The co-solvent effect of triolein over solubility of β-carotene in CO 2 was higher than ethanol. - Abstract: Modification of an experimental device and methodology improved speed and reproducibility of measurement of solubility of β-carotene in pure and modified SuperCritical (SC) CO 2 at (313 to 333) K. Solubilities of β-carotene in pure CO 2 at (17 to 34) MPa ranged (0.17 to 1.06) μmol/mol and agreed with values reported in literature. The solubility of β-carotene in CO 2 modified with (1.2 to 1.6) % mol ethanol increased by a factor of 1.7 to 3.0 as compared to its solubility in pure CO 2 under equivalent conditions. The concentration of triolein in equilibrated ternary (CO 2 + β-carotene + triolein) mixtures having excess triolein reached values (0.01 to 0.39) mmol/mol corresponding to its solubility in pure SC CO 2 under equivalent conditions. Under these conditions, the solubility of β-carotene in triolein-modified CO 2 increased by a factor of up to 4.0 in relation with its solubility in pure CO 2 at comparable system temperature and pressure, reaching an uppermost value of 3.3 μmol/mol at 333 K and 32 MPa. Unlike in the case of ethanol, where enhancements in solubility where relatively independent on system conditions, solubility enhancements using triolein as co-solvent increased markedly with system pressure, being larger than using (1.2 to 1.6) % mol ethanol at about (24 to 28) MPa, depending on system temperature. The increase in the solubility β-carotene in SC CO 2 as a result of using ethanol or triolein as co-solvent apparently does not depend on the increase in density associated with the dissolution of the co-solvent in CO 2 . Enhancements may be due to an increase in the polarizability of SC CO 2 , which possibly growths markedly as triolein

Hydrogen solubility in polycrystalline - and nonocrystalline niobium

International Nuclear Information System (INIS)

Ishikawa, T.T.; Silva, J.R.G. da

1981-01-01

Hydrogen solubility in polycrystalline and monocrystalline niobium was measured in the range 400 0 C to 1000 0 C at one atmosphere hydrogen partial pressure. The experimental technique consists of saturation of the solvent metal with hydrogen, followed by quenching and analysis of the solid solution. It is presented solubility curves versus reciprocal of the absolute doping temperature, associated with their thermodynamical equation. (Author) [pt

Respiratory carcinogenicity assessment of soluble nickel compounds.

OpenAIRE

Oller, Adriana R

2002-01-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear...

Aromatic Amino Acid Decarboxylase Deficiency Not Responding to Pyridoxine and Bromocriptine Therapy: Case Report and Review of Response to Treatment

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Majid Alfadhel

2014-01-01

Full Text Available Aromatic L-amino acid decarboxylase (AADC deficiency (MIM #608643 is an autosomal recessive inborn error of monoamines. It is caused by a mutation in the DDC gene that leads to a deficiency in the AADC enzyme. The clinical features of this condition include a combination of dopamine, noradrenaline, and serotonin deficiencies, and a patient may present with hypotonia, oculogyric crises, sweating, hypersalivation, autonomic dysfunction, and progressive encephalopathy with severe developmental delay. We report the case of an 8-month-old boy who presented with the abovementioned symptoms and who was diagnosed with AADC deficiency based on clinical, biochemical, and molecular investigations. Treatment with bromocriptine and pyridoxine showed no improvement. These data support the findings observed among previously reported cohorts that showed poor response of this disease to current regimens. Alternative therapies are needed to ameliorate the clinical complications associated with this disorder.

Water-Soluble Vitamin E-Tocopheryl Phosphate.

Science.gov (United States)

Zingg, Jean-Marc

The hydrophobicity of vitamin E poses transport and metabolic challenges to regulate its bioavailability and to prevent its accumulation in lipid-rich tissues such as adipose tissue, brain, and liver. Water-soluble precursors of vitamin E (α-tocopherol, αT), such as its esters with acetate (αTA), succinate (αTS), or phosphate (αTP), have increased solubility in water and stability against reaction with free radicals, but they are rapidly converted during their uptake into the lipid-soluble vitamin E. Therefore, the bioavailability of these precursors as intact molecules is low; nevertheless, at least for αTS and αTP, the recent research has revealed unique regulatory effects on signal transduction and gene expression and the modulation of cellular events ranging from proliferation, survival/apoptosis, lipid uptake and metabolism, phagocytosis, long term potentiation, cell migration, telomere maintenance, and angiogenesis. Moreover, water-soluble derivatives of vitamin E including some based on αTP are increasingly used as components of nanocarriers for enhanced and targeted delivery of drugs and other molecules (vitamins, including αT and αTP itself, vitamin D3, carnosine, caffeine, docosahexaenoic acid (DHA), insulin) and cofactors such as coenzyme Q10. In this review, the chemical characteristics, transport, metabolic pathways, and molecular mechanisms of action of αTP in cells and tissues are summarized and put into perspective with its possible role in the prevention of a number of diseases. © 2018 Elsevier Inc. All rights reserved.

Solubility of gases in water at high temperature

International Nuclear Information System (INIS)

Crovetto, Rosa; Fernandez Prini, R.J.; Japas, M.L.

1981-01-01

In the primary circuits of the PWR, it is usual to find apolar gases such as the noble gases like, nitrogen, hydrogen (deuterium) and oxygen. These gases enter into the circuit partly due to failures in the fuel elements, accidental entries of air into the system and corrosion processes and radiolisis in the coolant media. For the operation of several auxiliary systems in the primary circuit, it is important to know the solubility of these gases in the flux of the circuit and the evaluation of physicochemical processes that take place. A cell has been built that allows to carry out determinations of solubility in the range of 350 deg C and 100 Mega Pascal. Three alternative experimental techniques have been developed to determine the solubility of the gases which are compared to each other. Measures of solubility of argon in H2O and D2O have been made in a wide range of temperatures. (V.B.) [es

Molecular Design of Soluble Biopolyimide with High Rigidity

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Sumant Dwivedi

2018-03-01

Full Text Available New soluble biopolyimides were prepared from a diamine derived from an exotic amino acid (4-aminocinnamic acid with several kinds of tetracarboxylic dianhydride. The biopolyimide molecular structural flexibility was tailored by modifying the tetracarboxylic dianhydride moiety. The obtained polyimides were soluble in various solvents such as N-methyl-2-pyrrolidone, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, and even tetrahydrofuran. It was observed that the biopolyimide solubility was greatly dependent upon the structural flexibility (torsion energy. Flexible structure facilitated greater solubility. The synthesized biopolyimides were largely amorphous and had number-average molecular weight (Mn in the range (5–8 × 105. The glass transition temperatures (Tg of the polymers ranged from 259–294 °C. These polymers exhibited good thermal stability without significant weight loss up to 410 °C. The temperatures at 10% weight loss (Td10 for synthesized biopolyimide ranged from 375–397 °C.

Experimental solubility measurements of lanthanides in liquid alkalis

Science.gov (United States)

Isler, Jeremy; Zhang, Jinsuo; Mariani, Robert; Unal, Cetin

2017-11-01

In metallic nuclear fuel, lanthanide fission products play a crucial role in the fuel burnup-limiting phenomena of fuel cladding-chemical interaction (FCCI). The lanthanides have been hypothesized to transport by a 'liquid-like' mechanism out of the metallic fuel to the fuel peripheral to cause FCCI. By liquid fission product cesium and liquid bond sodium, the lanthanides are transported to the peripheral of the fuel through the porosity of the fuel. This work investigates the interaction between the lanthanides and the alkali metals by experimentally measuring the solubility of lanthanides within liquid sodium, and neodymium in liquid cesium and mixtures of cesium and sodium. The temperature dependence of the solubility is experimentally determined within an inert environment. In addition, the dependence of the solubility on the alkali metal concentration in liquid mixtures of cesium and sodium was examined. In quantifying the solubility, the fundamental understanding of this transport mechanism can be better determined.

SORPTION AND SOLUBILITY OF LOW-SHRINKAGE RESIN-BASED DENTAL COMPOSITES

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Sevda Yantcheva

2016-04-01

Full Text Available Background: Resin-based composites are well-established restorative materials. However, these materials may absorb significant amounts of water when exposed to aqueous environments. Sorption and solubility are affecting composite restorations by two different mechanisms; the first is the up taking of water producing an increased weight and the second is the dissolution of materials in water, leading to a weight reduction of the final conditioned samples. Objective: To measure the water sorption and solubility of different low-shrinkage resin-based composites. Six materials were selected: Filtek P60, Filtek Ultimate, SonicFill, Filtek Silorane, Kalore and Venus Diamond. Materials and methods: Five disc specimens were prepared of each material and polymerized with diode light-curing unit. Water sorption and solubility of the different materials were were calculated by means of weighting the samples before and after water immersion and desiccation. Data were statistically analyzed using Shapiro-Wilk One Way Analysis of Variance followed by the Holm-Sidak comparison test . Results: There were significant differences (p<=0.001 between materials regarding sorption and solubility. Regarding sorption F. Silorane showed lowest values, followed by SonicFill, without significant difference between them. Statistical significant differences exist between F. Silorane and F.P60, F. Ultimate, Kalore. Significant differences exist between SonicFill and F. Ultimate. F.Silorane (-0.018 and Kalore (-0.010 showed lowest values of solubility but there were marginal difference among all composites investigated. Conclusions: 1.The material with lowest values of sorption and solubility was F.Silorane. 2. The attained sorption and solubility values for composites are influenced by the differences in resin matrix composition and filler contend. 3. Modifications of dimethacrylate matrix did not minimize significantly sorption and solubility of composites. 4. Besides water

Increased serum soluble corin in dyslipidemia: A cross-sectional study.

Science.gov (United States)

Wang, Xiaolei; Chen, Shi; Zhang, Qiu; Liu, Yan; Liu, Lu; Li, Huiling; Peng, Hao

2015-10-23

Natriuretic peptides have been associated with dyslipidemia. As a physiological activator of natriuretic peptides, corin might also be associated with dyslipidemia. However, this association has not yet been studied in Chinese populations. Serum soluble corin and blood lipid profiles were determined for 2496 participants aged above 30y. A logistic regression model was applied to evaluate the association between serum soluble corin and dyslipidemia. Serum soluble corin was significantly increased in participants with dyslipidemia in both men (Pdyslipidemia positively increased with increasing levels of serum soluble corin in men (P for trend=0.011) and women (P for trend=0.043). Participants with a high corin level were more likely to have dyslipidemia than those with a low corin level in men (OR, 95% CI: 1.45, 1.07-1.97) and women (OR, 95% CI: 1.33, 1.04-1.70). Serum soluble corin was significantly and positively associated with dyslipidemia. Our findings suggested that serum soluble corin may be a marker or risk factor for dyslipidemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Solubility Temperature Dependence Predicted from 2D Structure

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Alex Avdeef

2015-12-01

Full Text Available The objective of the study was to find a computational procedure to normalize solubility data determined at various temperatures (e.g., 10 – 50 oC to values at a “reference” temperature (e.g., 25 °C. A simple procedure was devised to predict enthalpies of solution, ΔHsol, from which the temperature dependence of intrinsic (uncharged form solubility, log S0, could be calculated. As dependent variables, values of ΔHsol at 25 °C were subjected to multiple linear regression (MLR analysis, using melting points (mp and Abraham solvation descriptors. Also, the enthalpy data were subjected to random forest regression (RFR and recursive partition tree (RPT analyses. A total of 626 molecules were examined, drawing on 2040 published solubility values measured at various temperatures, along with 77 direct calori    metric measurements. The three different prediction methods (RFR, RPT, MLR all indicated that the estimated standard deviations in the enthalpy data are 11-15 kJ mol-1, which is concordant with the 10 kJ mol-1 propagation error estimated from solubility measurements (assuming 0.05 log S errors, and consistent with the 7 kJ mol-1 average reproducibility in enthalpy values from interlaboratory replicates. According to the MLR model, higher values of mp, H‑bond acidity, polarizability/dipolarity, and dispersion forces relate to more positive (endothermic enthalpy values. However, molecules that are large and have high H-bond basicity are likely to possess negative (exothermic enthalpies of solution. With log S0 values normalized to 25 oC, it was shown that the interlaboratory average standard deviations in solubility measurement are reduced to 0.06 ‑ 0.17 log unit, with higher errors for the least-soluble druglike molecules. Such improvements in data mining are expected to contribute to more reliable in silico prediction models of solubility for use in drug discovery.

AW-101 entrained solids - Solubility versus temperature

International Nuclear Information System (INIS)

GJ Lumetta; RC Lettau; GF Piepel

2000-01-01

This report describes the results of a test conducted by Battelle to assess the solubility of the solids entrained in the diluted AW-101 low-activity waste (LAW) sample. BNFL requested Battelle to dilute the AW-1-1 sample using de-ionized water to mimic expected plant operating conditions. BNFL further requested Battelle to assess the solubility of the solids present in the diluted AW-101 sample versus temperature conditions of 30, 40, and 50 C. BNFL requested these tests to assess the composition of the LAW supernatant and solids versus expected plant-operating conditions. The work was conducted according to test plan BNFL-TP-29953-7, Rev. 0, Determination of the Solubility of LAW Entrained Solids. The test went according to plan, with no deviations from the test plan

Resveratrol cocrystals with enhanced solubility and tabletability.

Science.gov (United States)

Zhou, Zhengzheng; Li, Wanying; Sun, Wei-Jhe; Lu, Tongbu; Tong, Henry H Y; Sun, Changquan Calvin; Zheng, Ying

2016-07-25

Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT-IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development. Copyright © 2016 Elsevier B.V. All rights reserved.

Loss of autonoetic consciousness of recent autobiographical episodes and accelerated long-term forgetting in a patient with previously unrecognized glutamic acid decarboxylase antibody related limbic encephalitis

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Juri-Alexander eWitt

2015-06-01

Full Text Available We describe a 35-year old male patient presenting with depressed mood and emotional instability who complained about severe anterograde and retrograde memory deficits characterized by accelerated long-term forgetting and loss of autonoetic consciousness regarding autobiographical memories of the last three years. Months before he had experienced two breakdowns of unknown etiology giving rise to the differential diagnosis of epileptic seizures after various practitioners and clinics had suggested different etiologies such as a psychosomatic condition, burnout, depression or dissociative amnesia. Neuropsychological assessment indicated selectively impaired figural memory performance. Extended diagnostics confirmed accelerated forgetting of previously learned and retrievable verbal material. Structural imaging showed bilateral swelling and signal alterations of temporomesial structures (left > right. Video-EEG monitoring revealed a left temporal epileptic focus and subclincal seizure, but no overt seizures. Antibody tests in serum and liquor were positive for glutamic acid decarboxylase antibodies. These findings led to the diagnosis of glutamic acid decarboxylase antibody related limbic encephalitis. Monthly steroid pulses over six months led to recovery of subjective memory and to intermediate improvement but subsequent worsening of objective memory performance. During the course of treatment the patient reported de novo paroxysmal non-responsive states. Thus, antiepileptic treatment was started and the patient finally became seizure free. At the last visit vocational reintegration was successfully in progress.In conclusion, amygdala swelling, retrograde biographic memory impairment, accelerated long-term forgetting and emotional instability may serve as indicators of limbic encephalitis, even in the absence of overt epileptic seizures. The monitoring of such patients calls for a standardized and concerted multilevel diagnostic approach with

[Ornithine decarboxylase in mammalian organs and tissues at hibernation and artificial hypobiosis].

Science.gov (United States)

Logvinovich, O S; Aksenova, G E

2013-01-01

Ornithine decarboxylase (ODC, EC 4.1.1.17.) is a short-lived and dynamically regulated enzyme of polyamines biosynthesis. Regulation of functional, metabolic and proliferative state of organs and tissues involves the modifications of the ODC enzymatic activity. The organ-specific changes in ODC activity were revealed in organs and tissues (liver, spleen, bone marrow, kidney, and intestinal mucosa) of hibernating mammals - squirrels Spermophilus undulates - during the hibernating season. At that, a positive correlation was detected between the decline and recovery of the specialized functions of organs and tissues and the respective modifications of ODC activity during hibernation bouts. Investigation of changes in ODC activity in organs and tissues of non-hibernating mammals under artificial hypobiosis showed that in Wistar rats immediately after exposure to hypothermia-hypoxia-hypercapnia (hypobiosis) the level of ODC activity was low in thymus, spleen, small intestine mucosa, neocortex, and liver. The most marked reduction in enzyme activity was observed in actively proliferating tissues: thymus, spleen, small intestine mucosa. In bone marrow of squirrels, while in a state of torpor, as well as in thymus of rats after exposure to hypothermia-hypoxia-hypercapnia, changes in the ODC activity correlated with changes in the rate of cell proliferation (by the criterion of cells distribution over cell cycle). The results obtained, along with the critical analysis of published data, indicate that the ODC enzyme is involved in biochemical adaptation of mammals to natural and artificial hypobiosis. A decline in the ODC enzymatic activity indicates a decline in proliferative, functional, and metabolic activity of organs and tissues of mammals (bone marrow, mucosa of small intestine, thymus, spleen, neocortex, liver, kidneys) when entering the state of hypobiosis.

Cloning and Expression Vector Construction of Glutamate Decarboxylase Gene from Lactobacillus Plantarum

Directory of Open Access Journals (Sweden)

B Arabpour

2016-06-01

Full Text Available BACKGROUND AND OBJECTIVE: Gamma-aminobutyric acid (GABA is a four-carbon non-protein amino acid used in the treatment of hypertension, diabetes, inflammation, and depression. GABA is synthesized by glutamic acid decarboxylase (GAD enzyme in many organisms, including bacteria. Therefore, cloning of this enzyme is essential to the optimization of GABA production. This study aimed to clone and construct the expression vector of GAD gene from Lactobacillus plantarum PTCC 1058 bacterium. METHODS: In this experimental study, we investigated the morphological, biochemical, genetic and 16s rDNA sequencing of L. plantarum PTCC 1058 strain. Genomic DNA of the bacterium was isolated and amplified using the GAD gene via polymerase chain reaction (PCR. Afterwards, the gene was inserted into the pJET1.2/blunt cloning vector and subcloned in vector pET32a. Plasmid pET32a-gad expression vector was transformed in Escherichia coli BL21 strain, and protein expression was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE. FINDINGS: Morphological, biochemical and genetic analyses of 16s rDNA sequencing indicated that the studied substrain was of the L. plantarum strain. In addition, results of nucleotide sequencing of the fragmented segment via PCR showed the presence of GAD gene. Results of colony PCR and SDS-PAGE analysis confirmed the accuracy of the cloning and gene expression of the recombinant Escherichia coli BL21 strain. CONCLUSION: According to the results of this study, cloning of GAD gene from L. plantarum PTCC 1058 was successful. These cloned genes could grow rapidly in prokaryotic and eukaryotic systems and be used in cost-effective culture media and even non-recyclable waste.

Hydrogen terminal solubility in Zircaloy-4

International Nuclear Information System (INIS)

Vizcaino, Pablo; Banchik, Abrahan D.

1999-01-01

Terminal solubility temperature of hydrogen in zirconium and its alloys is an important parameter because hydrides precipitation embrittled these materials making them susceptible to the phenomenon known as retarded hydrogen cracking. This work continues the study presented in the 25 AATN Meeting. Within this framework, a study focused on determining these curves in recrystallized Zircaloy-4, using scanning differential calorimetric technique. Terminal solubility curves for Zircaloy-4 were constructed within a concentration range from 40 to 640 ppm in hydrogen weight and comparisons with results obtained by other authors were made. (author)

Analysis of americium, plutonium and technetium solubility in groundwater

International Nuclear Information System (INIS)

Takeda, Seiji

1999-08-01

Safety assessments for geologic disposal of radioactive waste generally use solubilities of radioactive elements as the parameter restricting the dissolution of the elements from a waste matrix. This study evaluated americium, plutonium and technetium solubilities under a variety of geochemical conditions using the geochemical model EQ3/6. Thermodynamic data of elements used in the analysis were provided in the JAERI-data base. Chemical properties of both natural groundwater and interstitial water in buffer materials (bentonite and concrete) were investigated to determine the variations in Eh, pH and ligand concentrations (CO 3 2- , F - , PO 4 3- , SO 4 2- , NO 3 - and NH 4 + ). These properties can play an important role in the complexation of radioactive elements. Effect of the groundwater chemical properties on the solubility and formation of chemical species for americium, plutonium and technetium was predicted based on the solubility analyses under a variety of geochemical conditions. The solubility and speciation of the radioactive elements were estimated, taking into account the possible range of chemical compositions determined from the groundwater investigation. (author)

Correlation of flow accelerated corrosion rate with iron solubility

International Nuclear Information System (INIS)

Fujiwara, K.; Domae, M.; Yoneda, K.; Inada, F.; Ohira, T.; Hisamune, K.; Takiguchi, H.

2009-01-01

Flow Accelerated Corrosion (FAC) of carbon steel is one of the most important subjects in coolant systems of power plants. FAC is influenced by material, flow condition, temperature, and water chemistry. It is considered that solubility is the most important factor to determine the effect of water chemistry on FAC. In the present study, effect of specific oxide on FAC rate was studied from the thermodynamic solubility of iron. The effects of temperature and pH on the iron solubility were evaluated by taking into consideration hydrolysis reactions of ferrous iron, dissolution equilibria of Fe 3 O 4 , FeO, and Fe(OH) 2 , and charge balance. The correlation between the iron solubility and FAC behavior was evaluated by using the normalized mass transfer coefficient. It is clarified that the product of iron solubility equilibrated with Fe 3 O 4 and normalized mass transfer coefficient can explain the temperature and pH dependence of FAC. These results indicate presence of magnetite on the surface of carbon steel. Diffusion of iron from the saturated layer determines the FAC rate from water chemistry aspect. (author)

Solubility of sulfur in Fe-Cr-Ni alloys

International Nuclear Information System (INIS)

Bogolyubskij, S.D.; Petrova, E.F.; Rogov, A.I.; Shvartsman, L.A.

1979-01-01

The solubility of 35 S was determined in Fe-Cr-Ni alloys in the range of temperatures between 910 and 1050 deg C by the method of radiometric analysis. It was found that the solubility of sulfur increases with the concentration of chromium in alloys with 20% Ni

Heat-induced alterations in cashew allergen solubility and IgE binding

Directory of Open Access Journals (Sweden)

Christopher P. Mattison

Full Text Available Cashew nuts are an increasingly common cause of food allergy. We compare the soluble protein profile of cashew nuts following heating. SDS-PAGE indicate that heating can alter the solubility of cashew nut proteins. The 11S legumin, Ana o 2, dominates the soluble protein content in ready to eat and mildly heated cashew nuts. However, we found that in dark-roasted cashew nuts, the soluble protein profile shifts and the 2S albumin Ana o 3 composes up to 40% of the soluble protein. Analysis of trypsin-treated extracts by LC/MS/MS indicate changes in the relative number and intensity of peptides. The relative cumulative intensity of the 5 most commonly observed Ana o 1 and 2 peptides are altered by heating, while those of the 5 most commonly observed Ana o 3 peptides remaine relatively constant. ELISA experiments indicate that there is a decrease in rabbit IgG and human serum IgE binding to soluble cashew proteins following heating. Our findings indicate that heating can alter the solubility of cashew allergens, resulting in altered IgE binding. Our results support the use of both Ana o 2 and Ana o 3 as potential cashew allergen diagnostic targets. Keywords: Cashew nut, Food allergy, Immunoglobulin E, Mass-spectrometry, Peptide, Solubility

Determination of mangiferin solubility in solvents used in the biopharmaceutical industry

Directory of Open Access Journals (Sweden)

Jhoany Acosta

2016-04-01

Full Text Available Context: Pharmacological properties and studies of methods of extraction of mangiferin have been reported, but there are not studies related to the solubility of mangiferin in the solvents used in the pharmaceutical industry. Aims: Study the solubility of mangiferin in different solvents used in the pharmaceutical industry. Methods: The mangiferin used had a purity of 97.3% determined by High-Performance Liquid Chromatographic (HPLC, and solubility measurements were made in ethanol, methanol, water, acetone, diethyl ether, and hexane at 5, 15, 30, 40, 50 and 600C of temperature. The mangiferin concentrations were determined by ultraviolet spectrometry at 254 nm. The experimental solubility data were correlated with the Van´t Hoff equation and the dissolution heat determined. Results: The solubility of mangiferin in pure solvents decreases with increasing of temperature and in the following order: ethanol>methanol>water>diethyl ether>acetone>n hexane. Conclusions: This results indicated that mangiferin is slightly soluble in ethanol, sparingly soluble in methanol and water and practically insoluble in diethyl ether, acetone, and n-hexane.

Investigation of samarium solubility in the magnesium based solid solution

International Nuclear Information System (INIS)

Rokhlin, L.L.; Padezhnova, E.M.; Guzej, L.S.

1976-01-01

Electric resistance measurements and microscopic analysis were used to investigate the solubility of samarium in a magnesium-based solid solution. The constitutional diagram Mg-Sm on the magnesium side is of an eutectic type with the temperature of the eutectic transformation of 542 deg C. Samarium is partly soluble in solid magnesium, the less so, the lower is the temperature. The maximum solubility of samarium in magnesium (at the eutectic transformation point) is 5.8 % by mass (0.99 at. %). At 200 deg C, the solubility of samarium in magnesium is 0.4 % by mass (0.063 at. %)

DEPENDENCY OF SULFATE SOLUBILITY ON MELT COMPOSITION AND MELT POLYMERIZATION

International Nuclear Information System (INIS)

JANTZEN, CAROL M.

2004-01-01

Sulfate and sulfate salts are not very soluble in borosilicate waste glass. When sulfate is present in excess it can form water soluble secondary phases and/or a molten salt layer (gall) on the melt pool surface which is purported to cause steam explosions in slurry fed melters. Therefore, sulfate can impact glass durability while formation of a molten salt layer on the melt pool can impact processing. Sulfate solubility has been shown to be compositionally dependent in various studies, (e.g. , B2O3, Li2O, CaO, MgO, Na2O, and Fe2O3 were shown to increase sulfate solubility while Al2O3 and SiO2 decreased sulfate solubility). This compositional dependency is shown to be related to the calculated melt viscosity at various temperatures and hence the melt polymerization

Poly(aspartic acid) with adjustable pH-dependent solubility.

Science.gov (United States)

Németh, Csaba; Gyarmati, Benjámin; Abdullin, Timur; László, Krisztina; Szilágyi, András

2017-02-01

Poly(aspartic acid) (PASP) derivatives with adjustable pH-dependent solubility were synthesized and characterized to establish the relationship between their structure and solubility in order to predict their applicability as a basic material for enteric coatings. Polysuccinimide, the precursor of PASP, was modified with short chain alkylamines, and the residual succinimide rings were subsequently opened to prepare the corresponding PASP derivatives. Study of the effect of the type and concentration of the side groups on the pH-dependent solubility of PASP showed that solubility can be adjusted by proper selection of the chemical structure. The Henderson-Hasselbalch (HH) and the extended HH equations were used to describe the pH-dependent solubility of the polymers quantitatively. The estimate provided by the HH equation is poor, but an accurate description of the pH-dependent solubility can be found with the extended HH equation. The dissolution rate of a polymer film prepared from a selected PASP derivative was determined by fluorescence marking. The film dissolved rapidly when the pH was increased above its pK a . Cellular viability tests show that PASP derivatives are non-toxic to a human cell line. These polymers are thus of great interest as starting materials for enteric coatings. Poly(amino acid) type biocompatible polymers were synthesized for future use as pharmaceutical film coatings. To this end, we tailored the pH-dependent solubility of poly(aspartic acid) (PASP). It was found that both the solubility and the pK a values of the modified PASP depended strongly on composition. Fluorescent marking was used to characterize the dissolution of a chosen PASP derivative. In acidic media only a negligible amount of the polymer dissolved, but dissolution was very fast and complete at the pH values that prevail in the small intestine. As a consequence, enteric coatings based on such PASP derivatives may be used for drug delivery in the gastrointestinal tract

Solubility and Permeability Studies of Aceclofenac in Different Oils

African Journals Online (AJOL)

The solubility and permeability of aceclofenac were compared with the hydroalcoholic solution of ... the use of lipid based systems such as micro- or .... carriers/vehicles for enhanced solubility and permeability ... modifications: A recent review.

Solubility of magnetite in high temperature water and an approach to generalized solubility computations

International Nuclear Information System (INIS)

Dinov, K.; Ishigure, K.; Matsuura, C.; Hiroishi, D.

1993-01-01

Magnetite solubility in pure water was measured at 423 K in a fully teflon-covered autoclave system. A fairly good agreement was found to exist between the experimental data and calculation results obtained from the thermodynamical model, based on the assumption of Fe 3 O 4 dissolution and Fe 2 O 3 deposition reactions. A generalized thermodynamical approach to the solubility computations under complex conditions on the basis of minimization of the total system Gibbs free energy was proposed. The forms of the chemical equilibria were obtained for various systems initially defined and successfully justified by the subsequent computations. A [Fe 3+ ] T -[Fe 2+ ] T phase diagram was introduced as a tool for systematic understanding of the magnetite dissolution phenomena in pure water and under oxidizing and reducing conditions. (orig.)

Mechanisms for oral absorption of poorly water-soluble compounds

DEFF Research Database (Denmark)

Lind, Marianne Ladegaard

Abstract A large part of the new drug candidates discovered by the pharmaceutical industry have poor solubility in aqueous media. The preferred route of drug administration is the oral route, but for these poorly water-soluble drug candidates the oral bioavailability can be low and variable. Often......, phospholipids) and exogenous surfactants used in pharmaceutical formulations on the oral absorption of poorly water-soluble drug substances. Three different models were used for this purpose. The first model was the in vitro Caco-2 cell model. Simulated intestinal fluids which did not decrease cellular...... products are important for the solubilization of poorly water-soluble drug substances and thus absorption. The second model used was the lipoprotein secreting Caco-2 cell model, which was used to simulate intestinal lymphatic transport in vitro. Various simulated intestinal fluids were composed...

Solubility of Plutonium (IV) Oxalate During Americium/Curium Pretreatment

International Nuclear Information System (INIS)

Rudisill, T.S.

1999-01-01

Approximately 15,000 L of solution containing isotopes of americium and curium (Am/Cm) will undergo stabilization by vitrification at the Savannah River Site (SRS). Prior to vitrification, an in-tank pretreatment will be used to remove metal impurities from the solution using an oxalate precipitation process. Material balance calculations for this process, based on solubility data in pure nitric acid, predict approximately 80 percent of the plutonium in the solution will be lost to waste. Due to the uncertainty associated with the plutonium losses during processing, solubility experiments were performed to measure the recovery of plutonium during pretreatment and a subsequent precipitation process to prepare a slurry feed for a batch melter. A good estimate of the plutonium content of the glass is required for planning the shipment of the vitrified Am/Cm product to Oak Ridge National Laboratory (ORNL).The plutonium solubility in the oxalate precipitation supernate during pretreatment was 10 mg/mL at 35 degrees C. In two subsequent washes with a 0.25M oxalic acid/0.5M nitric acid solution, the solubility dropped to less than 5 mg/mL. During the precipitation and washing steps, lanthanide fission products in the solution were mostly insoluble. Uranium, and alkali, alkaline earth, and transition metal impurities were soluble as expected. An elemental material balance for plutonium showed that greater than 94 percent of the plutonium was recovered in the dissolved precipitate. The recovery of the lanthanide elements was generally 94 percent or higher except for the more soluble lanthanum. The recovery of soluble metal impurities from the precipitate slurry ranged from 15 to 22 percent. Theoretically, 16 percent of the soluble oxalates should have been present in the dissolved slurry based on the dilution effects and volumes of supernate and wash solutions removed. A trace level material balance showed greater than 97 percent recovery of americium-241 (from the beta dec

Anomalous Solubility Behavior of Several Acidic Drugs

Directory of Open Access Journals (Sweden)

Alex Avdeef

2014-04-01

Full Text Available The “anomalous solubility behavior at higher pH values” of several acidic drugs originally studied by Higuchi et al. in 1953 [1], but hitherto not fully rationalized, has been re-analyzed using a novel solubility-pH analysis computer program, pDISOL-XTM. The program internally derives implicit solubility equations, given a set of proposed equilibria and constants (iteratively refined by weighted nonlinear regression, and does not require explicit Henderson-Hasselbalch equations. The re-analyzed original barbital, phenobarbital, oxytetracycline, and sulfathiazole solubility-pH data of Higuchi et al. is consistent with the presence of dimers in saturated solutions. In the case of barbital, phenobarbital and sulfathiazole, anionic dimers, reaching peak concentrations near pH 8. However, oxytetracycline indicated a pronounced tendency to form a cationic dimer, peaking near pH 2. Under the conditions of the original study, only barbital indicated a slight tendency to form a salt precipitate at pH > 6.8, with a highly unusual stoichiometry (consistent with a slope of 0.55 in the log S – pH plot: K+ + A2H- + 3HA D KA5H4(s. Thus the “anomaly” in the Higuchi data can be rationalized by invoking specific aggregated species.

SOLUBILITY AND BIOAVAILABILITY ENHANCEMENT STRATEGIES FOR EFFECTIVE DELIVERY OF POORLY WATER SOLUBLE DRUGS BY NANO FORMULATIONS AND SOLID DISPERSIONS

OpenAIRE

Rayapolu Ranga Goud*, Gunnala Krishnaveni, Girija Prasad Patro

2018-01-01

For the ancient few years, there has been a substantial research done on diverse methodologies for poorly water soluble and lipophilic drugs. More in modern times voluminous molecules cannot be distributed due to low solubility. Now a day frequently, particulate vesicle systems such as nanoparticles, liposomes, microspheres, niosomes, pronisomes, ethosomes, and proliposomes have been used as drug carriers. Drug delivery designates the technique and methodology to conveying medications or drug...

Equilibrium Solubility of CO2 in Alkanolamines

DEFF Research Database (Denmark)

Waseem Arshad, Muhammad; Fosbøl, Philip Loldrup; von Solms, Nicolas

2014-01-01

Equilibrium solubility of CO2 were measured in aqueous solutions of Monoethanolamine (MEA) and N,N-diethylethanolamine(DEEA). Equilibrium cells are generally used for these measurements. In this study, the equilibrium data were measured from the calorimetry. For this purpose a reaction calorimeter...... (model CPA 122 from ChemiSens AB, Sweden) was used. The advantage of this method is being the measurement of both heats of absorption and equilibrium solubility data of CO2 at the same time. The measurements were performed for 30 mass % MEA and 5M DEEA solutions as a function of CO2 loading at three...... different temperatures 40, 80 and 120 ºC. The measured 30 mass % MEA and 5M DEEA data were compared with the literature data obtained from different equilibrium cells which validated the use of calorimeters for equilibrium solubility measurements....

Spermidine mediates degradation of ornithine decarboxylase by a non-lysosomal, ubiquitin-independent mechanism

International Nuclear Information System (INIS)

Glass, J.R.; Gerner, E.W.

1987-01-01

The mechanism of spermidine-induced ornithine decarboxylase (OCD, E.C. 4.1.1.17) inactivation was investigated using Chinese hamster ovary (CHO) cells, maintained in serum-free medium, which display a stabilization of ODC owing to the lack of accumulation of putrescine and spermidine. Treatment of cells with 10 μM exogenous spermidine leads to rapid decay of ODC activity accompanied by a parallel decrease in enzyme protein. Analysis of the decay of [ 35 S]methionine-labeled ODC and separation by two-dimensional electrophoresis revealed no detectable modification in ODC structure during enhanced degradation. Spermidine-mediated inactivation of ODC occurred in a temperature-dependent manner exhibiting pseudo-first-order kinetics over a temperature range of 22-37 0 C. In cultures treated continuously, an initial lag was observed after treatment with spermidine, followed by a rapid decline in activity as an apparent critical concentration of intracellular spermidine was achieved. Treating cells at 22 0 C for 3 hours with 10 μ M spermidine, followed by removal of exogenous polyamine, and then shifting to varying temperatures, resulted in rates of ODC inactivation identical with that determined with a continuous treatment. Arrhenius analysis showed that polyamine mediated inactivation of ODC occurred with an activation energy of approximately 16 kcal/mol. Treatment of cells with lysosomotrophic agents had no effect of ODC degradation. ODC turnover was not dependent on ubiquitin-dependent proteolysis. These data support the hypothesis that spermidine regulates ODC degradation via a mechanism requiring new protein synthesis, and that this occurs via a non-lysosomal, ubiquitin-independent pathway

Solubility of plutonium and waste evaporation

International Nuclear Information System (INIS)

Karraker, D.G.

1993-01-01

Chemical processing of irradiated reactor elements at the Savannah River Site separates uranium, plutonium and fission products; fission products and process-added chemicals are mixed with an excess of NaOH and discharged as a basic slurry into large underground tanks for temporary storage. The slurry is composed of base-insoluble solids that settle to the bottom of the tank; the liquid supemate contains a mixture of base-soluble chemicals--nitrates, nitrites aluminate, sulfate, etc. To conserve space in the waste tanks, the supemate is concentrated by evaporation. As the evaporation proceeds, the solubilities of some components are exceeded, and these species crystallize from solution. Normally, these components are soluble in the hot solution discharged from the waste tank evaporator and do not crystallize until the solution cools. However, concern was aroused at West Valley over the possibility that plutonium would precipitate and accumulate in the evaporator, conceivably to the point that a nuclear accident was possible. There is also a concern at SRS from evaporation of sludge washes, which arise from washing the base-insoluble solids (open-quote sludge close-quote) with ca. 1M NaOH to reduce the Al and S0 4 -2 content. The sludge washes of necessity extract a low level of Pu from the sludge and are evaporated to reduce their volume, presenting the possibility of precipitating Pu. Measurements of the solubility of Pu in synthetic solutions of similar composition to waste supernate and sludge washes are described in this report

Near-field solubility studies

International Nuclear Information System (INIS)

Thomason, H.P.; Williams, S.J.

1992-02-01

Experimental determinations of the solubilities of americium, plutonium, neptunium, protactinium, thorium, radium, lead, tin, palladium and zirconium are reported. These elements have radioactive isotopes of concern in assessments of radioactive waste disposal. All measurements were made under the highly alkaline conditions typical of the near field of a radioactive waste repository which uses cementitious materials for many of the immobilisation matrices, the backfill and the engineered structures. Low redox potentials, typical of those resulting from the corrosion of iron and steel, were simulated for those elements having more than one accessible oxidation state. The dissolved concentrations of the elements were defined using ultrafiltration. In addition, the corrosion of iron and stainless steel was shown to generate low redox potentials in solution and the solubility of iron(II) at high pH was measured and found to be sufficient for it to act as a redox buffer with respect to neptunium and plutonium. (author)

Solubility of hydrogen isotopes in stressed hydride-forming metals

International Nuclear Information System (INIS)

Coleman, C.E.; Ambler, J.F.R.

1983-01-01

Components made from hydride-forming metals can be brittle when particles of hydride are present. The solid solubility limit of hydrogen in these metals needs to be known so that fracture resistance can be properly assessed. Stress affects the solubility of hydrogen in metals. As hydrogen dissolves the metal volume increases, an applied hydrostatic tensile stress supplies work to increase the solubility. Precipitation of hydrides increases the volume further. A hydrostatic tensile stress promotes the formation of hydrides and tends to reduce the terminal solubility. For materials containing hydrogen in solution in equilibrium with hydrides, the effect of stress on the terminal solubility is given. Hydrogen migrates up tensile stress gradients because of the effect of stress on the solubility and solubility limit. Consequently, hydrogen concentrates at flaws. When hydrides are present in the metal matrix, those remote from the flaw tip will preferentially dissolve in favor of those precipitated at the flaw. If the stress is large enough, at some critical condition the hydrides at the flaw will crack. This is delayed hydrogen cracking. Notched and fatigue-cracked cantilever beam specimens (6) (38 x 4 x 3 mm) were machined from the circumferential direction of several cold-worked Zr-2.5 at. % Nb pressure tubes. The chemical compositions had the ranges (in atomic %) Nb - 2.5 to 2.7; O - 0.58 to 0.71; H - 0.018 to 0.18. The effect of test temperature is for a specimen containing 0.13 at. % protium and 0.29 at .% deuterium. Between 505 K and 530 K was less than 1 hr, between 530 K and 537 K it increased to 25.8 h, while at 538 K no cracking was observed up to the 54 h

Molecular Simulation of Gas Solubility in Nitrile Butadiene Rubber.

Science.gov (United States)

Khawaja, M; Sutton, A P; Mostofi, A A

2017-01-12

Molecular simulation is used to compute the solubility of small gases in nitrile butadiene rubber (NBR) with a Widom particle-insertion technique biased by local free volume. The convergence of the method is examined as a function of the number of snapshots upon which the insertions are performed and the number of insertions per snapshot and is compared to the convergence of the unbiased Widom insertion technique. The effect of varying the definition of local free volume is also investigated. The acrylonitrile content of the polymer is altered to examine its influence on the solubility of helium, CO 2 , and H 2 O, and the solubilities of polar gases are found to be enhanced relative to those of nonpolar gases, in qualitative agreement with experiment. To probe this phenomenon further, the solubilities are decomposed into contributions from the neighborhoods of different atoms, using a Voronoi cell construction, and a strong bias is found for CO 2 and H 2 O in particular to be situated near nitrogen sites in the elastomer. Temperature is shown to suppress the solubility of CO 2 and H 2 O but to increase that of helium. Increasing pressure is found to suppress the solubility of all gases but at different rates, according to a balance between their molecular sizes and electrostatic interactions with the polymer. These results are relevant to the use of NBR seals at elevated temperatures and pressures, such as in oil and gas wells.

Recovery from inhibition by UV-irradiation of ornithine decarboxylase induction in human cells: implication of excision repair

Energy Technology Data Exchange (ETDEWEB)

Ben-Hur, E.; Prager, A. (Nuclear Research Centre-Negev, Beer-Sheva (Israel)); Buonaguro, F. (Argonne National Lab., IL (USA))

1982-05-01

Exposure of stationary-phase human breast carcinoma (T-47D) cells to far-UV light (254nm) inhibited the appearance of induced ornithine decarboxylase (ODC) activity. The fluence response curve had a shoulder (Dsub(q)=2Jm/sup -2/) followed by an exponential decline (D/sub 0/=4.2Jm/sup -2/). The cells could recover from this inhibition when the stimulus of induction of ODC was delayed for 20-24h after irradiation. Hydroxyurea (HU) when present at 3mM during the recovery period eliminated completely the ability of the cells to recover. This effect of HU on ODC induction was partially reversed by 50..mu..M of the four deoxyribonucleosides required for DNA synthesis. Neither HU nor the deoxyribonucleosides by themselves affected ODC induction in unirradiated cells. Since HU inhibited the recovery from potentially lethal UV damage and is a known inhibitor of excision repair, it is suggested that recovery from UV-induced inhibition of ODC induction depends on excision-repair of DNA damage. This interpretation is strongly supported by the finding that specific photolysis of 5-bromodeoxyuridine, incorporated into DNA during the recovery period, inhibited recovery of ODC induction from inhibition by UV light.

Comparison of the effects of an ornithine decarboxylase inhibitor on the intestinal epithelium and on intestinal tumors.

Science.gov (United States)

Tutton, P J; Barkla, D H

1986-12-01

Ornithine decarboxylase (ODC) catalyzes the rate-limiting step in the synthesis of polyamines, it has a short half-life, and its synthesis is under hormonal control. Recently, insight into the role of ODC and thus into the physiology of polyamines has been gained by the use of an inhibitor of ODC, difluoromethylornithine (DFMO). In the present report cell proliferation was measured by a stathmokinetic method in the crypt epithelium of the jejunum and colon of normal rats and in dimethylhydrazine-induced colonic tumors. Growth of human colon tumor xenografts in immunosuppressed mice and mouse colon tumor isografts was also assessed. Cell proliferation in primary colonic tumors was substantially suppressed by a single dose of DFMO at 100 mg/kg whereas the normal crypt epithelium of the small and large intestine required two doses at 400 mg/kg to produce a similar magnitude of inhibition of cell proliferation. DFMO was also found to suppress cell proliferation in, and the growth of, the transplantable colon cancers. Because of the apparent selectivity of the antimitotic activity of DFMO towards tumors, ODC inhibitors may prove to be useful anticancer drugs.

Study on REE bound water-soluble polysaccharides in plant

International Nuclear Information System (INIS)

Wang Yuqi; Guo Fanqing; Xu Lei; Chen Hongmin; Sun Jingxin; Cao Guoyin

1999-01-01

The binding of REE with water-soluble polysaccharides (PSs) in leaves of fern Dicranopteris Dichotoma (DD) has been studied by molecular activation analysis. The cold-water-soluble and hot-water-soluble PSs in leaves of DD were obtained by using biochemical separation techniques. The PSs of non-deproteinization and deproteinization, were separated on Sephadex G-200 gel permeation chromatography. The absorption curves of elution for the PSs were obtained by colorimetry, and the proteins were detected using Coomassic brilliant G-250. Eight REEs (La, Ce, Nd, Sm, Eu, Tb, Yb and Lu) in these PSs were determined by instrumental neutron activation analysis. The results obtained show that the REEs are bound firmly with the water-soluble PSs in the plant. A measurement demonstrates that the PSs bound with REEs are mainly of smaller molecular weight (10,000 to 20,000 Dalton)

CCN activation of fumed silica aerosols mixed with soluble pollutants

Science.gov (United States)

Dalirian, M.; Keskinen, H.; Ahlm, L.; Ylisirniö, A.; Romakkaniemi, S.; Laaksonen, A.; Virtanen, A.; Riipinen, I.

2014-09-01

Particle-water interactions of completely soluble or insoluble particles are fairly well understood but less is known of aerosols consisting of mixtures of soluble and insoluble components. In this study, laboratory measurements were performed to investigate cloud condensation nuclei (CCN) activity of silica particles coated with ammonium sulphate (a salt), sucrose (a sugar) and bovine serum albumin known as BSA (a protein). In addition, the agglomerated structure of the silica particles was investigated by estimating the surface equivalent diameter based on measurements with a Differential Mobility Analyzer (DMA) and an Aerosol Particle Mass Analyzer (APM). By using the surface equivalent diameter the non-sphericity of the particles containing silica was accounted for when estimating CCN activation. Furthermore, characterizing critical supersaturations of particles consisting of pure soluble on insoluble compounds using existing frameworks showed that the CCN activation of single component particles was in good agreement with Köhler and adsorption theory based models when the agglomerated structure was accounted for. For mixed particles the CCN activation was governed by the soluble components, and the soluble fraction varied considerably with particle size for our wet-generated aerosols. Our results confirm the hypothesis that knowing the soluble fraction is the key parameter needed for describing the CCN activation of mixed aerosols, and highlight the importance of controlled coating techniques for acquiring a detailed understanding of the CCN activation of atmospheric insoluble particles mixed with soluble pollutants.

Empirical evaluation of lung solubilities of airborne contamination at Harwell facilities

International Nuclear Information System (INIS)

Bull, R. K.; Wilson, G.

2011-01-01

Lung solubility is the key parameter in determining intakes and doses from inhalation of airborne contamination. However, information on lung solubility can be difficult to acquire, particularly for the historical exposures that are of relevance to lifetime-dose reconstruction. In this study, an empirical approach has been made in which over 200 dose assessments, mainly for Pu and Am, from the period 1986 to 2005 were re-evaluated and the solubility mix required for the best fit to the data was determined. The average of these solubility mixtures for any building or facility can be used as the default solubility for retrospective dose assessments for that facility. Results are presented for a radiochemistry facility, a materials development facility and a waste-storage/handling building at Harwell. The latter two areas are characterised by aerosols that are predominantly insoluble (type S), whereas the radiochemistry facility has a heterogeneous mixture of insoluble and soluble aerosols. The implications of these results for dose reconstruction are discussed in the paper. (authors)

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

Science.gov (United States)

Ahuja, Naveen; Katare, Om Prakash; Singh, Bhupinder

2007-01-01

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

Glutamic acid decarboxylase autoantibody-positivity post-partum is associated with impaired β-cell function in women with gestational diabetes mellitus

DEFF Research Database (Denmark)

Lundberg, T. P.; Højlund, K.; Snogdal, L. S.

2015-01-01

AIMS: To investigate whether the presence of glutamic acid decarboxylase (GAD) autoantibodies post-partum in women with prior gestational diabetes mellitus was associated with changes in metabolic characteristics, including β-cell function and insulin sensitivity. METHODS: During 1997-2010, 407...... women with gestational diabetes mellitus were offered a 3-month post-partum follow-up including anthropometrics, serum lipid profile, HbA1c and GAD autoantibodies, as well as a 2-h oral glucose tolerance test (OGTT) with blood glucose, serum insulin and C-peptide at 0, 30 and 120 min. Indices of insulin...... similar age and prevalence of diabetes mellitus. Women who were GAD+ve had significantly higher 2-h OGTT glucose concentrations during their index-pregnancy (10.5 vs. 9.8 mmol/l, P = 0.001), higher fasting glucose (5.2 vs. 5.0 mmol/l, P = 0.02) and higher 2-h glucose (7.8 vs. 7.1 mmol/l, P = 0.05) post...

Lack of Association Between Polymorphisms in Dopa Decarboxylase and Dopamine Receptor-1 Genes With Childhood Autism in Chinese Han Population.

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Yu, Hong; Liu, Jun; Yang, Aiping; Yang, Guohui; Yang, Wenjun; Lei, Heyue; Quan, Jianjun; Zhang, Zengyu

2016-04-01

Genetic factors play an important role in childhood autism. This study is to determine the association of single-nucleotide polymorphisms in dopa decarboxylase (DDC) and dopamine receptor-1 (DRD1) genes with childhood autism, in a Chinese Han population. A total of 211 autistic children and 250 age- and gender-matched healthy controls were recruited. The severity of disease was determined by Children Autism Rating Scale scores. TaqMan Probe by real-time polymerase chain reaction was used to determine genotypes and allele frequencies of single-nucleotide polymorphism rs6592961 in DDC and rs251937 in DRD1. Case-control and case-only studies were respectively performed, to determine the contribution of both single-nucleotide polymorphisms to the predisposition of disease and its severity. Our results showed that there was no significant association of the genotypes and allele frequencies of both single-nucleotide polymorphisms concerning childhood autism and its severity. More studies with larger samples are needed to corroborate their predicting roles. © The Author(s) 2015.

Correlation of Helium Solubility in Liquid Nitrogen

Science.gov (United States)

VanDresar, Neil T.; Zimmerli, Gregory A.

2012-01-01

A correlation has been developed for the equilibrium mole fraction of soluble gaseous helium in liquid nitrogen as a function of temperature and pressure. Experimental solubility data was compiled and provided by National Institute of Standards and Technology (NIST). Data from six sources was used to develop a correlation within the range of 0.5 to 9.9 MPa and 72.0 to 119.6 K. The relative standard deviation of the correlation is 6.9 percent.

Screening and kinetics of glutaminase and glutamate decarboxylase producing lactic acid bacteria from fermented Thai foods

Directory of Open Access Journals (Sweden)

Sasimar Woraharn

2014-12-01

Full Text Available L-glutaminase and glutamic acid decarboxylase (GAD catalyzes the hydrolysis of L-glutamine and glutamate, respectively. L-glutaminase widely used in cancer therapy along with a combination of other enzymes and most importantly these enzymes were used in food industries, as a major catalyst of bioconversion. The current investigation was aimed to screen and select L-glutaminase, and GAD producing lactic acid bacteria (LAB. A total of 338 LAB were isolated from fermented meat, fermented fish, fermented soya bean, fermented vegetables and fruits. Among 338 isolates, 22 and 237 LAB has been found to be positive for L-glutaminase and GAD, respectively. We found that 30 days of incubation at 35 ºC and pH 6.0 was the optimum condition for glutaminase activity by G507/1. G254/2 was found to be the best for GAD activity with the optimum condition of pH 6.5, temperature 40 ºC and ten days of incubation. These LAB strains, G507/1 and G254/2, were identified as close relative of Lactobacillus brevis ATCC 14869 and Lactobacillus fermentum NBRC 3956, respectively by 16S rRNA sequencing. Further, improvements in up-stream of the fermentation process with these LAB strains are currently under development.

Histidine Decarboxylase Knockout Mice as a Model of the Pathophysiology of Tourette Syndrome and Related Conditions.

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Pittenger, Christopher

2017-01-01

While the normal functions of histamine (HA) in the central nervous system have gradually come into focus over the past 30 years, the relationship of abnormalities in neurotransmitter HA to human disease has been slower to emerge. New insight came with the 2010 description of a rare nonsense mutation in the biosynthetic enzyme histidine decarboxylase (Hdc) that was associated with Tourette syndrome (TS) and related conditions in a single family pedigree. Subsequent genetic work has provided further support for abnormalities of HA signaling in sporadic TS. As a result of this genetic work, Hdc knockout mice, which were generated more than 15 years ago, have been reexamined as a model of the pathophysiology of TS and related conditions. Parallel work in these KO mice and in human carriers of the Hdc mutation has revealed abnormalities in the basal ganglia system and its modulation by dopamine (DA) and has confirmed the etiologic, face, and predictive validity of the model. The Hdc-KO model thus serves as a unique platform to probe the pathophysiology of TS and related conditions, and to generate specific hypotheses for subsequent testing in humans. This chapter summarizes the development and validation of this model and recent and ongoing work using it to further investigate pathophysiological changes that may contribute to these disorders.

Current concepts on the physiology and genetics of neurotransmitters-mediating enzyme-aromatic L-amino acid decarboxylase

International Nuclear Information System (INIS)

Rahman, M.K.

1993-03-01

Two most important neurotransmitters, dopamine and serotonin are mediated by the enzyme aromatic L-amino acid decarboxylase (AADC). Because of their importance in the regulation of neuronal functions, behaviour and emotion of higher animals, many researchers are working on this enzyme to elucidate its physiological properties, structure and genetic aspects. We have discovered this enzyme in the mammalian blood, we established sensitive assay methods for the assay of the activities of this enzyme. We have made systematic studies on this enzyme in the tissues and brains of rats, and human subjects. We have found an endogenous inhibitor of this enzyme in the monkey's blood. The amino acid sequences of human AADC has been compared to rat or bovine. A full-length cDNA clone encoding human AADC has been isolated. Very recently the structure of human AADC gene including 5'-flaking region has been characterized and the transcriptional starting point has been determined. The human AADC gene assigned to chromosome 7. Up-to-date research data have shown that AADC is encoded by a single gene. Recently two patients with AADC deficiency were reported. This paper describes the systematic up-to-date review studies on AADC. (author). 62 refs, 5 figs, 8 tabs

Disruption of pknG enhances production of gamma-aminobutyric acid by Corynebacterium glutamicum expressing glutamate decarboxylase.

Science.gov (United States)

Okai, Naoko; Takahashi, Chihiro; Hatada, Kazuki; Ogino, Chiaki; Kondo, Akihiko

2014-01-01

Gamma-aminobutyric acid (GABA), a building block of the biodegradable plastic polyamide 4, is synthesized from glucose by Corynebacterium glutamicum that expresses Escherichia coli glutamate decarboxylase (GAD) B encoded by gadB. This strain was engineered to produce GABA more efficiently from biomass-derived sugars. To enhance GABA production further by increasing the intracellular concentration of its precursor glutamate, we focused on engineering pknG (encoding serine/threonine protein kinase G), which controls the activity of 2-oxoglutarate dehydrogenase (Odh) in the tricarboxylic acid cycle branch point leading to glutamate synthesis. We succeeded in expressing GadB in a C. glutamicum strain harboring a deletion of pknG. C. glutamicum strains GAD and GAD ∆pknG were cultured in GP2 medium containing 100 g L(-1) glucose and 0.1 mM pyridoxal 5'-phosphate. Strain GAD∆pknG produced 31.1 ± 0.41 g L(-1) (0.259 g L(-1) h(-1)) of GABA in 120 hours, representing a 2.29-fold higher level compared with GAD. The production yield of GABA from glucose by GAD∆pknG reached 0.893 mol mol(-1).

Solubility of simulated PWR primary circuit corrosion products

International Nuclear Information System (INIS)

Kunig, R.H.; Sandler, Y.L.

1986-08-01

The solubility behavior of non-stoichiometric nickel ferrites, nickel-cobalt ferrites, and magnetite, as model substances for the corrosion products (''crud'') formed in nuclear pressurized water reactors, was studied in a flow system in aqueous solutions of lithium hydroxide, boric acid, and hydrogen with pH, temperature, and hydrogen concentrations as parameters. Below the temperature region of 300 to 330 0 C, at hydrogen concentrations of 25 to 40 cm 3 /kg H 2 O as used during reactor operation, the solubility of nickel-cobalt ferrite is the same as that of Ni and Co/sub x/Fe/sub 3-x/O 4 (x 3 /kg of hydrogen, the equilibrium iron and nickel solubilities increase congruently down to about 100 0 C, in a manner consistent with the solubility of Fe 3 O 4 , but sharply decline at lower temperatures, apparently due to formation of a borated layer. A cooldown experiment on a time scale of a typical Westinghouse reactor shutdown, as well as static experiments carried out on various ferrite samples at 60 0 C show that after addition of oxygen or peroxide evolution of nickel (and possibly cobalt) above the equilibrium solubility in hydrogen depends on the presence of dissociation products prior to oxidation. Thermodynamic calculations of various reduction and oxidative decomposition reactions for stoichiometric and non-stoichiometric nickel ferrite and cobalt ferrite are presented. Their significance to evolutions of nickel and cobalt on reactor shutdown is discussed. 30 refs., 38 figs., 34 tabs

Solubility study of Tc(Ⅳ) in a granitic water

International Nuclear Information System (INIS)

Liu Dejun; Yao Jun; Wang Bo

2008-01-01

The deep geological disposal of the high level radioactive wastes is expected to be a safe disposal method in most countries. The long-lived fission product 99 Tc is present in large quantities in nuclear wastes and its chemical behavior in aqueous solution is of considerable interest. Under oxidizing conditions technetium exists as the anionic species TcO 4 - whereas under the reducing conditions, expected to exist in a deep geological repository, it is generally predicted that technetium will be present as TcO 2 -nH 2 O. Hence, the mobility of Tc(Ⅳ) in reducing groundwater may be limited by the solubility of TcO 2 ·nH 2 O under these conditions. Due to this fact it is important to investigate the solubility of TcO 2 ·nH 2 O. The solubility determines the release of radionuclides from waste form and is used as a source term in radionuclide migration analysis in performance assessment of radioactive waste repository. Technetium (Ⅳ) was prepared by reduction of a technetate solution with Sn 2+ . The solubility of Tc(Ⅳ) has been determined in simulated groundwater and redistilled water under aerobic and anaerobic conditions. The effects of pH and CO 3 2- concentration of solution on solubility of Tc(Ⅳ) were studied. The concentration of total technetium and Tc(Ⅳ) species in the solutions were periodically determined by separating the oxidized and reduced technetium species using a solvent extraction procedure and counting the beta activity of the 99 Tc with a liquid scintillation counter. The experimental results show that the rate of oxidation of Tc(Ⅳ) in simulated groundwater and redistilled water is about (1.49-1.86)x10 -9 mol·L -1 d -1 under aerobic conditions, while no Tc(Ⅳ) oxidation was detected in simulated groundwater and redistilled water under anaerobic conditions. Under aerobic or anaerobic conditions the solubility of Tc(Ⅳ) in simulated groundwater and redistilled water is equal on the whole after centrifugation or ultrafiltration. The

Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

Science.gov (United States)

Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

2016-08-01

The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

Thermodynamic Solubility Profile of Carbamazepine-Cinnamic Acid Cocrystal at Different pH.

Science.gov (United States)

Keramatnia, Fatemeh; Shayanfar, Ali; Jouyban, Abolghasem

2015-08-01

Pharmaceutical cocrystal formation is a direct way to dramatically influence physicochemical properties of drug substances, especially their solubility and dissolution rate. Because of their instability in the solution, thermodynamic solubility of cocrystals could not be determined in the common way like other compounds; therefore, the thermodynamic solubility is calculated through concentration of their components in the eutectic point. The objective of this study is to investigate the effect of an ionizable coformer in cocrystal with a nonionizable drug at different pH. Carbamazepine (CBZ), a nonionizable drug with cinnamic acid (CIN), which is an acidic coformer, was selected to prepare CBZ-CIN cocrystal and its thermodynamic solubility was studied in pH range 2-7. Instead of HPLC that is a costly and time-consuming method, a chemometric-based approach, net analyte signal standard addition method, was selected for simultaneous determination of CBZ and CIN in solution. The result showed that, as pH increases, CIN ionization leads to change in CBZ-CIN cocrystal solubility and stability in solution. In addition, the results of this study indicated that there is no significant difference between intrinsic solubility of CBZ and cocrystal despite the higher ideal solubility of cocrystal. This verifies that ideal solubility is not good parameter to predict cocrystal solubility. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Polyamine metabolism in ripening tomato fruit. II. Polyamine metabolism and synthesis in relation to enhanced putrescine content and storage life of alc tomato fruit

International Nuclear Information System (INIS)

Rastogi, R.; Davies, P.J.

1991-01-01

The fruit of the Alcobaca landrace of tomato (Lycopersicon esculentum Mill.) have prolonged keeping qualities (determined by the allele alc) and contain three times as much putrescine as the standard Rutgers variety (Alc) at the ripe stage. Polyamine metabolism and biosynthesis were compared in fruit from Rutgers and Rutgers-alc-a near isogenic line possessing the allele alc, at four different stages of ripening. The levels of soluble polyamine conjugates as well as wall bound polyamines in the pericarp tissue and jelly were very low or nondetectable in both genotypes. The increase in putrescine content in alc pericarp is not related to normal ripening as it occurred with time and whether or not the fruit ripened. Pericarp discs of both normal and alc fruit showed a decrease in the metabolism of [1,4- 14 C]putrescine and [terminal labeled- 3 H]spermidine with ripening, but there were no significant differences between the two genotypes. The activity of ornithine decarboxylase was similar in the fruit pericarp of the two lines. Arginine decarboxylase activity decreased during ripening in Rutgers but decreased and rose again in Rutgers-alc fruit, and as a result it was significantly higher in alc fruit than in the normal fruit at the ripe stage. The elevated putrescine levels in alc fruit appear, therefore, to be due to an increase in the activity of arginine decarboxylase

Some thermodynamic aspects of the solubility of iron in sodium

International Nuclear Information System (INIS)

Awasthi, S.P.; Sundaresan, M.

1984-01-01

Because of the use of liquid sodium as a heat transfer fluid in fast breeder reactors, its interaction with Fe and some alloying elements, has assumed great importance. Solubility is an important manifestation of this interaction, but there exists in literature a wide divergence in the data on the solubility of iron, which is known to have an intimate relationship with temperature and the concentration of available oxygen in sodium. An attempt has been made, here, to arrive at the mechanism of the observed enhanced solubility of iron in presence of oxygen by analysing the available experimental isothermal and athermal data on solubilities in literature by computing the relevant thermodynamic parameters for various probable interactions in the Na-O-Fe system. From comparison of these with the sign and magnitude of the theoretically calculated thermodynamic values, it has been shown that the predominant iron species existing in liquid sodium in presence of higher concentrations of oxygen is the soluble compound Na 4 FeO 3 . The most probable mechanism of the enhanced solubility of iron can be explained in terms of a sequence involving the initial formation of iron oxide (FeO) in liquid sodium, followed by its conversion to the compound Na 4 FeO 3 . (author)

Concomitant intake of alcohol may increase the absorption of poorly soluble drugs.

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Fagerberg, Jonas H; Sjögren, Erik; Bergström, Christel A S

2015-01-25

Ethanol can increase the solubility of poorly soluble and hence present a higher drug concentration in the gastrointestinal tract. This may produce a faster and more effective absorption resulting in variable and/or high drug plasma concentrations, both of which can lead to adverse drug reactions. In this work we therefore studied the solubility and absorption effects of nine diverse compounds when ethanol was present. The apparent solubility was measured using the μDiss Profiler Plus (pION, MA) in four media representing gastric conditions with and without ethanol. The solubility results were combined with in-house data on solubility in intestinal fluids (with and without ethanol) and pharmacokinetic parameters extracted from the literature and used as input in compartmental absorption simulations using the software GI-Sim. Apparent solubility increased more than 7-fold for non-ionized compounds in simulated gastric fluid containing 20% ethanol. Compounds with weak base functions (cinnarizine, dipyridamole and terfenadine) were completely ionized at the studied gastric pH and their solubility was therefore unaffected by ethanol. Compounds with low solubility in intestinal media and a pronounced solubility increase due to ethanol in the upper gastric compartments showed an increased absorption in the simulations. The rate of absorption of the acidic compounds indomethacin and indoprofen was slightly increased but the extent of absorption was unaffected as the complete doses were readily absorbed even without ethanol. This was likely due to a high apparent solubility in the intestinal compartment where the weak acids are ionized. The absorption of the studied non-ionizable compounds increased when ethanol was present in the gastric and intestinal media. These results indicate that concomitant intake of alcohol may significantly increase the solubility and hence, the plasma concentration for non-ionizable, lipophilic compounds with the potential of adverse drug

On solubility of rare earth chlorides in water at different temperatures

International Nuclear Information System (INIS)

Nikolaev, A.V.; Sorokina, A.A.; Sokolova, N.P.; Kotlyar-Shapirov, G.S.; Bagryantseva, L.I.

1978-01-01

Solubility of rare earth chlorides at -5, -10 and -15 deg C is studied. Rare earth chloride solubility dependences on the temperature in the interval from -15 to 50 deg C are presented. Decrease of solubility temperature coefficient to a zero is observed at temperature drop almost for all rare earth chlorides. Solubility temperature coefficient at the same temperature but for different rare earth chlorides reduces appreciably with the growth of rare earth chloride serial number. This testifies to the corresponding decrease of integral solution heat of rare earth chloride crystallohydrates

Solubility of calcium in CaO-CaCl2

International Nuclear Information System (INIS)

Perry, G.S.; Shaw, S.J.

1991-06-01

The Direct Oxide Reduction (DOR) process is well established as a process to produce plutonium metal from plutonium dioxide by reaction with calcium. Calcium chloride is added to dissolve the calcium oxide produced, allowing the metal to coalesce into a button. Since calcium metal melts at 840 0 C and DOR can take place successfully below this temperature, it is likely calcium dissolved in calcium chloride reacts with the plutonium dioxide. The solubility of calcium in calcium chloride is reasonably well established but the effect of the CaO formed during the DOR process on the solubility of calcium has not been previously determined. For this reason the solubility of calcium in CaCl 2 -CaO melts at 800 o C has been studied. The solubility decreases from 2.7 mol % in CaCl 2 to 0.4 mol % in 9 mol % CaO-CaCl 2 . (author)

Tryptophan decarboxylase plays an important role in ajmalicine biosynthesis in Rauvolfia verticillata.

Science.gov (United States)

Liu, Wanhong; Chen, Rong; Chen, Min; Zhang, Haoxing; Peng, Meifang; Yang, Chunxian; Ming, Xingjia; Lan, Xiaozhong; Liao, Zhihua

2012-07-01

Tryptophan decarboxylase (TDC) converts tryptophan into tryptamine that is the indole moiety of ajmalicine. The full-length cDNA of Rauvolfia verticillata (RvTDC) was 1,772 bps that contained a 1,500-bp ORF encoding a 499-amino-acid polypeptide. Recombinant 55.5 kDa RvTDC converted tryptophan into tryptamine. The K (m) of RvTDC for tryptophan was 2.89 mM, higher than those reported in other TIAs-producing plants. It demonstrated that RvTDC had lower affinity to tryptophan than other plant TDCs. The K (m) of RvTDC was also much higher than that of strictosidine synthase and strictosidine glucosidase in Rauvolfia. This suggested that TDC might be the committed-step enzyme involved in ajmalicine biosynthesis in R. verticillata. The expression of RvTDC was slightly upregulated by MeJA; the five MEP pathway genes and SGD showed no positive response to MeJA; and STR was sharply downregulated by MeJA. MeJA-treated hairy roots produced higher level of ajmalicine (0.270 mg g(-1) DW) than the EtOH control (0.183 mg g(-1) DW). Highest RvTDC expression level was detected in hairy root, about respectively 11, 19, 65, and 109-fold higher than in bark, young leaf, old leaf, and root. Highest ajmalicine content was also found in hairy root (0.249 mg g(-1) DW) followed by in bark (0.161 mg g(-1) DW) and young leaf (0.130 mg g(-1) DW), and least in root (0.014 mg g(-1) DW). Generally, the expression level of RvTDC was positively consistent with the accumulation of ajmalicine. Therefore, it could be deduced that TDC might be the key enzyme involved in ajmalicine biosynthesis in Rauvolfia.

Structural Basis for Nucleotide Binding and Reaction Catalysis in Mevalonate Diphosphate Decarboxylase

Energy Technology Data Exchange (ETDEWEB)

Barta, Michael L.; McWhorter, William J.; Miziorko, Henry M.; Geisbrecht, Brian V. (UMKC)

2012-09-17

Mevalonate diphosphate decarboxylase (MDD) catalyzes the final step of the mevalonate pathway, the Mg{sup 2+}-ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP), producing isopentenyl diphosphate (IPP). Synthesis of IPP, an isoprenoid precursor molecule that is a critical intermediate in peptidoglycan and polyisoprenoid biosynthesis, is essential in Gram-positive bacteria (e.g., Staphylococcus, Streptococcus, and Enterococcus spp.), and thus the enzymes of the mevalonate pathway are ideal antimicrobial targets. MDD belongs to the GHMP superfamily of metabolite kinases that have been extensively studied for the past 50 years, yet the crystallization of GHMP kinase ternary complexes has proven to be difficult. To further our understanding of the catalytic mechanism of GHMP kinases with the purpose of developing broad spectrum antimicrobial agents that target the substrate and nucleotide binding sites, we report the crystal structures of wild-type and mutant (S192A and D283A) ternary complexes of Staphylococcus epidermidis MDD. Comparison of apo, MVAPP-bound, and ternary complex wild-type MDD provides structural information about the mode of substrate binding and the catalytic mechanism. Structural characterization of ternary complexes of catalytically deficient MDD S192A and D283A (k{sub cat} decreased 10{sup 3}- and 10{sup 5}-fold, respectively) provides insight into MDD function. The carboxylate side chain of invariant Asp{sup 283} functions as a catalytic base and is essential for the proper orientation of the MVAPP C3-hydroxyl group within the active site funnel. Several MDD amino acids within the conserved phosphate binding loop ('P-loop') provide key interactions, stabilizing the nucleotide triphosphoryl moiety. The crystal structures presented here provide a useful foundation for structure-based drug design.

"JCE" Classroom Activity #105. A Sticky Situation: Chewing Gum and Solubility

Science.gov (United States)

Montes-Gonzalez, Ingrid; Cintron-Maldonado, Jose A.; Perez-Medina, Ilia E.; Montes-Berrios, Veronica; Roman-Lopez, Saurie N.

2010-01-01

In this Activity, students perform several solubility tests using common food items such as chocolate, chewing gum, water, sugar, and oil. From their observations during the Activity, students will initially classify the substances tested as soluble or insoluble. They will then use their understanding of the chemistry of solubility to classify the…

Facilitating protein solubility by use of peptide extensions

Science.gov (United States)

Freimuth, Paul I; Zhang, Yian-Biao; Howitt, Jason

2013-09-17

Expression vectors for expression of a protein or polypeptide of interest as a fusion product composed of the protein or polypeptide of interest fused at one terminus to a solubility enhancing peptide extension are provided. Sequences encoding the peptide extensions are provided. The invention further comprises antibodies which bind specifically to one or more of the solubility enhancing peptide extensions.

Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study

Directory of Open Access Journals (Sweden)

A. Vigo

2007-07-01

Full Text Available To efficiently examine the association of glutamic acid decarboxylase antibody (GADA positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65 were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (³1 U/mL was 7.3%. Baseline risk factors, with the exception of smoking and interleukin-6 (P £ 0.02, were generally similar between GADA-positive and -negative individuals. GADA positivity did not predict incident diabetes in multiply adjusted (HR = 1.04; 95%CI = 0.55, 1.96 proportional hazard analyses. However, a small non-significant adjusted risk (HR = 1.29; 95%CI = 0.58, 2.88 was seen for those in the highest tertile (³2.38 U/mL of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95%CI = 3.4, 28.5. In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.

Measurement of soluble nuclide dissolution rates from spent fuel

International Nuclear Information System (INIS)

Wilson, C.N.; Gray, W.J.

1990-01-01

Gaining a better understanding of the potential release behavior of water-soluble radionuclides is the focus of new laboratory spent fuel dissolution studies being planned in support of the Yucca Mountain Project. Previous studies have suggested that maximum release rates for actinide nuclides, which account for most of the long-term radioactivity in spent fuel, should be solubility-limited and should not depend on the characteristics or durability of the spent fuel waste form. Maximum actinide concentrations should be sufficiently low to meet the NRC (Nuclear Regulatory Commission) annual release limits. Potential release rates for soluble nuclides such as 99 Tc, 135 Cs, 14 C and 129 I, which account for about 1-2% of the activity in spent fuel at 1,000 years, are less certain and may depend on processes such as oxidation of the fuel in the repository air environment. Dissolution rates for several soluble nuclides have been measured from spent fuel specimens using static and semi-static methods. However, such tests do not provide a direct measurement of fuel matrix dissolution rates that may ultimately control soluble-nuclide release rates. Flow-through tests are being developed as a potential supplemental method for determining the matrix component of soluble-nuclide dissolution. Advantages and disadvantages of both semi-static and flow-through methods are discussed. Tests with fuel specimens representing a range of potential fuel states that may occur in the repository, including oxidized fuel, are proposed. Preliminary results from flow-through tests with unirradiated UO 2 suggesting that matrix dissolution rates are very sensitive to water composition are also presented

Bioinspired co-crystals of Imatinib providing enhanced kinetic solubility.

Science.gov (United States)

Reggane, Maude; Wiest, Johannes; Saedtler, Marco; Harlacher, Cornelius; Gutmann, Marcus; Zottnick, Sven H; Piechon, Philippe; Dix, Ina; Müller-Buschbaum, Klaus; Holzgrabe, Ulrike; Meinel, Lorenz; Galli, Bruno

2018-05-04

Realizing the full potential of co-crystals enhanced kinetic solubility demands a comprehensive understanding of the mechanisms of dissolution, phase conversion, nucleation and crystal growth, and of the complex interplay between the active pharmaceutical ingredient (API), the coformer and co-existing forms in aqueous media. One blueprint provided by nature to keep poorly water-soluble bases in solution is the complexation with phenolic acids. Consequently, we followed a bioinspired strategy for the engineering of co-crystals of a poorly water-soluble molecule - Imatinib - with a phenolic acid, syringic acid (SYA). The dynamics of dissolution and solution-mediated phase transformations were monitored by Nuclear Magnetic Resonance (NMR) spectroscopy, providing mechanistic insights into the 60 fold-increased long lasting concentrations achieved by the syringate co-crystals as compared to Imatinib base and Imatinib mesylate. This lasting effect was linked to SYA's ability to delay the formation and nucleation of Imatinib hydrate - the thermodynamically stable form in aqueous media - through a metastable association of SYA with Imatinib in solution. Results from permeability studies evidenced that SYA did not impact Imatinib's permeability across membranes while suggesting improved bioavailability through higher kinetic solubility at the biological barriers. These results reflect that some degree of hydrophobicity of the coformer might be key to extend the kinetic solubility of co-crystals with hydrophobic APIs. Understanding how kinetic supersaturation can be shaped by the selection of an interactive coformer may help achieving the needed performance of new forms of poorly water-soluble, slowly dissolving APIs. Copyright © 2018. Published by Elsevier B.V.

Solubility of ferrocyanide compounds. Ferrocyanide Safety Project, Interim report FY1994

International Nuclear Information System (INIS)

Rai, D.; Felmy, A.R.; Smith, S.C.; Ryan, J.L.

1994-10-01

The solubility of Cs 2 NiFe(CN) 6 (c) [1] as a function of NaOH and temperature was determined to ascertain whether [1] shows retrograde solubility (i.e., decreasing solubility with increasing temperature), which would have bearing on the possible formation of ''hot spots'' in the tanks and thus the safety of the ferrocyanide tanks. The results show that the aqueous concentrations of Cs in equilibrium with [1] at 25, 60, 75 and 90 C are similar (within the limits of experimental error), indicating that [1] does not show retrograde solubility. To understand general solubility relationships of Ni 2 Fe(CN) 6 (c) [2] and to determine the influence on solubility of high electrolyte concentrations (e.g., NaNO 3 ) that are commonly encountered in the ferrocyanide tanks, the solubility of [2] as a function of CsNO 3 , NiCl 2 , and NaNO 3 was determined. In general, [2] is fairly insoluble and shows slightly increased solubility at high electrolyte concentrations only. For [2] in NiCl 2 , the aqueous Fe concentrations show first a decrease and then an increase with the increase in NiCl 2 concentrations. The increase in Fe concentrations at high Ni concentrations appears to be the result of replacement of Fe by Ni in the [2] structure. For [2] in CsNO 3 and at 0.001 M Na 4 Fe(CN) 6 , the Cs is quantitatively removed from solution at low added Cs concentrations and appears to approach the final solid composition of [1]. The solubility of [2] in NaNO 3 and at 0.001 M Na 4 Fe(CN) 6 shows an increase in Ni concentrations to about 0.5 mg/l at NaNO 3 concentrations > 1.0 M. These increased Ni concentrations may be the result of substitution of Na for Ni in the solid phase

Reversible, reagentless solubility changes in phosphatidylcholine-stabilized gold nanoparticles

International Nuclear Information System (INIS)

Mackiewicz, Marilyn R; Ayres, Benjamin R; Reed, Scott M

2008-01-01

Phosphatidylcholine (PC) is a versatile ligand for synthesizing gold nanoparticles that are soluble in either organic or aqueous media. Here we report a novel route to organic-soluble, PC-stabilized gold nanoparticles that can be re-suspended in water after removal of the organic solvent. Similarly, we show that PC-stabilized gold nanoparticles synthesized in water can be re-suspended in organic solvents after complete removal of water. Without complete removal of the solvent, the nanoparticles retain their original solubility and do not phase transfer. This change in solvent preference from organic to aqueous and vice versa without the use of an additional phase transfer reagent is novel, visually striking, and of utility for synthetic modification of nanoparticles. This approach allows chemical reactions to be performed on nanoparticles in organic solvents followed by conversion of the products to water-soluble materials. A narrow distribution of PC-stabilized gold nanoparticles was obtained after phase transfer to water as characterized by UV-visible (UV-vis) spectroscopy and transmission electron microscopy (TEM), demonstrating that the narrow distribution obtained from the organic synthesis is retained after transfer to water. This method produces water-soluble nanoparticles with a narrower dispersity than is possible with direct aqueous synthesis

Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

Science.gov (United States)

Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

2016-01-01

Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

Solubility study of Tc(IV) in a granitic water

International Nuclear Information System (INIS)

Liu, D.J.; Yao, J.; Wang, B.; Bruggeman, C.; Maes, N.

2007-01-01

The deep geological disposal of the high level radioactive wastes is expected to be a safe disposal method in most countries. The long-lived fission product 99 Tc is present in large quantities in nuclear wastes and its chemical behavior in aqueous solution is of considerable interest. Under oxidizing conditions technetium exists as the anionic species TcO 4 - whereas under the reducing conditions, expected to exist in a deep geological repository, it is generally predicted that technetium will be present as TcO 2 .nH 2 O. Hence, the mobility of Tc(IV) in reducing groundwater may be limited by the solubility of TcO 2 .nH 2 O under these conditions. Due to this fact it is important to investigate the solubility of TcO 2 .nH 2 O. The solubility determines the release of radionuclides from waste form and is used as a source term in radionuclide migration analysis in performance assessment of radioactive waste repository. Technetium(IV) was prepared by reduction of a technetate solution with Sn 2+ . The solubility of Tc(IV) has been determined in simulated groundwater and redistilled water under aerobic and anaerobic conditions. The effects of pH and CO 3 2- concentration of solution on solubility of Tc(IV) were studied. The concentration of total technetium and Tc(IV) species in the solutions were periodically determined by separating the oxidized and reduced technetium species using a solvent extraction procedure and counting the beta activity of the 99 Tc with a liquid scintillation counter. The experimental results show that the rate of oxidation of Tc(IV) in simulated groundwater and redistilled water is about (1.49 ∝ 1.86) x 10 -9 mol L -1 d -1 under aerobic conditions, while no Tc(IV) oxidation was detected in simulated groundwater and redistilled water under anaerobic conditions. Under aerobic or anaerobic conditions the solubility of Tc(IV) in simulated groundwater and redistilled water is equal on the whole after centrifugation or ultrafiltration. The

[Variation of polysaccharides and alcohol-soluble extracts content of Dendrobium officinale].

Science.gov (United States)

Yu, Qiao-xian; Guo, Ying-ying; Si, Jin-ping; Wu, Ling-shang; Wang, Lin-hua

2014-12-01

To reveal the variation of polysaccharides and alcohol-soluble extract contents of Dendrobium officinale, the polysaccharides and alcohol-soluble extracts contents of three D. officinale strains were determined by phenol-sulfuric acid method and hot-dip method, respectively. The results showed that the contents of polysaccharides and alcohol-soluble extracts and their total content were significantly different among D. officinale samples collected in different periods, and the variations were closely related to the phenology of D. officinale. Additionally, the quality variation of polysaccharides was closely related to the flowering of D. officinale, while the alcohol-soluble extracts was closely associated to the formation and germination of buds. According to the dynamic variation of these two compounds, it is more reasonable to harvest D. officinale at biennials pre-bloom than at specific harvesting month considering polysaccharides content. It is better to harvest before the germination of buds considering alcohol-soluble extracts. While with regards to both polysaccharides and alcohol-soluble extract, it is better to harvest this plant at the period from the sprouting to pre-bloom next year.

Buckminsterfullerene's (C60) octanol-water partition coefficient (Kow) and aqueous solubility.

Science.gov (United States)

Jafvert, Chad T; Kulkarni, Pradnya P

2008-08-15

To assess the risk and fate of fullerene C60 in the environment, its water solubility and partition coefficients in various systems are useful. In this study, the log Kow of C60 was measured to be 6.67, and the toluene-water partition coefficient was measured at log Ktw = 8.44. From these values and the respective solubilities of C60 in water-saturated octanol and water-saturated toluene, C60's aqueous solubility was calculated at 7.96 ng/L(1.11 x 10(-11) M) for the organic solvent-saturated aqueous phase. Additionally, the solubility of C60 was measured in mixtures of ethanol-water and tetrahydrofuran-water and modeled with Wohl's equation to confirm the accuracy of the calculated solubility value. Results of a generator column experiment strongly support the hypothesis that clusters form at aqueous concentrations below or near this calculated solubility. The Kow value is compared to those of other hydrophobic organic compounds, and bioconcentration factors for C60 were estimated on the basis of Kow.

Data representing two separate LC-MS methods for detection and quantification of water-soluble and fat-soluble vitamins in tears and blood serum

Directory of Open Access Journals (Sweden)

Maryam Khaksari

2017-04-01

Full Text Available Two separate liquid chromatography (LC-mass spectrometry (MS methods were developed for determination and quantification of water-soluble and fat-soluble vitamins in human tear and blood serum samples. The water-soluble vitamin method was originally developed to detect vitamins B1, B2, B3 (nicotinamide, B5, B6 (pyridoxine, B7, B9 and B12 while the fat-soluble vitamin method detected vitamins A, D3, 25(OHD3, E and K1. These methods were then validated with tear and blood serum samples. In this data in brief article, we provide details on the two LC-MS methods development, methods sensitivity, as well as precision and accuracy for determination of vitamins in human tears and blood serum. These methods were then used to determine the vitamin concentrations in infant and parent samples under a clinical study which were reported in "Determination of Water-Soluble and Fat-Soluble Vitamins in Tears and Blood Serum of Infants and Parents by Liquid Chromatography/Mass Spectrometry DOI:10.1016/j.exer.2016.12.007 [1]". This article provides more details on comparison of vitamin concentrations in the samples with the ranges reported in the literature along with the medically accepted normal ranges. The details on concentrations below the limits of detection (LOD and limits of quantification (LOQ are also discussed. Vitamin concentrations were also compared and cross-correlated with clinical data and nutritional information. Significant differences and strongly correlated data were reported in [1]. This article provides comprehensive details on the data with slight differences or slight correlations.

Data representing two separate LC-MS methods for detection and quantification of water-soluble and fat-soluble vitamins in tears and blood serum.

Science.gov (United States)

Khaksari, Maryam; Mazzoleni, Lynn R; Ruan, Chunhai; Kennedy, Robert T; Minerick, Adrienne R

2017-04-01

Two separate liquid chromatography (LC)-mass spectrometry (MS) methods were developed for determination and quantification of water-soluble and fat-soluble vitamins in human tear and blood serum samples. The water-soluble vitamin method was originally developed to detect vitamins B 1 , B 2 , B 3 (nicotinamide), B 5 , B 6 (pyridoxine), B 7 , B 9 and B 12 while the fat-soluble vitamin method detected vitamins A, D 3 , 25(OH)D 3, E and K 1 . These methods were then validated with tear and blood serum samples. In this data in brief article, we provide details on the two LC-MS methods development, methods sensitivity, as well as precision and accuracy for determination of vitamins in human tears and blood serum. These methods were then used to determine the vitamin concentrations in infant and parent samples under a clinical study which were reported in "Determination of Water-Soluble and Fat-Soluble Vitamins in Tears and Blood Serum of Infants and Parents by Liquid Chromatography/Mass Spectrometry DOI:10.1016/j.exer.2016.12.007 [1]". This article provides more details on comparison of vitamin concentrations in the samples with the ranges reported in the literature along with the medically accepted normal ranges. The details on concentrations below the limits of detection (LOD) and limits of quantification (LOQ) are also discussed. Vitamin concentrations were also compared and cross-correlated with clinical data and nutritional information. Significant differences and strongly correlated data were reported in [1]. This article provides comprehensive details on the data with slight differences or slight correlations.

Detection of colloidal silver chloride near solubility limit

Science.gov (United States)

Putri, K. Y.; Adawiah, R.

2018-03-01

Detection of nanoparticles in solution has been made possible by several means; one of them is laser-induced breakdown detection (LIBD). LIBD is able to distinguish colloids of various sizes and concentrations. This technique has been used in several solubility studies. In this study, the formation of colloids in a mixed system of silver nitrate and sodium chloride was observed by acoustic LIBD. Silver chloride has low solubility limit, therefore LIBD measurement is appropriate. Silver and chloride solutions with equal concentrations, set at below and above the solubility of silver chloride as the expected solid product, were mixed and the resulting colloids were observed. The result of LIBD measurement showed that larger particles were present as more silver and chloride introduced. However, once the concentrations exceeded the solubility limit of silver chloride, the detected particle size seemed to be decreasing, hence suggested the occurrence of coprecipitation process. This phenomenon indicated that the ability of LIBD to detect even small changes in colloid amounts might be a useful tool in study on formation and stability of colloids, i.e. to confirm whether nanoparticles synthesis has been successfully performed and whether the system is stable or not.

Enhancement of soluble CD28 levels in the serum of Graves' disease.

Science.gov (United States)

Sun, Zhongwen; Yi, Lixian; Tao, Hong; Huang, Jingfang; Jin, Zhenghong; Xiao, Yang; Feng, Caiyun; Sun, Jing

2014-01-01

Graves' disease is an autoimmune disease of the thyroid gland mediated by T cells. CD28, a member of costimulatory molecules, plays a pivotal role in regulating T-cell responses. Plasma-soluble CD28 is one form of CD28 in peripheral blood. To investigate the concentrations of soluble CD28 in patients with Graves' disease, we used a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of CD28. Our results suggested that mean concentrations of soluble CD28 in plasma of patients with Graves' disease were 1.79 ±1.52 ng/ml, and levels of soluble CD28 in healthy subjects were only 0.83 ±1.35 ng/ml. Concentrations of soluble CD28 detected in patients with Graves' disease were significantly higher than those of healthy subjects (p Graves' disease. Therefore, aberrant elevation of plasma-soluble CD28 in patients with Graves' disease may reflect the dysregulation of immune system, and may serve as a useful biomarker in Graves' disease diagnosis.

Molecular model for solubility of gases in flexible polymers

DEFF Research Database (Denmark)

Neergaard, Jesper; Hassager, Ole; Szabo, Peter

1999-01-01

We propose a model for a priori prediction of the solubility of gases in flexible polymers. The model is based on the concept of ideal solubility of gases in liquids. According to this concept, the mole fraction of gases in liquids is given by Raoult's law with the total pressure and the vapor...... pressure of the gas, where the latter may have to be extrapolated. However, instead of considering each polymer molecule as a rigid structure, we estimate the effective number of degrees of freedom from an equivalent freely jointed bead-rod model for the flexible polymer. In this model, we associate...... the length of the rods with the molecular weight corresponding to a Kuhn step. The model provides a tool for crude estimation of the gas solubility on the basis of only the monomer unit of the polymer and properties of the gas. A comparison with the solubility data for several gases in poly...

Solubility correlation of anthraquinone derivatives in supercritical carbon dioxide

Science.gov (United States)

Alwi, Ratna Surya; Tamura, Kazuhiro; Tanaka, Tatsuro; Shimizu, Keisuke

2017-05-01

In this work, solubilites of anthraquinone dyestuffs in supercritical carbon dioxide (sc-CO2) were correlated by semiempirical models, expressed in terms of CO2 density. All solubility data used, experimentally measured by us, and were described in details elsewhere; namely, 1,4-diaminoanthraquinone and 1,4-bis(ethylamino)anthraquinone [J. Chem. Thermo-dyn. 74, 119-125 (2014)]; 1-amino-4-hydroxyanthraquinone and 1-hydroxy-4-nitroanthraquionone [Dyes Pigm.113, 351-356 (2015)]; 1,4-diamino-2,3-dichloroanthraquinone and 1,8-dihydroxy-4,5-dinitroanthraquinone [J. Chem. Eng. Data 60, 3046-3052 (2015)], and 1-aminoanthraquinone and 1-nitroanthraquinone [J. Chem. Thermodyn. 104, 162-168 (2017)]. It was found that 1-aminoanthraquinone shows the highest solubility at 383,15 K and pressure of 25 MPa, and the solubility of anthraquinone derivatives in sc-CO2 changed by the substituent groups. Satisfactory agreement between the experimental data used and calculated solubilities of the anthraquinone derivatives was obtained.

Anion Effects on Gas Solubility in Ionic Liquids

OpenAIRE

Anthony, Jennifer L.; Anderson, Jessica L.; Maginn, Edward J.; Brennecke, Joan F.

2005-01-01

This work presents the results of solubility measurements for a series of gases in 1-n-butyl-3-methyl imidazolium tetrafluoroborate and 1-n-butyl-3-methyl imidazolium bis(trifluoromethylsulfonyl) imide. The gases considered include benzene, carbon dioxide, nitrous oxide, ethylene, ethane, oxygen, and carbon monoxide. Carbon dioxide and oxygen solubilities are also reported in methyl-tributylammonium bis(trifluoromethylsulfonyl) imide, butyl-methyl pyrrolidinium bis(trifluoromethylsulfonyl) im...

Soluble and stable zethrenebis(dicarboximide) and its quinone

KAUST Repository

Sun, Zhe

2010-10-15

Soluble and stable zethrenebis(dicarboximide) (1) was synthesized by an in situ Stille cross coupling/transannular cyclization reaction. 1 showed largely improved photostability and solubility compared with the very unstable zethrene and it also exhibited far-red absorption and emission with high photoluminescence quantum yield. Bromination of 1 with NBS/DMF gave its quinone form 2 via an unusual pathway. © 2010 American Chemical Society.

Nanonization strategies for poorly water-soluble drugs.

Science.gov (United States)

Chen, Huabing; Khemtong, Chalermchai; Yang, Xiangliang; Chang, Xueling; Gao, Jinming

2011-04-01

Poor water solubility for many drugs and drug candidates remains a major obstacle to their development and clinical application. Conventional formulations to improve solubility suffer from low bioavailability and poor pharmacokinetics, with some carriers rendering systemic toxicities (e.g. Cremophor(®) EL). In this review, several major nanonization techniques that seek to overcome these limitations for drug solubilization are presented. Strategies including drug nanocrystals, nanoemulsions and polymeric micelles are reviewed. Finally, perspectives on existing challenges and future opportunities are highlighted. Published by Elsevier Ltd.

Solubility of Aragonite in Subduction Water-Rich Fluids

Science.gov (United States)

Daniel, I.; Facq, S.; Petitgirard, S.; Cardon, H.; Sverjensky, D. A.

2017-12-01

Carbonate dissolution in subduction zone fluids is critical to the carbon budget in subduction zones. Depending on the solubility of carbonate minerals in aqueous fluids, the subducting lithosphere may be either strongly depleted and the mantle metasomatized if the solubility is high, as recently suggested by natural samples or transport carbon deeper into the Earth's mantle if the solubility is low enough [1, 2]. Dissolution of carbonate minerals strongly depends on pressure and temperature as well as on the chemistry of the fluid, leading to a highly variable speciation of aqueous carbon. Thanks to recent advances in theoretical aqueous geochemistry [3, 4], combined experimental and theoretical efforts now allow the investigation of speciation and solubility of carbonate minerals in aqueous fluids at PT conditions higher than previously feasible [4, 5]. In this study, we present new in situ X-ray fluorescence measurements of aragonite dissolution up to 5 GPa and 500°C and the subsequent thermodynamic model of aragonite solubility in aqueous fluids thanks to the Deep Earth Water model. The amount of dissolved aragonite in the fluid was calculated from challenging and unprecedented measurements of the Ca fluorescence K-lines at low-energy. Experiments were performed at the ESRF, beamline ID27 using a dedicated design of an externally-heated diamond anvil cell and an incident high-flux and highly focused monochromatic X-Ray beam at 20 keV. The results show a spectacularly high solubility of aragonite at HP-HT in water, further enhanced in presence of NaCl and silica in the solution. [1] Frezzotti, M. L. et al. (2011) doi:10.1038/ngeo1246. [2] Ague, J. J. and Nicolescu, S. (2014) doi:10.1038/ngeo2143. [3] Pan, D. et al. (2013) doi: 10.1073/pnas.1221581110. [4] Sverjensky, D. A et al. (2014) doi: 10.1016/j.gca.2013.12.019. [5] Facq, S. et al. (2014) doi: 10.1016/j.gca.2014.01.030.

The solubility of hydrogen and deuterium in alloyed, unalloyed and impure plutonium metal

Energy Technology Data Exchange (ETDEWEB)

Richmond, Scott [Los Alamos National Laboratory; Bridgewater, Jon S [Los Alamos National Laboratory; Ward, John W [Los Alamos National Laboratory; Allen, Thomas A [Los Alamos National Laboratory

2009-01-01

Pressure-Composition-Temperature (PCT) data are presented for the plutonium-hydrogen (Pu-H) and plutonium-deuterium (Pu-D) systems in the solubility region up to terminal solubility (precipitation of PuH{sub 2}). The heats of solution for PuH{sub s} and PuD{sub s} are determined from PCT data in the ranges 350-625 C for gallium alloyed Pu and 400-575 C for unalloyed Pu. The solubility of high purity plutonium alloyed with 2 at.% gallium is compared to high purity unalloyed plutonium. Significant differences are found in hydrogen solubility for unalloyed Pu versus gallium alloyed Pu. Differences in hydrogen solubility due to an apparent phase change are observable in the alloyed and unalloyed solubilities. The effect of iron impurities on Pu-Ga alloyed Pu is shown via hydrogen solubility data as preventing complete homogenization.

The solubility of hydrogen and deuterium in alloyed, unalloyed and impure plutonium metal

International Nuclear Information System (INIS)

Richmond, S; Bridgewater, J S; Ward, J W; Allen, T H

2010-01-01

Pressure-Composition-Temperature (PCT) data are presented for the plutonium-hydrogen (Pu-H) and plutonium-deuterium (Pu-D) systems in the solubility region up to terminal solubility (precipitation of PuH 2 ). The heats of solution for PuH S and PuD S are determined from PCT data in the ranges 350-625 deg. C for gallium alloyed Pu and 400-575 deg. C for unalloyed Pu. The solubility of high purity plutonium alloyed with 2 at.% gallium is compared to high purity unalloyed plutonium. Significant differences are found in hydrogen solubility for unalloyed Pu versus gallium alloyed Pu. Differences in hydrogen solubility due to an apparent phase change are observable in the alloyed and unalloyed solubilities. The effect of iron impurities on Pu-Ga alloyed Pu is shown via hydrogen solubility data as preventing complete homogenization.

Leaching behavior of water-soluble carbohydrates from almond hulls

Science.gov (United States)

Over 58% of the dry matter content of the hulls from the commercial almond (Prunus dulcis (Miller) D.A. Webb) is soluble in warm water (50-70°C) extraction. The water-soluble extractables include useful amounts of fermentable sugars (glucose, fructose, sucrose), sugar alcohols (inositol and sorbito...

Solubility of {beta}-carotene in ethanol- and triolein-modified CO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Araus, Karina A. [Departamento de Ingenieria Quimica y Bioprocesos, Pontificia Universidad Catolica de Chile, Avda. Vicuna Mackenna 4860, Macul, Santiago (Chile); Canales, Roberto I. [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Avda. Espana 1680, Valparaiso (Chile); Valle, Jose M. del [Departamento de Ingenieria Quimica y Bioprocesos, Pontificia Universidad Catolica de Chile, Avda. Vicuna Mackenna 4860, Macul, Santiago (Chile); Fuente, Juan C. de la, E-mail: juan.delafuente@usm.cl [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Avda. Espana 1680, Valparaiso (Chile); Centro Regional de Estudios en Alimentos Saludables, Blanco 1623, Valparaiso (Chile)

2011-12-15

Highlights: > We measure solubility of {beta}-carotene in pure CO{sub 2}, and with ethanol and triolein as co-solvents. > We model the solubility of {beta}-carotene in pure CO{sub 2}, and with co-solvents. > The co-solvent effect of triolein over solubility of {beta}-carotene in CO{sub 2} was higher than ethanol. - Abstract: Modification of an experimental device and methodology improved speed and reproducibility of measurement of solubility of {beta}-carotene in pure and modified SuperCritical (SC) CO{sub 2} at (313 to 333) K. Solubilities of {beta}-carotene in pure CO{sub 2} at (17 to 34) MPa ranged (0.17 to 1.06) {mu}mol/mol and agreed with values reported in literature. The solubility of {beta}-carotene in CO{sub 2} modified with (1.2 to 1.6) % mol ethanol increased by a factor of 1.7 to 3.0 as compared to its solubility in pure CO{sub 2} under equivalent conditions. The concentration of triolein in equilibrated ternary (CO{sub 2} + {beta}-carotene + triolein) mixtures having excess triolein reached values (0.01 to 0.39) mmol/mol corresponding to its solubility in pure SC CO{sub 2} under equivalent conditions. Under these conditions, the solubility of {beta}-carotene in triolein-modified CO{sub 2} increased by a factor of up to 4.0 in relation with its solubility in pure CO{sub 2} at comparable system temperature and pressure, reaching an uppermost value of 3.3 {mu}mol/mol at 333 K and 32 MPa. Unlike in the case of ethanol, where enhancements in solubility where relatively independent on system conditions, solubility enhancements using triolein as co-solvent increased markedly with system pressure, being larger than using (1.2 to 1.6) % mol ethanol at about (24 to 28) MPa, depending on system temperature. The increase in the solubility {beta}-carotene in SC CO{sub 2} as a result of using ethanol or triolein as co-solvent apparently does not depend on the increase in density associated with the dissolution of the co-solvent in CO{sub 2}. Enhancements may be due

Thermodynamic Approach to Boron Nitride Nanotube Solubility and Dispersion

Science.gov (United States)

Tiano, A. L.; Gibbons, L.; Tsui, M.; Applin, S. I.; Silva, R.; Park, C.; Fay, C. C.

2016-01-01

Inadequate dispersion of nanomaterials is a critical issue that significantly limits the potential properties of nanocomposites and when overcome, will enable further enhancement of material properties. The most common methods used to improve dispersion include surface functionalization, surfactants, polymer wrapping, and sonication. Although these approaches have proven effective, they often achieve dispersion by altering the surface or structure of the nanomaterial and ultimately, their intrinsic properties. Co-solvents are commonly utilized in the polymer, paint, and art conservation industries to selectively dissolve materials. These co-solvents are utilized based on thermodynamic interaction parameters and are chosen so that the original materials are not affected. The same concept was applied to enhance the dispersion of boron nitride nanotubes (BNNTs) to facilitate the fabrication of BNNT nanocomposites. Of the solvents tested, dimethylacetamide (DMAc) exhibited the most stable, uniform dispersion of BNNTs, followed by N,N-dimethylformamide (DMF), acetone, and N-methyl-2-pyrrolidone (NMP). Utilizing the known Hansen solubility parameters of these solvents in comparison to the BNNT dispersion state, a region of good solubility was proposed. This solubility region was used to identify co-solvent systems that led to improved BNNT dispersion in poor solvents such as toluene, hexane, and ethanol. Incorporating the data from the co-solvent studies further refined the proposed solubility region. From this region, the Hansen solubility parameters for BNNTs are thought to lie at the midpoint of the solubility sphere: 16.8, 10.7, and 9.0 MPa(exp 1/2) for delta d, delta p, and delta h, respectively, with a calculated Hildebrand parameter of 21.8 MPa)exp 1/2).

Iron solubility related to particle sulfur content in source emission and ambient fine particles.

Science.gov (United States)

Oakes, M; Ingall, E D; Lai, B; Shafer, M M; Hays, M D; Liu, Z G; Russell, A G; Weber, R J

2012-06-19

The chemical factors influencing iron solubility (soluble iron/total iron) were investigated in source emission (e.g., biomass burning, coal fly ash, mineral dust, and mobile exhaust) and ambient (Atlanta, GA) fine particles (PM2.5). Chemical properties (speciation and mixing state) of iron-containing particles were characterized using X-ray absorption near edge structure (XANES) spectroscopy and micro-X-ray fluorescence measurements. Bulk iron solubility (soluble iron/total iron) of the samples was quantified by leaching experiments. Major differences were observed in iron solubility in source emission samples, ranging from low solubility (iron solubility did not correspond to silicon content or Fe(II) content. However, source emission and ambient samples with high iron solubility corresponded to the sulfur content observed in single particles. A similar correspondence between bulk iron solubility and bulk sulfate content in a series of Atlanta PM2.5 fine particle samples (N = 358) further supported this trend. In addition, results of linear combination fitting experiments show the presence of iron sulfates in several high iron solubility source emission and ambient PM2.5 samples. These results suggest that the sulfate content (related to the presence of iron sulfates and/or acid-processing mechanisms by H(2)SO(4)) of iron-containing particles is an important proxy for iron solubility.

Characterisation of the broad substrate specificity 2-keto acid decarboxylase Aro10p of Saccharomyces kudriavzevii and its implication in aroma development.

Science.gov (United States)

Stribny, Jiri; Romagnoli, Gabriele; Pérez-Torrado, Roberto; Daran, Jean-Marc; Querol, Amparo

2016-03-12

The yeast amino acid catabolism plays an important role in flavour generation since higher alcohols and acetate esters, amino acid catabolism end products, are key components of overall flavour and aroma in fermented products. Comparative studies have shown that other Saccharomyces species, such as S. kudriavzevii, differ during the production of aroma-active higher alcohols and their esters compared to S. cerevisiae. In this study, we performed a comparative analysis of the enzymes involved in the amino acid catabolism of S. kudriavzevii with their potential to improve the flavour production capacity of S. cerevisiae. In silico screening, based on the severity of amino acid substitutions evaluated by Grantham matrix, revealed four candidates, of which S. kudriavzevii Aro10p (SkAro10p) had the highest score. The analysis of higher alcohols and esters produced by S. cerevisiae then revealed enhanced formation of isobutanol, isoamyl alcohol and their esters when endogenous ARO10 was replaced with ARO10 from S. kudriavzevii. Also, significant differences in the aroma profile were found in fermentations of synthetic wine must. Substrate specificities of SkAro10p were compared with those of S. cerevisiae Aro10p (ScAro10p) by their expression in a 2-keto acid decarboxylase-null S. cerevisiae strain. Unlike the cell extracts with expressed ScAro10p which showed greater activity for phenylpyruvate, which suggests this phenylalanine-derivative to be the preferred substrate, the decarboxylation activities measured in the cell extracts with SkAro10p ranged with all the tested substrates at the same level. The activities of SkAro10p towards substrates (except phenylpyruvate) were higher than of those for ScAro10p. The results indicate that the amino acid variations observed between the orthologues decarboxylases encoded by SkARO10 and ScARO10 could be the reason for the distinct enzyme properties, which possibly lead to the enhanced production of several flavour compounds. The

The Apparent Solubility Of Aluminum(III) In Hanford High-Level Waste Tanks

International Nuclear Information System (INIS)

Reynolds, J.G.

2012-01-01

The solubility of aluminum in Hanford nuclear waste impacts on the process ability of the waste by a number of proposed treatment options. For many years, Hanford staff has anecdotally noted that aluminum appears to be considerably more soluble in Hanford waste than the simpler electrolyte solutions used as analogues. There has been minimal scientific study to confirm these anecdotal observations, however. The present study determines the apparent solubility product for gibbsite in 50 tank samples. The ratio of hydroxide to aluminum in the liquid phase for the samples is calculated and plotted as a function of total sodium molarity. Total sodium molarity is used as a surrogate for ionic strength, because the relative ratios of mono, di and trivalent anions are not available for all of the samples. These results were compared to the simple NaOH-NaAl(OH 4 )H 2 O system, and the NaOH-NaAl(OH 4 )NaCl-H 2 O system data retrieved from the literature. The results show that gibbsite is apparently more soluble in the samples than in the simple systems whenever the sodium molarity is greater than two. This apparent enhanced solubility cannot be explained solely by differences in ionic strength. The change in solubility with ionic strength in simple systems is small compared to the difference between aluminum solubility in Hanford waste and the simple systems. The reason for the apparent enhanced solubility is unknown, but could include. kinetic or thermodynamic factors that are not present in the simple electrolyte systems. Any kinetic explanation would have to explain why the samples are always supersaturated whenever the sodium molarity is above two. Real waste characterization data should not be used to validate thermodynamic solubility models until it can be confirmed that the apparent enhanced gibbsite solubility is a thermodynamic effect and not a kinetic effect.

The physicochemical properties and solubility of pharmaceuticals – Methyl xanthines

International Nuclear Information System (INIS)

Pobudkowska, Aneta; Domańska, Urszula; Kryska, Justyna A.

2014-01-01

Highlights: • Solubility of methyl xanthines in water and alcohols was measured. • Solubility in water, or alcohols was of the order of 10 −4 in mole fraction. • Experimental aqueous pK a ’s values are reported for the selected drugs. • The basic thermodynamic functions were determined. - Abstract: The aim of this study was to evaluate the physio-chemical properties and solubility of three pharmaceuticals (Phs): theophylline, 7-(β-hydroxyethyl) theophylline, and theobromine in binary systems in different solvents. The solvents used were water, ethanol, and 1-octanol. Score of the solubility of these substances is being important for their dissolution effect inside the cell, the transportation by body fluids and the penetration possibility of lipid membranes. The Phs were classified to the group of methyl xanthines, which contain purine in their structure. Although they are mainly obtained via chemical synthesis, they can be also found in natural ingredients such as cocoa beans and tea leaves. These drugs are mainly acting on the central nervous system but are also used in the treatment of asthma or blood vessels. Solubility of 7 (β-hydroxyethyl) theophylline and theophylline were tested using synthetic method. In case of theobromine, which solubility is very small in the solvents noted, the spectrophotometric method has been used to measure its solubility. After designating phase diagrams of each of the solubility in the bipolar system, the experimental points have been correlated with the equations: Wilson, NRTL, UNIQUAC. Results show that theophylline and its derivatives show the best solubility from all tested Phs. Another method also used during this study was the differential scanning calorimetry (DSC), which allowed designation of the thermal properties of Phs. The fusion temperature and the enthalpy of melting were measured. Unfortunately, it was not possible to determine the fusion temperature and enthalpy of melting of theobromine, because of

Solubilities of sodium nitrate, sodium nitrite, and sodium aluminate in simulated nuclear waste

International Nuclear Information System (INIS)

Reynolds, D.A.; Herting, D.L.

1984-09-01

Solubilities were determined for sodium nitrate, sodium nitrite, and sodium aluminate in synthetic nuclear waste liquor. Solubilities were determined as a function of temperature and solution composition (concentrations of sodium hydroxide, sodium nitrate, sodium nitrite, and sodium aluminate). Temperature had the greatest effect on the solubilities of sodium nitrate and sodium nitrite and a somewhat lesser effect on sodium aluminate solubility. Hydroxide had a great effect on the solubilities of all three salts. Other solution components had minor effects. 2 references, 8 figures, 11 tables

Preparation, characterization and solubility product constant of AmOHCO3

International Nuclear Information System (INIS)

Silva, R.J.

1985-01-01

An investigation into the nature and solubility of a stable solid phase formed by a trivalent actinide, 243 Am 3+ , in dilute aqueous carbonate solutions was conducted. The compound exhibited an x-ray powder diffraction pattern which was nearly identical to that reported for NdOHCO 3 - type A. The pattern could be indexed in the orthorhombic system with unit cell parameters a = 4.958, b = 8.487, and c = 7.215 A. The steady-state solubility of the compound was determined from the results of both dissolution and precipitation experiments. The average solubility product quotient for 0.1M ionic strength, 25 +- 1 0 C and 1 atmosphere pressure was found to be 583 +- 206. The solubility product constant for zero ionic strength was estimated to be 335 +- 120. 22 references, 3 tables

Determination of water-soluble and fat-soluble vitamins in tears and blood serum of infants and parents by liquid chromatography/mass spectrometry.

Science.gov (United States)

Khaksari, Maryam; Mazzoleni, Lynn R; Ruan, Chunhai; Kennedy, Robert T; Minerick, Adrienne R

2017-02-01

Tears serve as a viable diagnostic fluid with advantages including less invasive sample to collect and less complex to prepare for analysis. Several water-soluble and fat-soluble vitamins were detected and quantified in human tears and compared with blood serum levels. Samples from 15 family pairs, each pair consisting of a four-month-old infant and one parent were analyzed; vitamin concentrations were compared between tears and blood serum for individual subjects, between infants and parents, and against self-reported dietary intakes. Water-soluble vitamins B 1 , B 2 , B 3 (nicotinamide), B 5 , B 9 and fat-soluble vitamin E (α-tocopherol) were routinely detected in tears and blood serum while fat-soluble vitamin A (retinol) was detected only in blood serum. Water-soluble vitamin concentrations measured in tears and blood serum of single subjects were comparable, while higher concentrations were measured in infants compared to their parents. Fat-soluble vitamin E concentrations were lower in tears than blood serum with no significant difference between infants and parents. Serum vitamin A concentrations were higher in parents than infants. Population trends were compiled and quantified using a cross correlation factor. Strong positive correlations were found between tear and blood serum concentrations of vitamin E from infants and parents and vitamin B 3 concentrations from parents, while slight positive correlations were detected for infants B 3 and parents B 1 and B 2 concentrations. Correlations between infants and parents were found for the concentrations of B 1 , B 2 , B 3 , and E in tears, and the concentrations of B 2, A, and E in blood serum. Stronger vitamin concentration correlations were found between infants and parents for the breast-fed infants, while no significant difference was observed between breast-fed and bottle-fed infants. This work is the first to demonstrate simultaneous vitamin A, B, and E detection and to quantify correlations between

Factors affecting the solubility of Bacillus halmapalus alpha-amylase

DEFF Research Database (Denmark)

Faber, Cornelius; Hobley, Timothy John; Mollerup, Jørgen

2008-01-01

A detailed study of the solubility of recombinant Bacillus halmapalus alpha-amylase has been conducted. A semi-purified preparation from a bulk crystallisation was chos en that contained six isoforms with pI-values of between 5.5 and 6.1. The solubility was strongly affected by pH and could...

Modeling of Salt Solubilities in Mixed Solvents

DEFF Research Database (Denmark)

Chiavone-Filho, O.; Rasmussen, Peter

2000-01-01

A method to correlate and predict salt solubilities in mixed solvents using a UNIQUAC+Debye-Huckel model is developed. The UNIQUAC equation is applied in a form with temperature-dependent parameters. The Debye-Huckel model is extended to mixed solvents by properly evaluating the dielectric...... constants and the liquid densities of the solvent media. To normalize the activity coefficients, the symmetric convention is adopted. Thermochemical properties of the salt are used to estimate the solubility product. It is shown that the proposed procedure can describe with good accuracy a series of salt...

Effect of amides on lithium tetraborate solubility

Energy Technology Data Exchange (ETDEWEB)

Tsekhanskij, R S; Skvortsov, V C; Molodkin, A K; Sadetdi-pov, Sh V [Chuvashskij Gosudarstvennyj Pedagogicheskij Inst., Cheboksary (USSR); Universitet Druzhby Narodov, Moscow (USSR))

1983-03-01

Using the methods of solubility, densi- and refractometry at 25 deg C, it has been established that the systems lithium tetraborate-formamide (acetamide, dimethyl-formamide)-water are of a simple eutonic type. Amides decrease the salt solubility. Lyotropic effect, as calculated for molar concentrations (-Lsub(M)) relative to the absolute value, increases from formamide to dimethyl-formamide. The sequence is determined by the fact that, when there is one or two hydrophilic methyl groups in amide molecules which are in contact with tetraborate, they decrease the hydration energy of lithium cations.

Effect of amides on sodium tetraborate solubility

International Nuclear Information System (INIS)

Tsekhanskij, R.S.; Skvortsov, V.G.; Molodkin, A.K.; Sadetdinov, Sh.V.

1986-01-01

Methods of solubility and refractometry at 25 deg C were applied to investigate sodium tetraborate - formamide (dimethylformamide) - water systems. It is stated that they are of simple eutonic type as well as the earlier described sodium tetraborate-acetamide-water system. Amides reduce solubility of the salt. The effect of contact interaction between dissolved substances on salt cation hydration and thus on the value of liotropic amide effect is confirmed. This value is found to be also depend on the number of molecules of coordination water in the initial crystalline hydrate

Effect of amides on lithium tetraborate solubility

International Nuclear Information System (INIS)

Tsekhanskij, R.S.; Skvortsov, V.C.; Molodkin, A.K.; Sadetdi- pov, Sh.V.

1983-01-01

Using the methods of solubility, densi- and refractometry at 25 deg C, it has been established that the systemS lithium tetraborate-formamide (acetamide, dimethyl-formamide)-water are of a simple eutonic type. Amides decrease the salt solubility. Lyotropic effect, as calculated for molar concentrations (-Lsub(M)) relative to the absolute value, increases from formamide to dimethylformamide. The sequence is determined by the fact that, when there is one or two hydrophilic methyl groups in amide molecules which are in contact with tetraborate, they decrease the hydration energy of lithium cations

Effect of amides on sodium tetraborate solubility

Energy Technology Data Exchange (ETDEWEB)

Tsekhanskij, R S; Skvortsov, V G; Molodkin, A K; Sadetdinov, Sh V

1986-11-01

Methods of solubility and refractometry at 25 deg C were applied to investigate sodium tetraborate - formamide (dimethylformamide) - water systems. It is stated that they are of simple eutonic type as well as the earlier described sodium tetraborate-acetamide-water system. Amides reduce solubility of the salt. The effect of contact interaction between dissolved substances on salt cation hydration and thus on the value of liotropic amide effect is confirmed. This value is found to be also depend on the number of molecules of coordination water in the initial crystalline hydrate.

Solubility of 1-aminoanthraquinone and 1-nitroanthraquinone in supercritical carbon dioxide

International Nuclear Information System (INIS)

Tamura, Kazuhiro; Alwi, Ratna Surya; Tanaka, Tatsuro; Shimizu, Keisuke

2017-01-01

Highlights: • Solubility of 1-aminoanthraquinone and 1-nitroanthraquinone in scCO 2 were measured. • Temperature ranges of (323.15–383.15) K and pressures of (12.5–25.0) MPa. • Solubility of 1-aminoanthraquinone was higher than that of 1-nitroanthraquinone. • Demonstrated effect of amino and nitro groups on the solubility of anthraquinones. • Correlated well by CO 2 density models and thermodynamic models. - Abstract: The solubility of 1-aminoanthraquinone (Smoke Orange G) and 1-nitroanthraquinone in supercritical carbon dioxide (scCO 2 ) was measured at the temperatures (323.15, 353.15 and 383.15) K and over the pressure range of (12.5–25.0) MPa by a flow type apparatus. Mole fraction solubility of 1-aminoanthraquinone, 3.51 × 10 −5 , was significantly higher than that of 1-nitroanthraquinone, 2.52 × 10 −5 , as compared at 383.15 K and 25 MPa. It was found that amino group in 1-aminoanthraquinone effects to enhance the solubility of anthraquinone derivatives in supercritical carbon dioxide in comparison with nitro group in 1-nitroanthraquinone. Seven different kinds of semi-empirical models, expressed in terms of CO 2 density, were used to correlate the experimental results. Moreover, the solubilities of anthraquinone derivatives were analysed thermodynamically by the regular solution model with the Flory–Huggins theory and by the Peng–Robinson equation of state with a modification of Stryjek and Vera (PRSV-EOS). Good agreement with slightly less than 15 per cent of relative deviation between the experimental and calculated solubilities of the anthraquinone derivatives was obtained.

The solubilities of benzene polycarboxylic acids in water

International Nuclear Information System (INIS)

Apelblat, Alexander; Manzurola, Emanuel; Abo Balal, Nazmia

2006-01-01

The solubilities in water of all benzene polycarboxylic acids are discussed, using data determined in this work (benzoic, terephthalic, trimellitic, trimesic, and pyromellitic acids) and available from the literature (benzoic, phthalic, isophthalic, terephthalic, hemimellitic, trimelitic, trimesic, mellophanic, prehnitic, pyromellitic, benzene-pentacarboxylic and mellitic acids). The apparent molar enthalpies of solution at the saturation point for these benzene polycarboxylic acids were determined from the temperature dependence of the solubilities

Thermodynamic properties of soddyite from solubility and calorimetry measurements

International Nuclear Information System (INIS)

Gorman-Lewis, Drew; Mazeina, Lena; Fein, Jeremy B.; Szymanowski, Jennifer E.S.; Burns, Peter C.; Navrotsky, Alexandra

2007-01-01

The release of uranium from geologic nuclear waste repositories under oxidizing conditions can only be modeled if the thermodynamic properties of the secondary uranyl minerals that form in the repository setting are known. Toward this end, we synthesized soddyite ((UO 2 ) 2 (SiO 4 )(H 2 O) 2 ), and performed solubility measurements from both undersaturation and supersaturation. The solubility measurements rigorously constrain the value of the solubility product of synthetic soddyite, and consequently its standard-state Gibbs free energy of formation. The log solubility product (lg K sp ) with its error (1σ) is (6.43 + 0.20/-0.37), and the standard-state Gibbs free energy of formation is (-3652.2 ± 4.2 (2σ)) kJ mol -1 . High-temperature drop solution calorimetry was conducted, yielding a calculated standard-state enthalpy of formation of soddyite of (-4045.4 ± 4.9 (2σ)) kJ . mol -1 . The standard-state Gibbs free energy and enthalpy of formation yield a calculated standard-state entropy of formation of soddyite of (-1318.7 ± 21.7 (2σ)) J . mol -1 . K -1 . The measurements and associated thermodynamic calculations not only describe the T = 298 K stability and solubility of soddyite, but they also can be used in predictions of repository performance through extrapolation of these properties to repository temperatures

Knocking out Ornithine Decarboxylase Antizyme 1 (OAZ1 Improves Recombinant Protein Expression in the HEK293 Cell Line

Directory of Open Access Journals (Sweden)

Laura Abaandou

2018-06-01

Full Text Available Creating efficient cell lines is a priority for the biopharmaceutical industry, which produces biologicals for various uses. A recent approach to achieving this goal is the use of non-coding RNAs, microRNA (miRNA and small interfering RNA (siRNA, to identify key genes that can potentially improve production or growth. The ornithine decarboxylase antizyme 1 (OAZ1 gene, a negative regulator of polyamine biosynthesis, was identified in a genome-wide siRNA screen as a potential engineering target, because its knock down by siRNA increased recombinant protein expression from human embryonic kidney 293 (HEK293 cells by two-fold. To investigate this further, the OAZ1 gene in HEK293 cells was knocked out using CRISPR genome editing. The OAZ1 knockout cell lines displayed up to four-fold higher expression of both stably and transiently expressed proteins, with comparable growth and metabolic activity to the parental cell line; and an approximately three-fold increase in intracellular polyamine content. The results indicate that genetic inactivation of OAZ1 in HEK293 cells is an effective strategy to improve recombinant protein expression in HEK293 cells.

Gclust Server: 73176 [Gclust Server

Lifescience Database Archive (English)

Full Text Available nner membrane transporter, transports oxaloacetate, sulfate, and thiosulfate 1 1.00e-45 0.0 0.0 0.0 0.0 0.0 ... annotation Mitochondrial inner membrane transporter, transports oxaloacetate, sulfate, and thiosulfate Numb

Measurement and correlation of solubility of ciclesonide in seven pure organic solvents

International Nuclear Information System (INIS)

Zhou, Lina; Yin, Qiuxiang; Guo, Zhiqiang; Lu, Haijiao; Liu, Mingyan; Chen, Wei; Hou, Baohong

2017-01-01

Highlights: • The solubility of ciclesonide in seven pure organic solvents was determined by gravimetric method. • The solubility order was interpreted by virtue of density function theory (DFT). • The experimental solubility of ciclesonide was correlated by four thermodynamic models. • Mixing thermodynamic properties of ciclesonide were calculated and discussed. - Abstract: The solubility of ciclesonide in seven organic solvents (ethanol, 2-propanol, 1-propanol, 1-butanol, acetonitrile, toluene and ethyl acetate) in the temperature range from 278.15 K to 313.15 K was measured by gravimetrical method under atmospheric pressure. The results indicate that the solubility of ciclesonide increases with elevating temperature in all investigated solvents. The solubility order in different solvents was interpreted through comparing interaction force between solute and solvent molecules by virtue of density function theory (DFT). Thermodynamic equations including the modified Apelblat equation, λh equation, Wilson equation and NRTL equation are all suitable to correlate the solubility results. Based on the Wilson equation, the thermodynamic parameters from the mixing process are calculated, and the results indicate the mixing process of ciclesonide in the selected pure solvents is spontaneous and entropy-driven.

Effect of surfactants on the fluorescence spectra of water-soluble ...

Indian Academy of Sciences (India)

TECS

Effect of surfactants on the fluorescence spectra of water-soluble. MEHPPV ... polyacrylic acid (PAA) chains grafted onto their backbone were found to be water soluble, and they exhi- ..... in other words the variation of emission intensity.

Occurrence of Type 1 Diabetes in Graves' Disease Patients Who Are Positive for Antiglutamic Acid Decarboxylase Antibodies: An 8-Year Followup Study

Directory of Open Access Journals (Sweden)

Matsuo Taniyama

2011-01-01

Full Text Available Glutamic acid decarboxylase antibodies (GADAs are one of the markers of islet cell autoimmunity and are sometimes present before the onset of type 1 diabetes (T1D. GADA can be present in Graves' patients without diabetes; however, the outcome of GADA-positive Graves' patients is not fully understood, and the predictive value of GADA for the development of T1D in Graves' patients remains to be clarified. We investigated the prevalence of GADA in 158 patients with Graves' disease and detected GADA in 10 patients. They were followed up to discover whether or not T1D developed. In the course of eight years, 2 patients with high titers of GADA developed T1D, both had long-standing antithyroid drug-resistant Graves' disease. Thus, Graves' disease with high GADA titer seems to be at high risk for T1D.

The Prodrug Approach: A Successful Tool for Improving Drug Solubility

Directory of Open Access Journals (Sweden)

Daniela Hartmann Jornada

2015-12-01

Full Text Available Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug development. This review aims to describe recent advances in the improvement of solubility via the prodrug approach. The main chemical carriers and examples of successful strategies will be discussed, highlighting the advances of this field in the last ten years.

Study of N-cinnamoylphenylhydroxylaminate solubility in water and organic solvents

International Nuclear Information System (INIS)

Pilipenko, A.T.; Shpak, Eh.A.; Samchuk, A.I.

1975-01-01

The composition of complexes of N-cinnamoylphenylhydroxylamine with copper, cadmium, lead, indium, iron, gallium, titanium, zirconium, hafnium, niobium, tantalum, tungsten, molybdenum and vanadium was determined. The solubility products of the N-cinnamoylphenylhydroxylaminates of copper, cadmium, indium, gallium and iron were determined by the method of measuring the solubility of precipitates in acid. The solubility of N-cinnamoylphenylhydroxalaminates of cadmium, indium, iron, titanium, zirconium, hafnium, niobium, tantalum, vanadium, molybdenum and tungsten in organic solvents was studied. Two-phase constants for the stability of the complexes were calculated. (author)

Solubilities of Actinide Oxides in the KURT Groundwater

International Nuclear Information System (INIS)

Kim, Seung Soo; Baik, Min Hoon; Choi, Jong Won

2009-12-01

For the estimation of solubilities of actinides in a deep underground condition, The solubilities of UO 2 , ThO 2 , NpO 2 and Am(OH) 3 in the KURT ground water have been measured under various redox conditions, and their solubilities and aqueous species in the same conditions as the experimental solutions were also calculated by using a geochemical code. Then these results were compared with each other as well as with literature results. For the calculation of solubility of a radionuclide, the thermodynamic data of the radionuclide complex from OECD/NEA, Nagra/PSI, KAERI, JAEA, SKB and recent literatures were collected and compared. Additionally, the methods for the correction of ionic strength and temperature of the solution were described in this report. The analysis techniques and recent research for measurement of species of actinides were also introduced. The concentrations of U, Th and Np dissolved were less than 10 -7 mol/L under Eh≤-0.2 of reducing condition from experiment and calculation, and the solubility of PuO 2 (cr) was estimated as lower than that of UO 2 (cr) by 1 ∼ 2 orders. However if amount of carbonate ion in the ground water increased, the concentration of tetra-valance actinides at pH 8 ∼ 11 would be greatly increased. The 1x10 -6 mol/L of americium might be a little conservative value in KURT groundwater. While carbonate or hydroxo-carbonatec complexes were presumed to be the dominant aqueous species in -0.2 ∼ -0.3 V of Eh and weakly alkaline solution, hydroxo complexes are dominant in strong reducing and high pH solution

Some physicochemical aspects of water-soluble mineral flotation.

Science.gov (United States)

Wu, Zhijian; Wang, Xuming; Liu, Haining; Zhang, Huifang; Miller, Jan D

2016-09-01

Some physicochemical aspects of water-soluble mineral flotation including hydration phenomena, associations and interactions between collectors, air bubbles, and water-soluble mineral particles are presented. Flotation carried out in saturated salt solutions, and a wide range of collector concentrations for effective flotation of different salts are two basic aspects of water-soluble mineral flotation. Hydration of salt ions, mineral particle surfaces, collector molecules or ions, and collector aggregates play an important role in water-soluble mineral flotation. The adsorption of collectors onto bubble surfaces is suggested to be the precondition for the association of mineral particles with bubbles. The association of collectors with water-soluble minerals is a complicated process, which may include the adsorption of collector molecules or ions onto such surfaces, and/or the attachment of collector precipitates or crystals onto the mineral surfaces. The interactions between the collectors and the minerals include electrostatic and hydrophobic interactions, hydrogen bonding, and specific interactions, with electrostatic and hydrophobic interactions being the common mechanisms. For the association of ionic collectors with minerals with an opposite charge, electrostatic and hydrophobic interactions could have a synergistic effect, with the hydrophobic interactions between the hydrophobic groups of the previously associated collectors and the hydrophobic groups of oncoming collectors being an important attractive force. Association between solid particles and air bubbles is the key to froth flotation, which is affected by hydrophobicity of the mineral particle surfaces, surface charges of mineral particles and bubbles, mineral particle size and shape, temperature, bubble size, etc. The use of a collector together with a frother and the use of mixed surfactants as collectors are suggested to improve flotation. Copyright © 2016 Elsevier B.V. All rights reserved.

Gamma radiation inhibits the appearance of induced ornithine decarboxylase activity in Chinese hamster cells

International Nuclear Information System (INIS)

Ben-Hur, E.; Heimer, Y.M.; Riklis, E.

1981-01-01

Ornithine decarboxylase activity of Chinese hamster cells (ODC, EC 4.1.1.17) can be induced in plateau phase by change of medium. Exposure of the cells to gamma radiation before induction reduces the amount of ODC activity induced. The dose-response curve is exponential with a D 0 of 106 krad. Exposure of BUdR-substituted cells is more effective in reducing ODC induction at high doses, with a D 0 of 38 krad. Cells can recover from the reduction incurred by 74 krad if enzyme induction is delayed for 2 hours after exposure. Treatment of the cells with psoralen-plus-light completely inhibits RNA synthesis without affecting protein synthesis (Heimer, Ben-Hur and Riklis 1977, 1978). Using this procedure it is shown that the effect of gamma radiation on inducible ODC activity is due not only to DNA damage but also involves a post-transcriptional effect. This conclusion is supported by employing a heat shock to inhibit protein synthesis prior to gamma-irradiation of log-phase cells. In such cells the increased activity of ODC upon transfer to 37 0 C is due primarily to enzyme synthesis using pre-existing RNA species during the first few hours. A low concentration of actinomycin D, which inhibits rRNA synthesis, applied during the recovery period, prevents the recovery of the cells' capacity for maximal ODC induction. This may indicate that, in order to recover, the cells have to repair damage to the ribosomes as well as to DNA. (author)

Actinide solution equlibria and solubilities in geologic systems

International Nuclear Information System (INIS)

Allard, B.

1983-04-01

Stability constants and solubility products for actinide (Th, U, Np, Pu and Am) hydroxide and carbonate complexes have been collected, and total solubilities have been calculated under conditions representative of deep granitic groundwaters (pH 7-9.5; high total carbonate concentration according to log (CO 3 )=0.76pH-10.83; redox potentials corresponding to oxic systems, Eh>0.8-0.06pH, and reducing systems, Eh 2 (s), UO 2 (s), NpO 2 (s), PuO 2 (s) and Am 2 (CO 3 ) 3 (s)m, respectively, and the corresponding calculated maximum solubilities are 3 times 10- 10 M(0.07 μg/1) for Th, 0.3-250 times 10- 10 M (0.01-6 μg/1) for U (depending on the carbonate concentration), 1 times 10- 10 M(0.03 μg/1) for Np, 1-3 times 10- 9 M (0.2-0.7 μg/1) for Pu and 0.6-2 times 10- 7 M (15-50 μg/1) for Am. The calculated solubilities for U are in fair agreement with observed uranium concentrations in natural deep groundwaters. Hexavalent uranium carbonate species would dominate in solution except under highly reducing conditions (Eh 5 -10- 6 M (mg/1-level). (author)

Solubility of rosuvastatin calcium in different neat solvents at different temperatures

International Nuclear Information System (INIS)

Alshora, Doaa H.; Haq, Nazrul; Alanazi, Fars K.; Ibrahim, Mohamed A.; Shakeel, Faiyaz

2016-01-01

Highlights: • Solubility of rosuvastatin calcium (ROSCa) in seven neat solvents was determined. • The solubility of ROSCa was recorded highest in propylene glycol. • Experimental solubilities were correlated with Apelblat and ideal models. • Good correlation was existed between experimental and calculated solubilities. - Abstract: In the current research work, the solubility of rosuvastatin calcium (ROSCa) in seven different neat solvents such as water, ethanol, 1-butanol, 2-butanol, ethylene glycol (EG), isopropyl alcohol (IPA) and propane-1,2-diol (PG) was measured at five different temperatures i.e. T = (298.15 to 318.15) K and atmospheric pressure. Values of the experimental solubility of ROSCa were correlated with Apelblat and ideal models which showed good correlation and model fitting. The solubility (as mole fraction) of ROSCa was recorded highest in PG (1.89 · 10"−"2 at T = 318.15 K) followed by 1-butanol (8.20 · 10"−"4 at T = 318.15 K), ethanol (6.81 · 10"−"4 at T = 318.15 K), IPA (5.66 · 10"−"4 at T = 318.15 K), EG (5.03 · 10"−"4 at T = 318.15 K), 2-butanol (1.08 · 10"−"4 at T = 318.15 K) and water (1.40 · 10"−"5 at T = 318.15 K). The experimental results from this research work would be helpful in the development of conventional and advanced liquid dosage forms of ROSCa.

Simplified Method for Rapid Purification of Soluble Histones

Directory of Open Access Journals (Sweden)

Nives Ivić

2016-06-01

Full Text Available Functional and structural studies of histone-chaperone complexes, nucleosome modifications, their interactions with remodelers and regulatory proteins rely on obtaining recombinant histones from bacteria. In the present study, we show that co-expression of Xenopus laevis histone pairs leads to production of soluble H2AH2B heterodimer and (H3H42 heterotetramer. The soluble histone complexes are purified by simple chromatographic techniques. Obtained H2AH2B dimer and H3H4 tetramer are proficient in histone chaperone binding and histone octamer and nucleosome formation. Our optimized protocol enables rapid purification of multiple soluble histone variants with a remarkable high yield and simplifies histone octamer preparation. We expect that this simple approach will contribute to the histone chaperone and chromatin research. This work is licensed under a Creative Commons Attribution 4.0 International License.

Mass transport of soluble species through backfill into surrounding rock

International Nuclear Information System (INIS)

Kang, Chul Hyung; Park, Hun Hwee

1992-01-01

Some soluble species may not be solubility-limited or congruent-released with the matrix species. For example, during the operation of the nuclear reactor, the fission products can be accumulated in the fuel-cladding gap, void, and grain boundaries of the fuel rods. In the waste package for spent-fuel placed in a geologic repository, the high solubility species of these fission products accumulated in the 'gap', e.g. cesium or iodine are expected to dissolve rapidly when ground water penetrates fuel rods. The time and space dependent mass transport for high solubility nuclides in the gap is analyzed, and its numerical illustrations are demonstrated. The approximate solution that is valid for all times is developed, and validated by comparison with an asymptotic solution and the solution obtained by the numerical inversion of Laplace transform covering the entire time span. (Author)

Solubility data for cement hydrate phases (25oC)

International Nuclear Information System (INIS)

Atkins, M.; Glasser, F.P.; Kindness, A.; Macphee, D.E.

1991-05-01

Solubility measurements were performed on most of the more thermodynamically-stable cement hydrate phases, at 25 o C. The results for each hydrate phase are summarised in the form of datasheets. Solubility properties are discussed, and where possible a K sp value is calculated. The data are compared with the data in the literature. (author)

Two novel heat-soluble protein families abundantly expressed in an anhydrobiotic tardigrade.

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Ayami Yamaguchi

Full Text Available Tardigrades are able to tolerate almost complete dehydration by reversibly switching to an ametabolic state. This ability is called anhydrobiosis. In the anhydrobiotic state, tardigrades can withstand various extreme environments including space, but their molecular basis remains largely unknown. Late embryogenesis abundant (LEA proteins are heat-soluble proteins and can prevent protein-aggregation in dehydrated conditions in other anhydrobiotic organisms, but their relevance to tardigrade anhydrobiosis is not clarified. In this study, we focused on the heat-soluble property characteristic of LEA proteins and conducted heat-soluble proteomics using an anhydrobiotic tardigrade. Our heat-soluble proteomics identified five abundant heat-soluble proteins. All of them showed no sequence similarity with LEA proteins and formed two novel protein families with distinct subcellular localizations. We named them Cytoplasmic Abundant Heat Soluble (CAHS and Secretory Abundant Heat Soluble (SAHS protein families, according to their localization. Both protein families were conserved among tardigrades, but not found in other phyla. Although CAHS protein was intrinsically unstructured and SAHS protein was rich in β-structure in the hydrated condition, proteins in both families changed their conformation to an α-helical structure in water-deficient conditions as LEA proteins do. Two conserved repeats of 19-mer motifs in CAHS proteins were capable to form amphiphilic stripes in α-helices, suggesting their roles as molecular shield in water-deficient condition, though charge distribution pattern in α-helices were different between CAHS and LEA proteins. Tardigrades might have evolved novel protein families with a heat-soluble property and this study revealed a novel repertoire of major heat-soluble proteins in these anhydrobiotic animals.

Solubility of polyvalent cations in fogwater at an urban site in Strasbourg (France)

Science.gov (United States)

Millet, M.; Wortham, H.; Mirabel, Ph.

The concentrations in the soluble and total (soluble + insoluble) fractions of Mg, Ca, Fe, Mn, Zn, Al, Cd and Pb have been analysed by "inductively coupled plasma (ICP)" in 14 fog events collected in 1992 at an urban site in France (Strasbourg). For each fog event, two droplet size categories (2-6 μm and 5-8 μm) have been collected separately. For the analysis of the polyvalent cations in the soluble and total fractions, an analytical procedure using ICP and filtration on cellulose/PVC filters has been developed. The study of the solubility of some polyvalent cations has shown that two of the most important factors controlling the partitioning between the soluble and insoluble fraction are the nature of the particles and the pH of the fogwater. The influence of pH depended on the element. The solubility of Pb, Cd, Al, Fe, Mg, and Ca were pH dependent whereas, Zn and Mn solubility varied but no relationship with pH existed, ranging between 25 and 100% and 10 and 100%, respectively. On the other hand, Mg, Pb and Ca were predominantly present in the soluble phase, whereas Al was prevalent in the insoluble fraction. In the case of Cd and Fe., the presence in the soluble or insoluble phase depended largely on the fogwater pH.

A molecular study of gas solubility in nitrile rubber

Science.gov (United States)

Khawaja, Musab; Mostofi, Arash; Sutton, Adrian

2015-03-01

One of the most important uses of elastomers in the oil industry is for seals to encase and protect sensitive monitoring equipment from contamination by gases and liquids at the high pressures and temperatures in the well. Failure of such seals sometimes occurs on decompression when they are returned to the surface. The conditions in the well lead to gases being absorbed by Nitrile rubber (NBR) seals. NBR exhibits a strong permselectivity towards CO2 compared to other gases; something attributed experimentally to the enhanced solubility of CO2. In this study an explanation is sought at the molecular level for this phenomenon. A series of molecular mechanics calculations are performed to compute solubilities of different gases in NBR. The effect of acrylonitrile content on their solubilities is studied for the first time by simulation, and we discuss the important issue of convergence with respect to the sampling of different elastomer configurations. It is observed that the presence of cyano groups has a marked impact on the solubility of CO2 and an explanation is offered.

Solid Phospholipid Dispersions for Oral Delivery of Poorly Soluble Drugs

DEFF Research Database (Denmark)

Fong, Sophia Yui Kau; Martins, Susana A. M.; Brandl, Martin

2016-01-01

Celecoxib (CXB) is a Biopharmaceutical Classification System class II drug in which its oral bioavailability is limited by poor aqueous solubility. Although a range of formulations aiming to increase the solubility of CXB have been developed, it is not completely understood, whether (1) an increase...... the importance of evaluating both, solubility and permeability, and the use of biorelevant medium for testing the candidate-enabling performance of liposomal formulations. Mechanisms at molecular level that may explain the effect of PL formulations on the permeability of CXB are also discussed....

Formulation of a Novel Nano emulsion System for Enhanced Solubility of a Sparingly Water Soluble Antibiotic, Clarithromycin

International Nuclear Information System (INIS)

Vatsraj, S.; Pathak, H.; Chauhan, K.

2014-01-01

The sparingly water soluble property of majority of medicinally significant drugs acts as a potential barrier towards its utilization for therapeutic purpose. The present study was thus aimed at development of a novel oil-in-water (o/w) nano emulsion (NE) system having ability to function as carrier for poorly soluble drugs with clarithromycin as a model antibiotic. The therapeutically effective concentration of clarithromycin, 5 mg/mL, was achieved using polysorbate 80 combined with olive oil as lipophilic counterion. A three-level three-factorial central composite experimental design was utilized to conduct the experiments. The effects of selected variables, polysorbate 80 and olive oil content and concentration of polyvinyl alcohol, were investigated. The particle size of clarithromycin for the optimized formulation was observed to be 30 nm. The morphology of the nano emulsion was explored using transmission electron microscopy (TEM). The emulsions prepared with the optimized formula demonstrated good physical stability during storage at room temperature. Antibacterial activity was conducted with the optimized nano emulsion NESH 01 and compared with free clarithromycin. Zone of inhibition was larger for NESH 01 as compared to that with free clarithromycin. This implies that the solubility and hence the bioavailability of clarithromycin has increased in the formulated nano emulsion system.

Poliovirus Mutants Resistant to Neutralization with Soluble Cell Receptors

Science.gov (United States)

Kaplan, Gerardo; Peters, David; Racaniello, Vincent R.

1990-12-01

Poliovirus mutants resistant to neutralization with soluble cellular receptor were isolated. Replication of soluble receptor-resistant (srr) mutants was blocked by a monoclonal antibody directed against the HeLa cell receptor for poliovirus, indicating that the mutants use this receptor to enter cells. The srr mutants showed reduced binding to HeLa cells and cell membranes. However, the reduced binding phenotype did not have a major impact on viral replication, as judged by plaque size and one-step growth curves. These results suggest that the use of soluble receptors as antiviral agents could lead to the selection of neutralization-resistant mutants that are able to bind cell surface receptors, replicate, and cause disease.

Abalone water-soluble matrix for self-healing biomineralization of tooth defects

Energy Technology Data Exchange (ETDEWEB)

Wen, Zhenliang [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Chen, Jingdi, E-mail: ibptcjd@fzu.edu.cn [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Wang, Hailiang [The Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou 350002 (China); Zhong, Shengnan; Hu, Yimin; Wang, Zhili [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Zhang, Qiqing, E-mail: zhangqiq@126.com [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192 (China)

2016-10-01

Enamel cannot heal by itself if damaged. Hydroxyapatite (HAP) is main component of human enamel. Formation of enamel-like materials for healing enamel defects remains a challenge. In this paper, we successfully isolated the abalone water-soluble matrix (AWSM) with 1.53 wt% the abalone water-soluble protein (AWSPro) and 2.04 wt% the abalone water-soluble polysaccharide (AWSPs) from abandoned abalone shell, and self-healing biomineralization of tooth defects was successfully achieved in vitro. Based on X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), hot field emission scanning electron microscopy (HFESEM) and energy dispersive spectrometer (EDS) analysis, the results showed that the AWSM can efficiently induce remineralization of HAP. The enamel-like HAP was successfully achieved onto etched enamel's surface due to the presence of the AWSM. Moreover, the remineralized effect of eroded enamel was growing with the increase of the AWSM. This study provides a solution to the resource waste and environmental pollution caused by abandoned abalone shell, and we provides a new method for self-healing remineralization of enamel defects by AWSM and develops a novel dental material for potential clinical dentistry application. - Graphical abstract: In this paper, we successfully isolated the abalone water-soluble matrix (AWSM) with 1.53 wt% abalone water-soluble protein (AWSPro) and 2.04 wt% abalone water-soluble polysaccharide (AWSPs) from abandoned abalone shell, and self-healing biomineralization of tooth defects was successfully achieved in vitro by self-organized. Display Omitted - Highlights: • Provides a solution to the resource waste and environmental pollution caused by abandoned abalone shell. • The abalone shell water-soluble matrix contains protein and polysaccharide. • The abalone water-soluble matrix can efficiently induce remineralization of HAP by self-organized. • Achieved self-healing biomineralization of tooth defects in

Abalone water-soluble matrix for self-healing biomineralization of tooth defects

International Nuclear Information System (INIS)

Wen, Zhenliang; Chen, Jingdi; Wang, Hailiang; Zhong, Shengnan; Hu, Yimin; Wang, Zhili; Zhang, Qiqing

2016-01-01

Enamel cannot heal by itself if damaged. Hydroxyapatite (HAP) is main component of human enamel. Formation of enamel-like materials for healing enamel defects remains a challenge. In this paper, we successfully isolated the abalone water-soluble matrix (AWSM) with 1.53 wt% the abalone water-soluble protein (AWSPro) and 2.04 wt% the abalone water-soluble polysaccharide (AWSPs) from abandoned abalone shell, and self-healing biomineralization of tooth defects was successfully achieved in vitro. Based on X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), hot field emission scanning electron microscopy (HFESEM) and energy dispersive spectrometer (EDS) analysis, the results showed that the AWSM can efficiently induce remineralization of HAP. The enamel-like HAP was successfully achieved onto etched enamel's surface due to the presence of the AWSM. Moreover, the remineralized effect of eroded enamel was growing with the increase of the AWSM. This study provides a solution to the resource waste and environmental pollution caused by abandoned abalone shell, and we provides a new method for self-healing remineralization of enamel defects by AWSM and develops a novel dental material for potential clinical dentistry application. - Graphical abstract: In this paper, we successfully isolated the abalone water-soluble matrix (AWSM) with 1.53 wt% abalone water-soluble protein (AWSPro) and 2.04 wt% abalone water-soluble polysaccharide (AWSPs) from abandoned abalone shell, and self-healing biomineralization of tooth defects was successfully achieved in vitro by self-organized. Display Omitted - Highlights: • Provides a solution to the resource waste and environmental pollution caused by abandoned abalone shell. • The abalone shell water-soluble matrix contains protein and polysaccharide. • The abalone water-soluble matrix can efficiently induce remineralization of HAP by self-organized. • Achieved self-healing biomineralization of tooth defects in vitro.

Effect of triolein addition on the solubility of capsanthin in supercritical carbon dioxide

International Nuclear Information System (INIS)

Araus, Karina A.; Valle, José M. del; Robert, Paz S.; Fuente, Juan C. de la

2012-01-01

Highlights: ► We isolated capsanthin from red pepper (Capsicum annuum L.). ► We measured its solubility in pure CO 2 and with triolein as cosolvent. ► We model the solubility of capsanthin in pure CO 2 and with triolein. ► Solubility of triolein in mixtures CO 2 + capsanthin was similar to pure CO 2 . ► Triolein has cosolvent effect over solubility of capsanthin in CO 2 . - Abstract: This manuscript presents new phase equilibrium data for capsanthin in pure and triolein-entrained Supercritical (SC) carbon dioxide (CO 2 ). The aim of the work was to determine the cosolvent effect of triolein on capsanthin by comparing solubility results in a ternary (CO 2 + triolein + capsanthin) system and binary (CO 2 + capsanthin) system at (313 or 333) K and (19 to 34) MPa. For this, authors isolated capsanthin from red pepper (Capsicum annuum L.) and tested it using a dynamic-analytical method in an apparatus with recirculation and online analysis of the CO 2 -rich phase. Within the experimental region, the solubility of capsanthin in pure SC–CO 2 increased with system temperature at isobaric conditions and also increased with pressure at isothermal conditions. Solubilities ranged from a minimal of 0.65 μmol/mol at 313 K and 19 MPa to a maximal of 1.97 μmol/mol at 333 K and 32 MPa. The concentration of triolein in the ternary system was equivalent to that its solubility in pure SC–CO 2 depending on system temperature and pressure conditions. Crossover pressure was determined experimentally at 29.6 MPa, below which solubility of triolein decreased with temperature (effect of density). Above the crossover pressure, solubility of triolein increased with temperature (vapor pressure effect). Values of solubility within this range were 0.16 mmol/mol at 19 MPa and 313 K to 0.41 mmol/mol at 33 MPa and 333 K. Independent of system temperature and pressure, capsanthin solubility in triolein-entrained SC–CO 2 increased by a factor of about 3 (triolein-induced enhancement

Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1

Science.gov (United States)

Koch, Alisa E.; Halloran, Margaret M.; Haskell, Catherine J.; Shah, Manisha R.; Polverini, Peter J.

1995-08-01

ENDOTHELIAL adhesion molecules facilitate the entry of leukocytes into inflamed tissues. This in turn promotes neovascularization, a process central to the progression of rheumatoid arthritis, tumour growth and wound repair1. Here we test the hypothesis that soluble endothelial adhesion molecules promote angiogenesis2á¤-4. Human recombinant soluble E-selectin and soluble vascular cell adhesion molecule-1 induced chemotaxis of human endothelial cells in vitro and were angiogenic in rat cornea. Soluble E-selectin acted on endothelial cells in part through a sialyl Lewis-X-dependent mechanism, while soluble vascular cell adhesion molecule-1 acted on endothelial cells in part through a very late antigen (VLA)-4 dependent mechanism. The chemotactic activity of rheumatoid synovial fluid for endothelial cells, and also its angiogenic activity, were blocked by antibodies to either soluble E-selectin or soluble vascular cell adhesion molecule-1. These results suggest a novel function for soluble endothelial adhesion molecules as mediators of angiogenesis.

pH-dependent solubility of indomethacin-saccharin and carbamazepine-saccharin cocrystals in aqueous media.

Science.gov (United States)

Alhalaweh, Amjad; Roy, Lilly; Rodríguez-Hornedo, Naír; Velaga, Sitaram P

2012-09-04

Cocrystals constitute an important class of pharmaceutical solids for their remarkable ability to modulate solubility and pH dependence of water insoluble drugs. Here we show how cocrystals of indomethacin-saccharin (IND-SAC) and carbamazepine-saccharin (CBZ-SAC) enhance solubility and impart a pH-sensitivity different from that of the drugs. IND-SAC exhibited solubilities 13 to 65 times higher than IND at pH values of 1 to 3, whereas CBZ-SAC exhibited a 2 to 10 times higher solubility than CBZ dihydrate. Cocrystal solubility dependence on pH predicted from mathematical models using cocrystal K(sp), and cocrystal component K(a) values, was in excellent agreement with experimental measurements. The cocrystal solubility increase relative to drug was predicted to reach a limiting value for a cocrystal with two acidic components. This limiting value is determined by the ionization constants of cocrystal components. Eutectic constants are shown to be meaningful indicators of cocrystal solubility and its pH dependence. The two contributions to solubility, cocrystal lattice and solvation, were evaluated by thermal and solubility determinations. The results show that solvation is the main barrier for the aqueous solubility of these drugs and their cocrystals, which are orders of magnitude higher than their lattice barriers. Cocrystal increase in solubility is thus a result of decreasing the solvation barrier compared to that of the drug. This work demonstrates the favorable properties of cocrystals and strategies that facilitate their meaningful characterization.

Equilibrium solubility versus intrinsic dissolution: characterization of lamivudine, stavudine and zidovudine for BCS classification

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André Bersani Dezani

2013-12-01

Full Text Available Solubility and dissolution rate of drugs are of major importance in pre-formulation studies of pharmaceutical dosage forms. The solubility improvement allows the drugs to be potential biowaiver candidates and may be a good way to develop more dose-efficient formulations. Solubility behaviour of lamivudine, stavudine and zidovudine in individual solvents (under pH range of 1.2 to 7.5 was studied by equilibrium solubility and intrinsic dissolution methods. In solubility study by equilibrium method (shake-flask technique, known amounts of drug were added in each media until to reach saturation and the mixture was subjected to agitation of 150 rpm for 72 hours at 37 ºC. In intrinsic dissolution test, known amount of each drug was compressed in the matrix of Wood's apparatus and subjected to dissolution in each media with agitation of 50 rpm at 37 ºC. In solubility by equilibrium method, lamivudine and zidovudine can be considered as highly soluble drugs. Although stavudine present high solubility in pH 4.5, 6.8, 7.5 and water, the solubility determination in pH 1.2 was not possible due stability problems. Regarding to intrinsic dissolution, lamivudine and stavudine present high speed of dissolution. Considering a boundary value presented by Yu and colleagues (2004, all drugs studied present high solubility characteristics in intrinsic dissolution method. Based on the obtained results, intrinsic dissolution seems to be superior for solubility studies as an alternative method for biopharmaceutical classification purposes.

Solubilities of benzoic acid in binary (benzyl alcohol + benzaldehyde) solvent mixtures

International Nuclear Information System (INIS)

Wang, Hui; Wang, Qinbo; Xiong, Zhenhua; Chen, Chuxiong; Shen, Binwei

2015-01-01

Highlights: • Solubilities of benzoic acid in (benzyl alcohol + benzaldehyde) mixtures were measured at 1 atm. • The experimental temperature ranges at (298.35 to 355.65) K. • Effects of benzyl alcohol mass concentration at (0.00 to 1.00) on the solubilities of benzoic acid were studied. • The experimental data were correlated with NRTL model. • Thermodynamic functions of dissolution of benzoic acid in (benzyl alcohol + benzaldehyde) mixtures were discussed. - Abstract: The solubility of benzoic acid in binary (benzyl alcohol + benzaldehyde) solvent mixtures was measured at temperature from (298.35 to 355.65) K and atmospheric pressure. The measured solubility increases with the increasing temperature at constant solvent composition. The effects of mass fraction benzaldehyde in the solvent mixtures at (0.0 to 1.00) on the solubility were studied. The measured solubility decreases with the increasing mass fraction of benzaldehyde. The experimental results were correlated with the non-random two-liquid (NRTL) equations, and good agreement between the correlated and the experimental values was obtained. Thermodynamic functions for the solution of benzoic acid in binary (benzyl alcohol + benzaldehyde) solvent mixtures were calculated with the van’t Hoff plot. The apparent dissolution Gibbs free energy change was also calculated

Iron solubility driven by speciation in dust sources to the ocean

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Schroth, A.W.; Crusius, John; Sholkovitz, E.R.; Bostick, B.C.

2009-01-01

Although abundant in the Earths crust, iron is present at trace concentrations in sea water and is a limiting nutrient for phytoplankton in approximately 40% of the ocean. Current literature suggests that aerosols are the primary external source of iron to offshore waters, yet controls on iron aerosol solubility remain unclear. Here we demonstrate that iron speciation (oxidation state and bonding environment) drives iron solubility in arid region soils, glacial weathering products (flour) and oil combustion products (oil fly ash). Iron speciation varies by aerosol source, with soils in arid regions dominated by ferric (oxy)hydroxides, glacial flour by primary and secondary ferrous silicates and oil fly ash by ferric sulphate salts. Variation in iron speciation produces systematic differences in iron solubility: less than 1% of the iron in arid soils was soluble, compared with 2-3% in glacial products and 77-81% in oil combustion products, which is directly linked to fractions of more soluble phases. We conclude that spatial and temporal variations in aerosol iron speciation, driven by the distribution of deserts, glaciers and fossil-fuel combustion, could have a pronounced effect on aerosol iron solubility and therefore on biological productivity and the carbon cycle in the ocean. ?? 2009 Macmillan Publishers Limited.

Water Solubility of Plutonium and Uranium Compounds and Residues at TA-55

International Nuclear Information System (INIS)

Reilly, Sean Douglas; Smith, Paul Herrick; Jarvinen, Gordon D.; Prochnow, David Adrian; Schulte, Louis D.; DeBurgomaster, Paul Christopher; Fife, Keith William; Rubin, Jim; Worl, Laura Ann

2016-01-01

Understanding the water solubility of plutonium and uranium compounds and residues at TA-55 is necessary to provide a technical basis for appropriate criticality safety, safety basis and accountability controls. Individual compound solubility was determined using published solubility data and solution thermodynamic modeling. Residue solubility was estimated using a combination of published technical reports and process knowledge of constituent compounds. The scope of materials considered includes all compounds and residues at TA-55 as of March 2016 that contain Pu-239 or U-235 where any single item in the facility has more than 500 g of nuclear material. This analysis indicates that the following materials are not appreciably soluble in water: plutonium dioxide (IDC=C21), plutonium phosphate (IDC=C66), plutonium tetrafluoride (IDC=C80), plutonium filter residue (IDC=R26), plutonium hydroxide precipitate (IDC=R41), plutonium DOR salt (IDC=R42), plutonium incinerator ash (IDC=R47), uranium carbide (IDC=C13), uranium dioxide (IDC=C21), U 3 O 8 (IDC=C88), and uranium filter residue (IDC=R26). This analysis also indicates that the following materials are soluble in water: plutonium chloride (IDC=C19) and uranium nitrate (IDC=C52). Equilibrium calculations suggest that PuOCl is water soluble under certain conditions, but some plutonium processing reports indicate that it is insoluble when present in electrorefining residues (R65). Plutonium molten salt extraction residues (IDC=R83) contain significant quantities of PuCl 3 , and are expected to be soluble in water. The solubility of the following plutonium residues is indeterminate due to conflicting reports, insufficient process knowledge or process-dependent composition: calcium salt (IDC=R09), electrorefining salt (IDC=R65), salt (IDC=R71), silica (IDC=R73) and sweepings/screenings (IDC=R78). Solution thermodynamic modeling also indicates that fire suppression water buffered with a commercially-available phosphate

Water Solubility of Plutonium and Uranium Compounds and Residues at TA-55

Energy Technology Data Exchange (ETDEWEB)

Reilly, Sean Douglas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Smith, Paul Herrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Jarvinen, Gordon D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Prochnow, David Adrian [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Schulte, Louis D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; DeBurgomaster, Paul Christopher [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Fife, Keith William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Rubin, Jim [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Worl, Laura Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States

2016-06-13

Understanding the water solubility of plutonium and uranium compounds and residues at TA-55 is necessary to provide a technical basis for appropriate criticality safety, safety basis and accountability controls. Individual compound solubility was determined using published solubility data and solution thermodynamic modeling. Residue solubility was estimated using a combination of published technical reports and process knowledge of constituent compounds. The scope of materials considered includes all compounds and residues at TA-55 as of March 2016 that contain Pu-239 or U-235 where any single item in the facility has more than 500 g of nuclear material. This analysis indicates that the following materials are not appreciably soluble in water: plutonium dioxide (IDC=C21), plutonium phosphate (IDC=C66), plutonium tetrafluoride (IDC=C80), plutonium filter residue (IDC=R26), plutonium hydroxide precipitate (IDC=R41), plutonium DOR salt (IDC=R42), plutonium incinerator ash (IDC=R47), uranium carbide (IDC=C13), uranium dioxide (IDC=C21), U₃O₈ (IDC=C88), and uranium filter residue (IDC=R26). This analysis also indicates that the following materials are soluble in water: plutonium chloride (IDC=C19) and uranium nitrate (IDC=C52). Equilibrium calculations suggest that PuOCl is water soluble under certain conditions, but some plutonium processing reports indicate that it is insoluble when present in electrorefining residues (R65). Plutonium molten salt extraction residues (IDC=R83) contain significant quantities of PuCl₃, and are expected to be soluble in water. The solubility of the following plutonium residues is indeterminate due to conflicting reports, insufficient process knowledge or process-dependent composition: calcium salt (IDC=R09), electrorefining salt (IDC=R65), salt (IDC=R71), silica (IDC=R73) and sweepings/screenings (IDC=R78). Solution thermodynamic modeling also indicates that fire suppression water buffered with a

Nitrogen solubility in nickel base multicomponent melts

International Nuclear Information System (INIS)

Bol'shov, L.A.; Stomakhin, A.Ya.; Sokolov, V.M.; Teterin, V.G.

1984-01-01

Applicability of various methods for calculation of nitrogen solubility in high-alloyed nickel base alloys, containing Cr, Fe, W, Mo, Ti, Nb, has been estimated. A possibility is shown to use the formUla, derived for the calculation of nitrogen solubility in iron on the basis of statistical theory for a grid model of solution which does not require limitations for the content of a solvent component. The calculation method has been used for nickel alloys, with the concentration of solvent, iron, being accepted equal to zero, and employing parameters of nitrogen interaction as determined for iron-base alloys

Radiochemical investigations on the solubility of molybdatophosphate in phosphate determination

International Nuclear Information System (INIS)

Noack, S.

1975-01-01

The solubility of various molybdatophosphates was determined under the conditions of a gravimetric phosphate determination by radiochemical means by labelling PO 4 3- with P-32. Starting with various conditions for phosphate determination via the molybdatophosphate of quinoline, 8-hydroxyquinoline, dimorpholino ethane, N,N,N',N'-tetrakis-β-hydroxypropyl ethylene diamine and N,N,N',N'-tetrakis-β-hydroxybutyl ethylene diamine, a general working rule was developed to determine the solubility. Taking the example of quinoline molybdatophosphates, a series of influencing factors - work, concentration and measuring parameters - were investigated in order to be able to limit the reliability region of the gravimetric phosphate determination. Depending on the conditions, the measured solubilities were between 10 -10 and 10 -6 Mol/l, the corresponding degrees of precipitation between 99.0 and 99.9999%. Apparent solubility products were calculated for the different molybdatophosphates using computer programmes especially developed for this purpose. (orig./RB) [de

EFFECT OF HEAT TREATMENT ON SOYBEAN PROTEIN SOLUBILITY

Directory of Open Access Journals (Sweden)

RODICA CĂPRIŢĂ

2007-05-01

Full Text Available The use of soybean products in animal feeds is limited due to the presence of antinutritional factors (ANF. Proper heat processing is required to destroy ANF naturally present in raw soybeans and to remove solvent remaining from the oil extraction process. Over and under toasting of soybean causes lower nutritional value. Excessive heat treatment causes Maillard reaction which affects the availability of lysine in particular and produces changes to the chemical structure of proteins resulting in a decrease of the nutritive value. The objective of this study was to evaluate the effect of heating time on the protein solubility. The investigation of the heating time on protein solubility in soybean meal (SBM revealed a negative correlation (r = -0.9596. Since the urease index is suitable only for detecting under processed SBM, the protein solubility is an important index for monitoring SBM quality.

Evaluation of antitumour activity of Calotropis gigantea L. root bark against Ehrlich ascites carcinoma in Swiss albino mice.

Science.gov (United States)

Habib, M Rowshahul; Karim, M Rezaul

2011-10-01

To investigate experimentally the possible antitumor effect of methanol extract (ME) of Calotropis gigantea L. (C. gigantean) root bark and its petroleum ether (PEF) and chloroform (CF) soluble fractions against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. The effects of ME (10 and 20 mg/kg), PEF (40 and 80 mg/kg) and CF (20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied. Hematological profile and biochemical parameters (SALP, SGPT and SGOT) were also estimated. Results of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one. The life span of ME and CF treated animals was significantly (PSALP) and serum glutamate oxaloacetate transaminase (SGOT). Methanol extract (ME) of C. gigantea root bark and its chloroform soluble fraction (CF) possesses significant antitumor activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin.

Science.gov (United States)

Mohanty, Chandana; Das, Manasi; Sahoo, Sanjeeb K

2012-11-01

Curcumin is a safe, affordable and natural bioactive molecule of turmeric (Curcuma longa). It has gained considerable attention in recent years for its multiple pharmacological activities. However, its optimum pharmaceutical potential has been limited by its lack of aqueous solubility and poor bioavailability. To mitigate the above limitations, recently various nanostructured water-soluble delivery systems were developed to increase the solubility and bioavailability of curcumin. Major reasons contributing to the low bioavailability of curcumin appear to be owing to its poor solubility, low absorption, rapid metabolism and rapid systemic elimination. The present review summarizes the strategies using curcumin in various nanocarrier delivery systems to overcome poor solubility and inconsistent bioavailability of curcumin and describes the current status and challenges for the future. The development of various drug delivery systems to deliver curcumin will certainly provide a step up towards augmenting the therapeutic activity of curcumin thereby increasing the solubility and bioavailability of curcumin. However, the future of such delivery technology will be highly dependent on the development of safe, non-toxic and non-immunogenic nanocarriers.

Solubility of drugs in aqueous polymeric solution: effect of ovalbumin on microencapsulation process.

Science.gov (United States)

Aziz, Hesham Abdul; Tan, Yvonne Tze Fung; Peh, Kok Khiang

2012-03-01

Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and water-insoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.

Physico-chemical characterization antituberculosis thioacetazone: Vapor pressure, solubility and lipophilicity

International Nuclear Information System (INIS)

Sharapova, Angelica; Ol'khovich, Marina; Blokhina, Svetlana; Perlovich, German

2017-01-01

Highlights: • Vapor pressures of antituberculosis thioacetazone were determined by transpiration method. • Solubilities of the TAZ in four modeling solvents were measured at different temperatures. • Temperature dependence of octanol/buffer pH 7.4 partition coefficients was obtained. • Thermodynamics parameters of solubility, sublimation, solvation and transfer were calculated. - Abstract: Vapor pressure of thioacetazone (TAZ) has been determined in the temperature range of 404.15–429.15 K by the transpiration method. The obtained data were used to calculate the standard molar enthalpy of sublimation that was found to be 164.1 kJ/mol at T = 298.15 K. The drug solubility was measured at seven temperatures from 288.15 to 318.15 K in modeling solvents: octanol, hexane and aqueous buffers pH 2.0 and 7.4 by the saturation shake-flask method by using spectrophotometric analysis. It has been found that TAZ has poor solubility in hexane and buffer solutions and limited solubility in octanol. The experimental data were well correlated by van’t Hoff and modified Apelblat equations. A temperature dependence of TAZ partition coefficient in the octanol/buffer pH 7.4 system has been derived. The partition coefficient value in this system (logP = 1.82) refers to the optimal interval for oral absorption drugs. The thermodynamic parameters of sublimation, solubility, solvation and transfer have been determined based on experimental data. The dominant effect of enthalpy and entropy contributions to the Gibbs energy of the investigated processes has been revealed.

Effect of acetamide, carbamide and thiocarbamide on sodium tetraborate solubility

Energy Technology Data Exchange (ETDEWEB)

Sadetdinov, Sh V

1985-07-01

By the methods of solubility and refractometry it is ascertained that sodium tetraborate-acetamide (carbamide, thiocarbamide)-water systems are of a simple eutonic type. Amides reduce salt solubility. Lyotropic effect on conversion to mole concentrations grows from acetamide to thiocarbamide by the absolute value.

Effect of acetamide, carbamide and thiocarbamide on sodium tetraborate solubility

International Nuclear Information System (INIS)

Sadetdinov, Sh.V.

1985-01-01

By the methods of solubility and refractometry it is ascertained that sodium tetraborate-acetamide (carbamide, thiocarbamide)-water systems are of a simple eutonic type. Amides reduce salt solubility. Lyotropic effect on conversion to mole concentrations grows from acetamide to thiocarbamide by the absolute value

How cocrystals of weakly basic drugs and acidic coformers might modulate solubility and stability.

Science.gov (United States)

Kuminek, G; Rodríguez-Hornedo, N; Siedler, S; Rocha, H V A; Cuffini, S L; Cardoso, S G

2016-04-30

Cocrystals of a weakly basic drug (nevirapine) with acidic coformers are shown to alter the solubility dependence on pH, and to exhibit a pHmax above which a less soluble cocrystal becomes more soluble than the drug. The cocrystal solubility advantage can be dialed up or down by solution pH.

Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine.

Science.gov (United States)

Rao, Monica R P; Chaudhari, Jagruti; Trotta, Francesco; Caldera, Fabrizio

2018-06-04

Rilpivrine is BCS class II drug used for treatment of HIV infection. The drug has low aqueous solubility (0.0166 mg/ml) and dissolution rate leading to low bioavailability (32%). Aim of this work was to enhance solubility and dissolution of rilpivirine using beta-cyclodextrin-based nanosponges. These nanosponges are biocompatible nanoporous particles having high loading capacity to form supramolecular inclusion and non-inclusion complexes with hydrophilic and lipophilic drugs for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonyl diimidazole and pyromellitic dianhydride to prepare nanosponges. The nanosponges were loaded with rilpivirine by solvent evaporation method. Binary and ternary complexes of drug with β-CD, HP-β-CD, nanosponges, and tocopherol polyethylene glycol succinate were prepared and characterized by phase solubility, saturation solubility in different media, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry was performed. Results obtained from spectral characterization confirmed inclusion complexation. Phase solubility studies indicated stable complex formation. Saturation solubility was found to be 10-13-folds higher with ternary complexes in distilled water and 12-14-fold higher in 0.1 N HCl. Solubility enhancement was evident in biorelevant media. Molecular modeling studies revealed possible mode of entrapment of rilpivirine within β-CD cavities. A 3-fold increase in dissolution with ternary complexes was observed. Animal studies revealed nearly 2-fold increase in oral bioavailability of rilpivirine. It was inferred that electronic interactions, hydrogen bonding, and van der Waals forces are involved in the supramolecular interactions.

Predicting trace metal solubility and fractionation in Urban soils from isotopic exchangeability

International Nuclear Information System (INIS)

Mao, L.C.; Young, S.D.; Tye, A.M.; Bailey, E.H.

2017-01-01

Metal-salt amended soils (MA, n = 23), and historically-contaminated urban soils from two English cities (Urban, n = 50), were investigated to assess the effects of soil properties and contaminant source on metal lability and solubility. A stable isotope dilution method, with and without a resin purification step, was used to measure the lability of Cd, Cu, Ni, Pb and Zn. For all five metals in MA soils, lability (%E-values) could be reasonably well predicted from soil pH value with a simple logistic equation. However, there was evidence of continuing time-dependent fixation of Cd and Zn in the MA soils, following more than a decade of storage under air-dried conditions, mainly in high pH soils. All five metals in MA soils remained much more labile than in Urban soils, strongly indicating an effect of contaminant source on metal lability in the latter. Metal solubility was predicted for both sets of soil by the geochemical speciation model WHAM-VII, using E-value as an input variable. For soils with low metal solution concentrations, over-estimation of Cd, Ni and Zn solubility was associated with binding to the Fe oxide fraction while accurate prediction of Cu solubility was dependent on humic acid content. Lead solubility was most poorly described, especially in the Urban soils. Generally, slightly poorer estimation of metal solubility was observed in Urban soils, possibly due to a greater incidence of high pH values. The use of isotopically exchangeable metal to predict solubility is appropriate both for historically contaminated soils and where amendment with soluble forms of metal is used, as in toxicological trials. However, the major limitation to predicting solubility may lie with the accuracy of model input variables such as humic acid and Fe oxide contents where there is often a reliance on relatively crude analytical estimations of these variables. Trace metal reactivity in urban soils depends on both soil properties and the original source material

Measuring Compartment Size and Gas Solubility in Marine Mammals

Science.gov (United States)

2015-09-30

bends? Effect of diving behaviour and physiology on modelled gas exchange for three species: Ziphius cavirostris, Mesoplodon densirostris and Hyperoodon...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Measuring Compartment Size and Gas Solubility in Marine...is to develop methods to estimate marine mamal tissue compartment sizes, and tissue gas solubility. We aim to improve the data available for the