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Sample records for 5a1 succinate semialdehyde

  1. LIPID ABNORMALITIES IN SUCCINATE SEMIALDEHYDE DEHYDROGENASE (Aldh5a1−/−) DEFICIENT MOUSE BRAIN PROVIDE ADDITIONAL EVIDENCE FOR MYELIN ALTERATIONS

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    Barcelo-Coblijn, G.; Murphy, E.J.; Mills, K.; Winchester, B; Jakobs, C.; Snead, O.C.; Gibson, K. M.

    2007-01-01

    Lipid abnormalities in succinate semialdehyde dehydrogenase (aldh5a1-/-) deficient mouse brain provide additional evidence for myelin alterations correspondence: Corresponding author. Tel.: +1 412 692 7608; fax: +1 412 692 7816. (Gibson, K.M.) (Gibson, K.M.) Department of Pharmacology - Physiology--> , and Therapeutics--> , School of Medicine and Health Sciences--> , University of North Dakota--...

  2. Comparative genomics of aldehyde dehydrogenase 5a1 (succinate semialdehyde dehydrogenase and accumulation of gamma-hydroxybutyrate associated with its deficiency

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    Malaspina Patrizia

    2009-01-01

    Full Text Available Abstract Succinic semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5A1 [ALDH5A1]; locus 6p22 occupies a central position in central nervous system (CNS neurotransmitter metabolism as one of two enzymes necessary for γ-aminobutyric acid (GABA recycling from the synaptic cleft. Its importance is highlighted by the neurometabolic disease associated with its inherited deficiency in humans, as well as the severe epileptic phenotype observed in Aldh5a1-/- knockout mice. Expanding evidence now suggests, however, that even subtle decreases in human SSADH activity, associated with rare and common single nucleotide polymorphisms, may produce subclinical pathological effects. SSADH, in conjunction with aldo-keto reductase 7A2 (AKR7A2, represent two neural enzymes responsible for further catabolism of succinic semialdehyde, producing either succinate (SSADH or γ-hydroxybutyrate (GHB; AKR7A2. A GABA analogue, GHB is a short-chain fatty alcohol with unusual properties in the CNS and a long pharmacological history. Moreover, SSADH occupies a further role in the CNS as the enzyme responsible for further metabolism of the lipid peroxidation aldehyde 4-hydroxy-2-nonenal (4-HNE, an intermediate known to induce oxidant stress. Accordingly, subtle decreases in SSADH activity may have the capacity to lead to regional accumulation of neurotoxic intermediates (GHB, 4-HNE. Polymorphisms in SSADH gene structure may also associate with quantitative traits, including intelligence quotient and life expectancy. Further population-based studies of human SSADH activity promise to reveal additional properties of its function and additional roles in CNS tissue.

  3. Succinic semialdehyde as a substrate for the formation of gamma-aminobutyric acid.

    Science.gov (United States)

    van Bemmelen, F J; Schouten, M J; Fekkes, D; Bruinvels, J

    1985-11-01

    The conversion of succinic semialdehyde into gamma-aminobutyric acid (GABA) by GABA-transaminase was measured in rat brain homogenate in the presence of different concentrations of the cosubstrate glutamate. The calculated kinetic parameters of succinic semialdehyde for GABA-transaminase were a limiting Km value of 168 microM and a limiting Vmax value of 38 mumol g-1 h-1. Combination with previously obtained data for the conversion of GABA into succinic semialdehyde revealed a kEq value of 0.04, indicating that equilibrium of GABA-transaminase is biased toward the formation of GABA. The increased formation of GABA in the presence of succinic semialdehyde was not due to an increased conversion of glutamate into GABA by glutamic acid decarboxylase. Therefore these results indicate that succinic semialdehyde can act as a precursor for GABA synthesis.

  4. Neurotransmitter alterations in embryonic succinate semialdehyde dehydrogenase (SSADH deficiency suggest a heightened excitatory state during development

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    Snead O Carter

    2008-11-01

    Full Text Available Abstract Background SSADH (aldehyde dehydrogenase 5a1 (Aldh5a1; γ-hydroxybutyric (GHB aciduria deficiency is a defect of GABA degradation in which the neuromodulators GABA and GHB accumulate. The human phenotype is that of nonprogressive encephalopathy with prominent bilateral discoloration of the globi pallidi and variable seizures, the latter displayed prominently in Aldh5a1-/- mice with lethal convulsions. Metabolic studies in murine neural tissue have revealed elevated GABA [and its derivatives succinate semialdehyde (SSA, homocarnosine (HC, 4,5-dihydroxyhexanoic acid (DHHA and guanidinobutyrate (GB] and GHB [and its analogue D-2-hydroxyglutarate (D-2-HG] at birth. Because of early onset seizures and the neurostructural anomalies observed in patients, we examined metabolite features during Aldh5a1-/- embryo development. Methods Embryos were obtained from pregnant dams sacrificed at E (embryo day of life 10–13, 14–15, 16–17, 18–19 and newborn mice. Intact embryos were extracted and metabolites quantified by isotope dilution mass spectrometry (n = 5–15 subjects, Aldh5a1+/+ and Aldh5a1-/- for each gestational age group. Data was evaluated using the t test and one-way ANOVA with Tukey post hoc analysis. Significance was set at the 95th centile. Results GABA and DHHA were significantly elevated at all gestational ages in Aldh5a1-/- mice, while GB was increased only late in gestation; SSA was not elevated at any time point. GHB and D-2-HG increased in an approximately linear fashion with gestational age. Correlative studies in human amniotic fluid from SSADH-deficient pregnancies (n = 5 also revealed significantly increased GABA. Conclusion Our findings indicate early GABAergic alterations in Aldh5a1-/- mice, possibly exacerbated by other metabolites, which likely induce a heightened excitatory state that may predispose neural networks to epilepsy in these animals.

  5. Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency

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    Anna-Kaisa Niemi

    2014-01-01

    Full Text Available The pathophysiology of succinic semialdehyde dehydrogenase (SSADH deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH, and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a potential therapeutic approach if our findings are confirmed in other patients.

  6. Identification of succinic semialdehyde reductases from Geobacter: expression, purification, crystallization, preliminary functional, and crystallographic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanfeng; Gao, Xiaoli; Zheng, Yi; Garavito, R. Michael (MSU)

    2012-04-30

    Succinic semialdehyde reductase (SSAR) is an important enzyme involved in {gamma}-aminobutyrate (GABA) metabolism. By converting succinic semialdehyde (SSA) to {gamma}-hydroxybutyrate (GHB), the SSAR facilitates an alternative pathway for GABA degradation. In this study, we identified SSARs from Geobacter sulfurreducens and Geobacter metallireducens (GsSSAR and GmSSAR, respectively). The enzymes were over-expressed in Escherichia coli and purified to near homogeneity. Both GsSSAR and GmSSAR showed the activity of reducing SSA using nicotinamide adenine dinucleotide phosphate as a co-factor. The oligomeric sizes of GsSSAR and GmSSAR, as determined by analytical size exclusion chromatography, suggest that the enzymes presumably exist as tetramers in solution. The recombinant GsSSAR and GmSSAR crystallized in the presence of NADP{sup +}, and the resulting crystals diffracted to 1.89 {angstrom} (GsSSAR) and 2.25 {angstrom} (GmSSAR) resolution. The GsSSAR and GmSSAR crystals belong to the space groups P2{sub 1}22{sub 1} (a = 99.61 {angstrom}, b = 147.49 {angstrom}, c = 182.47 {angstrom}) and P1 (a = 75.97 {angstrom}, b = 79.14 {angstrom}, c = 95.47 {angstrom}, {alpha} = 82.15{sup o}, {beta} = 88.80{sup o}, {gamma} = 87.66{sup o}), respectively. Preliminary crystallographic data analysis suggests the presence of eight protein monomers in the asymmetric units for both GsSSAR and GmSSAR.

  7. Identification of succinic semialdehyde reductases from Geobacter: expression,purification, crystallization, preliminary functional, and crystallographic analysis

    Institute of Scientific and Technical Information of China (English)

    Yanfeng Zhang; Xiaoli Gao; Yi Zheng; R. Michae; Garavito

    2011-01-01

    Succinic semialdehyde reductase (SSAR) is an important enzyme involved in γ-aminobutyrate (GABA) metabolism.By converting succinic semialdehyde (SSA) to γ-hydroxybutyrate (GHB),the SSAR facilitates an alternative pathway for GABA degradation.In this study,we identified SSARs from Geobacter sulfurreducens and Geobacter metallireducens (GsSSAR and GmSSAR,respectively).The enzymes were over-expressed in Escherichia coil and purified to near homogeneity.Both GsSSAR and GmSSAR showed the activity of reducing SSA using nicotinamide adenine dinucleotide phosphate as a co-factor.The oligomeric sizes of GsSSAR and GmSSAR,as determined by analytical size exclusion chromatography,suggest that the enzymes presumably exist as tetramers in solution.The recombinant GsSSAR and GmSSAR crystallized in the presence of NADP+,and the resulting crystals diffracted to 1.89 (A) (GsSSAR) and 2.25 (A)(GmSSAR) resolution.The GsSSAR and GmSSAR crystals belong to the space groups P21221 (a =99.61 (A),b =147.49 (A),c =182.47 A) and P1 (a =75.97 (A) b =79.14 (A) c =95.47 (A),α =82.15°,β =88.80°,γ=87.66°),respectively.Preliminary crystallographic data analysis suggests the presence of eight protein monomers in the asymmetric units for both GsSSAR and GmSSAR.

  8. The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.

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    Christopher G Langendorf

    Full Text Available BACKGROUND: In mammals succinic semialdehyde dehydrogenase (SSADH plays an essential role in the metabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA to succinic acid (SA. Deficiency of SSADH in humans results in elevated levels of GABA and gamma-Hydroxybutyric acid (GHB, which leads to psychomotor retardation, muscular hypotonia, non-progressive ataxia and seizures. In Escherichia coli, two genetically distinct forms of SSADHs had been described that are essential for preventing accumulation of toxic levels of succinic semialdehyde (SSA in cells. METHODOLOGY/PRINCIPAL FINDINGS: Here we structurally characterise SSADH encoded by the E coli gabD gene by X-ray crystallographic studies and compare these data with the structure of human SSADH. In the E. coli SSADH structure, electron density for the complete NADP+ cofactor in the binding sites is clearly evident; these data in particular revealing how the nicotinamide ring of the cofactor is positioned in each active site. CONCLUSIONS/SIGNIFICANCE: Our structural data suggest that a deletion of three amino acids in E. coli SSADH permits this enzyme to use NADP+, whereas in contrast the human enzyme utilises NAD+. Furthermore, the structure of E. coli SSADH gives additional insight into human mutations that result in disease.

  9. 琥珀酸半醛脱氢酶缺陷病%Succinic semialdehyde dehydrogenase deficiency

    Institute of Scientific and Technical Information of China (English)

    邓小鹿; 尹飞; 向秋莲; 刘沉涛; 彭镜

    2011-01-01

    琥珀酸半醛脱氢酶(SSADH)缺陷病是一种少见的常染色休隐性遗传病.本研究总结3例SSADH缺陷病患儿的临床资料并复习相关文献.3例患儿均为婴幼儿,主要表现为智力运动、语言发育落后,抽搐和肌张力低下.3例患儿脑电图均表现异常;2例脑MRI检查异常,表现为大脑脚对称性长T2高信号和基底节损害;3例尿液的气相色谱-质谱(GC-MS)分析均显示4-羟基丁酸增高,根据临床表现及尿液GC-MS分析确诊为SSADH缺陷病.对不明原因发育迟缓、智力运动障碍和癫病的患儿应早期进行尿液有机酸分析,对明确诊断具有重要意义.%Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder. This paper reports three cases of SSADH deficiency in infants. Hie infants developed the symptoms including developmental delay, intellectual disability, hypotonia, hyporeflexia and seizures. The electroencephalogram (EEC) showed background slowing and focal spike discharges in all of 3 patients. Head magnetic resonance imaging ( MRI) demonstrated abnormalities in 2 patients, including basal ganglia damage and increased T2-weighted signal in bilateral cerebral peduncles. Urinary organic acid analysis with gas chromatography-mass spectrometry (GC-MS) revealed increased levels of 4-hydroxybutyrate (CHB) in 3 patients. SSADH deficiency was definitely diagnosed based on the clinical manifestations and the results of urinary organic acid analysis in the 3 children. It was concluded that early urine organic acid analysis is essential for children presenting with mental retardation, neuropsychiatric disturbance or epilepsy of unknown etiology.

  10. Mutants of GABA transaminase (POP2 suppress the severe phenotype of succinic semialdehyde dehydrogenase (ssadh mutants in Arabidopsis.

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    Frank Ludewig

    Full Text Available BACKGROUND: The gamma-aminubutyrate (GABA shunt bypasses two steps of the tricarboxylic acid cycle, and is present in both prokaryotes and eukaryotes. In plants, the pathway is composed of the calcium/calmodulin-regulated cytosolic enzyme glutamate decarboxylase (GAD, the mitochondrial enzymes GABA transaminase (GABA-T; POP2 and succinic semialdehyde dehydrogenase (SSADH. We have previously shown that compromising the function of the GABA-shunt, by disrupting the SSADH gene of Arabidopsis, causes enhanced accumulation of reactive oxygen intermediates (ROIs and cell death in response to light and heat stress. However, to date, genetic investigations of the relationships between enzymes of the GABA shunt have not been reported. PRINCIPAL FINDINGS: To elucidate the role of succinic semialdehyde (SSA, gamma-hydroxybutyrate (GHB and GABA in the accumulation of ROIs, we combined two genetic approaches to suppress the severe phenotype of ssadh mutants. Analysis of double pop2 ssadh mutants revealed that pop2 is epistatic to ssadh. Moreover, we isolated EMS-generated mutants suppressing the phenotype of ssadh revealing two new pop2 alleles. By measuring thermoluminescence at high temperature, the peroxide contents of ssadh and pop2 mutants were evaluated, showing that only ssadh plants accumulate peroxides. In addition, pop2 ssadh seedlings are more sensitive to exogenous SSA or GHB relative to wild type, because GHB and/or SSA accumulate in these plants. SIGNIFICANCE: We conclude that the lack of supply of succinate and NADH to the TCA cycle is not responsible for the oxidative stress and growth retardations of ssadh mutants. Rather, we suggest that the accumulation of SSA, GHB, or both, produced downstream of the GABA-T transamination step, is toxic to the plants, resulting in high ROI levels and impaired development.

  11. Structural characterization of a β-hydroxyacid dehydrogenase from Geobacter sulfurreducens and Geobacter metallireducens with succinic semialdehyde reductase activity

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    Zhang, Yanfeng; Zheng, Yi; Qin, Ling; Wang, Shihua; Buchko, Garry W.; Garavito, Michael R.

    2014-07-30

    Beta-hydroxyacid dehydrogenase (β-HAD) genes have been identified in all sequenced genomes of eukaryotes and prokaryotes. Their gene products catalyze the NAD+- or NADP+-dependent oxidation of various β-hydroxy acid substrates into their corresponding semialdehyde. In many fungal and bacterial genomes, multiple β-HAD genes are observed leading to the hypothesis that these gene products may have unique, uncharacterized metabolic roles specific to their species. The genomes of Geobacter sulfurreducens and Geobacter metallireducens each contain two potential β-HAD genes. The protein sequences of one pair of these genes, Gs-βHAD (Q74DE4) and Gm-βHAD (Q39R98), have 65% sequence identity and 77% sequence similarity with each other. Both proteins reduce succinic semialdehyde, a metabolite of the GABA shunt. To further explore the structural and functional characteristics of these two β-HADs with a potentially unique substrate specificity, crystal structures for Gs-βHAD and Gm-βHAD in complex with NADP+ were determined to a resolution of 1.89 Å and 2.07 Å, respectively. The structure of both proteins are similar, composed of 14 α-helices and nine β-strands organized into two domains. Domain One (1-165) adopts a typical Rossmann fold composed of two α/β units: a six-strand parallel β-sheet surrounded by six α-helices (α1 – α6) followed by a mixed three-strand β-sheet surrounded by two α-helices (α7 and α8). Domain Two (166-287) is composed of a bundle of seven α-helices (α9 – α14). Four functional regions conserved in all β-HADs are spatially located near each other at the interdomain cleft in both Gs-βHAD and Gm-βHAD with a buried molecule of NADP+. The structural features of Gs-βHAD and Gm-βHAD are described in relation to the four conserved consensus sequences characteristic of β-HADs and the potential biochemical importance of these enzymes as an alternative pathway for the degradation of succinic semialdehyde.

  12. Structural characterization of a β-hydroxyacid dehydrogenase from Geobacter sulfurreducens and Geobacter metallireducens with succinic semialdehyde reductase activity.

    Science.gov (United States)

    Zhang, Yanfeng; Zheng, Yi; Qin, Ling; Wang, Shihua; Buchko, Garry W; Garavito, R Michael

    2014-09-01

    Beta-hydroxyacid dehydrogenase (β-HAD) genes have been identified in all sequenced genomes of eukaryotes and prokaryotes. Their gene products catalyze the NAD(+)- or NADP(+)-dependent oxidation of various β-hydroxy acid substrates into their corresponding semialdehyde. In many fungal and bacterial genomes, multiple β-HAD genes are observed leading to the hypothesis that these gene products may have unique, uncharacterized metabolic roles specific to their species. The genomes of Geobacter sulfurreducens and Geobacter metallireducens each contain two potential β-HAD genes. The protein sequences of one pair of these genes, Gs-βHAD (Q74DE4) and Gm-βHAD (Q39R98), have 65% sequence identity and 77% sequence similarity with each other. Both proteins are observed to reduce succinic semialdehyde, a 4-carbon substrate instead of the typical β-HAD 3-carbon substrate, to γ-hydroxybutyric acid. To further explore the structural and functional characteristics of these two β-HADs with a less frequently observed substrate specificity, crystal structures for Gs-βHAD and Gm-βHAD in complex with NADP(+) were determined to a resolution of 1.89 Å and 2.07 Å, respectively. The structures of both proteins are similar, composed of 14 α-helices and nine β-strands organized into two domains. Domain 1 (1-165) adopts a typical Rossmann fold composed of two α/β units: a six-strand parallel β-sheet surrounded by six α-helices (α1-α6) followed by a mixed three-strand β-sheet surrounded by two α-helices (α7 and α8). Domain 2 (166-287) is composed of a bundle of seven α-helices (α9-α14). Four functional regions conserved in all β-HADs are spatially located near each other, with a buried molecule of NADP(+), at the interdomain cleft. Comparison of these Geobacter structures to a closely related β-HAD from Arabidopsis thaliana in the apo-NADP(+) and apo-substrate bound state suggests that NADP(+) binding effects a rigid body rotation between Domains 1 and 2. Bound

  13. The Succinated Proteome

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    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John; Frizell, Norma

    2014-03-30

    Succination is a chemical modification of cysteine in protein by the Krebs cycle intermediate, fumarate, yielding S-(2-succino)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane, in concert with mitochondrial, endoplasmic reticulum (ER) and oxidative stress in adipocytes grown in high glucose medium and in adipose tissue in obesity and diabetes. Increased succination of proteins is also detected in the kidney of a fumarase conditional knock-out mouse which develops renal tumors. Keap1, the gatekeeper of the antioxidant response, was identified as a major succinated protein in renal cancer cells, suggesting that succination may play a role in activation of the antioxidant response. A wide range of proteins is subject to succination, including enzymes, adipokines, cytoskeletal proteins and ER chaperones with functional cysteine residues. There is also significant overlap between succinated and glutathionylated proteins, and with proteins containing cysteine residues that are readily oxidized to the sulfenic (cysteic) acid. Succination of adipocyte proteins is inhibited by uncouplers, which discharge the mitochondrial membrane potential (Δψm) and by ER stress inhibitors. 2SC serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes and cancer, and recent studies suggest that succination is a mechanistic link between mitochondrial dysfunction, oxidative and ER stress, and cellular progression toward apoptosis. In this article, we review the history of the succinated proteome and the challenges associated with measuring this non-enzymatic post-translational modification of proteins by proteomics approaches.

  14. Bis(4-methylimidazolium succinate succinic acid solvate

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    2009-03-01

    Full Text Available In the title compound, 2C4H7N2+·C4H4O42−·C4H6O4, the asymmetric unit consists of two 4-methylimidazolium cations, one succinate dianion and one netrual succinic acid molecule and within the latter components, the C—O, C=O and C...;O bonds are clearly evidenced from their relative distances. In the crystal structure, the individual components are linked by intermolecular N—H...O, O—H...O and C—H...O hydrogen bonds into a two-dimensional network parallel to the (101 plane in which R33(9, R33(12 and R44(18 hydrogen-bond motifs are present.

  15. A putrescine-inducible pathway comprising PuuE-YneI in which gamma-aminobutyrate is degraded into succinate in Escherichia coli K-12.

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    Kurihara, Shin; Kato, Kenji; Asada, Kei; Kumagai, Hidehiko; Suzuki, Hideyuki

    2010-09-01

    Gamma-aminobutyrate (GABA) is metabolized to succinic semialdehyde by GABA aminotransferase (GABA-AT), and the succinic semialdehyde is subsequently oxidized to succinate by succinic semialdehyde dehydrogenase (SSADH). In Escherichia coli, there are duplicate GABA-ATs (GabT and PuuE) and duplicate SSADHs (GabD and YneI). While GabT and GabD have been well studied previously, the characterization and expression analysis of PuuE and YneI are yet to be investigated. By analyzing the amino acid profiles in cells of DeltapuuE and/or DeltagabT mutants, this study demonstrated that PuuE plays an important role in GABA metabolism in E. coli cells. The similarity of the amino acid sequences of PuuE and GabT is 67.4%, and it was biochemically demonstrated that the catalytic center of GabT is conserved as an amino acid residue important for the enzymatic activity in PuuE as Lys-247. However, the regulation of expression of PuuE is significantly different from that of GabT. PuuE is induced by the addition of putrescine to the medium and is repressed by succinate and low aeration conditions; in contrast, GabT is almost constitutive. Similarly, YneI is induced by putrescine, while GabD is not. For E. coli, PuuE is important for utilization of putrescine as a sole nitrogen source and both PuuE and YneI are important for utilization of putrescine as a sole carbon source. The results demonstrate that the PuuE-YneI pathway was a putrescine-inducible GABA degradation pathway for utilizing putrescine as a nutrient source.

  16. Gamma-Hydroxybutyrate (GHB) Content in Hair Samples Correlates Negatively with Age in Succinic Semialdehyde Dehydrogenase Deficiency

    DEFF Research Database (Denmark)

    Johansen, S S; Wang, X.; Pedersen, Daniel Sejer

    2017-01-01

    shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD. We quantified GHB in hair derived from ten patients with SSADHD, and documented...

  17. Characterization of the different spectral forms of glutamate 1-semialdehyde aminotransferase by mass spectrometry

    DEFF Research Database (Denmark)

    Brody, S; Andersen, Jens S.; Kannangara, C G

    1995-01-01

    Glutamate 1-semialdehyde aminotransferase produces delta-aminolevulinate for the synthesis of chlorophyll, heme, and other tetrapyrrole pigments. The native enzyme from Synechococcus is pale yellow and has absorption maxima at 338 and 418 nm from vitamin B6. Yellow, colorless, and pink forms...

  18. Succination of proteins in diabetes.

    Science.gov (United States)

    Frizzell, Norma; Lima, Maria; Baynes, John W

    2011-01-01

    Cysteine is arguably the most reactive amino acid in protein. A wide range of cysteine derivatives is formed in vivo, resulting from oxidation, nitrosation, alkylation and acylation reactions. This review describes succination of proteins, an irreversible chemical modification of cysteine by the Krebs cycle intermediate, fumarate, yielding S-(2-succinyl)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane and develop in concert with mitochondrial and oxidative stress in diabetes. Increased succination of glyceraldehyde-3-phosphate dehydrogenase explains the loss in specific activity of this enzyme in muscle of streptozotocin-diabetic rats and increased succination of adiponectin may explain the decreased secretion of adiponectin from adipose tissue in type 2 diabetes. In addition to GAPDH and adiponectin, other succinated proteins identified in adipocytes include cytoskeletal proteins (tubulin, actin) and chaperone proteins in the endoplasmic reticulum. Succination of adipocyte protein in vitro is inhibited by uncouplers of oxidative phosphorylation and by inhibitors of ER stress. 2SC serves as a biomarker of mitochondrial stress and recent studies suggest that succination is the mechanistic link between mitochondrial and ER stress in diabetes.

  19. Chemoreactome analysis of ethylmethylhydroxypyridine succinate

    OpenAIRE

    2016-01-01

    Ethylmethylhydroxypyridine succinate (EMHPS) is used in the therapy of ischemic stroke. A more complete understanding of the conditions that can affect the clinical efficacy of EMHPS needs the most complete information about its molecular mechanisms of action.Objective: to comparatively analyze the properties of EMHPS using the newest area of postgenomic pharmacology – chemoreactome simulation. Succinic acid and citicoline were used as the molecules of comparison (control molecules).Material ...

  20. Crystal structure of glutamate-1-semialdehyde-2,1-aminomutase from Arabidopsis thaliana

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    Song, Yingxian; Pu, Hua; Jiang, Tian; Zhang, Lixin; Ouyang, Min, E-mail: ouyangmin@ibcas.ac.cn [Chinese Academy of Sciences, Beijing 100093, People’s Republic of (China)

    2016-05-23

    A structural study of A. thaliana glutamate-1-semialdehyde-2,1-aminomutase (GSAM) has revealed asymmetry in cofactor binding as well as in the gating-loop orientation, which supports the previously proposed negative cooperativity between monomers of GSAM. Glutamate-1-semialdehyde-2,1-aminomutase (GSAM) catalyzes the isomerization of glutamate-1-semialdehyde (GSA) to 5-aminolevulinate (ALA) and is distributed in archaea, most bacteria and plants. Although structures of GSAM from archaea and bacteria have been resolved, a GSAM structure from a higher plant is not available, preventing further structure–function analysis. Here, the structure of GSAM from Arabidopsis thaliana (AtGSA1) obtained by X-ray crystallography is reported at 1.25 Å resolution. AtGSA1 forms an asymmetric dimer and displays asymmetry in cofactor binding as well as in the gating-loop orientation, which is consistent with previously reported Synechococcus GSAM structures. While one monomer binds PMP with the gating loop fixed in the open state, the other monomer binds either PMP or PLP and the gating loop is ready to close. The data also reveal the mobility of residues Gly163, Ser164 and Gly165, which are important for reorientation of the gating loop. Furthermore, the asymmetry of the AtGSA1 structure supports the previously proposed negative cooperativity between monomers of GSAM.

  1. Characterization of SLCO5A1/OATP5A1, a solute carrier transport protein with non-classical function.

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    Katrin Sebastian

    Full Text Available Organic anion transporting polypeptides (OATP/SLCO have been identified to mediate the uptake of a broad range of mainly amphipathic molecules. Human OATP5A1 was found to be expressed in the epithelium of many cancerous and non-cancerous tissues throughout the body but protein characterization and functional analysis have not yet been performed. This study focused on the biochemical characterization of OATP5A1 using Xenopus laevis oocytes and Flp-In T-REx-HeLa cells providing evidence regarding a possible OATP5A1 function. SLCO5A1 is highly expressed in mature dendritic cells compared to immature dendritic cells (∼6.5-fold and SLCO5A1 expression correlates with the differentiation status of primary blood cells. A core- and complex- N-glycosylated polypeptide monomer of ∼105 kDa and ∼130 kDa could be localized in intracellular membranes and on the plasma membrane, respectively. Inducible expression of SLCO5A1 in HeLa cells led to an inhibitory effect of ∼20% after 96 h on cell proliferation. Gene expression profiling with these cells identified immunologically relevant genes (e.g. CCL20 and genes implicated in developmental processes (e.g. TGM2. A single nucleotide polymorphism leading to the exchange of amino acid 33 (L→F revealed no differences regarding protein expression and function. In conclusion, we provide evidence that OATP5A1 might be a non-classical OATP family member which is involved in biological processes that require the reorganization of the cell shape, such as differentiation and migration.

  2. Synthesis of carbon-14 labeled doxylamine succinate

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    Rao, P.N.; Damodaran, K.M.

    1986-05-01

    Doxylamine succinate, N,N-dimethyl-2-(1-phenyl-1-(2-pyridinyl)-ethoxy)ethanamine succinate is an antihistamine used primarily as a sedative. Carbon-14 labeled doxylamine succinate, required for toxicological studies, was synthesized in two steps starting from 2-benzoyl pyridine.

  3. Asymmetry of the Active Site Loop Conformation between Subunits of Glutamate-1-semialdehyde Aminomutase in Solution

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    Barbara Campanini

    2013-01-01

    Full Text Available Glutamate-1-semialdehyde aminomutase (GSAM is a dimeric, pyridoxal 5′-phosphate (PLP- dependent enzyme catalysing in plants and some bacteria the isomerization of L-glutamate-1-semialdehyde to 5-aminolevulinate, a common precursor of chlorophyll, haem, coenzyme B12, and other tetrapyrrolic compounds. During the catalytic cycle, the coenzyme undergoes conversion from pyridoxamine 5′-phosphate (PMP to PLP. The entrance of the catalytic site is protected by a loop that is believed to switch from an open to a closed conformation during catalysis. Crystallographic studies indicated that the structure of the mobile loop is related to the form of the cofactor bound to the active site, allowing for asymmetry within the dimer. Since no information on structural and functional asymmetry of the enzyme in solution is available in the literature, we investigated the active site accessibility by determining the cofactor fluorescence quenching of PMP- and PLP-GSAM forms. PLP-GSAM is partially quenched by potassium iodide, suggesting that at least one catalytic site is accessible to the anionic quencher and therefore confirming the asymmetry observed in the crystal structure. Iodide induces release of the cofactor from PMP-GSAM, apparently from only one catalytic site, therefore suggesting an asymmetry also in this form of the enzyme in solution, in contrast with the crystallographic data.

  4. The measurement of urinary Delta(1)-piperideine-6-carboxylate, the alter ego of alpha-aminoadipic semialdehyde, in Antiquitin deficiency.

    NARCIS (Netherlands)

    Struys, E.A.; Bok, L.A.; Emal, D.; Houterman, S.; Willemsen, M.A.A.P.; Jakobs, C.

    2012-01-01

    The assessment of urinary alpha-aminoadipic semialdehyde (alpha-AASA) has become the diagnostic laboratory test for pyridoxine dependent seizures (PDS). alpha-AASA is in spontaneous equilibrium with its cyclic form Delta(1)-piperideine-6-carboxylate (P6C); a molecule with a heterocyclic ring structu

  5. Expansion of the aspartate [beta]-semialdehyde dehydrogenase family: the first structure of a fungal ortholog

    Energy Technology Data Exchange (ETDEWEB)

    Arachea, B.T.; Liu, X.; Pavlovsky, A.G.; Viola, R.E. (Toledo)

    2010-08-13

    The enzyme aspartate semialdehyde dehydrogenase (ASADH) catalyzes a critical transformation that produces the first branch-point intermediate in an essential microbial amino-acid biosynthetic pathway. The first structure of an ASADH isolated from a fungal species (Candida albicans) has been determined as a complex with its pyridine nucleotide cofactor. This enzyme is a functional dimer, with a similar overall fold and domain organization to the structurally characterized bacterial ASADHs. However, there are differences in the secondary-structural elements and in cofactor binding that are likely to cause the lower catalytic efficiency of this fungal enzyme. Alterations in the dimer interface, through deletion of a helical subdomain and replacement of amino acids that participate in a hydrogen-bonding network, interrupt the intersubunit-communication channels required to support an alternating-site catalytic mechanism. The detailed functional information derived from this new structure will allow an assessment of ASADH as a possible target for antifungal drug development.

  6. Succinic acid production from Jerusalem artichoke

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Karakashev, Dimitar Borisov; Angelidaki, Irini

    In this work, A. succinogenes 130Z was used to produce succinic acid from Jerusalem artichoke tuber hydrolysate. Results showed that both fructose and glucose in the tuber hydrolysate were utilized for succinic acid production. The sugar utilization was found to be dependent on process control......, hence, when pH was fixed at 6.8 the sugar utilization of fructose was increased from 68.6% to 96.5% and the succinic acid production was also increased by 26.4% to yield 26.8 g/L succinic acid. In this study a one-step pretreatment/hydrolysis method was used where no enzymes were used. Our work suggests...... that Jerusalem artichoke tubers could be utilized for production of bio-succinic acid....

  7. Chemoreactome analysis of ethylmethylhydroxypyridine succinate

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2016-01-01

    Full Text Available Ethylmethylhydroxypyridine succinate (EMHPS is used in the therapy of ischemic stroke. A more complete understanding of the conditions that can affect the clinical efficacy of EMHPS needs the most complete information about its molecular mechanisms of action.Objective: to comparatively analyze the properties of EMHPS using the newest area of postgenomic pharmacology – chemoreactome simulation. Succinic acid and citicoline were used as the molecules of comparison (control molecules.Material and methods. Chemoreactome analysis was employed to assess the biological activity of a test molecule (simulation of the affinity profile of the examined molecular structure for various proteome proteins. A new mathematical method based on the combinatorial theory of solvability was devised for chemoinformational analysis.Results and discussion. Chemoreactome simulation has shown that EMHPS may be an agonist of acetylcholine and GABA receptors, as well as that of cannabinoid receptor type 2. The anti-inflammatory effect of an EMHPS molecule may be due to the inhibition of synthesis of proinflammatory prostaglandins. Its higher safety (a weaker effect on serotonin and opioid receptors and lower interaction with Erg channels and the enzymes monoamine oxidase and cytochrome CYP1A1 distinguish EMHPS from the molecules of comparison (citicolne and succinic acid. The predicted properties of the molecule of EMHPS make a substantial contribution to its neuroprotective effect.Conclusion. The results of chemoreactome analysis could reveal not only quite unexpected mechanisms of action of EMHPS, but also its mechanisms of synergic action with pyridoxine and magnesium. Owing to a combination of EMHPS with pyridoxine and magnesium, there is an increase in the antioxidant, anticonvulsant, stress- and neuroprotective, nootropic, and anxiolytic effects of EMHPS via activation of pyridoxine-dependent and magnesium-dependent proteins. The combination of EMHPS with

  8. Pyridoxine-dependent epilepsy with elevated urinary α-amino adipic semialdehyde in molybdenum cofactor deficiency.

    Science.gov (United States)

    Struys, Eduard Alexander; Nota, Benjamin; Bakkali, Abdellatif; Al Shahwan, Saad; Salomons, Gajja Sophi; Tabarki, Brahim

    2012-12-01

    α-Amino adipic semialdehyde (α-AASA) accumulates in body fluids from patients with pyridoxine-dependent epilepsy because of mutations in antiquitin (ALDH7A1) and serves as the biomarker for this condition. We have recently found that the urinary excretion of α-AASA was also increased in molybdenum cofactor and sulfite oxidase deficiencies. The seizures in pyridoxine-dependent epilepsy are caused by lowered cerebral levels of pyridoxal-5-phosphate (PLP), the bioactive form of pyridoxine (vitamin B(6)), which can be corrected by the supplementation of pyridoxine. The nonenzymatic trapping of PLP by the cyclic form of α-AASA is causative for the lowered cerebral PLP levels. We describe 2 siblings with clinically evident pyridoxine-responsive seizures associated with increased urinary excretion of α-AASA. Subsequent metabolic investigations revealed several metabolic abnormities, all indicative for molybdenum cofactor deficiency. Molecular investigations indeed revealed a known homozygous mutation in the MOCS2 gene. Based upon the clinically evident pyridoxine-responsive seizures in these 2 siblings, we recommend considering pyridoxine supplementation to patients affected with molybdenum cofactor or sulfite oxidase deficiencies.

  9. Identification and Validation of Aspartic Acid Semialdehyde Dehydrogenase as a New Anti-Mycobacterium Tuberculosis Target.

    Science.gov (United States)

    Meng, Jianzhou; Yang, Yanhui; Xiao, Chunling; Guan, Yan; Hao, Xueqin; Deng, Qi; Lu, Zhongyang

    2015-09-30

    Aspartic acid semialdehyde dehydrogenase (ASADH) lies at the first branch point in the essential aspartic acid biosynthetic pathway that is found in bacteria and plants but is absent from animals. Mutations in the asadh gene encoding ASADH produce an inactive enzyme, which is lethal. Therefore, in this study, we investigated the hypothesis that ASADH represents a new anti-Mycobacterium tuberculosis (MTB) target. An asadh promoter-replacement mutant MTB, designated MTB::asadh, in which asadh gene expression is regulated by pristinamycin, was constructed to investigate the physiological functions of ASADH in the host bacteria. Bacterial growth was evaluated by monitoring OD600 and ASADH expression was analyzed by Western blotting. The results showed that the growth and survival of MTB::asadh was completely inhibited in the absence of the inducer pristinamycin. Furthermore, the growth of the mutant was rigorously dependent on the presence of the inducer in the medium. The starved mutant exhibited a marked reduction (approximately 80%) in the cell wall materials compared to the wild-type, in addition to obvious morphological differences that were apparent in scanning electron microscopy studies; however, with the addition of pristinamycin, the cell wall contents and morphology similar to those of the wild-type strain were recovered. The starved mutant also exhibited almost no pathogenicity in an in vitro model of infection using mouse macrophage J774A.1 cells. The mutant showed a concentration-dependent recovery of pathogenicity with the addition of the inducer. These findings implicate ASADH as a promising target for the development of novel anti-MTB drugs.

  10. Identification and Validation of Aspartic Acid Semialdehyde Dehydrogenase as a New Anti-Mycobacterium Tuberculosis Target

    Directory of Open Access Journals (Sweden)

    Jianzhou Meng

    2015-09-01

    Full Text Available Aspartic acid semialdehyde dehydrogenase (ASADH lies at the first branch point in the essential aspartic acid biosynthetic pathway that is found in bacteria and plants but is absent from animals. Mutations in the asadh gene encoding ASADH produce an inactive enzyme, which is lethal. Therefore, in this study, we investigated the hypothesis that ASADH represents a new anti-Mycobacterium tuberculosis (MTB target. An asadh promoter-replacement mutant MTB, designated MTB::asadh, in which asadh gene expression is regulated by pristinamycin, was constructed to investigate the physiological functions of ASADH in the host bacteria. Bacterial growth was evaluated by monitoring OD600 and ASADH expression was analyzed by Western blotting. The results showed that the growth and survival of MTB::asadh was completely inhibited in the absence of the inducer pristinamycin. Furthermore, the growth of the mutant was rigorously dependent on the presence of the inducer in the medium. The starved mutant exhibited a marked reduction (approximately 80% in the cell wall materials compared to the wild-type, in addition to obvious morphological differences that were apparent in scanning electron microscopy studies; however, with the addition of pristinamycin, the cell wall contents and morphology similar to those of the wild-type strain were recovered. The starved mutant also exhibited almost no pathogenicity in an in vitro model of infection using mouse macrophage J774A.1 cells. The mutant showed a concentration-dependent recovery of pathogenicity with the addition of the inducer. These findings implicate ASADH as a promising target for the development of novel anti-MTB drugs.

  11. Crystal structure of the bis(cyclohexylammonium succinate succinic acid salt adduct

    Directory of Open Access Journals (Sweden)

    Modou Sarr

    2015-08-01

    Full Text Available The crystal structure of the title salt adduct, 2C6H14N+·C4H4O42−·C4H6O4, consists of two cyclohexylammonium cations, one succcinate dianion and one neutral succinic acid molecule. Succinate dianions and succinic acid molecules are self-assembled head-to-tail through O—H...O hydrogen bonds and adopt a syn–syn configuration, leading to a strand-like arrangement along [101]. The cyclohexylammonium cations have a chair conformation and act as multidentate hydrogen-bond donors linking adjacent strands through intermolecular N—H...O interactions to both the succinate and the succinic acid components. This results in two-dimensional supramolecular layered structures lying parallel to (010.

  12. 21 CFR 522.784 - Doxylamine succinate injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Doxylamine succinate injection. 522.784 Section... § 522.784 Doxylamine succinate injection. (a) Specifications. Each milliliter of the drug contains 11.36 mg of doxylamine succinate. (b) Sponsor. See No. 000061 in § 510.600(c) of this chapter....

  13. 21 CFR 520.784 - Doxylamine succinate tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Doxylamine succinate tablets. 520.784 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  14. Bacterial mutants for enhanced succinate production

    NARCIS (Netherlands)

    Baart, G.J.E.; Beauprez, J.J.R.; Foulquie, M.M.R.; Heijnen, J.J.; Maertens, J.

    2010-01-01

    The present invention relates to a method for obtaining enhanced metabolite production in micro-organisms, and to mutants and/or transformants obtained with said method. More particularly, it relates to bacterial mutants and/or transformants for enhanced succinate production, especially mutants and/

  15. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

    DEFF Research Database (Denmark)

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine

    2016-01-01

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date......, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose...... homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN...

  16. Tartronate semialdehyde reductase defines a novel rate-limiting step in assimilation and bioconversion of glycerol in Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    Yanbin Liu

    Full Text Available BACKGROUND: Glycerol is a by-product of biodiesel production. Currently, it has limited applications with low bioconversion efficiency to most metabolites reported. This is partly attributed to the poor knowledge on the glycerol metabolic pathway in bacteria and fungi. METHODOLOGY/PRINCIPAL FINDINGS: We have established a fast screening method for identification of genes that improve glycerol utilization in Ustilago maydis. This was done by comparing the growth rates of T-DNA tagged mutant colonies on solid medium using glycerol as the sole carbon source. We present a detailed characterization of one of the mutants, GUM1, which contains a T-DNA element inserted into the promoter region of UM02592 locus (MIPS Ustilago maydis database, MUMDB, leading to enhanced and constitutive expression of its mRNA. We have demonstrated that um02592 encodes a functional tartronate semialdehyde reductase (Tsr1, which showed dual specificity to cofactors NAD(+ and NADP(+ and strong substrate specificity and enantioselectivity for D-glycerate. Improved glycerol assimilation in GUM1 was associated with elevated expression of tsr1 mRNA and this could be phenocopied by over-expression of the gene. Glycolipid accumulation was reduced by 45.2% in the knockout mutant whereas introduction of an extra copy of tsr1 driven by the glyceraldehyde phosphate dehydrogenase promoter increased it by 40.4%. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that tartronate semialdehyde reductase (TSR plays an important role in glycerol assimilation in U. maydis and defines a novel target in genetic engineering for improved conversion of glycerol to higher value products. Our results add significant depth to the understanding of the glycerol metabolic pathway in fungi. We have demonstrated, for the first time, a biological role of a eukaryotic TSR.

  17. Data of evolutionary structure change: 1AZ5A-1HTGA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AZ5A-1HTGA 1AZ5 1HTG A A PQFHLWKRPVVTAHIEGQPVEVLLDTGADDSIVTGIELG...PHYTPKIV----GFINTKEYKNVEVEVLGKRIKGTIMTGDTPINIFGRNLLTALGMSLNF PQITLWQRPLVTIKIGGQLKEALLDTGADDTVLE...THR CA 318 1HTG A 1HTGA

  18. Is the COL5A1 rs12722 gene polymorphism associated with running economy?

    Directory of Open Access Journals (Sweden)

    Rômulo Bertuzzi

    Full Text Available The COL5A1 rs12722 polymorphism is considered to be a novel genetic marker for endurance running performance. It has been postulated that COL5A1 rs12722 may influence the elasticity of tendons and the energetic cost of running. To date, there are no experimental data in the literature supporting the relationship between range of motion, running economy, and the COL5A1 rs12722 gene polymorphism. Therefore, the main purpose of the current study was to analyze the influence of the COL5A1rs12722 polymorphism on running economy and range of motion. One hundred and fifty (n = 150 physically active young men performed the following tests: a a maximal incremental treadmill test, b two constant-speed running tests (10 km · h(-1 and 12 km · h(-1 to determine the running economy, and c a sit-and-reach test to determine the range of motion. All of the subjects were genotyped for the COL5A1 rs12722 single-nucleotide polymorphism. The genotype frequencies were TT = 27.9%, CT = 55.8%, and CC = 16.3%. There were no significant differences between COL5A1 genotypes for running economy measured at 10 km · h(-1 (p = 0.232 and 12 km · h(-1 (p = 0.259. Similarly, there were no significant differences between COL5A1 genotypes for range of motion (p = 0.337. These findings suggest that the previous relationship reported between COL5A1 rs12722 genotypes and running endurance performance might not be mediated by the energetic cost of running.

  19. Enhanced succinate production from glycerol by engineered Escherichia coli strains.

    Science.gov (United States)

    Li, Qing; Wu, Hui; Li, Zhimin; Ye, Qin

    2016-10-01

    In this study, an engineered strain Escherichia coli MLB (ldhA(-)pflB(-)) was constructed for production of succinate from glycerol. The succinate yield was 0.37mol/mol in anaerobic culture, however, the growth and glycerol consumption rates were very slow, resulting in a low succinate level. Two-stage fermentation was performed in flasks, and the succinate yield reached 0.93mol/mol, but the succinate titer was still low. Hence, overexpression of malate dehydrogenase, malic enzyme, phosphoenolpyruvate (PEP) carboxylase and PEP carboxykinase (PCK) from E. coli, and pyruvate carboxylase from Corynebacterium glutamicum in MLB was investigated for improving succinate production. Overexpression of PCK resulted in remarkable enhancement of glycerol consumption and succinate production. In flask experiments, the succinate concentration reached 118.1mM, and in a 1.5-L bioreactor the succinate concentration further increased to 360.2mM. The highest succinate yield achieved 0.93mol/mol, which was 93% of the theoretical yield, in the anaerobic stage.

  20. BER-Myriant Succinic Acid Biorefinery

    Energy Technology Data Exchange (ETDEWEB)

    Shmorhun, Mark [Myriant Lake Providence, Inc., Lake Providence, LA (United States)

    2015-12-31

    Myriant Corporation (Myriant) has successfully produced the bioproduct succinic acid by the fermentation of glucose at a commercial scale operation in Lake Providence, Louisiana. The MySAB facility (Myriant Succinic Acid Biorefinery) came on stream in May 2013 and has been producing product since then. The MySAB facility is a demonstration-scale plant, capable of utilizing sorghum grits and commercially available dextrose, to ferment glucose into succinic acid. A downstream processing train has demonstrated the ability to produce an industrial, a standard and a polymer grade product. It consists of cell separation, membrane filtration, continuous chromatography, polishing to remove ionic and color bodies impurities, and final evaporation and crystallization. A by-product of the process is ammonium sulfate which is sold as a liquid fertilizer product. Since 2007 when development work began in the Woburn, Massachusetts R&D laboratories, the succinic acid bio-process has evolved through: Process development (microbiology, fermentation, and downstream) – R&D development laboratories; Piloting efforts at Fermic S.A. de C.V., Mexico City, Mexico – upstream and downstream processes; Design, construction, commissioning, and commercial production operations at the MySAB facility Additionally, Myriant became a wholly-owned subsidiary of the PTT Global Chemical Plc., Thailand, in late 2015, their investment into and support of Myriant goes back to 2011. The support of PTT Global Chemical Plc. helped to improve the upstream and downstream processes, and produce significant metric ton quantities of high quality bio-based succinic acid. The product has gone into a number of commercial markets worldwide for customer applications, development and production. The experience base gained via operations at the MySAB facility since May 2013, along with continued R&D development efforts involving Microbiology, Fermentation, and Downstream processes, at both the Woburn, Massachusetts

  1. Acute pancreatitis and acute renal failure complicating doxylamine succinate intoxication.

    Science.gov (United States)

    Lee, Yang Deok; Lee, Soo Teik

    2002-06-01

    Doxylamine succinate is an antihistaminic drugwith additional hypnotic, anticholinergic and local anesthetic effects first described in 1948. In Korea and many other countries, it is a common-over-the counter medication frequently involved in overdoses. Clinical symtomatology of doxylamine succinate overdose includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. We report a case of acute renal failure and acute pancreatitis complicating a doxylamine succinate intoxication.

  2. Bis(ethanolaminium succinate–succinic acid (1/1

    Directory of Open Access Journals (Sweden)

    Miao Zhang

    2011-09-01

    Full Text Available The asymmetric unit of the title compound, 2C2H8NO+·C4H4O42−·C4H6O4, consists of half a succinate anion, half a succinic acid molecule and one ethanolaminium cation. The succinate anion and succinic acid molecule, both of which are located on inversion centres, are linked by O—H...O hydrogen bonds, forming a chain along the [2overline{1}0] direction. The chain and the ethanolaminium cation are further connected by O—H...O and N—H...O hydrogen bonds.

  3. Data of evolutionary structure change: 1AT5A-1IOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AT5A-1IOTA 1AT5 1IOT A A KVFGRCELAAAMKRHGLDNYRGYSLGNWVCAAKFESNFN... 1IOT A 1IOTA...5 0.36800000071525574 tion> 0.9990000128746033 -0.03400000184774399 0.003000000026077032 -0.019999999552965164 -0.0020000000949949026 1.0 ti

  4. Data of evolutionary structure change: 1AR5A-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 7178 EVID> 3 1UNF...1AR5A-1UNFX 1AR5 1UNF A X ---AVYTLPELPYDYSALEPYISGEIMELHHDKHHKAYV...EEEEEEEEGGG EEEEEEE EEE EEE HHHH HHHHHHHHHH EEHHHHHHHHHHHHHH EVID> 1UNF X 1UNFX VNP...2.935019016265869 5.316431999206543 EVID>

  5. TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2015-12-01

    Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

  6. Biodegradable polyesters based on succinic acid

    Directory of Open Access Journals (Sweden)

    Nikolić Marija S.

    2003-01-01

    Full Text Available Two series of aliphatic polyesters based on succinic acid were synthesized by copolymerization with adipic acid for the first series of saturated polyesters, and with fumaric acid for the second series. Polyesters were prepared starting from the corresponding dimethyl esters and 1,4-butanediol by melt transesterification in the presence of a highly effective catalyst tetra-n-butyl-titanate, Ti(0Bu4. The molecular structure and composition of the copolyesters was determined by 1H NMR spectroscopy. The effect of copolymer composition on the physical and thermal properties of these random polyesters were investigated using differential scanning calorimetry. The degree of crystallinity was determined by DSC and wide angle X-ray. The degrees of crystallinity of the saturated and unsaturated copolyesters were generally reduced with respect to poly(butylene succinate, PBS. The melting temperatures of the saturated polyesters were lower, while the melting temperatures of the unsaturated copolyesters were higher than the melting temperature of PBS. The biodegradability of the polyesters was investigated by enzymatic degradation tests. The enzymatic degradation tests were performed in a buffer solution with Candida cylindracea lipase and for the unsaturated polyesters with Rhizopus arrhizus lipase. The extent of biodegradation was quantified as the weight loss of polyester films. Also the surface of the polyester films after degradation was observed using optical microscopy. It could be concluded that the biodegradability depended strongly on the degree of crystallinity, but also on the flexibility of the chain backbone. The highest biodegradation was observed for copolyesters containing 50 mol.% of adipic acid units, and in the series of unsaturated polyesters for copolyesters containing 5 and 10 mol.% of fumarate units. Although the degree of crystallinity of the unsaturated polyesters decreased slightly with increasing unsaturation, the biodegradation

  7. Data on the mechanisms underlying succinate-induced aortic contraction.

    Science.gov (United States)

    Gonzaga, Natália A; Simplicio, Janaina A; Leite, Letícia N; Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-12-01

    We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled "Pharmacological characterization of the mechanisms underlying the vascular effects of succinate" (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016) [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004) [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor), SP600125 (JNK inhibitor) and Y27632 (Rho-kinase inhibitor) reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor) did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor), H7 (protein kinase C inhibitor), verapamil (Ca(2+) channel blocker) and tiron (superoxide anion scavenger).

  8. Biologically produced succinic acid: A new route to chemical intermediates

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    The national laboratory consortium has undertaken an R&D project with the Michigan Biotechnology Institute (MBI) to demonstrate the feasibility of producing a chemical intermediate, succinic acid, and various derivatives, from renewable agricultural resources. The projects near-term goal is to demonstrate an economically competetive process for producing 1,4-butanediol and other derivatives from biologically produced succinic acid without generating a major salt waste. The competitiveness to the petrochemical process must be demonstrated.

  9. Data on the mechanisms underlying succinate-induced aortic contraction

    Directory of Open Access Journals (Sweden)

    Natália A. Gonzaga

    2016-12-01

    Full Text Available We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled “Pharmacological characterization of the mechanisms underlying the vascular effects of succinate” (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016 [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, “Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors” (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004 [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor, SP600125 (JNK inhibitor and Y27632 (Rho-kinase inhibitor reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor, H7 (protein kinase C inhibitor, verapamil (Ca2+ channel blocker and tiron (superoxide anion scavenger.

  10. Succination of thiol groups in adipose tissue proteins in diabetes: succination inhibits polymerization and secretion of adiponectin.

    Science.gov (United States)

    Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J; Nagai, Ryoji; Carson, James A; Thorpe, Suzanne R; Baynes, John W

    2009-09-18

    S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219-34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for approximately 7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes.

  11. Limited contribution of NR5A1 (SF-1) mutations in women with primary ovarian insufficiency (POI)

    NARCIS (Netherlands)

    Janse, Femi; de With, Larissa M; Duran, Karen J; Kloosterman, Wigard P; Goverde, Angelique J; Lambalk, Cornelius B; Laven, Joop S E; Fauser, Bart C J M; Giltay, Jacques C; Hoek, Annemieke

    2012-01-01

    OBJECTIVE: To evaluate the significance of NR5A1 mutations in a large, well-phenotyped cohort of women with primary ovarian insufficiency (POI). Mutations in the NR5A1 gene (SF-1) were previously described in disorders of sexual development and adrenal insufficiency. Recently, a high frequency of NR

  12. In vivo bioavailability studies of sumatriptan succinate buccal tablets

    Directory of Open Access Journals (Sweden)

    B Jayakar

    2011-07-01

    Full Text Available    Back ground and the purpose of study: Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first - pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability. Methods:Mucoadhesive polymers carbopol 934 (Carbopol, HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets . In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard. Results:Bilayered buccal tablets (BBT containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1 had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1 followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1 was found to be 140.78%. Conclusions: Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability.

  13. Succinic Acid Synthesis by Ethanol-Grown Yeasts

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    Svetlana V. Kamzolova

    2009-01-01

    Full Text Available The synthesis of succinic acid in ethanol-containing media has been tested in 32 yeasts of different genera (Debaryomyces, Candida, Pichia, Saccharomyces, Torulopsis. The capability of succinic acid synthesis was revealed in 29 strains, from which two most effective producers were selected. When grown in a fermentor under high aeration in mineral medium with pulsed addition of ethanol, the strain Candida catenulata VKM Y-5 produced succinic acid up to 5.2 g/L with mass yield of 32.6 % and energy yield of 14.8 %; the other strain, Candida zeylanoides VKM Y-2324, excreted 9.4 g/L of succinic acid with mass and energy yields of 39 and 17.8 %, respectively. It was indicated that succinic acid formation in the yeasts was accompanied by the synthesis of considerable amounts of malic acid, which was apparently due to a high activity of the glyoxylate cycle. Growth characteristics of both strains were studied in dependence on the concentrations of ethanol, zinc ions and nitrogen in the medium.

  14. MODIFIKASI ASAM SUKSINAT - GELOMBANG PENDEK UNTUK\tPRODUKSI TAPIOKA SUKSINAT Succinic Acid-Microwave Modification to Produce Succinic Tapioca

    Directory of Open Access Journals (Sweden)

    Heny Herawati

    2012-05-01

    Full Text Available Indonesia as tropical country has great cassava potency. The great chance of cassava product development could be increased its added value through modified tapioca processing. One of modified starch that could be implemented as a food additive is succinic starch. The tapioca succinilation processed through combination process of reacting tapioca with succinic acid and microwave treatment. The research method was conducted by factorial design with 3 factors: substrate concentration (30 %, 40 %, succinic acid concentration (1 %, 3 %, 5 %, and drying method (oven and microwave. Succinic tapioca was analyzed both physical and chemical characteristics, while optimal product was fur- ther analyzed for nutrition contents and surface microstructure using SEM. Succinic acid and microwave modification influenced to the physical and chemical succinic tapioca, except ash content. The highest substitution degree value was 0.929 which was obtained by combination of substrate concentration 40 %, succinic acid added 5 % and microwave processed. The change of granule size was not significant, just the distribution among granule correlated with the tapi- oca modification. The succinic tapioca granule size ranged 5.35 µm until 17.20 µm with average 11.15 µm. Succinic tapioca characteristic hopefully could be advanced food implementation. ABSTRAK Indonesia merupakan negara tropis yang memiliki potensi produksi ubi kayu yang cukup besar. Peluang pengem- bangan produk berbasis ubi kayu di Indonesia masih cukup besar diantaranya yaitu peningkatan nilai tambah ubi kayu melalui proses modifikasi tapioka. Salah satu potensi pati termodifikasi yang dapat dipergunakan untuk bahan tambahan makanan yaitu pati suksinat. Pada penelitian ini proses suksinilasi tapioka dilakukan dengan cara mereak- sikan asam suksinat yang dikombinasikan dengan mempergunakan microwave. Metodologi penelitian yang dilakukan menggunakan rancangan faktorial dengan 3 faktor, yaitu konsentrasi

  15. DESIGN, DEVELOPMENT AND EVALUATION OF SUMATRIPTAN SUCCINATE TRANSDERMAL PATCHES

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    Gururaj S. Kulkarni* and D. Narasinha Reddy

    2012-06-01

    Full Text Available Most of the therapeutic agents are recommended through an oral route, but oral route has disadvantages like first pass metabolism, liver toxicity, etc, due to gastrointestinal pH. This leads poor bioavailability of drugs, which are not stable in G.I pH. To overcome this problem, increase the bioiavailibility, reduce the dose and dose dumping Transdermal delivery system is better option as novel drug delivery system, which bypass the hepatic first pass metabolism, and avoid drug degradation due to systemic absorption of the drug. Minimize plasma level fluctuations and extend the drug activity besides improving patient compliance. Sumatriptan succinate is a selective 5-hydroxytryptamine receptor subtype agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylaminoethyl]-N-methyl-indole-5-methanesulfonamide succinate. Sumatriptan succinate is a white to off-white powder that is readily soluble in water. Oral administration of Sumatriptan succinate suffers from poorbioavailability, partly due to presystemic metabolism- some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. Sumatriptan is metabolized primarily by monoamine oxidase A into an indole acetic acid analogue, part of which is further conjugated with glucuronic acid. These metabolites excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged. Because of this the bioavailability is only 15% with half life is 2.5 hrs. In this work, the effort has done to improve bioavailability of the sumatriptan succinate by transdermal patches dosage form by using polymers HPMCK4M, carbopol934 and Dibutylpthalate as used as plasticizers.

  16. Simulating Succinate-Promoted Dissolution at Calcite {104} Steps

    Science.gov (United States)

    Mkhonto, D.; Sahai, N.

    2008-12-01

    Organic molecules of a wide range of molecular weights from small organic acids, amino-acids, acidic peptides and acidic proteins to humic and fulvic acids play a key role in modulating nucleation, crystal growth and dissolution of calcium carbonate polymorphs. In general, these acidic molecules inhibit calcite growth and, promote dissolution preferentially along specific crystallographic directions, in the process, regulating crystal shape and size, and even whether a metastable polymorph (e.g., vaterite or aragonite) is nucleated first. For example, chiral faces of calcite are selected by chiral amino-acids and the unusual {hk0} faces are expressed in the presence of amino-acids [Orme et al., 2001], and unusual heptagonal dissolution etch-pit are seen in the presence of succinate compared to the normal rhombohedral pits in water alone [Teng et al., 2006]. Thus, the presence of unusual crystal morphologies may indicate organic-mediated growth, thus serving as a biosignature. We have conducted the Molecular Dynamics (MD) simulations using the Consistent Valence Force Field (CVFF) as implemented in the FORCITE© module of the Materials Studio © software package (Accelrys, Inc. TM) to model the adsorption of succinate, a dicarboxylic acid, and charge- balancing Na+ ions on dry and hydrated steps in different directions on the {104} cleavage face of calcite [Mkhonto and Sahai, in prep.]. At the site of succinate adsorption, we find elongation of the interatomic distances (Ca-OCO3,i) between surface Ca2+ cation and the oxygen of the underlying inorganic CO32- anion the first surface layer of calcite, compared to the corresponding distances in the presence of water alone, suggesting greater ease of surface Ca2+ detachment. This result is consistent with the empirically observed increase in overall dissolution rate with succinate [Teng et al., 2006]. Furthermore, succinate adsorption lowers the step energies, which explains the appearance of steps in the unsusual [42

  17. Metabolic engineering of Saccharomyces cerevisiae to improve succinic acid production based on metabolic profiling.

    Science.gov (United States)

    Ito, Yuma; Hirasawa, Takashi; Shimizu, Hiroshi

    2014-01-01

    We performed metabolic engineering on the budding yeast Saccharomyces cerevisiae for enhanced production of succinic acid. Aerobic succinic acid production in S. cerevisiae was achieved by disrupting the SDH1 and SDH2 genes, which encode the catalytic subunits of succinic acid dehydrogenase. Increased succinic acid production was achieved by eliminating the ethanol biosynthesis pathways. Metabolic profiling analysis revealed that succinic acid accumulated intracellularly following disruption of the SDH1 and SDH2 genes, which suggests that enhancing the export of intracellular succinic acid outside of cells increases succinic acid production in S. cerevisiae. The mae1 gene encoding the Schizosaccharomyces pombe malic acid transporter was introduced into S. cerevisiae, and as a result, succinic acid production was successfully improved. Metabolic profiling analysis is useful in producing chemicals for metabolic engineering of microorganisms.

  18. Pyridoxine-dependent seizures caused by alpha amino adipic semialdehyde dehydrogenase deficiency: the first polish case with confirmed biochemical and molecular pathology.

    Science.gov (United States)

    Kaczorowska, Magdalena; Kmiec, Tomasz; Jakobs, Cornelis; Kacinski, Marek; Kroczka, Slawomir; Salomons, Gajja S; Struys, Eduard A; Jozwiak, Sergiusz

    2008-12-01

    Pyridoxine-dependent seizures are a rare condition recognized when numerous seizures respond to pyridoxine treatment and recur on pyridoxine withdrawal. For decades the diagnosis was confirmed only with pyridoxine treatment withdrawal trial. Recently described biochemical and molecular pathology improved the diagnostic process for those cases in which seizures are caused by alpha amino adipic semialdehyde dehydrogenase deficiency. This article presents a girl with recurrent status epilepticus episodes resistant to phenobarbital and phenytoin and partly responding to midazolam. Eventually the seizures were completely controlled with pyridoxine; however, due to the severe condition of this child when seizing, no trial of withdrawal has been performed. The diagnosis of pyridoxine-dependent seizures was confirmed with biochemical and molecular testing revealing elevated alpha-AASA excretion and the presence of 2 different mutations in the antiquitin ( ALDH7A1) gene. Due to the availability of reliable laboratory testing, confirmation of the diagnosis was made without the life-threatening trial of pyridoxine withdrawal.

  19. Wide spectrum of NR5A1‐related phenotypes in 46,XY and 46,XX individuals

    Science.gov (United States)

    Domenice, Sorahia; Machado, Aline Zamboni; Ferreira, Frederico Moraes; Ferraz‐de‐Souza, Bruno; Lerario, Antonio Marcondes; Lin, Lin; Nishi, Mirian Yumie; Gomes, Nathalia Lisboa; da Silva, Thatiana Evelin; Silva, Rosana Barbosa; Correa, Rafaela Vieira; Montenegro, Luciana Ribeiro; Narciso, Amanda; Costa, Elaine Maria Frade; Achermann, John C

    2016-01-01

    Steroidogenic factor 1 (NR5A1, SF‐1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1‐related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype‐phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian‐determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1‐related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever‐expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal

  20. Mutations associated with succinate dehydrogenase D-related malignant paragangliomas.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Pacak, K.; Bertherat, J.; Lenders, J.W.M.; Duet, M.; Eisenhofer, G.; Stratakis, C.A.; Niccoli-Sire, P.; Tran, B.H.; Burnichon, N.; Gimenez-Roqueplo, A.P.

    2008-01-01

    OBJECTIVE: Hereditary paraganglioma (PGL) syndromes result from germline mutations in genes encoding subunits B, C and D of the mitochondrial enzyme succinate dehydrogenase (SDHB, SDHC and SDHD). SDHB-related PGLs are known in particular for their high malignant potential. Recently, however, maligna

  1. Melatonin and succinate reduce rat liver mitochondrial dysfunction in diabetes.

    Science.gov (United States)

    Zavodnik, I B; Lapshina, E A; Cheshchevik, V T; Dremza, I K; Kujawa, J; Zabrodskaya, S V; Reiter, R J

    2011-08-01

    Mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species in response to hyperglycemia during diabetes lead to pathological consequences of hyperglycemia. The aim of the present work was to investigate the role of a specific functional damage in rat liver mitochondria during diabetes as well as to evaluate the possibility of metabolic and antioxidative correction of mitochondrial disorders by pharmacological doses of succinate and melatonin. In rat liver mitochondria, streptozotocin-induced diabetes was accompanied by marked impairments of metabolism: we observed a significant activation of α-ketoglutarate dehydrogenase (by 60%, pdiabetic animals, melatonin (10 mg/kg b.w., 30 days) or succinate (50 mg/kg b.w., 30 days) reversed the oxygen consumption rate V(3) and the acceptor control ratio to those in nondiabetic animals. Melatonin enhanced the inhibited activity of catalase in the cytoplasm of liver cells and prevented mitochondrial glutathione-S-transferase inhibition while succinate administration prevented α-ketoglutarate dehydrogenase activation. The mitochondria dysfunction associated with diabetes was partially remedied by succinate or melatonin administration. Thus, these molecules may have benefits for the treatment of diabetes. The protective mechanism may be related to improvements in mitochondrial physiology and the antioxidative status of cells.

  2. Succinate dehydrogenase is the regulator of respiration in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Travis Hartman

    2014-11-01

    Full Text Available In chronic infection, Mycobacterium tuberculosis bacilli are thought to enter a metabolic program that provides sufficient energy for maintenance of the protonmotive force, but is insufficient to meet the demands of cellular growth. We sought to understand this metabolic downshift genetically by targeting succinate dehydrogenase, the enzyme which couples the growth processes controlled by the TCA cycle with the energy production resulting from the electron transport chain. M. tuberculosis contains two operons which are predicted to encode succinate dehydrogenase enzymes (sdh-1 and sdh-2; we found that deletion of Sdh1 contributes to an inability to survive long term stationary phase. Stable isotope labeling and mass spectrometry revealed that Sdh1 functions as a succinate dehydrogenase during aerobic growth, and that Sdh2 is dispensable for this catalysis, but partially overlapping activities ensure that the loss of one enzyme can incompletely compensate for loss of the other. Deletion of Sdh1 disturbs the rate of respiration via the mycobacterial electron transport chain, resulting in an increased proportion of reduced electron carrier (menaquinol which leads to increased oxygen consumption. The loss of respiratory control leads to an inability to recover from stationary phase. We propose a model in which succinate dehydrogenase is a governor of cellular respiration in the adaptation to low oxygen environments.

  3. Does succinate oxidation yield FADH(2) or ubiquinol?

    Science.gov (United States)

    Brown

    2000-01-01

    Most textbooks still show the oxidation of succinate in the tricarboxylic acid (TCA) cycle resulting in the reduction of FADH(2). Such a presentation does not reflect the reaction catalysed by the enzyme in vivo or in vitro, does not simplify the treatment of the reaction, and is unnecessarily misleading and confusing.

  4. Pharmacological characterization of the mechanisms underlying the vascular effects of succinate.

    Science.gov (United States)

    Leite, Letícia N; Gonzaga, Natália A; Simplicio, Janaina A; do Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-10-15

    We investigated the mechanisms underlying the vascular effects of succinate. Vascular reactivity experiments were performed in aortic rings isolated from male Wistar rats and C57BL/6 wild type (WT) or GPR91(-/-) mice. Nitrate/nitrite (NOx) was measured colorimetrically whereas 6-keto-prostaglandin F1α (stable product of prostacyclin) was measured by enzyme immunoassay (EIA). Phosphorylation of endothelial nitric oxide synthase (eNOS) was assessed by western immunoblotting. Functional assays revealed that the direct effect of succinate in the vasculature is biphasic. At lower concentrations succinate induced relaxation while at higher concentrations succinate induced vascular contraction. Succinate concentration dependently relaxed rat aortic rings with intact endothelium. Endothelial removal reduced, but not abolished succinate-induced relaxation. Similarly, succinate relaxed endothelium-intact and endothelium-denuded aortas isolated from both C57BL/6 and GPR91(-/-) mice. Pre-incubation of endothelium-intact, but not endothelium-denuded rat aortic rings with l-NAME, indomethacin and tetraethylammonium (TEA) reduced succinate-induced relaxation. In endothelium-intact rings, succinate-induced relaxation was attenuated by ODQ, haemoglobin, Rp-8-Br-Pet-cGMPS, thapsigargin, wortmannin and SC-560. Blockade of K(+) channels with 4-aminopyridine, apamin and charybdotoxin reduced succinate-induced relaxation. Succinate increased the concentration of NOx and 6-keto-prostaglandin F1α as well as eNOS phosphorylation at ser(1177) residue. CaCl2-induced contraction of endothelium-intact or endothelium-denuded aortas was not affected by succinate. The major finding of our study is that it first demonstrates a direct effect of succinate in the vasculature. Succinate displays a biphasic and concentration-dependent effect. The vascular relaxation induced by succinate is partially mediated by endothelial GPR91 receptors via the NO-cGMP pathway, a vasodilator cyclooxygenase (COX

  5. Elementary Mode Analysis for the Rational Design of Efficient Succinate Conversion from Glycerol by Escherichia coli

    Directory of Open Access Journals (Sweden)

    Zhen Chen

    2010-01-01

    Full Text Available By integrating the restriction of oxygen and redox sensing/regulatory system, elementary mode analysis was used to predict the metabolic potential of glycerol for succinate production by E. coli under either anaerobic or aerobic conditions. It was found that although the theoretical maximum succinate yields under both anaerobic and aerobic conditions are 1.0 mol/mol glycerol, the aerobic condition was considered to be more favorable for succinate production. Although increase of the oxygen concentration would reduce the succinate yield, the calculation suggests that controlling the molar fraction of oxygen to be under 0.65 mol/mol would be beneficial for increasing the succinate productivity. Based on the elementary mode analysis, the rational genetic modification strategies for efficient succinate production under aerobic and anaerobic conditions were obtained, respectively. Overexpressing the phosphoenolpyruvate carboxylase or heterogonous pyruvate carboxylase is considered to be the most efficient strategy to increase the succinate yield.

  6. Marked hypertriglyceridemia in a woman receiving metoprolol succinate.

    Science.gov (United States)

    Kim, Yeunjung; Miller, Michael

    2014-01-01

    β-blockers are commonly used therapies after acute myocardial infarction and in the management of congestive heart failure and hypertension. We report a case of a middle-aged woman with a history of mild hypertension who was placed on metoprolol succinate. Before initiation of the β-blocker, her triglyceride level was in the borderline-high range (150-199 mg/dL). On treatment, her triglyceride levels exceeded 1000 mg/dL. She developed fatigue and mild abdominal discomfort but without biochemical evidence of pancreatitis. After discontinuation of metoprolol succinate, her triglyceride levels receded. This case illustrates an uncommon side effect with a very commonly used therapy in clinical practice. Clinicians should closely evaluate medications and/or other therapies in patients presenting with new-onset hypertriglyceridemia especially when levels are sufficiently elevated to pose increased risk of pancreatitis.

  7. A novel organic nonlinear optical crystal: Creatininium succinate

    Energy Technology Data Exchange (ETDEWEB)

    Thirumurugan, R.; Anitha, K., E-mail: singlecerystalxrd@gmail.ciom [School of Physics, Madurai Kamraj University, Madurai 625021 (India)

    2015-06-24

    A novel organic material complex of creatininium succinate (CS) has been synthesized and single crystals were grown by the reaction of creatinine and succinic acid from aqueous solution by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated using single crystal X-ray diffraction analysis and the structure was refined by least-squares method to R = 0.027 for 1840 reflections. FT-IR spectral investigation has been carried out to identify the various functional groups in the title compound. UV–Vis transmission was carried out which shows the crystal has a good optical transmittance in the visible region with lower cutoff wavelength around 220 nm. Nonlinear optical property of the crystal was confirmed by Kurtz-Perry powder technique.

  8. Menaquinone-dependent succinate dehydrogenase of bacteria catalyzes reversed electron transport driven by the proton potential.

    Science.gov (United States)

    Schirawski, J; Unden, G

    1998-10-01

    Succinate dehydrogenases from bacteria and archaea using menaquinone (MK) as an electron acceptor (succinate/menaquinone oxidoreductases) contain, or are predicted to contain, two heme-B groups in the membrane-anchoring protein(s), located close to opposite sides of the membrane. All succinate/ubiquinone oxidoreductases, however, contain only one heme-B molecule. In Bacillus subtilis and other bacteria that use MK as the respiratory quinone, the succinate oxidase activity (succinate-->O2), and the succinate/menaquinone oxidoreductase activity were specifically inhibited by uncoupler (CCCP, carbonyl cyanide m-chlorophenylhydrazone) or by agents dissipating the membrane potential (valinomycin). Other parts of the respiratory chains were not affected by the agents. Succinate oxidase or succinate/ubiquinone oxidoreductase from bacteria using ubiquinone as an acceptor were not inhibited. We propose that the endergonic electron transport from succinate (Eo' = +30 mV) to MK (Eo' approximately/= -80 mV) in succinate/menaquinone oxidoreductase includes a reversed electron transport across the cytoplasmic membrane from the inner (negative) to the outer (positive) side via the two heme-B groups. The reversed electron transport is driven by the proton or electrical potential, which provides the driving force for MK reduction.

  9. Adipocyte protein modification by Krebs cycle intermediates and fumarate ester-derived succination.

    Science.gov (United States)

    Manuel, Allison M; Frizzell, Norma

    2013-11-01

    Protein succination, the non-enzymatic modification of cysteine residues by fumarate, is distinguishable from succinylation, an enzymatic reaction forming an amide bond between lysine residues and succinyl-CoA. Treatment of adipocytes with 30 mM glucose significantly increases protein succination with only a small change in succinylation. Protein succination may be significantly increased intracellularly after treatment with fumaric acid esters, however, the ester must be removed by saponification to permit 2SC-antibody detection of the fumarate adduct.

  10. Requirement of succinate dehydrogenase activity for symbiotic bacteroid differentiation of Rhizobium meliloti in alfalfa nodules.

    OpenAIRE

    Gardiol, A E; Truchet, G L; Dazzo, F. B.

    1987-01-01

    Transmission electron microscopy was used to study the cellular morphologies of a wild-type Rhizobium meliloti strain (L5-30), a nitrogen fixation-ineffective (Fix-) succinate dehydrogenase mutant (Sdh-) strain, and a Fix+ Sdh+ revertant strain within alfalfa nodules and after free-living growth in a minimal medium containing 27 mM mannitol plus 20 mM succinate. The results showed a requirement of succinate dehydrogenase activity for symbiotic differentiation and maintenance of R. meliloti ba...

  11. Effect of succinic acid concentration in poly(glycerol citrate/succinate) properties; Efeito da concentracao do acido succinico nas propriedades do poli(glicerol citrato/succinato)

    Energy Technology Data Exchange (ETDEWEB)

    Brioude, Michel M.; Guimaraes, Danilo H.; Fiuza, Raigenis P.; Jose, Nadia M. [Universidade Federal da Bahia - UFBA, Instituto de Quimica, Salvador, BA (Brazil)

    2011-07-01

    In this work were prepared and characterized polymer based on glycerol, citric and succinic acid, in three different ratios to evaluate the effect of succinic acid concentration in materials properties. The polymers were obtained by polycondensation reaction between polyol and poly acids, and were characterized by X-ray diffraction (XRD), infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning differential calorimetry (DSC), scanning electron microscopy (SEM). The materials are amorphous polyesters and its thermal and morphological properties change depending on the succinic acid concentration. (author)

  12. Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II

    Energy Technology Data Exchange (ETDEWEB)

    De Paepe, A.; Nuytinck, L.; Naeyaert, J.M. [Universitaets-Hautklinik Heidelberg (Germany)] [and others

    1997-03-01

    The Ehlers-Danlos syndrome (EDS) is a heterogeneous connective-tissue disorder of which at least nine subtypes are recognized. Considerable clinical overlap exists between the EDS I and II subtypes, suggesting that both are allelic disorders. Recent evidence based on linkage and transgenic mice studies suggest that collagen V is causally involved in human EDS. Collagen V forms heterotypic fibrils with collagen I in many tissues and plays an important role in collagen I fibrillogenesis. We have identified a mutation in COL5A1, the gene encoding the pro{alpha}1(V) collagen chain, segregating with EDS I in a four-generation family. The mutation causes the substitution of the most 5{prime} cysteine residue by a serine within a highly conserved sequence of the pro{alpha}1(V) C-propeptide domain and causes reduction of collagen V by preventing incorporation of the mutant pro{alpha}1 (V) chains in the collagen V trimers. In addition, we have detected splicing defects in the COL5A1 gene in a patient with EDS I and in a family with EDS II. These findings confirm the causal role of collagen V in at least a subgroup of EDS I, prove that EDS I and II are allelic conditions, and represent a, so far, unique example of a human collagen disorder caused by substitution of a highly conserved cysteine residue in the C-propeptide domain of a fibrillar collagen. 30 refs., 6 figs., 2 tabs.

  13. Whole exome sequencing combined with linkage analysis identifies a novel 3 bp deletion in NR5A1.

    Science.gov (United States)

    Eggers, Stefanie; Smith, Katherine R; Bahlo, Melanie; Looijenga, Leendert H J; Drop, Stenvert L S; Juniarto, Zulfa A; Harley, Vincent R; Koopman, Peter; Faradz, Sultana M H; Sinclair, Andrew H

    2015-04-01

    Disorders of sex development (DSDs) encompass a broad spectrum of conditions affecting the development of the gonads and genitalia. The underlying causes for DSDs include gain or loss of function variants in genes responsible for gonad development or steroidogenesis. Most patients with DSD have an unknown genetic etiology and cannot be given an accurate diagnosis. We used whole exome capture and massively parallel sequencing to analyse a large family with 46,XY DSD and 46,XX premature ovarian insufficiency. In addition, we used a recently developed method for linkage analysis using genotypes extracted from the MPS data. This approach identified a unique linkage peak on chromosome 9 and a novel, 3 bp, in-frame deletion in exon six of NR5A1 (steroidogenic factor-1 or SF1) in all affected individuals. We confirmed that the variant disrupts the SF1 protein and its ability to bind and regulate downstream genes. NR5A1 has key roles at multiple points in gonad development and steroidogenic pathways. The variant described here affects the function of SF1 in early testis development and later ovarian function, ultimately leading to the 46,XY DSD and 46,XX premature ovarian insufficiency phenotypes, respectively. This study shows that even at low coverage, whole exome sequencing, when combined with linkage analysis, can be a powerful tool to identify rapidly the disease-causing variant in large pedigrees.

  14. The measurement of urinary Δ¹-piperideine-6-carboxylate, the alter ego of α-aminoadipic semialdehyde, in Antiquitin deficiency.

    Science.gov (United States)

    Struys, Eduard A; Bok, Levinus A; Emal, Dina; Houterman, Saskia; Willemsen, Michel A; Jakobs, Cornelis

    2012-09-01

    The assessment of urinary α-aminoadipic semialdehyde (α-AASA) has become the diagnostic laboratory test for pyridoxine dependent seizures (PDS). α-AASA is in spontaneous equilibrium with its cyclic form Δ(1)-piperideine-6-carboxylate (P6C); a molecule with a heterocyclic ring structure. Ongoing diagnostic screening and monitoring revealed that in some individuals with milder ALDH7A1 variants, and patients co-treated with a lysine restricted diet, α-AASA was only modestly increased. This prompted us to investigate the diagnostic power and added value of the assessment of urinary P6C compared to α-AASA. Urine samples were diluted to a creatinine content of 0.1 mmol/L, followed by the addition of 0.01 nmol [(2)H(9)]pipecolic acid as internal standard (IS) and 5 μL was injected onto a Waters C(18) T3 HPLC column. Chromatography was performed using water/methanol 97/3 (v/v) including 0.03 % formic acid by volume with a flow rate of 150 μL/min and detection was accomplished in the multiple reaction monitoring mode: P6C m/z 128.1 > 82.1; [(2)H(9)]pipecolic acid m/z 139.1 > 93.1. Due to the dualistic nature of α-AASA/P6C, and the lack of a proper internal standard, the method is semi quantitative. The intra-assay CVs (n = 10) for two urine samples of proven PDS patients with only modest P6C increases were 4.7% and 8.1%, whereas their inter-assay CVs (n = 10) were 16 and 18% respectively. In all 40 urine samples from 35 individuals with proven PDS, we detected increased levels of P6C. Therefore, we conclude that the diagnostic power of the assessments of urinary P6C and α-AASA is comparable.

  15. Non-isothermal crystallization kinetics and characterization of biodegradable poly(butylene succinate-co-neopentyl glycol succinate) copolyesters.

    Science.gov (United States)

    Xie, Wen-Jie; Zhou, Xiao-Ming

    2015-01-01

    Both biodegradable aliphatic neat poly(butylene succinate) (PBS) and poly(butylene succinate-co-neopentyl glycol succinate) (P(BS-co-NPGS)) copolyesters with different 1,4-butanediol/neopentyl glycol ratios were synthesized through a two-step process of transesterification and polycondensation using stannous chloride and 4-Methylbenzenesulfonic acid as the co-catalysts. The structure, non-isothermal crystallization behavior, crystalline morphology and crystal structure of neat PBS and P(BS-co-NPGS) copolyesters were characterized by (1)H NMR, differential scanning calorimetry (DSC), polarized optical microscope (POM) and wide angle X-ray diffraction (WAXD), respectively. The Avrami equation modified by Jeziorny and Mo's method was employed to describe the non-isothermal crystallization kinetics of the neat PBS and its copolyesters. The modified Avrami equation could adequately describe the primary stage of non-isothermal crystallization kinetics of the neat PBS and its copolyesters. Mo's method provided a fairly satisfactory description of the non-isothermal crystallization of neat PBS and its copolyesters. Interestingly, the values of 1/t1/2, Zc and F(T) obtained by the modified Avrami equation and Mo's method analysis indicated that the crystallization rate increased first and then decreased with an increase of NPGS content compared that of neat PBS, whereas the crystallization mechanism almost kept unchanged. The results of tensile testing showed that the ductility of PBS was largely improved by incorporating NPGS units. The elongation at break increased remarkably with increasing NPGS content. In particular, the sample with 20% NPGS content showed around 548% elongation at break.

  16. Structural basis for the binding of succinate to succinyl-CoA synthetase.

    Science.gov (United States)

    Huang, Ji; Fraser, Marie E

    2016-08-01

    Succinyl-CoA synthetase catalyzes the only step in the citric acid cycle that provides substrate-level phosphorylation. Although the binding sites for the substrates CoA, phosphate, and the nucleotides ADP and ATP or GDP and GTP have been identified, the binding site for succinate has not. To determine this binding site, pig GTP-specific succinyl-CoA synthetase was crystallized in the presence of succinate, magnesium ions and CoA, and the structure of the complex was determined by X-ray crystallography to 2.2 Å resolution. Succinate binds in the carboxy-terminal domain of the β-subunit. The succinate-binding site is near both the active-site histidine residue that is phosphorylated in the reaction and the free thiol of CoA. The carboxy-terminal domain rearranges when succinate binds, burying this active site. However, succinate is not in position for transfer of the phosphoryl group from phosphohistidine. Here, it is proposed that when the active-site histidine residue has been phosphorylated by GTP, the phosphohistidine displaces phosphate and triggers the movement of the carboxylate of succinate into position to be phosphorylated. The structure shows why succinyl-CoA synthetase is specific for succinate and does not react appreciably with citrate nor with the other C4-dicarboxylic acids of the citric acid cycle, fumarate and oxaloacetate, but shows some activity with L-malate.

  17. Study of the role of anaerobic metabolism in succinate production by Enterobacter aerogenes.

    Science.gov (United States)

    Tajima, Yoshinori; Kaida, Kenichi; Hayakawa, Atsushi; Fukui, Keita; Nishio, Yousuke; Hashiguchi, Kenichi; Fudou, Ryosuke; Matsui, Kazuhiko; Usuda, Yoshihiro; Sode, Koji

    2014-09-01

    Succinate is a core biochemical building block; optimizing succinate production from biomass by microbial fermentation is a focus of basic and applied biotechnology research. Lowering pH in anaerobic succinate fermentation culture is a cost-effective and environmentally friendly approach to reducing the use of sub-raw materials such as alkali, which are needed for neutralization. To evaluate the potential of bacteria-based succinate fermentation under weak acidic (pH Enterobacter aerogenes AJ110637, which rapidly assimilates glucose at pH 5.0. Based on the profile of anaerobic products, we constructed single-gene knockout mutants to eliminate the main anaerobic metabolic pathways involved in NADH re-oxidation. These single-gene knockout studies showed that the ethanol synthesis pathway serves as the dominant NADH re-oxidation pathway in this organism. To generate a metabolically engineered strain for succinate production, we eliminated ethanol formation and introduced a heterogeneous carboxylation enzyme, yielding E. aerogenes strain ΔadhE/PCK. The strain produced succinate from glucose with a 60.5% yield (grams of succinate produced per gram of glucose consumed) at pH <6.2 and anaerobic conditions. Thus, we showed the potential of bacteria-based succinate fermentation under weak acidic conditions.

  18. atp mutants of Escherichia coli fail to grow on succinate due to a transport deficiency

    DEFF Research Database (Denmark)

    Boogerd, Fred; Boe, Lars; Michelsen, Ole;

    1998-01-01

    Escherichia coli atp mutants, which lack a functional Hf-ATPase complex, are capable of growth on glucose but not on succinate or other C-4-dicarboxylates (Suc(-) phenotype). Suc(+) revertants of an atp deletion strain were isolated which were capable of growth on succinate even though they lack ...

  19. Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency

    NARCIS (Netherlands)

    Richter, S; Peitzsch, M.; Rapizzi, E.; Lenders, J.W.M.; Qin, N.; Cubas, A.A. de; Schiavi, F.; Rao, J.U.; Beuschlein, F.; Quinkler, M.; Timmers, H.J.L.M.; Opocher, G.; Mannelli, M.; Pacak, K.; Robledo, M.; Eisenhofer, G.

    2014-01-01

    CONTEXT: Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. OBJECTIVE: We assessed whether altered succinate dehydrogenase product

  20. Evaporation of methyl- and dimethyl-substituted malonic, succinic, glutaric and adipic acid particles at ambient temperatures

    DEFF Research Database (Denmark)

    Mønster, Jacob Garbrecht; Rosenørn, Thomas; Svenningsson, Birgitta

    2004-01-01

    Evaporation; organic aerosols; vapor pressure; dicarboxylic acid; maonic acid; succinic acid; glutaric acid; adipic acid......Evaporation; organic aerosols; vapor pressure; dicarboxylic acid; maonic acid; succinic acid; glutaric acid; adipic acid...

  1. Pharmacokinetic considerations of formulation: extended-release metoprolol succinate in the treatment of heart failure.

    Science.gov (United States)

    Wikstrand, John; Andersson, Bert; Kendall, Martin J; Stanbrook, Hilary; Klibaner, Michael

    2003-02-01

    Extended-release (ER) metoprolol succinate is a controlled-release formulation designed to deliver metoprolol succinate at a near constant rate for approximately 20 h, independent of food intake and gastrointestinal pH. Once-daily dosing of ER metoprolol succinate 12.5-200 mg produces even plasma concentrations over a 24-h period, without the marked peaks and troughs characteristically observed with the immediate-release (IR) formulation. This leads to consistent beta1-blockade over 24 h, while maintaining cardioselectivity at doses up to 200 mg daily. Pharmacokinetic studies have also been performed in heart failure patients and have demonstrated that ER metoprolol succinate is associated with a more pronounced and even beta1-blockade over a 24-h period than the IR formulation. The efficacy and good tolerability of ER metoprolol succinate in heart failure patients has now been demonstrated in a large-scale clinical trial.

  2. Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.)

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Kuglarz, Mariusz; Karakashev, Dimitar Borisov

    2015-01-01

    The aim of this study was to develop an efficient thermochemical method for treatment of industrial hemp biomass, in order to increase its bioconversion to succinic acid. Industrial hemp was subjected to various thermochemical pretreatments using 0-3% H2SO4, NaOH or H2O2 at 121-180°C prior...... to enzymatic hydrolysis. The influence of the different pretreatments on hydrolysis and succinic acid production by Actinobacillus succinogenes 130Z was investigated in batch mode, using anaerobic bottles and bioreactors. Enzymatic hydrolysis and fermentation of hemp material pretreated with 3% H2O2 resulted...... in the highest overall sugar yield (73.5%), maximum succinic acid titer (21.9gL-1), as well as the highest succinic acid yield (83%). Results obtained clearly demonstrated the impact of different pretreatments on the bioconversion efficiency of industrial hemp into succinic acid....

  3. Succinic acid production from corn stover by simultaneous saccharification and fermentation using Actinobacillus succinogenes.

    Science.gov (United States)

    Zheng, Pu; Fang, Lin; Xu, Yan; Dong, Jin-Jun; Ni, Ye; Sun, Zhi-Hao

    2010-10-01

    Simultaneous saccharification and fermentation (SSF) technique was applied for succinic acid production by Actinobacillus succinogenes in a 5-l stirred bioreactor with corn stover as the raw material. The process parameters of SSF, including corn stover pretreatment condition, substrate concentration, enzyme loading and fermentation temperature were investigated. Results indicated that pretreating corn stover with diluted alkaline was beneficial for the succinic acid production, and succinic acid yield could be significantly increased when adding the cellulase supplemented with cellobiase. The maximal succinic acid concentration and yield could reach 47.4 g/l and 0.72 g/g-substrate, respectively. The corresponding operation conditions were summarized as follows: SSF operation at 38 °C for 48 h, diluted alkaline pretreated corn stover as substrate with concentration of 70 g/l, enzyme loading of 20FPU cellulase and 10 U cellobiase per gram substrate. This result suggested an industrial potential of succinic acid production by using SSF and corn stover.

  4. Succination of proteins by fumarate: mechanism of inactivation of glyceraldehyde-3-phosphate dehydrogenase in diabetes.

    Science.gov (United States)

    Blatnik, Matthew; Thorpe, Suzanne R; Baynes, John W

    2008-04-01

    S-(2-succinyl)cysteine (2SC) is a chemical modification of proteins formed by a Michael addition reaction between the Krebs cycle intermediate, fumarate, and thiol groups in protein--a process known as succination of protein. Succination causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in vitro. GAPDH was immunoprecipitated from muscle of diabetic rats, then analyzed by ultra-performance liquid chromatography-electrospray ionization-mass spectroscopy. Succination of GAPDH was increased in muscle of diabetic rats, and the extent of succination correlated strongly with the decrease in specific activity of the enzyme. We propose that 2SC is a biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins may provide the chemical link between glucotoxicity and the pathogenesis of diabetic complications.

  5. Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.).

    Science.gov (United States)

    Gunnarsson, Ingólfur B; Kuglarz, Mariusz; Karakashev, Dimitar; Angelidaki, Irini

    2015-04-01

    The aim of this study was to develop an efficient thermochemical method for treatment of industrial hemp biomass, in order to increase its bioconversion to succinic acid. Industrial hemp was subjected to various thermochemical pretreatments using 0-3% H2SO4, NaOH or H2O2 at 121-180°C prior to enzymatic hydrolysis. The influence of the different pretreatments on hydrolysis and succinic acid production by Actinobacillus succinogenes 130Z was investigated in batch mode, using anaerobic bottles and bioreactors. Enzymatic hydrolysis and fermentation of hemp material pretreated with 3% H2O2 resulted in the highest overall sugar yield (73.5%), maximum succinic acid titer (21.9 g L(-1)), as well as the highest succinic acid yield (83%). Results obtained clearly demonstrated the impact of different pretreatments on the bioconversion efficiency of industrial hemp into succinic acid.

  6. Metabolic engineering of Saccharomyces cerevisiae microbial cell factories for succinic acid production

    DEFF Research Database (Denmark)

    Otero, José Manuel; Olsson, Lisbeth; Nielsen, Jens

    2007-01-01

    products is 18, 14, 54, and 9 C-mol/C-mol-glucose, respectively, with acids, encompassing fumaric, malic, and succinic acid. Succinic acid is a key building block molecule...... for further conversion to precursor molecules such as tetrahydrofuran, 1,4-butanediol, and butyrolactone. Succinic acid has the potential to become a commodity chemical, with world-wide annual demand exceeding $2 billion USD and over 160 million kg currently produced from petrochemical conversion of maleic...... anhydride. There are several biomass platforms, all prokaryotic, for succinic acid production; however, overproduction of succinic acid in S. cerevisiae offers distinct process advantages. For example, S. cerevisiae has been awarded GRAS status for use in human consumables, grows well at low p...

  7. Succinate production from CO2-grown microalgal biomass as carbon source using engineered Corynebacterium glutamicum through consolidated bioprocessing

    OpenAIRE

    Lee, Jungseok; Sim, Sang Jun; Bott, Michael; Um, Youngsoon; Oh, Min-Kyu; Woo, Han Min

    2014-01-01

    The potential for production of chemicals from microalgal biomass has been considered as an alternative route for CO2 mitigation and establishment of biorefineries. This study presents the development of consolidated bioprocessing for succinate production from microalgal biomass using engineered Corynebacterium glutamicum. Starch-degrading and succinate-producing C. glutamicum strains produced succinate (0.16 g succinate/g total carbon source) from a mixture of starch and glucose as a model m...

  8. EPR and optical studies of VO2+ doped potassium succinate-succinic acid single crystal - Substitutional incorporation

    Science.gov (United States)

    Juliet sheela, K.; Radha Krishnan, S.; Shanmugam, V. M.; Subramanian, P.

    2017-03-01

    EPR and optical absorption studies of VO2+ doped potassium succinate-succinic acid (KSSA) single crystal has been examined at room temperature. EPR spectrum shows that well resolved hyperfine lines. The angular variation of the EPR spectra has shown that two different VO2+ complexes are located in different chemical environments. Among the number of sites, two sites have been followed and reported here. From the EPR analysis, spin Hamiltonian parameters g and A tensors and their directional cosines are evaluated. Both the sites experience rhombic crystal field symmetry around the impurity ion. The VO2+ ion entering the site location of potassium ion has coordination of eight oxygen atoms in a distorted dodecahedral arrangement. The Optical absorption spectrum studied at room temperature shows bands corresponding to C4v symmetry. The crystal field parameter and tetragonal field parameters are calculated. From the Optical and EPR data various molecular orbital coefficients are evaluated and the nature of bonding in the crystal is discussed.

  9. Screening and familial characterization of copy-number variations in NR5A1 in 46,XY disorders of sex development and premature ovarian failure.

    Science.gov (United States)

    Harrison, Steven M; Campbell, Ian M; Keays, Melise; Granberg, Candace F; Villanueva, Carlos; Tannin, Grace; Zinn, Andrew R; Castrillon, Diego H; Shaw, Chad A; Stankiewicz, Pawel; Baker, Linda A

    2013-10-01

    The NR5A1 gene encodes for steroidogenic factor 1, a nuclear receptor that regulates proper adrenal and gonadal development and function. Mutations identified by NR5A1 sequencing have been associated with disorders of sex development (DSD), ranging from sex reversal to severe hypospadias in 46,XY patients and premature ovarian failure (POF) in 46,XX patients. Previous reports have identified four families with a history of both 46,XY DSD and 46,XX POF carrying segregating NR5A1 sequence mutations. Recently, three 46,XY DSD sporadic cases with NR5A1 microdeletions have been reported. Here, we identify the first NR5A1 microdeletion transmitted in a pedigree with both 46,XY DSD and 46,XX POF. A 46,XY individual with DSD due to gonadal dysgenesis was born to a young mother who developed POF. Array CGH analysis revealed a maternally inherited 0.23 Mb microdeletion of chromosome 9q33.3, including the NR5A1 gene. Based on this finding, we screened patients with unexplained 46,XY DSD (n = 11), proximal hypospadias (n = 21) and 46,XX POF (n = 36) for possible NR5A1 copy-number variations (CNVs) via multiplex ligation-dependent probe amplification (MLPA), but did not identify any additional CNVs involving NR5A1. These data suggest that NR5A1 CNVs are an infrequent cause of these disorders but that array CGH and MLPA are useful genomic screening tools to uncover the genetic basis of such unexplained cases. This case is the first report of a familial NR5A1 CNV transmitting in a pedigree, causing both the male and female phenotypes associated with NR5A1 mutations, and the first report of a NR5A1 CNV associated with POF.

  10. Biologically produced succinic acid: A new route to chemical intermediates

    Energy Technology Data Exchange (ETDEWEB)

    1995-01-01

    The US Department of Energy (DOE) Alternative Feedstocks (AF) program is forging new links between the agricultural community and the chemicals industry through support of research and development (R & D) that uses `green` feedstocks to produce chemicals. The program promotes cost-effective industrial use of renewable biomass as feedstocks to manufacture high-volume chemical building blocks. Industrial commercialization of such processes would stimulate the agricultural sector by increasing the demand of agricultural and forestry commodities. New alternatives for American industry may lie in the nation`s forests and fields. The national laboratory consortium has undertaken a joint R&D project with the Michigan Biotechnology Institute to demonstrate the feasibility of producing a chemical intermediate, succinic acid, and various derivatives, from renewable agricultural resources.

  11. Succinic Acid Production from Lignocellulosic Hydrolysate by Basfia succiniciproducens

    Energy Technology Data Exchange (ETDEWEB)

    Salvachua, Davinia; Smith, Holly; John, Peter C.; Mohagheghi, Ali; Peterson, Darren J.; Black, Brenna A.; Dowe, Nancy; Beckham, Gregg T.

    2016-08-01

    The production of chemicals alongside fuels will be essential to enhance the feasibility of lignocellulosic biorefineries. Succinic acid (SA), a naturally occurring C4-diacid, is a primary intermediate of the tricarboxylic acid cycle and a promising building block chemical that has received significant industrial attention. Basfia succiniciproducens is a relatively unexplored SA-producing bacterium with advantageous features such as broad substrate utilization, genetic tractability, and facultative anaerobic metabolism. Here B. succiniciproducens is evaluated in high xylose-content hydrolysates from corn stover and different synthetic media in batch fermentation. SA titers in hydrolysate at an initial sugar concentration of 60 g/L reached up to 30 g/L, with metabolic yields of 0.69 g/g, and an overall productivity of 0.43 g/L/h. These results demonstrate that B. succiniciproducens may be an attractive platform organism for bio-SA production from biomass hydrolysates.

  12. Enhanced performance of alkylated graphene reinforced polybutylene succinate nanocomposite

    Science.gov (United States)

    Abidin, A. S. Zainal; Yusoh, K.; Jamari, S. S.; Abdullah, A. H.; Ismail, Z.

    2016-07-01

    Polybutylene succinate (PBS) was being grafted with octadecylamine-functionalized graphene oxide (GO-ODA) to produce novel PBS/GO-ODA nanocomposites by solution blending technique. Alkylated graphene oxide has superhydrophobic surface thus improved the affinity of the filler with low polar polymer such as PBS. The structure and compatibility of the filler and nanocomposites were being characterized using Fourier transform infrared spectroscopy (FTIR), Universal tensile machine (UTM) and thermogravimetric analysis (TGA). Enhancement of tensile strength and Young's modulus by 30% and 165% respectively was achieved with cooperation of 0.5% GO-ODA loading. The functionalization of GO-ODA in PBS matrix leads to the improvement in the nanocomposites properties.

  13. Biophysical properties of phenyl succinic acid derivatised hyaluronic acid

    DEFF Research Database (Denmark)

    Neves-Petersen, Maria Teresa; Klitgaard, Søren; Skovsen, Esben

    2010-01-01

    acid has been derivatised with the anhydride form of phenyl succinic acid (PheSA). The fluorescence of PheSA was efficiently quenched by the HA matrix. HA also acted as a singlet oxygen scavenger. Fluorescence lifetime(s) of PheSA in solution and when attached to the HA matrix has been monitored...... capacity of scavenging singlet oxygen and of quenching PheSA fluorescence. These studies revealed that HA-PheSA is a strong quencher of electronic excited state PheSA and acts as a scavenger of singlet oxygen, thus medical applications of this derivatised form of HA may protect tissues and organs...... with ps resolved streak camera technology. Structural and fluorescence properties changes induced on HA-PheSA due to the presence of singlet oxygen were monitored using static light scattering (SLS), steady state fluorescence and ps time resolved fluorescence studies. SLS studies provided insight...

  14. Non-isothermal crystallization kinetics and characterization of biodegradable poly(butylene succinate-co-neopentyl glycol succinate) copolyesters

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Wen-Jie; Zhou, Xiao-Ming, E-mail: xiaomingzhou@tust.edu.cn

    2015-01-01

    Both biodegradable aliphatic neat poly(butylene succinate) (PBS) and poly(butylene succinate-co-neopentyl glycol succinate) (P(BS-co-NPGS)) copolyesters with different 1,4-butanediol/neopentyl glycol ratios were synthesized through a two-step process of transesterification and polycondensation using stannous chloride and 4-Methylbenzenesulfonic acid as the co-catalysts. The structure, non-isothermal crystallization behavior, crystalline morphology and crystal structure of neat PBS and P(BS-co-NPGS) copolyesters were characterized by {sup 1}H NMR, differential scanning calorimetry (DSC), polarized optical microscope (POM) and wide angle X-ray diffraction (WAXD), respectively. The Avrami equation modified by Jeziorny and Mo's method was employed to describe the non-isothermal crystallization kinetics of the neat PBS and its copolyesters. The modified Avrami equation could adequately describe the primary stage of non-isothermal crystallization kinetics of the neat PBS and its copolyesters. Mo's method provided a fairly satisfactory description of the non-isothermal crystallization of neat PBS and its copolyesters. Interestingly, the values of 1/t{sub 1/2}, Z{sub c} and F(T) obtained by the modified Avrami equation and Mo's method analysis indicated that the crystallization rate increased first and then decreased with an increase of NPGS content compared that of neat PBS, whereas the crystallization mechanism almost kept unchanged. The results of tensile testing showed that the ductility of PBS was largely improved by incorporating NPGS units. The elongation at break increased remarkably with increasing NPGS content. In particular, the sample with 20% NPGS content showed around 548% elongation at break. - Highlights: • The incorporation of NPGS units reduced the spherulite size of BS unit. • The existence of NPGS units did not change the crystal structure of BS unit. • The NPGS units incorporated in PBS could significantly improve the ductility of

  15. Enhanced succinic acid production from corncob hydrolysate by microbial electrolysis cells.

    Science.gov (United States)

    Zhao, Yan; Cao, Weijia; Wang, Zhen; Zhang, Bowen; Chen, Kequan; Ouyang, Pingkai

    2016-02-01

    In this study, Actinobacillus succinogenes NJ113 microbial electrolysis cells (MECs) were used to enhance the reducing power responsible for succinic acid production from corncob hydrolysate. During corncob hydrolysate fermentation, electric MECs resulted in a 1.31-fold increase in succinic acid production and a 1.33-fold increase in the reducing power compared with those in non-electric MECs. When the hydrolysate was detoxified by combining Ca(OH)2, NaOH, and activated carbon, succinic acid production increased from 3.47 to 6.95 g/l. Using a constant potential of -1.8 V further increased succinic acid production to 7.18 g/l. A total of 18.09 g/l of succinic acid and a yield of 0.60 g/g total sugar were obtained after a 60-h fermentation when NaOH was used as a pH regulator. The improved succinic acid yield from corncob hydrolysate fermentation using A. succinogenes NJ113 in electric MECs demonstrates the great potential of using biomass as a feedstock to cost-effectively produce succinate.

  16. A method for determining thermophysical properties of organic material in aqueous solutions: Succinic acid

    Science.gov (United States)

    Riipinen, I.; Svenningsson, B.; Bilde, M.; Gaman, A.; Lehtinen, K. E. J.; Kulmala, M.

    2006-12-01

    A method for determining evaporation rates and thermodynamic properties of aqueous solution droplets is introduced. The method combines evaporation rate measurements using modified TDMA technique with data evaluation using an accurate evaporation model. The first set of data has been collected and evaluated for succinic acid aqueous solution droplets. Evaporation rates of succinic acid solution droplets have been measured using a TDMA system at controlled relative humidity (65%) and temperature (298 K). A temperature-dependent expression for the saturation vapour pressure of pure liquid phase succinic acid at atmospheric temperatures has been derived by analysing the evaporation rate data with a numerical model. The obtained saturation vapour pressure of liquid phase succinic acid is ln( p) = 118.41 - 16204.8/ T - 12.452ln( T). The vapour pressure is in unit of Pascal and the temperature in Kelvin. A linear expression for the enthalpy of vaporization for liquid state succinic acid is also presented. According to the results presented in the following, a literature expression for the vapour pressure of liquid phase succinic acid defined for temperatures higher than 461 K [Yaws, C.L., 2003. Yaws' Handbook of Thermodynamic and Physical Properties of Chemical Compounds, Knovel] can be extrapolated to atmospheric temperatures with very good accuracy. The results also suggest that at 298 K the mass accommodation coefficient of succinic acid is unity or very close to unity.

  17. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.

    Directory of Open Access Journals (Sweden)

    Ana Carolina eAriza

    2012-02-01

    Full Text Available The succinate receptor (also known as GPR91 is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin-angiotensin system, starts to unfold: The succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.

  18. Mitochondrial stress causes increased succination of proteins in adipocytes in response to glucotoxicity.

    Science.gov (United States)

    Frizzell, Norma; Thomas, Sonia A; Carson, James A; Baynes, John W

    2012-07-15

    2SC [S-(2-succino)-cysteine] is a chemical modification formed by a Michael addition reaction of fumarate with cysteine residues in proteins. Formation of 2SC, termed 'succination' of proteins, increases in adipocytes grown in high-glucose medium and in adipose tissues of Type 2 diabetic mice. However, the metabolic mechanisms leading to increased fumarate and succination of protein in the adipocyte are unknown. Treatment of 3T3 cells with high glucose (30 mM compared with 5 mM) caused a significant increase in cellular ATP/ADP, NADH/NAD+ and Δψm (mitochondrial membrane potential). There was also a significant increase in the cellular fumarate concentration and succination of proteins, which may be attributed to the increase in NADH/NAD+ and subsequent inhibition of tricarboxylic acid cycle NAD+-dependent dehydrogenases. Chemical uncouplers, which dissipated Δψm and reduced the NADH/NAD+ ratio, also decreased the fumarate concentration and protein succination. High glucose plus metformin, an inhibitor of complex I in the electron transport chain, caused an increase in fumarate and succination of protein. Thus excess fuel supply (glucotoxicity) appears to create a pseudohypoxic environment (high NADH/NAD+ without hypoxia), which drives the increase in succination of protein. We propose that increased succination of proteins is an early marker of glucotoxicity and mitochondrial stress in adipose tissue in diabetes.

  19. Succinic Acid Production from Cheese Whey using Actinobacillus succinogenes 130 Z

    Science.gov (United States)

    Wan, Caixia; Li, Yebo; Shahbazi, Abolghasem; Xiu, Shuangning

    Actinobacillus succinogenes 130 Z was used to produce succinic acid from cheese whey in this study. At the presence of external CO2 supply, the effects of initial cheese whey concentration, pH, and inoculum size on the succinic acid production were studied. The by-product formation during the fermentation process was also analyzed. The highest succinic acid yield of 0.57 was obtained at initial cheese whey concentration of 50 g/L, while the highest succinic acid productivity of 0.58 g h-1 L-1 was obtained at initial cheese whey concentration of 100 g/L. Increase in pH and inoculum size caused higher succinic acid yield and productivity. At the preferred fermentation condition of pH 6.8, inoculum size of 5% and initial cheese whey concentration of 50 g/L, succinic acid yield of 0.57, and productivity of 0.44 g h-1 L-1 were obtained. Acetic acid and formic acid were the main by-products throughout the fermentation run of 48 h. It is feasible to produce succinic acid using lactose from cheese whey as carbon resource by A. succinogenes 130 Z.

  20. Production of succinic Acid from citric Acid and related acids by lactobacillus strains.

    Science.gov (United States)

    Kaneuchi, C; Seki, M; Komagata, K

    1988-12-01

    A number of Lactobacillus strains produced succinic acid in de Man-Rogosa-Sharpe broth to various extents. Among 86 fresh isolates from fermented cane molasses in Thailand, 30 strains (35%) produced succinic acid; namely, 23 of 39 Lactobacillus reuteri strains, 6 of 18 L. cellobiosus strains, and 1 of 6 unidentified strains. All of 10 L. casei subsp. casei strains, 5 L. casei subsp. rhamnosus strains, 6 L. mali strains, and 2 L. buchneri strains did not produce succinic acid. Among 58 known strains including 48 type strains of different Lactobacillus species, the strains of L. acidophilus, L. crispatus, L. jensenii, and L. parvus produced succinic acid to the same extent as the most active fresh isolates, and those of L. alimentarius, L. collinoides, L. farciminis, L. fructivorans (1 of 2 strains tested), L. malefermentans, and L. reuteri were also positive, to lesser extents. Diammonium citrate in de Man-Rogosa-Sharpe broth was determined as a precursor of the succinic acid produced. Production rates were about 70% on a molar basis with two fresh strains tested. Succinic acid was also produced from fumaric and malic acids but not from dl-isocitric, alpha-ketoglutaric, and pyruvic acids. The present study is considered to provide the first evidence on the production of succinic acid, an important flavoring substance in dairy products and fermented beverages, from citrate by lactobacilli.

  1. [Effects of furfural and 5-hydroxymethylfurfural on succinic acid production by Escherichia coli].

    Science.gov (United States)

    Wang, Dan; Wang, Honghui; Wang, Jing; Wang, Nan; Zhang, Jie; Xing, Jianmin

    2013-10-01

    Succinic acid production by fermentation from biomass, especially the lignocellulosic hydrolysate, is an alternative to chemical synthesis. Many studies report the inhibition of cell growth and succinic acid production from lignocellulosic hydrolysate, hardly is known about the actual kinetic and mechanism of the inhibition of individual factors. In this study, we studied inhibition effects of furfurals and 5-hydroxymethylfurfural (5-HMF) on cell growth and succinic acid production of engineered E. coli. Cell growth and succinic acid titer were severely inhibited by furfural and HMF with both concentrations higher than 0.8 g/L. Cell growth was totally inhibited when the concentration of furfural was above 6.4 g/L, or the concentration of HMF was above 12.8 g/L. At the concentration of maximum toleration, which was 3.2 g/L, furfural decreased the cell mass by 77.8% and the succinic acid titer by 36.1%. HMF decreased the cell mass by 13.6% and the succinic acid titer by 18.3%. Activity measurements of key enzymes revealed that phosphoenolpyruvate carboxylase, malate dehydrogenase, fumarate reductase all were inhibited by furfural and HMF. This study gave a quantitative view to the succinic acid production under the inhibition of lignocellulose degradation products and will help overcome the difficulties of the lignocellulosic hydrolysate fermentation.

  2. Simultaneous determination of alpha-aminoadipic semialdehyde, piperideine-6-carboxylate and pipecolic acid by LC-MS/MS for pyridoxine-dependent seizures and folinic acid-responsive seizures.

    Science.gov (United States)

    Sadilkova, Katerina; Gospe, Sidney M; Hahn, Si Houn

    2009-10-30

    Pyridoxine-dependent seizures (PDS) is an autosomal recessive disorder characterized by seizures presenting in neonates or infants up to 3 years of age which respond to pharmacological doses of pyridoxine. Alpha-aminoadipic semialdehyde dehydrogenase (antiquitin) deficiency was identified as an underlying defect in PDS characterized by accumulation of alpha-aminoadipic semialdehyde (alpha-AASA) as a specific marker and recently folinic acid-responsive seizures (FRS) were found to be allelic to PDS as the putative mutations were identified in the antiquitin gene (ALDH7A1). alpha-AASA is known to be in reversible equilibrium with its cyclic Shiff base, delta(1)-piperideine-6-carboxylate (P6C). Pipecolic acid (PA) is another biomarker often elevated but is not specific to PDS. Here, we developed the liquid chromatography-mass spectrometry (LC-MS/MS) method to determine the analytes of alpha-AASA, P6C and PA simultaneously in plasma and validated the assay using samples from confirmed cases. This approach eliminates the extra time and expense of running multiple assays and provides valuable information for the rapid diagnosis and treatment of patients with PDS and FRS which potentially could lead to a better outcome with improved quality of life. The stability study showed that alpha-AASA and P6C were unstable even at -20 degrees C. A careful sample handling with immediate freezing and testing is required for reliable result.

  3. Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

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    Mashiur Rahman

    2014-12-01

    Full Text Available Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA was studied by equilibrium dialysis method (ED at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Results: Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 105 M-1 with low capacity (n1 = 2 and low affinity association (k2 = 4.0×105 M-1 constant with high capacity (n2 = 8 at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10-5 M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. Conclusion: This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

  4. Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function.

    Science.gov (United States)

    El-Khairi, Ranna; Martinez-Aguayo, Alejandro; Ferraz-de-Souza, Bruno; Lin, Lin; Achermann, John C

    2011-01-01

    The nuclear receptor transcription factors DAX-1 (NR0B1) and SF-1 (NR5A1) regulate many aspects of adrenal and reproductive development and function. Disruption of the genes encoding these factors can be associated with pediatric adrenal disease. DAX-1 mutations are classically associated with X-linked adrenal hypoplasia congenita, hypogonadotropic hypogonadism and impaired spermatogenesis. However, other phenotypes are also being reported, such as isolated mineralocorticoid insufficiency, premature sexual development, primary adrenal insufficiency in a 46, XX patient and late-onset X-linked adrenal hypoplasia congenita and/or hypogonadotropic hypogonadism. SF-1 mutations have also been associated with primary adrenal insufficiency, together with 46, XY disorders of sex development. However it is emerging that SF-1 changes are a relatively rare cause of primary adrenal failure in humans, and most individuals with SF-1 mutations have a spectrum of 46, XY disorders of sex development phenotypes. These conditions range from 46, XY females with streak gonads and müllerian structures, through children with ambiguous genitalia and inguinal testes, to severe penoscrotal hypospadias with undescended testes. Therefore, the human gonad appears to be more sensitive than the adrenal gland to loss of SF-1 function. This review will focus on the expanding range of phenotypes associated with DAX-1 and SF-1 mutations.

  5. Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1

    DEFF Research Database (Denmark)

    Carrozzo, Rosalba; Verrigni, Daniela; Rasmussen, Magnhild

    2016-01-01

    deficiency of complexes I and IV, but normal histological and biochemical findings in muscle did not preclude a diagnosis of succinate-CoA ligase deficiency. In five patients, the urinary excretion of methylmalonic acid was only marginally elevated, whereas elevated plasma methylmalonic acid was consistently......BACKGROUND: The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with deficiency of succinate-CoA ligase, caused by mutations in SUCLA2 or SUCLG1. We report here 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings...

  6. Separation and Concentration of Succinic Adic from Multicomponent Aqueous Solutions by Nanofiltration Technique

    Directory of Open Access Journals (Sweden)

    Antczak Jerzy

    2014-06-01

    Full Text Available This paper applies the determined suitability of nanofiltration (NF membrane separation for selective isolation and concentration of succinic acid from aqueous solutions which are post-fermentation multicomponent fluids. The study analyzed the influence of concentration and the pH of the separated solutions on the efficiency and selectivity of NF process that runs in a module equipped with a ceramic membrane. Moreover, the effect of applied trans-membrane pressure on the retention of succinic acid and sodium succinate has been studied. The investigations have shown that in the used NF module the retention of succinic acid salt is equal almost 50% in the case of a three-component model solution, although the degree of retention depends on both the transmembrane pressure and the initial concentration of separated salt.

  7. DNA methylation of the GC box in the promoter region mediates isolation rearing-induced suppression of srd5a1 transcription in the prefrontal cortex.

    Science.gov (United States)

    Araki, Ryota; Nishida, Shoji; Hiraki, Yosuke; Matsumoto, Kinzo; Yabe, Takeshi

    2015-10-01

    The levels of allopregnanolone (ALLO), a neurosteroid, in brain and serum are related to severity of depression and anxiety. Steroid 5α-reductase type I is the rate-limiting enzyme in ALLO biosynthesis and plays an important role in control of the ALLO level in mammalian brain. In this study, we examined an epigenetic mechanism for transcriptional regulation of srd5a1, which codes for steroid 5α-reductase type I, using isolation-reared mice. The mRNA level of srd5a1 was decreased in the prefrontal cortex (PFC) in isolation-reared mice. Rearing in social isolation increased methylation of cytosines at -82 and -12 bp downstream of the transcription start site, which are located in a GC box element in the promoter region of srd5a1. Binding of Sp1, a ubiquitous transcription factor, to the GC box was decreased in the promoter region of srd5a1 in the PFC in isolation-reared mice. Site-specific methylation at cytosine -12 of a srd5a1 promoter-luciferase reporter construct, but not that of cytosine -82, downregulated the promoter activity of srd5a1. These findings suggest that transcription of srd5a1 in brain is regulated by environmental factor-induced cytosine methylation in the promoter region. This finding could contribute to development of antidepressant and anxiolytic agents.

  8. Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid cell factory.

    Directory of Open Access Journals (Sweden)

    José Manuel Otero

    Full Text Available Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol, and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the α-keto-glutarate dehydrogenase catalyzed conversion of α-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2(nd-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we

  9. FORMULATION DEVELOPMENT AND EVALUATION OF QUICK DISSOLVING ORAL STRIPs CONTAINING SUMATRIPTAN SUCCINATE

    OpenAIRE

    Pandit Mihir; Gandhi Nirvi; Bonde Smita; Pandya Sudhir

    2012-01-01

    The present study was aimed to formulate and evaluate quick dissolving oral strips (QDOS) of Sumatriptan succinate for the treatment of migraine headaches. Sumatriptan succinate is 5-HT1D agonist which is antimigraine. Hydroxyl propyl methyl cellulose is used as film forming agent. Quick dissolving oral strips are meant to be dissolved in saliva and remain in oral cavity until swallowed. Hence, taste masking becomes critically important. The strips were prepared by solvent casting method and ...

  10. Is it possible to produce succinic acid at a low pH?

    Science.gov (United States)

    Yuzbashev, Tigran V; Yuzbasheva, Evgeniya Y; Laptev, Ivan A; Sobolevskaya, Tatiana I; Vybornaya, Tatiana V; Larina, Anna S; Gvilava, Ilia T; Antonova, Svetlana V; Sineoky, Sergey P

    2011-01-01

    Bio-based succinate is still a matter of special emphasis in biotechnology and adjacent research areas. The vast majority of natural and engineered producers are bacterial strains that accumulate succinate under anaerobic conditions. Recently, we succeeded in obtaining an aerobic yeast strain capable of producing succinic acid at low pH. Herein, we discuss some difficulties and advantages of microbial pathways producing "succinic acid" rather than "succinate." It was concluded that the peculiar properties of the constructed yeast strain could be clarified in view of a distorted energy balance. There is evidence that in an acidic environment, the majority of the cellular energy available as ATP will be spent for proton and anion efflux. The decreased ATP:ADP ratio could essentially reduce the growth rate or even completely inhibit growth. In the same way, the preference of this elaborated strain for certain carbon sources could be explained in terms of energy balance. Nevertheless, the opportunity to exclude alkali and mineral acid waste from microbial succinate production seems environmentally friendly and cost-effective.

  11. [Succinic acid production from sucrose and sugarcane molasses by metabolically engineered Escherichia coli].

    Science.gov (United States)

    Li, Feng; Ma, Jiangfeng; Wu, Mingke; Ji, Yaliang; Chen, Wufang; Ren, Xinyi; Jiang, Min

    2015-04-01

    Sugarcane molasses containing large amounts of sucrose is an economical substrate for succinic acid production. However, Escherichia coli AFP111 cannot metabolize sucrose although it is a promising candidate for succinic acid production. To achieve sucrose utilizing ability, we cloned and expressed cscBKA genes encoding sucrose permease, fructokinase and invertase of non-PTS sucrose-utilization system from E. coli W in E. coli AFP111 to generate a recombinant strain AFP111/pMD19T-cscBKA. After 72 h of anaerobic fermentation of the recombinant in serum bottles, 20 g/L sucrose was consumed and 12 g/L succinic acid was produced. During dual-phase fermentation comprised of initial aerobic growth phase followed by anaerobic fermentation phase, the concentration of succinic acid from sucrose and sugarcane molasses was 34 g/L and 30 g/L, respectively, at 30 h of anaerobic phase in a 3 L fermentor. The results show that the introduction of non-PTS sucrose-utilization system has sucrose-metabolizing capability for cell growth and succinic acid production, and can use cheap sugarcane molasses to produce succinic acid.

  12. Whey fermentation by anaerobiospirillum succiniciproducens for production of a succinate-based animal feed additive

    Science.gov (United States)

    Samuelov; Datta; Jain; Zeikus

    1999-05-01

    Anaerobic fermentation processes for the production of a succinate-rich animal feed supplement from raw whey were investigated with batch, continuous, and variable-volume fed-batch cultures with Anaerobiospirillum succiniciproducens. The highest succinate yield, 90%, was obtained in a variable-volume fed-batch process in comparison to 80% yield in a batch cultivation mode. In continuous culture, succinate productivity was 3 g/liter/h, and the yield was 60%. Under conditions of excess CO2, more than 90% of the whey-lactose was consumed, with an end product ratio of 4 succinate to 1 acetate. Under conditions of limited CO2, lactose was only partially consumed and lactate was the major end product, with lower levels of ethanol, succinate, and acetate. When the succinic acid in this fermentation product was added to rumen fluid, it was completely consumed by a mixed rumen population and was 90% decarboxylated to propionate on a molar basis. The whey fermentation product formed under excess CO2, which contained mainly organic acids and cells, could potentially be used as an animal feed supplement.

  13. Biotechnological route for sustainable succinate production utilizing oil palm frond and kenaf as potential carbon sources.

    Science.gov (United States)

    Luthfi, Abdullah Amru Indera; Manaf, Shareena Fairuz Abdul; Illias, Rosli Md; Harun, Shuhaida; Mohammad, Abdul Wahab; Jahim, Jamaliah Md

    2017-03-09

    Due to the world's dwindling energy supplies, greater thrust has been placed on the utilization of renewable resources for global succinate production. Exploration of such biotechnological route could be seen as an act of counterbalance to the continued fossil fuel dominance. Malaysia being a tropical country stands out among many other nations for its plenty of resources in the form of lignocellulosic biomass. To date, oil palm frond (OPF) contributes to the largest fraction of agricultural residues in Malaysia, while kenaf, a newly introduced fiber crop with relatively high growth rate, holds great potential for developing sustainable succinate production, apart from OPF. Utilization of non-food, inexhaustible, and low-cost derived biomass in the form of OPF and kenaf for bio-based succinate production remains largely untapped. Owing to the richness of carbohydrates in OPF and kenaf, bio-succinate commercialization using these sources appears as an attractive proposition for future sustainable developments. The aim of this paper was to review some research efforts in developing a biorefinery system based on OPF and kenaf as processing inputs. It presents the importance of the current progress in bio-succinate commercialization, in addition to describing the potential use of different succinate production hosts and various pretreatments-saccharifications under development for OPF and kenaf. Evaluations on the feasibility of OPF and kenaf as fermentation substrates are also discussed.

  14. Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells.

    Science.gov (United States)

    Robben, Joris H; Fenton, Robert A; Vargas, Sarah L; Schweer, Horst; Peti-Peterdi, Janos; Deen, Peter M T; Milligan, Graeme

    2009-12-01

    When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function.

  15. Improving succinic acid production by Actinobacillus succinogenes from raw industrial carob pods.

    Science.gov (United States)

    Carvalho, Margarida; Roca, Christophe; Reis, Maria A M

    2016-10-01

    Carob pods are an inexpensive by-product of locust bean gum industry that can be used as renewable feedstock for bio-based succinic acid. Here, for the first time, unprocessed raw carob pods were used to extract a highly enriched sugar solution, afterwards used as substrate to produce succinic acid using Actinobacillus succinogenes. Batch fermentations containing 30g/L sugars resulted in a production rate of 1.67gSA/L.h and a yield of 0.39gSA/g sugars. Taking advantage of A. succinogenes' metabolism, uncoupling cell growth from succinic acid production, a fed-batch mode was implemented to increase succinic acid yield and reduce by-products formation. This strategy resulted in a succinic acid yield of 0.94gSA/g sugars, the highest yield reported in the literature for fed-batch and continuous experiments, while maintaining by-products at residual values. Results demonstrate that raw carob pods are a highly efficient feedstock for bio-based succinic acid production.

  16. Production of succinic acid from oil palm empty fruit bunch cellulose using Actinobacillus succinogenes

    Science.gov (United States)

    Pasma, Satriani Aga; Daik, Rusli; Maskat, Mohamad Yusof

    2013-11-01

    Succinic acid is a common metabolite in plants, animals and microorganisms. It has been used widely in agricultural, food and pharmaceutical industries. Enzymatic hydrolysate glucose from oil palm empty fruit bunch (OPEFB) cellulose was used as a substrate for succinic acid production using Actinobacillus succinogenes. Using cellulose extraction from OPEFB can enhance the production of glucose as a main substrate for succinic acid production. The highest concentration of glucose produced from enzymatic hydrolysis is 167 mg/mL and the sugar recovery is 0.73 g/g of OPEFB. By optimizing the culture medium for succinic acid fermentation with enzymatic hydrolysate of OPEFB cellulose, the nitrogen sources could be reduced to just only 2.5 g yeast extract and 2.5 g corn step liquor. Batch fermentation was carried out using enzymatic hydrolysate of OPEFB cellulose with yeast extract, corn steep liquor and the salts mixture, 23.5 g/L succinic acid was obtained with consumption of 72 g/L glucose in enzymatic hydrolysate of OPEFB cellulose at 38 hours and 37°C. This study suggests that enzymatic hydrolysate of OPEFB cellulose maybe an alternative substrate for the efficient production of succinic acid by Actinobacillus succinogenes.

  17. Radiation Yield and Radicals Produced in Irradiated Poly (Butylene Succinate

    Directory of Open Access Journals (Sweden)

    Meri Suhartini

    2004-01-01

    Full Text Available The main chemical effects of ionizing irradiation on polymers are crosslinking and chain scission. Both processes occur simultaneously and their yields determine the final results of processing. The radiation yield of crosslinking could be determined by several methods depending on the characteristics of the material and properties of the gel. Radiation parameters of gelation, such as gelation dose and ratio of scission yield to crosslinking yield, as well as their values were estimated. In this study, those parameters depend on the amount of Trimethallyl isocyanurate (TMAIC in Poly(butylene succinate (PBS, molecular weight of PBS, and irradiation condition. In the absence of TMAIC, higher molecular weight of PBS required less energy to start gelation process compare to lower molecular weight of PBS. While in the presence of TMAIC all of the PBS samples require similar energy to start gelation process. The existence of macroradicals were observed by Electron Spin Resonance measurements. The result showed that the spectra consisted of signals derived from radicals on carbon nearby carbonyl, and signals derived from radicals on carbon reside between two similar carbon on polymer, both of radicals lead to crosslinking.

  18. Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

    Energy Technology Data Exchange (ETDEWEB)

    Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huang, Dong-Yang [Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Lau, Andy T.Y., E-mail: andytylau@stu.edu.cn [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China)

    2014-02-28

    Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

  19. Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates. A stable isotope tracer study.

    Science.gov (United States)

    Tserng, K Y; Jin, S J

    1991-02-15

    The metabolic conversion of dicarboxylic acids into succinate and other gluconeogenic intermediates in rat liver homogenates was investigated using [1,2,4-13C4]dodecanedioic acid as tracer. Isotope enrichments in 3-hydroxybutyrate, succinate, fumarate, and malate, as well as dicarboxylates (dodecanedioic, sebacic, suberic, and adipic acids) were measured with selected ion monitoring capillary column gas chromatograph-mass spectrometry. Significant enrichment in the M + 4 (four labeled carbons) ion of succinate (0.4-2.9%) was detected, unequivocally demonstrating the direct conversion of dicarboxylate into succinate. In addition, significant enrichment of the M + 2 ion of succinate was also observed. This labeled species was generated from labeled acetyl-CoA through the tricarboxylic acid cycle. The partition of acetyl-CoA into the tricarboxylic acid cycle relative to ketone body formation was higher in the beta oxidation of dicarboxylate than monocarboxylate. Therefore, in addition to the production of succinate, the beta oxidation of dodecanedioate resulted in the channeling of the acetyl-CoA produced to the tricarboxylic acid cycle instead of to acetoacetate production. The enrichments in lower chain dicarboxylates are consistent with a partial bidirectional beta oxidation of dodecanedioic acid. In addition to the expected M + 0 and M + 4 labels, significant M + 2 species were detected in suberic and adipic acids. These M + 2-labeled species were produced from the released free dicarboxylate intermediates which were then reactivated and metabolized. In these experiments, the overall succinate production was derived 4% from the direct conversion of dodecanedioic acid and 11% from the indirect route via acetyl-CoA through tricarboxylic acid.

  20. Preparation of biodegradable porous poly(butylene succinate microspheres

    Directory of Open Access Journals (Sweden)

    Pepić Dragana

    2008-01-01

    Full Text Available The aim of this study was to determine the optimal conditions for the fabrication of porous microspheres based on poly(butylene succinate, PBS. The biodegradable non-porous PBS microspheres were prepared by the oil-in-water (o/w emulsion solvent evaporation method using poly(vinyl alcohol, PVA, as the surfactant. Fabrication conditions, such as stirring rate, organic/aqueous ratio, PBS concentration and surfactant (PVA concentration, which have an important influence on both the particle size and the morphology of the microspheres, were varied. Scanning electron microscopy, SEM, observations confirmed the size, size distribution and surface morphology of the microspheres. The optimal conditions for the preparation of the non-porous microspheres were found to be: concentration the PBS solution, 10 mass%; PVA concentration, 1 mass%; the organic/ aqueous ratio CHCl3/H2O = 1/20 and stirring rate 800 rpm. Porous PBS microspheres were fabricated under the optimal conditions using various amounts of hexane and poly(ethylene oxide, PEO, as porogens. The influence of the amount of porogen on the pore size and the particle size was investigated using SEM and the apparent density. The microspheres exhibited various porosities and the pore sizes. The average particle size of the microspheres with PEO as the porogen was from 100 to 122μm and that of the microspheres with hexane as the porogen was from 87 to 97μm. The apparent density of the porous microspheres with PEO as the porogen, from 0.16 to 0.23 g/cm3, was much smaller than the non-porous microspheres, 0.40 g/cm3. In the in vitro degradation experiments, the porous microspheres were incubated in phosphate buffer solution (pH 7 at 37°C. After incubating for one month, the microspheres showed significant extent of the hydrolytic degradation of the porous PBS microspheres.

  1. The expression of succinate dehydrogenase in breast phyllodes tumor.

    Science.gov (United States)

    Choi, Junjeong; Kim, Do Hee; Jung, WooHee; Koo, Ja Seung

    2014-10-01

    The purpose of this study is to investigate the expression of succinate dehydrogenase (SDH)A, SDHB, and HIF-1α in phyllodes tumors and the association with clinic-pathologic factors. Using tissue microarray (TMA) for 206 phyllodes tumor cases, we performed immunohistochemical stains for SDHA, SDHB, and HIF-1α and analyzed their expression in regard to clinicopathologic parameters of each case. The cases were comprised of 156 benign, 34 borderline, and 16 malignant phyllodes tumors. The expression of stromal SDHA and epithelial- and stromal- SDHB increased as the tumor progressed from benign to malignant (P⟨0.001). There were five stromal SDHA-negative cases and 31 stromal SDHB-negative cases. SDHB negativity was associated with a lower histologic grade (P=0.054) and lower stromal atypia (P=0.048). Univariate analysis revealed that a shorter disease free survival (DFS) was associated with stromal SDHB high-positivity (P=0.013) and a shorter overall survival (OS) was associated with high-positivity of stromal SDHA and SDHB (P⟨0.001 and P⟨0.001, respectively). The multivariate Cox analysis with the variables stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, stromal SDHA expression, and stromal SDHB expression revealed that stromal overgrowth was associated with a shorter DFS (hazard ratio: 24.78, 95% CI: 3.126-196.5, P=0.002) and a shorter OS (hazard ratio: 176.7, 95% CI: 8.466-3691, P=0.001). In conclusion, Tumor grade is positively correlated with SDHA and SDHB expression in the tumor stroma in phyllodes tumors of the breast. This result may be attributed to the increased metabolic demand in high grade tumors.

  2. Novel NR5A1 missense mutation in premature ovarian failure: detection in han chinese indicates causation in different ethnic groups.

    Directory of Open Access Journals (Sweden)

    Xue Jiao

    Full Text Available BACKGROUND: The etiology of most premature ovarian failure (POF cases is usually elusive. Although genetic causes clearly exist and a likely susceptible region of 8q22.3 has been discovered, no predominant explanation exists for POF. More recently, evidences have indicated that mutations in NR5A1 gene could be causative for POF. We therefore screened for mutations in the NR5A1 gene in a large cohort of Chinese women with non-syndromic POF. METHODS: Mutation screening of NR5A1 gene was performed in 400 Han Chinese women with well-defined 46,XX idiopathic non-syndromic POF and 400 controls. Subsequently, functional characterization of the novel mutation identified was evaluated in vitro. RESULTS: A novel heterozygous missense mutation [c.13T>G (p.Tyr5Asp] in NR5A1 was identified in 1 of 384 patients (0.26%. This mutation impaired transcriptional activation on Amh, Inhibin-a, Cyp11a1 and Cyp19a1 gene, as shown by transactivation assays. However, no dominant negative effect was observed, nor was there impact on protein expression and nuclear localization. CONCLUSIONS: This novel mutation p.Tyr5Asp, in a novel non-domain region, is presumed to result in haploinsufficiency. Irrespectively, perturbation in NR5A1 is not a common explanation for POF in Chinese.

  3. Synthesis and Monolayer Behaviors of Succinic Acid-Type Gemini Surfactants Containing Semifluoroalkyl Groups.

    Science.gov (United States)

    Kawase, Tokuzo; Nagase, Youhei; Oida, Tatsuo

    2016-01-01

    In this work, novel succinic acid-type gemini surfactants containing semifluoroalkyl groups, dl- and meso-2,3-bis[Rf-(CH2)n]-succinic acids (Rf = C4F9, C6F13, C8F17; n = 2, 9), were successfully synthesized, and the effects of Rf, methylene chain length (n), and stereochemistry on their monolayer behaviors were studied. Critical micelle concentrations (CMC) of dl- and meso-2,3-bis[C4F9(CH2)9]-succinic acids were one order of magnitude smaller than that of the corresponding 1+1 type surfactant, C4F9(CH2)9COOH. From surface pressure-area (π-A) measurements, the lift-off areas of the geminis were found to decrease in the order C4F9 ≥ C6F13 > C8F17, regardless of methylene chain length and stereochemistry. The zero-pressure molecular areas of the geminis were twice those of the corresponding 1+1 type surfactants. Based on Gibbs compression modulus analysis, it was clarified that 2,3-bis[C8F17(CH2)n]-succinic gemini with short methylene chains (n = 2) would form more rigid monolayers than those having long methylene chains (n = 9). Unlike for 2,3-bis(alkyl)-succinic acids, the effects of stereochemistry on the monolayer behavior of semifluoroalkylated geminis were small.

  4. Ionic liquid pretreatment to increase succinic acid production from lignocellulosic biomass.

    Science.gov (United States)

    Wang, Caixia; Yan, Daojiang; Li, Qiang; Sun, Wei; Xing, Jianmin

    2014-11-01

    In this study, pinewood and corn stover pretreated with the ionic liquid (IL) 1-allyl-3-methylimidazolium chloride (AmimCl) were used as a feedstock for succinic acid production. Results reveal that 5% (v/v) AmimCl inhibited bacterial growth, whereas 0.01% (v/v) AmimCl inhibited succinic acid production. AmimCl was effective in extracting cellulose from pinewood and in degrading pinewood into a uniform pulp, as revealed by scanning electron microscopy (SEM). The rate of enzymatic hydrolysis of pinewood extract reached 72.16%. The combinations of AmimCl pretreatment with steam explosion or with hot compressed water were effective in treating corn stover, whereas AmimCl treatment alone did not result in a significant improvement. Pinewood extract produced 20.7g/L succinic acid with an average yield of 0.37g per gram of biomass. Workflow calculations indicated pine wood pretreated with IL has a theoretical yield of succinic acid of 57.1%. IL pretreatment led to increase in succinic acid yields.

  5. Succinate and Lactate Production from Euglena gracilis during Dark, Anaerobic Conditions

    Science.gov (United States)

    Tomita, Yuko; Yoshioka, Kazumasa; Iijima, Hiroko; Nakashima, Ayaka; Iwata, Osamu; Suzuki, Kengo; Hasunuma, Tomohisa; Kondo, Akihiko; Hirai, Masami Yokota; Osanai, Takashi

    2016-01-01

    Euglena gracilis is a eukaryotic, unicellular phytoflagellate that has been widely studied in basic science and applied science. Under dark, anaerobic conditions, the cells of E. gracilis produce a wax ester that can be converted into biofuel. Here, we demonstrate that under dark, anaerobic conditions, E. gracilis excretes organic acids, such as succinate and lactate, which are bulk chemicals used in the production of bioplastics. The levels of succinate were altered by changes in the medium and temperature during dark, anaerobic incubation. Succinate production was enhanced when cells were incubated in CM medium in the presence of NaHCO3. Excretion of lactate was minimal in the absence of external carbon sources, but lactate was produced in the presence of glucose during dark, anaerobic incubation. E. gracilis predominantly produced L-lactate; however, the percentage of D-lactate increased to 28.4% in CM medium at 30°C. Finally, we used a commercial strain of E. gracilis for succinate production and found that nitrogen-starved cells, incubated under dark, anaerobic conditions, produced 869.6 mg/L succinate over a 3-day incubation period, which was 70-fold higher than the amount produced by nitrogen-replete cells. This is the first study to demonstrate organic acid excretion by E. gracilis cells and to reveal novel aspects of primary carbon metabolism in this organism. PMID:28066371

  6. Tablet splitting: Product quality assessment of metoprolol succinate extended release tablets.

    Science.gov (United States)

    Zhao, Na; Zidan, Ahmed; Tawakkul, Mobin; Sayeed, Vilayat A; Khan, Mansoor

    2010-11-30

    Metoprolol succinate extended release tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval. Despite the flexibility that controlled release pellets may offer, segregation is one of the challenges that commonly occur during tableting for such drug delivery system. Since all commercial metoprolol succinate extended release tablets are scored, they are deemed suitable for splitting. The present study was aimed at utilizing an innovative technology to determine the dose uniformity for split tablets. Four marketed drug products consisting of innovator and generics were evaluated for effect of splitting on weight, assay and content uniformity. Novel analytical tool such as near infrared (NIR) chemical imaging was used to visualize the distribution of metoprolol succinate and functional excipients on the surfaces of the marketed tablets. The non-homogeneous distribution of directly compressed metoprolol succinate beads on the surface of the tablets as well as the split intersection explained the large variation in the split tablets' weight and content uniformity results. The obtained results indicated the usefulness of NIR chemical imaging to determine the need for content uniformity studies for certain split tablets.

  7. Optimization of succinic acid fermentation with Actinobacillus succinogenes by response surface methodology (RSM)

    Institute of Scientific and Technical Information of China (English)

    Yun-jian ZHANG; Qiang LI; Yu-xiu ZHANG; Dan WANG; Jian-min XING

    2012-01-01

    Succinic acid is considered as an important platform chemical.Succinic acid fermentation with Actinobacillus succinogenes strain BE-1 was optimized by central composite design (CCD) using a response surface methodology (RSM).The optimized production of succinic acid was predicted and the interactive effects between glucose,yeast extract,and magnesium carbonate were investigated.As a result,a model for predicting the concentration of succinic acid production was developed.The accuracy of the model was confirmed by the analysis of variance (ANOVA),and the validity was further proved by verification experiments showing that percentage errors between actual and predicted values varied from 3.02% to 6.38%.In addition,it was observed that the interactive effect between yeast extract and magnesium carbonate was statistically significant.In conclusion,RSM is an effective and useful method for optimizing the medium components and investigating the interactive effects,and can provide valuable information for succinic acid scale-up fermentation using A.succinogenes strain BE-1.

  8. Genotoxicity of meso-2,3-dimercapto succinic acid-coated silver sulfide quantum dot

    Directory of Open Access Journals (Sweden)

    Deniz Özkan Vardar

    2015-06-01

    Full Text Available Nanotecnology products have been used in wide applications in chemistry, electronics, energy generation, and medicine. Despite significant interest in developing quantum dots (QDs for biomedical applications, many researchers are convinced that QDs will never be used for the treatment of patients because of their potential toxicity. In various in vitro cell culture studies, the cytotoxic properties of some QD have been demonstrated and they have been suggested to be toxic in humans. In this study, the cytotoxic properties of Ag2S-(Meso-2,3-Dimercapto Succinic acid nanomaterials in V79 cells (Chinese lung fibroblast cell line were determined by MTT assay. The genotoxic effects of Ag2S-(Meso-2,3-Dimercapto Succinic acid were evaluated by the alkaline single cell gel electrophoresis. The cells were treated with Ag2S-(Meso-2,3-Dimercapto Succinic acid at the concentrations of 5- 2000 µg/ml. No cytotoxic effect of Ag2S-(Meso-2,3-Dimercapto Succinic acid at all concentrations studied was observed. No significant increases in DNA damage were found at the studied concentrations when compared to negative control in V79 cells. In conclusion, further in vitro and in vivo studies are required to determine the safety doses of Ag2S-(Meso-2,3-Dimercapto Succinic acid.

  9. FORMULATION AND EVALUATION OF CONTROLLED POROSITY OSMOTIC DRUG DELIVERY SYSTEM OF METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    Hardik Patel* and M. M. Patel

    2012-06-01

    Full Text Available Controlled porosity osmotic tablet of metoprolol succinate prepared and evaluated in this study. Metoprolol succinate is very high soluble drug, so complete drug release obtained very fast. It is difficult to formulate osmotic tablet of Metoprolol succinate which gives drug release up to 24 hr at zero order. To get desired dissolution profile various formulation parameters like osmogen concentration, level of weight gain and level of pore former concentration were studied. Hypromellose was added as release retardant to reduce its dissolution rate and get drug release up to 24 hr at zero order. As concentration of release retardant increases, dissolution rate decreases. Final optimized formulation with hypromellose was studied for effect of pH of dissolution media, agitation intensity and osmotic pressure of dissolution media. There is no effect of above variables on dissolution confirms that prepared metoprolol succinate tablet gives drug release with osmotic mechanism. Final optimized formulation complies with the USP criteria for the dissolution of metoprolol succinate extended release tablet.

  10. The effect of gamma radiation on some succinic acid derivatives in the solid state

    Science.gov (United States)

    Sütçü, Kerem; Osmanoǧlu, Y. Emre

    2017-01-01

    2,2-dimethyl succinic acid, 2,3-dimethyl succinic acid and monomethyl succinate were exposed to gamma radiation in the form of powder. EPR measurements were carried out to investigate the free radicals produced in all of them, following irradiation. Three of the radical species formed after irradiation were identified and spectroscopic parameters were discussed thereafter. The radical species were attributed to the ĊHCH2, HOOCCH(CH3)2ĊCOOH and H3COOCCH2ĊHCOOH radicals, respectively. The hyperfine splitting constants for all radicals were confirmed by the simulation of the experimental spectra. The radiation sensitivity of the samples was mainly attributed to the EPR line properties of stable radicals.

  11. PREPARATION OF STARCH SUCCINATE WITH INTERMEDIATE DS BY AQUEOUS SLURRY REACTION

    Institute of Scientific and Technical Information of China (English)

    ZHUChangying; WANGBin; 等

    2001-01-01

    The succinylation of cornstarch by slurry reaction has been studied using sodium hydroxide as catalyst.Several reaction parameters affecting the succinylation were investigated including the concentration of starch in water,the ratio of succinic anhydride to starch,the reaction time and the reaction temperature,The favorable conditions for an intermediate degree of substitution(DS) and reasonably high reaction efficiency(RE) are pH 8.5-9.0,50% starch by weight to water.succinic anhydride to starch 1/1(w/w),reaction time 4h,reaction temperature 30℃ .Under these conditions,the DS of 0.45 and RE of 28% were achieved.The addition of an adequate amount of crosslinking agent imparted starch succinate water absorbency.

  12. Solid/liquid phase diagram of the ammonium sulfate/succinic acid/water system.

    Science.gov (United States)

    Pearson, Christian S; Beyer, Keith D

    2015-05-14

    We have studied the low-temperature phase diagram and water activities of the ammonium sulfate/succinic acid/water system using differential scanning calorimetry and infrared spectroscopy of thin films. Using the results from our experiments, we have mapped the solid/liquid ternary phase diagram, determined the water activities based on the freezing point depression, and determined the ice/succinic acid phase boundary as well as the ternary eutectic composition and temperature. We also compared our results to the predictions of the extended AIM aerosol thermodynamics model (E-AIM) and found good agreement for the ice melting points in the ice primary phase field of this system; however, differences were found with respect to succinic acid solubility temperatures. We also compared the results of this study with those of previous studies that we have published on ammonium sulfate/dicarboxylic acid/water systems.

  13. On-line sample treatment and FT-IR determination of doxylamine succinate in pharmaceuticals.

    Science.gov (United States)

    Ventura-Gayete, Josep F; de la Guardia, Miguel; Garrigues, Salvador

    2006-12-15

    A low solvent consumption method for Fourier transform infrared spectroscopy (FT-IR) determination of doxylamine succinate in pharmaceuticals has been developed. The analyte was continuous and selectively extracted with a 13% (v/v) ethanol:chloroform solvent mixture, recirculating the solvent through the sample and monitoring the process by FT-IR. Doxylamine succinate was determined by on-line standard addition measuring the peak area in the regions 1730-1710 and 1485-1462cm(-1) corrected with a two-point baseline established between 2000 and 1800cm(-1). This new method implies low volumes of chloroformic solvent mixture, only 2.6mL per sample, in front of classical batch FT-IR methods, improving analytical efficiency and reducing waste generation. The on-line extraction and standard addition determination of doxylamine succinate allowed a throughput of 10h(-1).

  14. PREPARATION OF STARCH SUCCINATE WITH INTERMEDIATE DS BY AQUEOUS SLURRY REACTION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The succinylation of cornstarch by slurry reaction has been studied using sodium hydroxide as catalyst. Several reaction parameters afJecting the succinylation were investigated including the concentration of starch in water, the ratio of succinic anhydride to starch, the reaction time and the reaction temperature. The favorable conditions for an intermediate degree of substitution (DS) and reasonably high reaction efficiency (RE) are pH 8.5~9.0, 50% starch by weight to water, succinic anhydride to starch I/I (w/w), reaction time 4h, reaction temperature 30 ℃Under these conditions, the DS of 0.45 and RE of 28% were achieved. The addition of an adequate amount of crosslinking agent imparted starch succinate water absorbency.

  15. Unconventional biomasses as feedstocks for production of biofuels and succinic acid in a biorefinery concept

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi

    Biorefinery has the potential of displacing fossil fuels and oil-refinery based products. Within the biorefinery a palette of marketable commodities can be produced from biomass, including food, feed, biochemicals and biofuels. Which bioproducts are produced is largely dependent on the chemical....... The chemical composition of biomasses was determined in order to demonstrate their biorefinery potential. Bioethanol and biogas along with succinic acid production were the explored bioconversion routes, while potential production of other compounds was also investigated. Differences and changes in biomass...... biogas upgrading technologies deliver. Results obtained in this study constitute the first report for utilization of macroalgae, hemp and Jerusalem artichoke tuber biomass for fermentative succinic acid production. It was demonstrated that all biomasses are attractive biomass feedstocks for succinic acid...

  16. DEVELOPMENT AND VALIDATION OF ANALYTICAL METHOD FOR ESTIMATION OF CILNIDIPINE AND METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    Mo.Salauddin A Shaikh

    2015-07-01

    Full Text Available A simple, specific, accurate and precise reversed phase high performance liquid chromatographic method was developed and validated for the simultaneous estimation of Cilnidipine and Metoprolol Succinate, using a Cosmosil C18 (250 х 4.6 mm i.d. column and a mobile phase composed of 0.05M potassium dihydrogen phosphate buffer: Methanol (70:30 pH 3.5 adjusted with ophosphoric acid and at flow rate of 1.0 ml/min. The retention times of Cilnidipine and Metoprolol Succinate were found to be 3.493 min and 5.960 min, respectively. Linearity was established for Cilnidipine and Metoprolol Succinate in the range of 12.5-37.5 μg/ml and 2.5-7.5 μg/ml, respectively. The percentage recoveries of Cilnidipine and Metoprolol Succinate were found to be in the range of 100.13-100.40 % and 99.24-100.29 %, respectively. The correlation coefficients for both components were found to be 0.999. The developed methods were validated according to ICH guidelines and values of linearity, accuracy, precision and other analysis were found to be in good accordance with the prescribed values. This method can be successfully employed for simultaneous quantitative analysis of Cilnidipine and Metoprolol Succinate in its dosage form. The developed HPLC method was subjected to stability indicating studies for marketed formulation. Interfering peak from degraded products or solvent did not interfere with estimation of drugs and the developed method was found to be specific for estimation of Cilnidipine and Metoprolol Succinate.

  17. Maintenance of homeostasis in the aging hypothalamus: The central and peripheral roles of succinate

    Directory of Open Access Journals (Sweden)

    Thomas T. Chen

    2015-02-01

    Full Text Available Aging is the phenotype resulting from accumulation of genetic, cellular, and molecular damages. Many factors have been identified as either the cause or consequence of age-related decline in functions and repair mechanisms. The hypothalamus is the source and a target of many of these factors and hormones responsible for the overall homeostasis in the body. With advanced age, the sensitivity of the hypothalamus to various feedback signals begins to decline. In recent years, several aging-related genes have been identified and their signaling pathways elucidated. These gene products include mTOR, IKK-β/NF-κB complex, and HIF-1α, an important cellular survival signal. All of these activators/modulators of the aging process have also been identified in the hypothalamus and shown to play crucial roles in nutrient sensing, metabolic regulation, energy balance, reproductive function, and stress adaptation. This illustrates the central role of the hypothalamus in aging.Inside the mitochondria, succinate is one of the most prominent intermediates of the Krebs cycle. Succinate oxidation in mitochondria provides the most powerful energy output per unit time. Extra-mitochondrial succinate triggers a host of succinate receptor (SUCN1 or GPR91-mediated signaling pathways in many peripheral tissues including the hypothalamus. One of the actions of succinate is to stabilize the hypoxia and cellular stress conditions by inducing the transcriptional regulator HIF-1α. Through these actions, it is hypothesized that succinate has the potential to restore the gradual but significant loss in functions associated with cellular senescence and systemic aging.

  18. Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

    OpenAIRE

    Mashiur Rahman; Farzana Prianka; Mohammad Shohel; Md. Abdul Mazid

    2014-01-01

    Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA) was studied by equilibrium dialysis method (ED) at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 a...

  19. Poly(butylene succinate) and its copolymers: research, development and industrialization.

    Science.gov (United States)

    Xu, Jun; Guo, Bao-Hua

    2010-11-01

    Poly(butylene succinate) (PBS) and its copolymers are a family of biodegradable polymers with excellent biodegradability, thermoplastic processability and balanced mechanical properties. In this article, production of the monomers succinic acid and butanediol, synthesis, processing and properties of PBS and its copolymers are reviewed. The physical properties and biodegradation rate of PBS materials can be varied in a wide range through copolymerization with different types and various contents of monomers. PBS has a wide temperature window for thermoplastic processing, which makes the resin suitable for extrusion, injection molding, thermoforming and film blowing. Finally, we summarized industrialization and applications of PBS.

  20. Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli.

    Science.gov (United States)

    Zhu, Xinna; Tan, Zaigao; Xu, Hongtao; Chen, Jing; Tang, Jinlei; Zhang, Xueli

    2014-07-01

    Reducing equivalents are an important cofactor for efficient synthesis of target products. During metabolic evolution to improve succinate production in Escherichia coli strains, two reducing equivalent-conserving pathways were activated to increase succinate yield. The sensitivity of pyruvate dehydrogenase to NADH inhibition was eliminated by three nucleotide mutations in the lpdA gene. Pyruvate dehydrogenase activity increased under anaerobic conditions, which provided additional NADH. The pentose phosphate pathway and transhydrogenase were activated by increased activities of transketolase and soluble transhydrogenase SthA. These data suggest that more carbon flux went through the pentose phosphate pathway, thus leading to production of more reducing equivalent in the form of NADPH, which was then converted to NADH through soluble transhydrogenase for succinate production. Reverse metabolic engineering was further performed in a parent strain, which was not metabolically evolved, to verify the effects of activating these two reducing equivalent-conserving pathways for improving succinate yield. Activating pyruvate dehydrogenase increased succinate yield from 1.12 to 1.31mol/mol, whereas activating the pentose phosphate pathway and transhydrogenase increased succinate yield from 1.12 to 1.33mol/mol. Activating these two pathways in combination led to a succinate yield of 1.5mol/mol (88% of theoretical maximum), suggesting that they exhibited a synergistic effect for improving succinate yield.

  1. Application of cyclic ketones in MCR: Ugi/amide coupling based synthesis of fused tetrazolo[1,5-a][1,4]benzodiazepines

    NARCIS (Netherlands)

    Yerande, Swapnil; Newase, Kiran; Singh, Bhawani; Boltjes, André; Dömling, Alex

    2014-01-01

    Azido-Ugi reaction involving cyclic ketone, primary amine, isonitrile, and azide afforded substituted tetrazole derivatives 5. These intermediates were hydrolyzed to corresponding acid derivatives. EDAC/HOBt mediated amide bond formation of 5 gave fused tetrazolo[1,5-a][1,4]benzodiazepine 6 in high

  2. Pubertal androgenization and gonadal histology in two 46, XY adolescents with NR5A1 mutations and predominantly female phenotype at birth

    NARCIS (Netherlands)

    M.L. Cools (Martine); P. Hoebeke (Piet); K.P. Wolffenbuttel (Katja); J.A. Stoop (Hans); R. Hersmus (Remko); M. Barbaro (M.); A. Wedell; H.T. Brüggenwirth (Hennie); L.H.J. Looijenga (Leendert); S.L.S. Drop (Stenvert)

    2012-01-01

    textabstractObjective: Most patients with NR5A1 (SF-1) mutations and poor virilization at birth are sex-assigned female and receive early gonadectomy. Although studies in pituitary-specific Sf-1 knockout mice suggest hypogonadotropic hypogonadism, little is known about endocrine function at puberty

  3. NCBI nr-aa BLAST: CBRC-MLUC-01-0475 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-0475 ref|YP_002987403.1| succinic semialdehyde dehydrogenase [Dickeya dada...ntii Ech703] gb|ACS85581.1| succinic semialdehyde dehydrogenase [Dickeya dadantii Ech703] YP_002987403.1 0.69 32% ...

  4. [Determination of succinic acid in desvenlafaxine succinate by high performance ion-exclusion chromatography and high performance ion-exchange chromatography].

    Science.gov (United States)

    Zong, Yanping; Li, Jinghua; Sun, Wei; Liu, Guixia; Lu, Jinghua; Shan, Guangzhi

    2016-02-01

    New methods were developed for the determination of succinic acid in desvenlafaxine succinate (DVS) by high performance ion-exclusion chromatography (HPIEC) and high performance ion-exchange chromatography (HPIC). HPIEC and HPIC methods were used separately to determinate the succinic acid in DVS. With HPIEC, the sample was diluted with 2. 50 x 10(-3) mol/L sulfuric acid solution and filtrated by 0. 22 µm polyether sulfone filter membrane, and then analyzed by HPIEC directly without any further pretreatment. The analytical column was Phenomenex Rezex ROA-organic Acid H+(8%) (300 mmx7. 8 mm). The mobile phase was 2. 50x10(-3) mol/L sulfuric acid solution at the flow rate of 0. 5 mL/min. The column temperature was set at 40 °C, and the detection wavelength was 210 nm. The injection volume was 10 KL. The assay was quantified by external standard method. With HPIC, the sample was diluted with ultrapure water and filtrated by 0. 22 µm polyether sulfone filter membrane, and then analyzed by HPIC directly without any further pretreatment. The analytical column was Dionex IonPac AS11-HC (250 mm x 4 mm) with a guard column IonPacAG11-HC (50 mm x 4 mm). Isocratic KOH elute generator was used at the flow rate of 1. 0 mL/min. The detection was performed by a Dionex suppressed (DIONEX AERS 500 4-mm) conductivity detector. The injection volume was 10 µL. The content computation was performed with peak area external reference method. The results of HPIEC method for succinic acid were 28. 8%, 28. 9% and 28. 9%, while the results of HPIEC method were 28. 2%, 28. 6% and 28. 6%. The results of HPIEC and HPIC methods were not significantly different. The two methods can both be used to determine the contents of succinic acid in DVS. The surveillance analytical method should be chosen according to the situation.

  5. Efficient production of succinic acid from Palmaria palmata hydrolysate by metabolically engineered Escherichia coli.

    Science.gov (United States)

    Olajuyin, Ayobami Matthew; Yang, Maohua; Liu, Yilan; Mu, Tingzhen; Tian, Jiangnan; Adaramoye, Oluwatosin Adekunle; Xing, Jianmin

    2016-08-01

    Succinic acid, a C4 dicarboxylic acid is used in many fields such as food, agriculture, pharmaceutical and polymer industries. In this study, microbial production of succinic acid from Palmaria palmata was investigated for the first time. In engineered Escherichia coli KLPPP, lactate dehydrogenase, pyruvate formate lyase, phosphotransacetylase-acetate kinase and pyruvate oxidase genes were deleted while phosphoenolpyruvate carboxykinase was overexpressed. The recombinant exhibited higher molar yield of succinic acid on galactose (1.20±0.02mol/mol) than glucose (0.48±0.03mol/mol). The concentration and molar yield of succinic acid were 22.40±0.12g/L and 1.13±0.02mol/mol total sugar respectively after 72h dual phase fermentation from P. palmata hydrolysate which composed of glucose (12.57±0.17g/L) and galactose (18.03±0.10g/L). The results demonstrate that P. palmata red macroalgae biomass represents a novel and an economically alternative feedstock for biochemicals production.

  6. [The answer reaction of system complement on correction of hypoxia of hydazepam and succinic acid].

    Science.gov (United States)

    Kuznetsova, L N

    2011-01-01

    Investigated functionally activation of human complement in vivo an model of high hypoxia (6-7,5 km) as without correction, so at the phone of medicine hydazepam and succinic acid. Discover that by analysis of the sensitive to complement components one can estimate effects of high hypoxia and her pharmacological correction.

  7. Acetate:succinate CoA-transferase in the hydrogenosomes of Trichomonas vaginalis: Identification and characterization

    NARCIS (Netherlands)

    K.W.A. Grinsven; S. Rosnowsky (Silke); S.W.H. van Weelden (Susanne); S. Pütz (Simone); M. van der Giezen (Mark); W. Martin (William); J.J. van Hellemond (Jaap); A.G.M. Tielens (Aloysius); K. Henze (Katrin)

    2008-01-01

    textabstractAcetate:succinate CoA-transferases (ASCT) are acetate-producing enzymes in hydrogenosomes, anaerobically functioning mitochondria and in the aerobically functioning mitochondria of trypanosomatids. Although acetate is produced in the hydrogenosomes of a number of anaerobic microbial euka

  8. Bilayer mucoadhesive microparticles for the delivery of metoprolol succinate: Formulation and evaluation.

    Science.gov (United States)

    Kumar, Krishan; Dhawan, Neha; Sharma, Harshita; Patwal, Pramod S; Vaidya, Shubha; Vaidya, Bhuvaneshwar

    2015-01-01

    Metoprolol succinate is a very potent drug for the treatment of hypertension but suffers from poor bioavailability due to its erratic absorption in lower GI tract. Therefore, in the present study, it was hypothesized that by formulating mucoadhesive particles, the residence time in the GIT and release of drug may be prolonged that will enhance the bioavailability of metoprolol succinate. Metoprolol succinate loaded chitosan microparticles were prepared by ionic gelation method. The optimized microparticles were coated with sodium alginate to form a layer over chitosan microparticles to increase the mucoadhesive strength and to release the drug in controlled manner. Coated and uncoated microparticles were evaluated for particle size, zeta potential, morphology, entrapment efficiency, drug loading and in vitro drug release. The coated microparticles showed comparatively less drug release in the 0.1 N HCl while sustained release in PBS (pH 6.8) as compared to uncoated microparticles. The in vivo study on albino rats demonstrated an increase in bioavailability of the coated microparticles as compared to marketed formulation. From the study it can be concluded that alginate coated chitosan microparticles could be a useful carrier for the oral delivery of metoprolol succinate.

  9. Studies on Cross-linking of succinic acid with chitosan/collagen

    Directory of Open Access Journals (Sweden)

    Tapas Mitra

    2013-01-01

    Full Text Available The present study summarizes the cross-linking property of succinic acid with chitosan /collagen. In detail, the chemistry behind the cross-linking and the improvement in mechanical and thermal properties of the cross-linked material were discussed with suitable instruments and bioinformatics tools. The concentration of succinic acid with reference to the chosen polymers was optimized. A 3D scaffold prepared using an optimized concentration of succinic acid (0.2% (w/v with chitosan (1.0% (w/v and similarly with collagen (0.5% (w/v, was subjected to surface morphology, FT-IR analysis, tensile strength assessment, thermal stability and biocompatibility. Results revealed, cross-linking with succinic acid impart appreciable mechanical strength to the scaffold material. In silico analysis suggested the prevalence of non-covalent interactions, which played a crucial role in improving the mechanical and thermal properties of the cross-linked scaffold. The resultant 3D scaffold may find application as wound dressing material, as an implant in clinical applications and as a tissue engineering material.

  10. Cell recycled culture of succinic acid-producing Anaerobiospirillum succiniciproducens using an internal membrane filtration system.

    Science.gov (United States)

    Lee, Pyung-Cheon; Lee, Sang-Yup; Chang, Ho-Nam

    2008-07-01

    Cell recycled culture of succinic acid-producing Anaerobiospirillum succiniciproducens was anaerobically carried out using an internal membrane filter module in order to examine the physiological response of A. succiniciproducens to a high-cell-density environment. The optimal growth of A. succiniciproducens and its enhanced succinic acid productivity were observed under CO2-rich conditions, established by adding NaHCO3 and Na2CO3, in the cell recycled system. A. succiniciproducens grew up to 6.50 g-DCW/l, the highest cell concentration obtained so far, in cell recycled cultures. The cells did not change their morphology, which is known to be easily changed in unfavorable or stress environments. The maximum productivity of succinic acid was about 3.3 g/l/h, which is 3.3 times higher than those obtained in batch cultures. These results can serve as a guide for designing highly efficient cell recycled systems for succinic acid at a commercial level.

  11. Preventive effect of selenium, methionine and antioxidants against encephalomalacia of chicks induced by dilauryl succinate.

    Science.gov (United States)

    Yoshida, M; Hoshi, H

    1977-01-01

    The protective effect of supplemental selenium, methionine, ascorbic acid, menaquinone and five antioxidants against encephalomalacia of chicks fed a diet containing dilauryl succinate was examined. Diauryl succinate induces vitamin E deficiency signs such as fragility of the erythrocytes and encephalomalacia. Supplementation of selenium and methionine with or without simultaneous supplementation of a low level of dl-alpha-tocopheryl acetate had little effect on preventing encephalomalacia. The preventive effect of ascorbic acid, methylene blue, ethoyquine, 2,6-ditertiary-butyl-p-cresol and butylated hydroxyanisole was roughly in proportion to their dietary level, and a high level of any of them could almost completely protect the chicks from encephalomalacia, while diphenyl-p-phenylenediamine was not as effective and the effect was not proportional to the dose. Menaquinone had little effect. No difference was observed in the plasma tocopherol levels and peroxide levels in the adipose tissueof the chick fed eith er dilauryl succinate or cornstarch. The effect of dilauryl succinate appears to be independent of peroxides generated in the chick.

  12. 76 FR 59141 - Determination That LOXITANE (Loxapine Succinate) Capsules and Three Other Drug Products Were Not...

    Science.gov (United States)

    2011-09-23

    ... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6308, Silver... publishes this list as part of the ``Approved Drug Products With Therapeutic Equivalence Evaluations... marketed. Application No. Drug Applicant NDA 017525 LOXITANE (loxapine Watson Laboratories succinate)...

  13. [Effect of overexpression of malate dehydrogenase on succinic acid production in Escherichia coli NZN111].

    Science.gov (United States)

    Liang, Liya; Ma, Jiangfeng; Liu, Rongming; Wang, Guangming; Xu, Bing; Zhang, Min; Jiang, Min

    2011-07-01

    Escherichia coli NZN111 is a double mutant with lactate dehydrogenase (ldhA) and pyruvate formate-lyase (pflB) inactivated. Under anaerobic conditions, disequilibrium of coenzyme NADH and NAD+ causes Escherichia coli NZN111 losing the glucose utilizing capability. In this study, we constructed a recombinant strain E. coli NZN111/pTrc99a-mdh and overexpressed the mdh gene with 0.3 mmol/L of IPTG under anaerobic fermentation condition in sealed bottles. The specific malate dehydrogenase (MDH) activity in the recombinant strain was 14.8-fold higher than that in E. coli NZN111. The NADH/ NAD+ ratio decreased from 0.64 to 0.26 and the concentration of NAD+ and NADH increased 1.5-fold and 0.2-fold respectively. Under anaerobic conditions, the recombinant strain possessed the capability of growth and glucose absorption. We took dual-phase fermentation for succinate production. After the dry cell weight (DCW) reached 6.4 g/L under aerobic conditions, the cell culture was changed to anaerobic conditions. After 15 h, 14.75 g/L glucose was consumed and succinic acid reached 15.18 g/L. The yield of succinic acid was 1.03 g/g Glu and the productivity of succinic acid was 1.012 g/(L x h).

  14. Amorphous/crystal and polymer/filler interphases in biocomposites from poly(butylene succinate)

    Energy Technology Data Exchange (ETDEWEB)

    Signori, Francesca [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy); Pelagaggi, Martina [Universita di Pisa - Dipartimento di Chimica e Chimica Industriale, Via Risorgimento 35, I-56126 Pisa (Italy); Bronco, Simona [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy); Righetti, Maria Cristina, E-mail: righetti@ipcf.cnr.it [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy)

    2012-09-10

    Highlights: Black-Right-Pointing-Pointer The existence of intermolecular interactions between poly(butylene succinate) and hemp fibres was proved from specific heat capacities data. Black-Right-Pointing-Pointer Different degrees of mobility of the poly(butylene succinate) amorphous segments were evidenced at the amorphous/crystal interphase. Black-Right-Pointing-Pointer Devitrification of the rigid amorphous fraction in poly(butylene succinate) was found to occur before and simultaneously with the fusion. - Abstract: Poly(butylene succinate)-hemp composites (PBS-hemp), with hemp content in the range 0-40 wt.%, were prepared in the melt and characterized. This paper focuses on the detailed analysis of the thermal behaviour of the PBS-hemp composites, investigated by differential scanning calorimetry (DSC), to enlighten the polymer/fibre interphase features. The occurrence of specific intermolecular interactions between PBS and hemp was assessed from specific heat capacity data. Different degrees of mobility of the PBS amorphous segments were found at the amorphous/crystal interphases. A broadening of the bulk glass transition was observed, and attributed to the presence of polymer segments slightly constrained. Moreover, a rigid amorphous fraction that devitrifies at temperatures higher than the bulk glass transition, partly before the melting region and partly simultaneously with the fusion, was observed and quantified, and attributed to the presence of major constraints probably occurring in geometrically restricted areas.

  15. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Succistearin (stearoyl propylene glycol hydrogen succinate). 172.765 Section 172.765 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION...

  16. Succinate-based preparation alleviates manifestations of the climacteric syndrome in women.

    Science.gov (United States)

    Peskov, A B; Maevskii, E I; Uchitel', M L; Sakharova, N Yu; Vize-Khripunova, M A

    2005-09-01

    Clinical placebo-controlled study of Enerlit-Clima (bioactive succinate-based food additive) a showed positive effect of the preparation on general clinical and psychoemotional manifestations of the climacteric syndrome. A trend to an increase in estradiol level in early pathological climacteric and normalization of the endometrial status were observed.

  17. Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells.

    NARCIS (Netherlands)

    Robben, J.H.; Fenton, R.A.; Vargas, S.L.; Schweer, H.; Peti-Peterdi, J.; Deen, P.M.T.; Milligan, G.

    2009-01-01

    When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is loca

  18. Complex formation and solubility of Pu(IV) with malonic and succinic acids

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, T.; Kobayashi, T.; Takagi, I.; Moriyama, H. [Kyoto Univ. (Japan). Dept. of Nuclear Engineering; Fujiwara, A. [Radioactive Waste Management Funding and Research Center, Tokyo (Japan); Kulyako, Y.M.; Perevalov, S.A.; Myasoedov, B.F. [Russian Academy of Sciences (RAS), Moscow (RU). V.I. Vernadsky Inst. of Geochemistry and Analytical Chemistry (GEOKHI)

    2009-07-01

    The complex formation constants of tetravalent plutonium ion with malonic and succinic acids in aqueous solution were determined by the solvent-extraction method. Also, by taking the known values of the solubility products, the hydrolysis constants and the formation constants, the experimental solubility data of plutonium in the presence of carboxylates were analyzed. (orig.)

  19. Co- and Terpolyesters based on isosorbide and succinic acid for coating applications : synthesis and characterization

    NARCIS (Netherlands)

    Noordover, B.A.J.; Staalduinen, van V.G.; Duchateau, R.; Koning, C.E.; Benthem, van R.A.T.M.; Mak, M.; Heise, A.; Frissen, A.E.; Haveren, van J.

    2006-01-01

    Co- and terpolyesters based on succinic acid and isosorbide in combination with other renewable monomers such as 2,3-butanediol, 1,3-propanediol, and citric acid were synthesized and characterized. Linear polyesters were obtained via melt polycondensation of nonactivated dicarboxylic acids with OH f

  20. Bio-oil based biorefinery strategy for the production of succinic acid

    DEFF Research Database (Denmark)

    Wang, Caixia; Thygesen, Anders; Liu, Yilan

    2013-01-01

    Background: Succinic acid is one of the key platform chemicals which can be produced via biotechnology process instead of petrochemical process. Biomass derived bio-oil have been investigated intensively as an alternative of diesel and gasoline fuels. Bio-oil could be fractionized into organic...... phase and aqueous phase parts. The organic phase bio-oil can be easily upgraded to transport fuel. The aqueous phase bio-oil (AP-bio-oil) is of low value. There is no report for its usage or upgrading via biological methods. In this paper, the use of AP-bio-oil for the production of succinic acid...... was investigated. Results: The transgenic E. coli strain could grow in modified M9 medium containing 20 v/v% AP-bio-oil with an increase in OD from 0.25 to 1.09. And 0.38 g/L succinic acid was produced. With the presence of 4 g/L glucose in the medium, succinic acid concentration increased from 1.4 to 2.4 g...

  1. Nucleation kinetics of urea succinic acid –ferroelectric single crystal

    Energy Technology Data Exchange (ETDEWEB)

    Dhivya, R. [Crystal growth and Crystallography Division, School of Advanced Sciences, VIT University, Vellore-632014, Tamilnadu (India); Voohrees College, Vellore-632014, Tamilnadu (India); Vizhi, R. Ezhil, E-mail: rezhilvizhi@vit.ac.in, E-mail: revizhi@gmail.com; Babu, D. Rajan [Crystal growth and Crystallography Division, School of Advanced Sciences, VIT University, Vellore-632014, Tamilnadu (India)

    2015-06-24

    Single crystals of Urea Succinic Acid (USA) were grown by slow cooling technique. The crystalline system was confirmed by powder X-ray diffraction. The metastable zonewidth were carried out for various temperatures i.e., 35°, 40°, 45° and 50°C. The induction period is experimentally determined and various nucleation parameters have been estimated.

  2. Methods for upgrading of a fuel gas and succinic acid production

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention provides methods of upgrading of a CO2-containing fuel gas comprising the use of anaerobic succinic acid-producing microorganisms. Thus, the present invention provides a method for simultaneous upgrading of a CO2-containing fuel gas and biosuccinic acid production....

  3. Succinic Acid as a Byproduct in a Corn-based Ethanol Biorefinery

    Energy Technology Data Exchange (ETDEWEB)

    MBI International

    2007-12-31

    MBI endeavored to develop a process for succinic acid production suitable for integration into a corn-based ethanol biorefinery. The project investigated the fermentative production of succinic acid using byproducts of corn mill operations. The fermentation process was attuned to include raw starch, endosperm, as the sugar source. A clean-not-sterile process was established to treat the endosperm and release the monomeric sugars. We developed the fermentation process to utilize a byproduct of corn ethanol fermentations, thin stillage, as the source of complex nitrogen and vitamin components needed to support succinic acid production in A. succinogenes. Further supplementations were eliminated without lowering titers and yields and a productivity above 0.6 g l-1 hr-1was achieved. Strain development was accomplished through generation of a recombinant strain that increased yields of succinic acid production. Isolation of additional strains with improved features was also pursued and frozen stocks were prepared from enriched, characterized cultures. Two recovery processes were evaluated at pilot scale and data obtained was incorporated into our economic analyses.

  4. Electrospun Nanoporous Poly(butylenes succinate-co-bytylene terephthalate Nonwoven Mats

    Directory of Open Access Journals (Sweden)

    Liang Wang

    2011-01-01

    Full Text Available A traditional Chinese drug “Yunnan Baiyao” is used as an additive in poly(butylenes succinate-co-bytylene terephthalate (PBST solution, which is a kind of biodegradable aliphatic-aromatic copolyesters, to produce microspheres with nanoporosity by electrospinning; the tunable size of nanoporosity can be controlled by changing the voltage applied in the electrospinning process.

  5. Novel pathway engineering design of the anaerobic central metabolic pathway in Escherichia coli to increase succinate yield and productivity.

    Science.gov (United States)

    Sánchez, Ailen M; Bennett, George N; San, Ka-Yiu

    2005-05-01

    A novel in vivo method of producing succinate has been developed. A genetically engineered Escherichia coli strain has been constructed to meet the NADH requirement and carbon demand to produce high quantities and yield of succinate by strategically implementing metabolic pathway alterations. Currently, the maximum theoretical succinate yield under strictly anaerobic conditions through the fermentative succinate biosynthesis pathway is limited to one mole per mole of glucose due to NADH limitation. The implemented strategic design involves the construction of a dual succinate synthesis route, which diverts required quantities of NADH through the traditional fermentative pathway and maximizes the carbon converted to succinate by balancing the carbon flux through the fermentative pathway and the glyoxylate pathway (which has less NADH requirement). The synthesis of succinate uses a combination of the two pathways to balance the NADH. Consequently, experimental results indicated that these combined pathways gave the most efficient conversion of glucose to succinate with the highest yield using only 1.25 moles of NADH per mole of succinate in contrast to the sole fermentative pathway, which uses 2 moles of NADH per mole of succinate. A recombinant E. coli strain, SBS550MG, was created by deactivating adhE, ldhA and ack-pta from the central metabolic pathway and by activating the glyoxylate pathway through the inactivation of iclR, which encodes a transcriptional repressor protein of the glyoxylate bypass. The inactivation of these genes in SBS550MG increased the succinate yield from glucose to about 1.6 mol/mol with an average anaerobic productivity rate of 10 mM/h (approximately 0.64 mM/h-OD600). This strain is capable of fermenting high concentrations of glucose in less than 24 h. Additional derepression of the glyxoylate pathway by inactivation of arcA, leading to a strain designated as SBS660MG, did not significantly increase the succinate yield and it decreased

  6. Bilateral consecutive rupture of the quadriceps tendon in a man with BstUI polymorphism of the COL5A1 gene.

    Science.gov (United States)

    Longo, Umile Giuseppe; Fazio, Vito; Poeta, Maria Luana; Rabitti, Carla; Franceschi, Francesco; Maffulli, Nicola; Denaro, Vincenzo

    2010-04-01

    A genetic component has been implicated in tendinopathies involving tendon rupture. Type V collagen, a quantitatively minor fibrillar collagen which forms heterotypic fibrils with type I collagen, plays a role in the regulation of the size and configuration of fibrils of the much more abundant component type I collagen. To date, no data on the genetic component of bilateral rupture of the quadriceps tendon have been reported. We describe the presence of BstUI polymorphism of the COL5A1 gene in a man with bilateral rupture of the quadriceps tendon. The COL5A1 (the variant rs12722, BstUI RFLP) can be a candidate gene associated with the development of bilateral quadriceps tendon rupture.

  7. CLINICAL AND ECONOMICAL ASSESSMENTS OF METOPROLOL TARTRATE/SUCCINATE USAGE IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    M. V. Soura

    2008-01-01

    Full Text Available Clinical and clinicoeconomical studies review is presented as well as results of author’s comparative cost analysis on metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK usage in patients with ischemic heart disease. Efficacy of metoprolol therapy is proven in randomized clinical studies in patients with angina and myocardial infarction (MI. In angina patients metoprolol prevents cardiac attacks, MI, reduces nitroglycerine consumption, increases exercise tolerability, prolongs the exercise time before ST segment depression (succinate better than tartrate, decrease of angina intensity. In MI patients metoprolol therapy reduces mortality, sudden death, recurring MI and the rate of early post MI angina attacks. Nowadays metoprolol is the only β-blocker having indication on secondary MI prevention. Besides for the present metoprolol succinate is the only β-blocker with proven direct antisclerosis effect. According to Swedish clinicoeconomical study in patients after MI secondary prevention with metoprolol therapy saves the costs in comparison with placebo. American clinicoeconomical model of metoprolol and atenolol usage in all patients with MI could result in significant reduction in mortality and recurring MI rate, prolong the life and improve its quality, save financial resources. The cost of monthly treatment of angina patient with metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK is 135 and 354 rubles, respectively. The price range of comparative β-blockers in ascending order is the following: atenolol (Atenolol Nicomed → metoprolol tartrate (Betaloc → metoprolol succinate (Betaloc ZOK → bisoprolol (Concor → nebivolol (Nebilet. In conclusion, metoprolol therapy is the one of mostly economically reasonable approach.

  8. Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats.

    Science.gov (United States)

    Pelser, Andries; Müller, Douw G; du Plessis, Jeanetta; du Preez, Jan L; Goosen, Colleen

    2002-09-01

    The intranasal route of administration provides a potential useful way of administering a range of systemic drugs. In order to assess the feasibility of this approach for the treatment of nausea and vomiting, doxylamine succinate was studied in rats for the pharmacokinetics (AUC, C(max), t(max)) following intranasal, oral and intravenous administrations. Subjects (six male Sprague-Dawley rats per time interval for each route of administration) received 2-mg doses of doxylamine succinate orally and I-mg doses intranasally and intravenously, respectively. The various formulations were formulated in isotonic saline (0.9% w/v) at 25 +/- 1 degrees C. Doxylamine succinate concentrations in plasma were determined with a high-performance liquid chromatographic assay and a liquid-liquid extraction procedure. Intranasal and oral bioavailabilities were determined from AUC values relative to those after intravenous dosing. Intranasal bioavailability was greater than that of oral doxylamine succinate (70.8 vs 24.7%). The intranasal and oral routes of administration differed significantly from the intravenous route of administration. Peak plasma concentration (C(max)) was 887.6 ng/ml (S.D. 74.4), 281.4 ng/ml (S.D. 24.6) and 1296.4 ng/ml (S.D. 388.9) for the intranasal, oral and intravenous routes, respectively. The time to achieve C(max) for the intranasal route (t(max)=0.5 h) was faster than for the oral route (t(max)=1.5 h), but no statistically significant differences between the C(max) values were found using 95% confidence intervals. The results of this study show that doxylamine succinate is rapidly and effectively absorbed from the nasal mucosa.

  9. Activation of the succinate receptor GPR91 in macula densa cells causes renin release.

    Science.gov (United States)

    Vargas, Sarah Laurin; Toma, Ildikó; Kang, Jung Julie; Meer, Elliott James; Peti-Peterdi, János

    2009-05-01

    Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) are salt sensors and generate paracrine signals that control renal blood flow, glomerular filtration, and release of the prohypertensive hormone renin. We hypothesized that the recently identified succinate receptor GPR91 is present in MD cells and regulates renin release. Using immunohistochemistry, we identified GPR91 in the apical plasma membrane of MD cells. Treatment of MD cells with succinate activated mitogen-activated protein kinases (MAPKs; p38 and extracellular signal-regulated kinases 1/2) and cyclooxygenase 2 (COX-2) and induced the synthesis and release of prostaglandin E(2), a potent vasodilator and classic paracrine mediator of renin release. Using microperfused JGA and real-time confocal fluorescence imaging of quinacrine-labeled renin granules, we detected significant renin release in response to tubular succinate (EC(50) 350 microM). Genetic deletion of GPR91 (GPR91(-/-) mice) or pharmacologic inhibition of MAPK or COX-2 blocked succinate-induced renin release. Streptozotocin-induced diabetes caused GPR91-dependent upregulation of renal cortical phospho-p38, extracellular signal-regulated kinases 1/2, COX-2, and renin content. Salt depletion for 1 wk increased plasma renin activity seven-fold in wild-type mice but only 3.4-fold in GPR91(-/-) mice. In summary, MD cells can sense alterations in local tissue metabolism via accumulation of tubular succinate and GPR91 signaling, which involves the activation of MAPKs, COX-2, and the release of prostaglandin E(2). This mechanism may be integral in the regulation of renin release and activation of the renin-angiotensin system in health and disease.

  10. Comparing pyridoxine and doxylamine succinate-pyridoxine HCl for nausea and vomiting of pregnancy: A matched, controlled cohort study.

    Science.gov (United States)

    Pope, Eliza; Maltepe, Caroline; Koren, Gideon

    2015-07-01

    Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine (P doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores.

  11. Effects of eliminating pyruvate node pathways and of coexpression of heterogeneous carboxylation enzymes on succinate production by Enterobacter aerogenes.

    Science.gov (United States)

    Tajima, Yoshinori; Yamamoto, Yoko; Fukui, Keita; Nishio, Yousuke; Hashiguchi, Kenichi; Usuda, Yoshihiro; Sode, Koji

    2015-02-01

    Lowering the pH in bacterium-based succinate fermentation is considered a feasible approach to reduce total production costs. Newly isolated Enterobacter aerogenes strain AJ110637, a rapid carbon source assimilator under weakly acidic (pH 5.0) conditions, was selected as a platform for succinate production. Our previous work showed that the ΔadhE/PCK strain, developed from AJ110637 with inactivated ethanol dehydrogenase and introduced Actinobacillus succinogenes phosphoenolpyruvate carboxykinase (PCK), generated succinate as a major product of anaerobic mixed-acid fermentation from glucose under weakly acidic conditions (pH <6.2). To further improve the production of succinate by the ΔadhE/PCK strain, metabolically engineered strains were designed based on the elimination of pathways that produced undesirable products and the introduction of two carboxylation pathways from phosphoenolpyruvate and pyruvate to oxaloacetate. The highest production of succinate was observed with strain ES04/PCK+PYC, which had inactivated ethanol, lactate, acetate, and 2,3-butanediol pathways and coexpressed PCK and Corynebacterium glutamicum pyruvate carboxylase (PYC). This strain produced succinate from glucose with over 70% yield (gram per gram) without any measurable formation of ethanol, lactate, or 2,3-butanediol under weakly acidic conditions. The impact of lowering the pH from 7.0 to 5.5 on succinate production in this strain was evaluated under pH-controlled batch culture conditions and showed that the lower pH decreased the succinate titer but increased its yield. These findings can be applied to identify additional engineering targets to increase succinate production.

  12. Combinatorial optimization of CO2 transport and fixation to improve succinate production by promoter engineering.

    Science.gov (United States)

    Yu, Jun-Han; Zhu, Li-Wen; Xia, Shi-Tao; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

    2016-07-01

    To balance the flux of an engineered metabolic pathway to achieve high yield of target product is a major challenge in metabolic engineering. In previous work, the collaborative regulation of CO2 transport and fixation was investigated with co-overexpressing exogenous genes regulating both CO2 transport (sbtA and bicA) and PEP carboxylation (phosphoenolpyruvate (PEP) carboxylase (ppc) and carboxykinase (pck)) under trc promoter in Escherichia coli for succinate biosynthesis. For balancing metabolic flux to maximize succinate titer, a combinatorial optimization strategy to fine-tuning CO2 transport and fixation process was implemented by promoter engineering in this study. Firstly, based on the energy matrix a synthetic promoter library containing 20 rationally designed promoters with strengths ranging from 0.8% to 100% compared with the widely used trc promoter was generated. Evaluations of rfp and cat reporter genes provided evidence that the synthetic promoters were stably and had certain applicability. Secondly, four designed promoters with different strengths were used for combinatorial assembly of single CO2 transport gene (sbtA or bicA) and single CO2 fixation gene (ppc or pck) expression. Three combinations, such as Tang1519 (P4 -bicA + pP19 -pck), Tang1522 (P4 -sbtA + P4 -ppc), Tang1523 (P4 -sbtA + P17 -ppc) with a more than 10% increase in succinate production were screened in bioreactor. Finally, based on the above results, co-expression of the four transport and fixation genes were further investigated. Co-expression of sbtA, bicA, and ppc with weak promoter P4 and pck with strong promoter P19 (AFP111/pT-P4 -bicA-P4 -sbtA + pACYC-P19 -pck-P4 -ppc) provided the best succinate production among all the combinations. The highest succinate production of 89.4 g/L was 37.5% higher than that obtained with empty vector control. This work significantly enhanced succinate production through combinatorial optimization of CO2 transport and fixation

  13. [Breeding of Actinobacillus succiniogenes mutants with improved succinate production based on metabolic flux analysis].

    Science.gov (United States)

    Pan, Lijun; Li, Xingjiang; Jiang, Shaotong; Wei, Zhaojun; Chen, Xiaohui; Cai, Licheng; Wang, Hefeng; Jiang, Jijun

    2008-09-01

    It is very important to obtain high yield mutant strains on the base of metabolic flux analysis of Actinobacillus succinogenes S.JST for the industrial bioconversion of succinic acid. The metabolic pathway was analized at first and the flux of the metabolic networks was calculated by matrix. In order to decrease acetic acid flux, the strains mutated by soft X-ray of synchronous radiation were screened on the plates with high concentration of fluoroacetic acid. For decreasing the metabolic flux of ethanol the site-directed mutagenesis was carried out for the reduction of alcohol dehydrogenase(Adh) specific activity. Then the enzyme activity determination and the gene sequence analysis of the mutant strain was compared with those of the parent strain. Metabolic flux analysis of the parent strain indicated that the flux of succinic acid was 1.78(mmol/g/h) and that the flux of acetic acid and ethanol were 0.60 (mmol/g/h) and 1.04( mmol/g/h), respectively. Meanwhile the metabolic pathway analysis showed that the ethanol metabolism enhanced the lacking of H electron donor during the synthesis of succinic acid and that the succinic acid flux was weakened by the metabolism of byproducts ethanol and acetic acid. Compared with the parent strain, the acetic acid flux of anti-fluoroacetic mutant strain S.JST1 was 0.024 (mmol/g/h), decreasing by 96%. Then the enzyme determination showed that the specific activity unit of phosphotransacetylase(Pta) decreased from 602 to 74 and a mutated site was founded in the pta gene of the mutant strain S.JST1. Compared with that of the parent strain S.JST1 the ethanol flux of adh-site-directed mutant strain S.JST2 was 0.020 (mmol/g/h), decreasing by 98%. Then the enzyme determination showed that the specific activity unit of Adh decreased from 585 to 62 and the yield of end product succinic acid was 65.7 (g/L). The interdiction of Adh and Pta decreased the metabolism of byproducts and the H electron donor was well balanced, thus the succinic

  14. Effect of agitation speed on the morphology of Aspergillus niger HFD5A-1 hyphae and its pectinase production in submerged fermentation

    Institute of Scientific and Technical Information of China (English)

    Darah; Ibrahim; Haritharan; Weloosamy; Sheh-Hong; Lim

    2015-01-01

    AIM: To investigate the impact of agitation speed on pectinase production and morphological changing of Aspergillus niger(A. niger) HFD5A-1 in submerged fermentation. METHODS: A. niger HFM5A-1 was isolated from a rotted pomelo. The inoculum preparation was performed by adding 5.0 m L of sterile distilled water containing 0.1% Tween 80 to a sporulated culture. Cultivation was carried out with inoculated 1 × 107 spores/m L suspension and incubated at 30 ℃ with different agitation speed for 6 d. The samples were withdrawn after 6 d cultivation time and were assayed for pectinase activity and fungal growth determination. The culture broth was filtered through filter paper(Whatman No. 1, London) to separate the fungal mycelium. The cell-free culture filtrate containing the crude enzyme was then assayed for pectinase activity. The biomass was dried at 80 ℃ until constant weight. The fungal cell dry weight was then expressed as g/L. The 6 d old fungal mycelia were harvested from various agitation speed, 0, 50, 100, 150, 200 and 250 rpm. The morphological changing of samples was then viewed under the light microscope and scanning electron microscope.RESULTS: In the present study, agitation speed was found to influence pectinase production in a batch cultivation system. However, higher agitation speeds than the optimal speed(150 rpm) reduced pectinase production which due to shear forces and also collision among the suspended fungal cells in the cultivation medium. Enzyme activity increased with the increasing of agitation speed up to 150 rpm, where it achieved its maximal pectinase activity of 1.559 U/m L. There were significant different(Duncan, P < 0.05) of the pectinase production with the agitation speed at static, 50, 100, 200 and 250 rpm. At the static condition, a well growth mycelial mat was observed on the surface of the cultivation medium and sporulation occurred all over the fungal mycelial mat. However with the increased in agitation speed, the mycelial

  15. FORMULATION AND EVALUATION OF METOPROLOL SUCCINATE CONTROLLED RELEASE TABLETS USING NATURAL AND SYNTHETIC POLYMER

    Directory of Open Access Journals (Sweden)

    A. Sathyaraj

    2012-01-01

    Full Text Available The objective of the present study to develop controlled release tablets of Metoprolol succinate using Natural polymer, guar gum and synthetic polymer, carbopol as a rate controlling polymers.. It was also desired to study the effect of polymer concentration. Metoprolol succinate, β1- selective adrenergic receptor- blocking agent used in the management of hypertension, angina pectoris, cardiac arrthymias, myocardial infarction, heart failure, hyperthyroidism and in the prophylactic treatment of migraine. The half-life of drug is relatively short approximately 4-6 hrs and in normal course of therapy drug administration is required every 4-6 hrs, thus warrants the use of controlled release formulation for prolong action and to improve patient compliance. In the present investigation Natural polymer, guar gum and synthetic polymer, carbopol have been selected as matrix forming materials for the drug. The formulations are made by employing the conventional wet granulation method, to achieve prolonged release of medicaments.

  16. A case-based evaluation of SRD5A1, SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH.

    Science.gov (United States)

    Klotsman, M; Weinberg, C R; Davis, K; Binnie, C G; Hartmann, K E

    2004-01-01

    In men with a clinical diagnosis of benign prostatic hyperplasia (BPH), polytomous logistic regression analysis was conducted to evaluate associations between two silent polymorphisms in SRD5A1 (codon positions 30 and 116), two polymorphisms in SRD5A2 (Val89Leu substitution and C to T transition in intron 1), a trinucleotide (CAG)n repeat in androgen receptor (AR), and an Arg492Cys substitution in ADRA1A and clinical parameters that characterize severity of BPH. Candidate gene selection was based on two mechanistic pathways targeted by pharmacotherapy for BPH: (1) androgen metabolic loci contributing to prostate growth (static obstruction); and (2) factors affecting smooth muscle tone (dynamic obstruction). Polymorphisms in SRD5A2 were not associated with severity of BPH; however, SRD5A1 polymorphisms were associated with severity of BPH. The process(es) in which these silent single-nucleotide polymorphisms (SNPs) influence BPH phenotypes is unknown and additional studies will be needed to assess whether these SNPs have direct functional consequences. The characterization of additional molecular factors that contribute to static and dynamic obstruction may help predict response to pharmacotherapy and serve to identify novel drug targets for the clinical management of BPH.

  17. Structure-barrier property relationship of biodegradable poly(butylene succinate) and poly[(butylene succinate)-co-(butylene adipate)] nanocomposites: influence of the rigid amorphous fraction.

    Science.gov (United States)

    Charlon, S; Marais, S; Dargent, E; Soulestin, J; Sclavons, M; Follain, N

    2015-11-28

    Composites composed of polyesters, poly(butylene succinate) (PBS) or poly[(butylene succinate)-co-(butylene adipate)] (PBSA), and 5 wt% of montmorillonite (CNa) or organo-modified montmorillonite (C30B) were melt-processed and transformed into films by either compression-molding or extrusion-calendering. XRD, rheological measurements and TEM images clearly indicated that films containing CNa are microcomposites, while nanocomposites were observed for those containing C30B. Using Flash DSC, it was possible, for the first time, not only to measure the heat capacity step at the glass transition of these two materials in their amorphous state, but also to investigate whether the preparation technique influenced the Rigid Amorphous Fraction (RAF) in our PBS- and PBSA-based nanocomposites. In this work, we have successfully shown the correlation between the microstructure of the films and their barrier properties, and especially the role played by the RAF. Indeed, the lowest permeabilities to gases and to water were determined in the films containing the highest RAF in both PBS- and PBSA-based materials.

  18. Marked and variable inhibition by chemical fixation of cytochrome oxidase and succinate dehydrogenase in single motoneurons

    Science.gov (United States)

    Chalmers, G. R.; Edgerton, V. R.

    1989-01-01

    The effect of tissue fixation on succinate dehydrogenase and cytochrome oxidase activity in single motoneurons of the rat was demonstrated using a computer image processing system. Inhibition of enzyme activity by chemical fixation was variable, with some motoneurons being affected more than others. It was concluded that quantification of enzymatic activity in chemically fixed tissue provides an imprecise estimate of enzyme activities found in fresh-frozen tissues.

  19. FORMULATION AND EVALUATION OF SUSTAINED RELEASE LIQUISOLID TABLETS OF METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    Jarag Ravindra Jagannath

    2013-03-01

    Full Text Available Liquisolid technique is the novel concept of drug delivery via the oral route. This technique is applied to poorly water soluble, water insoluble or liphophilic drugs. According to the new formulation method of liquisolid compacts, liquid medications such as solutions or suspensions of water insoluble drugs in suitable non-volatile vehicles can be converted into acceptably flowing and compressible powders by blending with selected powder excipients. The present research endeavor is directed towards the development of liquisolid compact for the production of sustained release tablet of water-soluble Metoprolol succinate. Liquisolid compacts were prepared by using Tween 80 as the liquid vehicle or non-volatile solvent, Avicel PH 102 as absorbing carrier and Aerosil 200 as adsorbing coating material. The prepare dliquisolid systems were evaluated for their micromeretic properties and possible drug-excipients interactions. P-XRD analysis confirmed that no change in crystallinity of Metoprolol succinate Liquisolid compacts. The DSC and IR spectra analysis study ruled out no any significant interaction between the drug and excipients used in preparation of Metoprolol succinate Liquisolid compacts. The tableting properties were falling within acceptable limits. The in vitro dissolution study confirmed reduction in drug release from Liquisolid compacts compared to conventional matrix tablet, in-vivo study was carried out to check the plasma drug concentration. Tween 80 has plasticizer effect by which it can reduce the glass transition temperature of polymer and impart flexibility in sustaining the release of drug from liquisolid matrices. The results showed that wet granulation had a remarkable impact on the release rate of Metoprolol succinate from liquisolid compacts, reducing the release rate of drug from liquisolid compacts.

  20. DEVELOPMENT AND IN-VITRO EVALUATION OF METOPROLOL SUCCINATE CONTROLLED POROSITY OSMOTIC PUMP TABLETS

    OpenAIRE

    Veeramalla Anil Kumar; Madishetty Vamshikrishna; Indarapu Rajendra Prasad; Gudikandula Raj Kumar; Kadari Srinivas

    2013-01-01

    In the present research work, attempts were made to develop and evaluate Sustained release formulation of Metoprolol succinate based on osmotic technology.As Metoprolol is a short acting drug, developed formulation provides the advantages of controlled release formulations. The developed formulation provides advantages of less steps of manufacturing procedure, no need of laser drilling, and economical. All of these made the procedure easily amenable to mass production using conventional table...

  1. Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory

    DEFF Research Database (Denmark)

    Otero, José Manuel; Cimini, Donatella; Patil, Kiran Raosaheb

    2013-01-01

    Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought......-direction of carbon fluxes in S. cerevisiae, and hence show proof of concept that this is a potentially attractive cell factory for over-producing different platform chemicals....

  2. Food Effects on the Pharmacokinetics of Doxylamine Hydrogen Succinate 25 mg Film-Coated Tablets

    OpenAIRE

    Videla, Sebastián; Lahjou, Mounia; Guibord, Pascal; Xu, Zhengguo; Tolrà, Carles; Encina, Gregorio; Sicard, Eric; Sans, Artur

    2012-01-01

    Background Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. The data available on the pharmacokinetic profile of doxylamine in humans are limited, notwithstanding that this drug has been marketed in European countries for more than 50 years. In fact, no data on the effect of food on the pharmacokinetic parameters of doxylamine are available. Objective The objective of this study was to evaluate the pha...

  3. Volatility of NH3 from internally mixed sodium succinate-NH4SO4 particles

    Science.gov (United States)

    Wang, Na; Zhang, Yunhong

    2016-04-01

    Contributing the complicacy of atmospheric constituents, aerosol particles may undergo complicated heterogeneous reactions that have profound consequences on their hygroscopic properties and volatility. Ammonia (NH3) is a ubiquitous trace atmospheric gas in the troposphere and has negative effects on human health and climate forcing of ambient aerosols. In addition, atmospheric cycle of NH3 is complex in atmosphere, therefore it necessary to get insights to the complexity of gas-to-aerosol NH3 partitioning, which results in large uncertainties in the sources and distributions of NH3. By using in-situ Fourier transform infrared spectroscopy and attenuated total reflection (FTIR-ATR), we report here the volatility of NH3 from the laboratory generated sodium succinate with ammonium sulfate ((NH4)2SO4) at a 1:1 molar ratio as well as its effect on the hygroscopicity of the mixtures. The loss of the NH4+ peak at 1451cm-1 and the formation of peaks at 1718 and 1134 cm-1 due to C = O stretching asymmetric vibration of -COOH and ν3 (SO42-) stretching of sodium sulfate indicate that sodium succinate reacts with (NH4)2SO4, releasing NH3 and forming succinic acid and sodium sulfate on dehydration process. The formation of less hygroscopic succinic acid and volatility of NH3 in mixtures leads to a significant decrease in the total water content. To the best of our knowledge, this is the first report of the reaction between (NH4)2SO4 and dicarboxylate salts, which may represent an important particle-gas partitioning for ammonia and thus elucidate another underlying ammonia cycle in atmosphere. These results could be helpful to understand the mutual transformation process of dicarboxylic acids and dicarboxylate salts.

  4. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training

    Directory of Open Access Journals (Sweden)

    Hadi Sarir

    2015-01-01

    Full Text Available Aim and Scope: The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-a and interleukin-6 (IL-6 production induced by high-intensity interval training (HIIT. Materials and Methods: In the present study, 24 rats were randomly divided into control (C, supplementation (S, HIIT, and HIIT + supplementation (HIIT+S groups. HIIT training protocol on a treadmill (at a speed of 40-54 m/min and vitamin E succinate supplementation (60 mg/kg/day was conducted for 6 weeks. Results: Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002. Also, serum TNF-a concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001 in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-a when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05. However, no significant changes were observed in serum TNF-a (P = 0.31 and IL-6 (P = 0.52 concentrations in the HIIT + S group compared with the C group. Conclusion: HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate.

  5. Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior

    Science.gov (United States)

    Ishihara, A.; Roy, R. R.; Edgerton, V. R.

    1995-01-01

    The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data

  6. Development and Validation of First Order Derivative Spectrophotometric method for simultaneous estimation of Nifedipine and Metoprolol Succinate in Synthetic Mixture

    Directory of Open Access Journals (Sweden)

    Sojitra Rajanit

    2015-02-01

    Full Text Available The present manuscript describe simple, sensitive, rapid, accurate, precise and economical first derivative spectrophotometric method for the simultaneous determination of Nifedipine (NIFand Metoprolol Succinate (METin synthetic mixture. The derivative spectrophotometric method was based on the determination of both the drugs at their respective zero crossing point (ZCP. The first order derivative spectra was obtained in methanol and the determinations were made at 283.80 nm (ZCP of nifedipine for metoprolol succinate and 242.60 nm (ZCP of metoprolol succinate for nifedipine. The linearity was obtained in the concentration range of succinate 5-25 μg/ml for nifedipine and 25-125μg/ml for metoprolol. The mean recovery was 99.64 and 99.41 for Nifedipine and Metoprolol succinate, respectively. The method was found to be simple, sensitive, accurate and precise and was applicable for the simultaneous determination of Nifedipine and Metoprolol succinate in synthetic mixture. The results of analysis have been validated statistically and by recovery studies.

  7. Comparsion of the Effects of Succinate and NADH on Postmortem Metmyoglobin Redcutase Activity and Beef Colour Stability

    Institute of Scientific and Technical Information of China (English)

    GAO Xiao-guang; WANG Zhen-yu; TANG Meng-tian; MA Chang-wei; DAI Rui-tong

    2014-01-01

    In two experiments, the effects of succinate and NADH (reduced nicotinamide adenine dinucleotide) on metmyoglobin reductase activity and electron transport chain-linked metmyoglobin reduction were investigated and compared. In experiment 1, metmyoglobin (MetMb), substrate and inhibitors were incubated with mitochondria. Comparsion of the effects of succinate and NADH on MetMb reduction was investigated. The MetMb percentage in sample treated with 8 mol L-1 succinate decreased by about 69%after 3 h incubation, and the effect was inhibited by the addition of 10 mol L-1 electron transfer chain complex II inhibitor malonic acid;the MetMb percentage in samples treated with 2 mol L-1 NADH decreased by 56%and the effect was inhibited by the addition of 0.02 mol L-1 electron transport chain complex I inhibitor rotenone. These results indicated that electron transport chain played an important role in MetMb reduction. Both complex II and complex I take part in the MetMb reduction in mitochondria through different pathways. NADH-MetMb reduction system was less stable than succinate-MetMb system. In experiment 2, the beef longissimus dorsi muscle was blended with different concentrations of succinate or NADH. Enhancing patties with higher concentration of succinate or NADH improved colour stability in vacuum packaged samples (P<0.05). These results veriifed that mitochondria electron transport chain is related to the MetMb reduction in meat system.

  8. Mitochondrial lipid peroxidation by cumene hydroperoxide and its prevention by succinate.

    Science.gov (United States)

    Bindoli, A; Cavallini, L; Jocelyn, P

    1982-09-15

    Rat liver mitochondria form lipid hydroperoxides when they are incubated aerobically with cumene hydroperoxide. The rate of reaction is dependent on the initial concentration of the latter and involves the consumption of oxygen. Gradient-separated and cytochrome c-depleted mitochondria, mitoplasts and submitochondrial fractions also undergo this peroxidation. Mitochondrial lipid peroxidation by cumene hydroperoxide is strongly inhibited by SKF52A (an inhibitor of cytochrome P-450), by antioxidants and to a lesser extent by the enzymes superoxide dismutase and catalase. Conversely, rotenone and N-ethylmaleimide stimulate the reaction. Succinate protects against the lipid peroxidation and in some mitochondrial fractions the associated oxygen uptake is also inhibited. This protection by succinate is prevented by malonate but not by N-ethylmaleimide or antimycin. Lipid hydroperoxides present in previously peroxidised mitochondria are partly lost on reincubation with succinate and this reaction is also unaffected by N-ethylmaleimide but inhibited by both malonate and antimycin. The results suggest that reduction of mitochondrial ubiquinone may prevent the generation of lipid hydroperoxides but that their subsequent removal may require reduction at or beyond cytochrome b.

  9. Microbial production of Propionic and Succinic acid from Sorbitol using Propionibacterium acidipropionici.

    Science.gov (United States)

    Duarte, Juliana C; Valença, Gustavo P; Moran, Paulo J S; Rodrigues, J Augusto R

    2015-01-01

    Three sequential fermentative batches were carried out with cell recycle in four simultaneously operating bioreactors maintained at pH 6.5, 30°C, and 100 rpm. P. acidipropionici ATCC 4875 was able to produce propionic and succinic acid from sorbitol. The concentration of propionic acid decreased slightly from 39.5 ± 5.2 g L(-1) to 34.4 ± 1.9 g L(-1), and that of succinic acid increased significantly from 6.1 ± 2.1 g L(-1) to 14.8 ± 0.9 g L(-1) through the sequential batches. In addition, a small amount of acetic acid was produced that decreased from 3.3 ± 0.4 g L(-1) to 2.0 ± 0.3 g L(-1) through the batches. The major yield for propionic acid was 0.613 g g(-1) in the first batch and succinic acid it was 0.212 g g(-1) in the third batch. The minor yield of acetic acid was 0.029 g g(-1), in the second and third batches.

  10. Solid-Liquid Equilibria of Succinic Acid in Cyclohexanone, Cyclohexanol and Their Mixed Solvents

    Institute of Scientific and Technical Information of China (English)

    FAN Lihua; MA Peisheng; SONG Weiwei

    2007-01-01

    Solubilities were measured for succinic acid dissolved in cyclohexanone, cyclohexanol and 5 of their mixed solvents at the temperature range from 291.85 K to 358.37 K using a dynamic method. The solubility data were regressed by λh equation, withthe average absolute relative deviation 3.47%. The binary interaction parameter is 0.306 7 for the mixed solvent of cyclohexanone and cyclohexanol was determined by correlating the experimental solubilities with the modified λh equation. When the binary interaction parameter was determined, it can be used to extrapolate the solubilities of succinic acid in mixed solvents of cyclohexanone and cyclohexanol at any proportion. The average absolute relative deviation was 7.69% by using the modified λh equation to correlate the solubility data, however, the average absolute relative deviation was 8.89% by using NRTL equation to correlate the solubility data. The results show that the accuracy of the modified λh equation is better than that of the NRTL equation for the solubility of succinic acid in the 5 mixed solvents of cyclohexanone and cyclohexanol.

  11. Study on oil absorbency of succinic anhydride modified banana cellulose in ionic liquid.

    Science.gov (United States)

    Shang, Wenting; Sheng, Zhanwu; Shen, Yixiao; Ai, Binling; Zheng, Lili; Yang, Jingsong; Xu, Zhimin

    2016-05-05

    Banana cellulose contained number of hydrophilic hydroxyl groups which were succinylated to be hydrophobic groups with high oil affinity. Succinic anhydride was used to modify banana cellulose in 1-allyl-3-methylimidazolium chloride ionic liquid in this study. The modified banana cellulose had a high oil absorption capacity. The effects of reaction time, temperature, and molar ratio of succinic anhydride to anhydroglucose on the degree of substitution of modified banana cellulose were evaluated. The optimal reaction condition was at a ratio of succinic anhydride and anhydroglucose 6:1 (m:m), reaction time 60min and temperature 90°C. The maximum degree of acylation reaction reached to 0.37. The characterization analysis of the modified banana cellulose was performed using X-ray diffractometer, Fourier transform infrared spectrometer, scanning electron microscopy and thermogravimetry. The oil absorption capacity and kinetics of the modified banana cellulose were evaluated at the modified cellulose dose (0.025-0.3g), initial oil amount (5-30g), and temperature (15-35°C) conditions. The maximum oil absorption capacity was 32.12g/g at the condition of the cellulose dose (0.05g), initial oil amount (25g) and temperature (15°C). The kinetics of oil absorption of the cellulose followed a pseudo-second-order model. The results of this study demonstrated that the modified banana cellulose could be used as an efficient bio-sorbent for oil adsorption.

  12. [Absorption of Uranium with Tea Oil Tree Sawdust Modified by Succinic Acid].

    Science.gov (United States)

    Zhang, Xiao-feng; Chen, Di-yun; Peng, Yan; Liu, Yong-sheng; Xiong, Xue-ying

    2015-05-01

    In order to explore how the modification of succinic acid improves the adsorption of tea oil tree sawdust for uranium, the tea oil tree sawdust was modified by succinic acid, after the pretreatments of crushing, screening, alkalization and acidification. Infrared analysis indicated carboxylic acid groups and ester groups were added to the sawdust after modification, and scanning electron microscope demonstrated after modification the appearance of tea oil tree sawdust was transferred from the structure like compact and straight stripped into the structure like loose and wrinkled leaves, which meant modification increased its inner pores. By the static experiments, effects of reaction time between adsorbent and solvent, dosage of adsorbent, temperature, pH value and initial concentration of uranium were investigated. The results showed that after the modification by succinic acid, the absorption rate of tea oil tree sawdust for uranium increased significantly by about 20% in 12.5 mg · L(-1) initial concentration uranium solution. Adsorption equilibrium was achieved within 180 min, and the kinetic data can be well described by the pseudo-second-order kinetic model. The experimental adsorption isotherm followed the Langmuir and Freundlich models. In addition, the maximum adsorption amounts of tea oil tree sawdust after modification calculated from Langmuir equation raised from 21.413 3 to 31.545 7 mg · g(-1) at 35°C and pH 4.0.

  13. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept.

    Science.gov (United States)

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar; Angelidaki, Irini

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery (>95%) as well as significant hemicelluloses solubilization (49-59%) after acid-based method and lignin solubilization (35-41%) after alkaline H2O2 method were registered. Alkaline pretreatment showed to be superior over the acid-based method with respect to the rate of enzymatic hydrolysis and ethanol productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149kg of EtOH and 115kg of succinic acid can be obtained per 1ton of dry hemp. Results obtained in this study clearly document the potential of industrial hemp for a biorefinery.

  14. Synthesis of Vitamin E Succinate from Candida rugosa Lipase in Organic Medium

    Institute of Scientific and Technical Information of China (English)

    JIANG Xiang-jun; HU Yi; JIANG Ling; GONG Ji-hong; HUANG He

    2013-01-01

    A screening of commercially available lipases for the synthesis of vitamin E succinate showed that lipase from Candida rugosa presented the highest yield.The synthesis of vitamin E succinate in organic solvents with different lgP values ranging from-1.3 to 3.5 was investigated.Of particular interest was that dimethyl sulfoxide (DMSO) with the lowest lgP exhibited the highest yield among all the organic solvents used.It suggests that lgP is incapable of satisfactorily predicting the biocompatibility of organic solvents due to the complexity of enzymatic reaction with hydrophilic and hydrophobic substrates in organic solvent.Effects of different operating conditions,such as molar ratio of substrate,enzyme concentration,reaction temperature,mass transfer,and reaction time were also studied.Under the optimum conditions of 10 g/L enzyme,a stirring rate of 100 r/min,a substrate molar ratio of 5:1 at 55 C for 18 h,a satisfactory yield(46.95%) was obtained.The developed method has a potential to be used for efficient enzymatic production of vitamin E succinate.

  15. Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).

    Science.gov (United States)

    Loughlin, J; Irven, C; Hardwick, L J; Butcher, S; Walsh, S; Wordsworth, P; Sykes, B

    1995-09-01

    Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome. However, several candidate genes encoding proteins of the extracellular matrix have been excluded. Using an intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single large pedigree.

  16. Synthesis, Spectroscopic Properties and DFT Calculation of Novel Pyrrolo[1',5'-a]-1,8-naphthyridine Derivatives through a Facile One-pot Process

    Indian Academy of Sciences (India)

    GAO-ZHANG GOU; BO ZHOU; HE-PING YAN; YONG HONG; WEI LIU; SHAO-MING CHI; CHAO-YONG MANG

    2016-11-01

    Novel pyrrolo[1',5'-a]-1,8-naphthyridine compounds (L1-L4) have been synthesized through a facile one-pot process by the reaction of the corresponding 1,8-naphthyridines with aliphatic anhydride. The structures were established by spectroscopic data. Further, X-ray crystal analysis of 7-diacetamino-2,4-dimethy-1,8-naphthyridine (L1) identifies its molecular structure and reveals π-π stacking. The synthetic mechanisms for L2, L3 were studied by density functional theory calculations. And a comprehensive study of spectroscopic properties involving experimental data and theoretical studies is presented. L1 exhibited electronic absorption spectrum with λmax at ∼320 nm. L2-L4 exhibited similar electronic absorption spectra with λmax at ∼390 nm that is tentatively assigned to π→π* transition. The assignment was further supported by density functional theory (DFT) calculations.

  17. Toward homosuccinate fermentation: metabolic engineering of Corynebacterium glutamicum for anaerobic production of succinate from glucose and formate.

    Science.gov (United States)

    Litsanov, Boris; Brocker, Melanie; Bott, Michael

    2012-05-01

    Previous studies have demonstrated the capability of Corynebacterium glutamicum for anaerobic succinate production from glucose under nongrowing conditions. In this work, we have addressed two shortfalls of this process, the formation of significant amounts of by-products and the limitation of the yield by the redox balance. To eliminate acetate formation, a derivative of the type strain ATCC 13032 (strain BOL-1), which lacked all known pathways for acetate and lactate synthesis (Δcat Δpqo Δpta-ackA ΔldhA), was constructed. Chromosomal integration of the pyruvate carboxylase gene pyc(P458S) into BOL-1 resulted in strain BOL-2, which catalyzed fast succinate production from glucose with a yield of 1 mol/mol and showed only little acetate formation. In order to provide additional reducing equivalents derived from the cosubstrate formate, the fdh gene from Mycobacterium vaccae, coding for an NAD(+)-coupled formate dehydrogenase (FDH), was chromosomally integrated into BOL-2, leading to strain BOL-3. In an anaerobic batch process with strain BOL-3, a 20% higher succinate yield from glucose was obtained in the presence of formate. A temporary metabolic blockage of strain BOL-3 was prevented by plasmid-borne overexpression of the glyceraldehyde 3-phosphate dehydrogenase gene gapA. In an anaerobic fed-batch process with glucose and formate, strain BOL-3/pAN6-gap accumulated 1,134 mM succinate in 53 h with an average succinate production rate of 1.59 mmol per g cells (dry weight) (cdw) per h. The succinate yield of 1.67 mol/mol glucose is one of the highest currently described for anaerobic succinate producers and was accompanied by a very low level of by-products (0.10 mol/mol glucose).

  18. Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk.

    Science.gov (United States)

    Gohel, M C; Amin, A F; Chhabaria, M T; Panchal, M K; Lalwani, A N

    2000-01-01

    The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3(2) factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent.

  19. DEVELOPMENT AND VALIDATION OF HPTLC METHOD FOR SIMULTANEOUS DETERMINATION OF METOPROLOL SUCCINATE AND ATORVASTATIN CALCIUM IN A PHARMACEUTICAL DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Ginoya Charmi G.

    2013-02-01

    Full Text Available A new, simple, precise, accurate and selective high performance thin-layer chromatographic (HPTLC method has been developed and validated for the simultaneous determination of Metoprolol succinate and Atorvastatin calcium in a marketed formulation. Chromatographic separation was carried out on Merck TLC aluminium sheets of silica gel 60F254 using Acetonitrile: Methanol: Ethyl acetate: Glacial acetic acid (2: 4: 4: 0.06 % v/v/v/v as mobile phase followed by densitometric analysis at 223 nm. This system was found to give compact spots for Metoprolol succinate (Rf value of 0.32 ± 0.005 and Atorvastatin calcium (Rf value of 0.77 ± 0.004. The method was validated in terms of linearity, accuracy, precision, limit of detection, limit of quantification and specificity in accordance with International Conference on Harmonization (ICH guidelines. The calibration curve was found to be linear between 500 to 3000 and 200 to 1200 ng/spot for Metoprolol succinate and Atorvastatin calcium, respectively with significantly high value of correlation coefficient (r2 > 0.99. The limits of detection and quantitation were found to be 0.8432 and 2.5553 ng/spot, respectively for Metoprolol succinate and 27.8428 and 84.3662 ng/spot, respectively for Atorvastatin calcium. The proposed method was found to be accurate, precise, reproducible, specific and sensitive and can be applicable for the simultaneous determination of Metoprolol succinate and Atorvastatin calcium in marketed formulation.

  20. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei.

    Science.gov (United States)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K; Lübeck, Peter S

    2016-02-01

    Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact on the pattern and the amount of organic acids produced by A. saccharolyticus. The wild-type strain produced higher amount of malic acid and succinic acid in the pH buffered condition (pH 6.5) compared with the pH non-buffered condition. The enzyme assays showed that the rTCA branch was active in the acid production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led to an enhanced production of succinic acid in frd transformants compared with the wild-type in both pH buffered and pH non-buffered conditions with highest amount produced in the pH buffered condition (16.2 ± 0.5 g/L). This study demonstrates the feasibility of increasing succinic acid production through the cytosolic reductive pathway by genetic engineering in A. saccharolyticus.

  1. Stability-indicating micellar electrokinetic chromatography method for the analysis of sumatriptan succinate in pharmaceutical formulations.

    Science.gov (United States)

    Al Azzam, Khaldun M; Saad, Bahruddin; Tat, Chai Yuan; Mat, Ishak; Aboul-Enein, Hassan Y

    2011-12-15

    A micellar electrokinetic chromatography method for the determination of sumatriptan succinate in pharmaceutical formulations was developed. The effects of several factors such as pH, surfactant and buffer concentration, applied voltage, capillary temperature, and injection time were investigated. Separation took about 5 min using phenobarbital as internal standard. The separation was carried out in reversed polarity mode at 20 °C, 26 kV and using hydrodynamic injection for 10s. Separation was achieved using a bare fused-silica capillary 50 μm×40 cm and background electrolyte of 25 mM sodium dihydrogen phosphate-adjusted with concentrated phosphoric acid to pH 2.2, containing 125 mM sodium dodecyl sulfate and detection was at 226 nm. The method was validated with respect to linearity, limits of detection and quantification, accuracy, precision and selectivity. The calibration curve was linear over the range of 100-2000 μg mL(-1). The relative standard deviations of intra-day and inter-day precision for migration time, peak area, corrected peak area, ratio of corrected peak area and ratio of peak area were less than 0.68, 3.48, 3.28, 2.97 and 2.83% and 2.01, 5.50, 4.46, 4.92 and 4.07%, respectively. The proposed method was successfully applied to the determinations of the analyte in tablet. Forced degradation studies were conducted by introducing a sample of sumatriptan succinate standard solution to different forced degradation conditions using neutral (water), basic (0.1 M NaOH), acidic (0.1 M HCl), oxidative (10% H(2)O(2)) and photolytic (exposure to UV light at 254 nm for 2 h). It is concluded that the stability-indicating method for sumatriptan succinate can be used for the analysis of the drug in various samples.

  2. Equilibrium of Extraction of Succinic,Malic,Maleic and Fumaric Acids with Trioctylamine

    Institute of Scientific and Technical Information of China (English)

    LIZhenyu; QINWei; 等

    2002-01-01

    Extraction equilibrium features of succinic acid,malic acid,maleic acid and fumaric acid were investigated systematically with trioctylamine (TOA) in chloroform,4-methyl-2-pentanone (MIBK) and 1-octanol.Fourier transform-infrared(FTIR) spectroscopic analysis of organic samples loaded with the acid show that amine forms 1:1 complex of ion-pair association with succinic acid,malic acid and maleic acid,and 1:1,2:1 complex of ion-pair association with fumaric acid.It is proposed that the complex forms depend on the second dissociation constant of the dibasic acid,pKa2.Results of equilibrium experiments show that diluents affects extraction behavior,and depend on the solute concentration.Protic diluents,chloroform and 1-octanol,are more effective than the others when the equilibrium solute concentration.Protic diluents,chloroform and 1-octanol,are more effective tthan the others when the equilibrium solute concentration is lower than 1:1 stoichiometry of TOA to acid,otherwise the extraction ability shows that MIBK>1-octanol>chloroform for malic and maleic acids,and 1-octanol>MIBK>chloroform for succinic acid.Overloading(Solute concentration in organic phase is lager than TOA concentration) appears for all of the studied acids, and the sequence of overloading amount is the same as that of distribution constant of diluent.The results show that the sequence of extraction ability of different acid is the same as that of acidity at low equilibrium solute concentrations,while it is the same as the sequence of hydrophobicity at high equilibrium concentrations.

  3. High glucose and renin release: the role of succinate and GPR91.

    Science.gov (United States)

    Peti-Peterdi, János

    2010-12-01

    Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease. A classic hallmark of diabetes pathology is the activation of the intrarenal renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation has been elusive. Recently, we described the intrarenal localization of the novel metabolic receptor GPR91 and established some of its functions in diabetes. These include the triggering of renin release in early diabetes via both vascular (endothelial) and tubular (macula densa) sites in the juxtaglomerular apparatus as well as the activation of MAP kinases in the distal nephron-collecting duct, which are important signaling mechanisms in diabetic nephropathy (DN) and renal fibrosis. GPR91 is a cell surface receptor for succinate and during the past few years it has provided a new paradigm for the mechanism of cell stress response in many organs. Beyond its traditional role in the tricarboxylic acid cycle, succinate now has an unexpected hormone-like signaling function, which may provide a feedback between local tissue metabolism, mitochondrial stress, and organ functions. Succinate accumulation in the local tissue environment and GPR91 signaling appear to be important early mechanisms by which cells detect and respond to hyperglycemia and trigger tissue injury in DN. Also, the distal nephron-collecting duct system, which is the major source of (pro)renin in diabetes and has the highest level of GPR91 expression in the kidney, may have an important, active, and early role in the pathogenesis of DN in contrast to the existing glomerulus-centric paradigm.

  4. Salicylic Acid-Dependent Plant Stress Signaling via Mitochondrial Succinate Dehydrogenase1[OPEN

    Science.gov (United States)

    Thatcher, Louise F.

    2017-01-01

    Mitochondria are known for their role in ATP production and generation of reactive oxygen species, but little is known about the mechanism of their early involvement in plant stress signaling. The role of mitochondrial succinate dehydrogenase (SDH) in salicylic acid (SA) signaling was analyzed using two mutants: disrupted in stress response1 (dsr1), which is a point mutation in SDH1 identified in a loss of SA signaling screen, and a knockdown mutant (sdhaf2) for SDH assembly factor 2 that is required for FAD insertion into SDH1. Both mutants showed strongly decreased SA-inducible stress promoter responses and low SDH maximum capacity compared to wild type, while dsr1 also showed low succinate affinity, low catalytic efficiency, and increased resistance to SDH competitive inhibitors. The SA-induced promoter responses could be partially rescued in sdhaf2, but not in dsr1, by supplementing the plant growth media with succinate. Kinetic characterization showed that low concentrations of either SA or ubiquinone binding site inhibitors increased SDH activity and induced mitochondrial H2O2 production. Both dsr1 and sdhaf2 showed lower rates of SA-dependent H2O2 production in vitro in line with their low SA-dependent stress signaling responses in vivo. This provides quantitative and kinetic evidence that SA acts at or near the ubiquinone binding site of SDH to stimulate activity and contributes to plant stress signaling by increased rates of mitochondrial H2O2 production, leading to part of the SA-dependent transcriptional response in plant cells. PMID:28209841

  5. Prednisolone succinate-glucosamine conjugate: Synthesis, characterization and in vitro cellular uptake by kidney cell lines

    Institute of Scientific and Technical Information of China (English)

    Yan Lin; Xun Sun; Tao Gong; Zhi Rong Zhang

    2012-01-01

    Prednisolone succinate-glucosamine (PSG) conjugate,a prodrug for prednisolone,was synthesized and confirmed by NMR and MS spectrum.The stabilities of the prodrug in PBS (pH 2.50,5.00,7.20,and 7.89) were studied.Cytotoxicity and uptake assay of the prodrug were perfomed on HK-2 and MDCK cell lines.The results showed that compared with prednisolone,the PSG not only did not increase the cytotoxicity but also improved the uptake to 2.2 times of prednisolone by the cells.Thus,it indicated that glucosamine might be a potential carrier for kidney-targeting delivery of prednisolone.

  6. Studies on synthesis, growth, structural, optical properties of organic 8-hydroxyquinolinium succinate single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Thirumurugan, R., E-mail: singlecrystalxrd@gmail.com; Anitha, K., E-mail: singlecrystalxrd@gmail.com [School of Physics, Madurai Kamaraj University, Madurai-625021 (India)

    2014-04-24

    8-hydroxyquinolinium succinate (8HQSU), an organic material has been synthesized and single crystals were grown by employing the technique of slow evaporation. The structure of the grown crystal was elucidated by using single crystal X-ray diffraction analysis. 8HQSU crystal belongs to the monoclinic crystallographic system with non-centro symmetric space group of P2{sub 1}. FT-IR spectral investigation has been carried out to identify the various functional groups present in the grown crystal. UV–vis spectral studies reveal that 8HQSU crystals are transparent in the entire visible region and the cut-off wavelength has been found to be 220nm.

  7. Structural properties of aqueous metoprolol succinate solutions. Density, viscosity, and refractive index at 311 K

    Science.gov (United States)

    Deosarkar, S. D.; Kalyankar, T. M.

    2013-06-01

    Density, viscosity and refractive index of aqueous solutions of metoprolol succinate of different concentrations (0.005-0.05 mol dm-3) were measured at 38°C. Apparent molar volume of resultant solutions were calculated and fitted to the Masson's equation and apparent molar volume at infinite dilution was determined graphically. Viscosity data of solutions has been fitted to the Jone-Dole equation and viscosity A- and B-coefficients were determined graphically. Physicochemical data obtained were discussed in terms of molecular interactions.

  8. Six Month Oral Toxicity Study of WR238605 Succinate in Rats. Volume 2

    Science.gov (United States)

    1996-02-02

    STUDY MO: 1!>2 ABBR: HCV SEX: FEMALE UNITS: fL Animal ID Week U Week 13 Week 26 GROUP: 1-F:0 mg base/kg/day 426 57.8 55.4 57.9 427 58.8 55.5 57.5...Microscopic (Micro) Findings (Section V). The codes used as entries in these tables are explained in the Report Codes Table. The results of the bone...TOXICITY STUDY OF WR23 8605 SUCCINATE IN RATS SUMMARY OF CLINICAL CHEMISTRY TESTS TEST: Creatine Kinase [uj Ul STUDY ID: UIC-15B STUDY NO

  9. Challenges in Catalytic Manufacture of Renewable Pyrrolidinones from Fermentation Derived Succinate

    Energy Technology Data Exchange (ETDEWEB)

    White, James F.; Holladay, Johnathan E.; Zacher, Alan H.; Frye, John G.; Werpy, Todd A.

    2014-09-05

    Fermentation derived succinic acid ammonium salt is an ideal precursor for manufacture of renewable N-methyl pyrrolidinone (NMP) or 2-pyrrolidinone (2P) via heterogeneous catalysis. However, there are many challenges to making this a practical reality. Chief among the challenges is avoiding catalyst poisoning by fermentation by- and co-products. Battelle / Pacific Northwest National Laboratory (PNNL) have developed an economically effective technology strategy for this purpose. The technology is a combination of purely thermal processing, followed by simple catalytic hydrogenation that together avoids catalyst poisoning from fermentation impurities and provides high selectivity and yields of NMP or 2P.

  10. Isothermal Crystallization Behavior of Biodegradable Poly (butylene succinate-co-terephthalate)(PBST) Copolyesters at High Undercoolings

    Institute of Scientific and Technical Information of China (English)

    XU Xin-jian; LI Fa-xue; LUO Sheng-li; YU Jian-yong

    2008-01-01

    Poly(butylene succinate-co-terephthalate)(PBST)copolyesters were prepared by polycondensation.The isothermal crystallization behavior of the as-prepared copolyesters was investigated by depolarized light intensity(DLI)at high undercoolings.According to Avrami equation,the exponent n,independent of the crystallization temperature,is at a range of 2.5 to 3.4,which probably corresponds to the heterogeneous nucleation and a 3-dimensional spherulitic growth.The maximum crystallization rate,very useful to polymer processing,was foundat about 90℃ based on the half-crystallization time t1/2 analysis.

  11. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept

    DEFF Research Database (Denmark)

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar Borisov

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery...... (> 95%) as well as significant hemicelluloses solubilization (49-59%) after acid-based method and lignin solubilization (35-41%) after alkaline H2O2 method were registered. Alkaline pretreatment showed to be superior over the acid-based method with respect to the rate of enzymatic hydrolysis and ethanol...

  12. Uptake of vitamin E succinate by the skin, conversion to free vitamin E, and transport to internal organs.

    Science.gov (United States)

    Trevithick, J R; Mitton, K P

    1999-03-01

    The percent solubility at 34 degrees C (skin temperature) of radioactive tocopherol succinate was determined for a number of edible oils, and a semisynthetic oil, Myritol 318 (Henkel, Kankakee, IL, a medium chain triglyceride prepared from fractionated coconut oil). Its solubility in Myritol 318 was approximately 50% better than any of the other oils. 14C-tocopherol succinate was diluted (1) into pure Myritol 318, a cosmetic base or (2) 50% tocopherol succinate in Myritol 318. These preparations were applied topically to a 2 cm diameter circle of the back saddle skin of a hairless mouse (strain skh-1). After 24 hr, up to 65% of the label was absorbed by the skin and was also found in skin removed from areas of the back other than the application area, and internal organs such as liver and heart. Up to 6% was hydrolysed to free tocopherol. Topical treatment may be an alternative to oral administration in gastrointestinal malabsorption diseases.

  13. Solubility of α-Tocopheryl Succinate in Supercritical Carbon Dioxide Using Offline HPLC-MS/MS Analysis.

    Science.gov (United States)

    Hybertson, Brooks M

    2007-05-01

    The solubility of the vitamin E-related compound α-tocopheryl succinate in supercritical carbon dioxide was measured at pressures ranging from (15.0 to 30.0) MPa and temperatures of (40 and 50) °C using a simple microsampling type apparatus with a 100.5 μL sample loop to remove aliquots and collect them in ethanol for off line analysis. α-Tocopheryl succinate concentrations in the collected samples were measured using HPLC-MS/MS analysis. The solubility of α-tocopheryl succinate in supercritical carbon dioxide ranged from mole fractions of 0.28 × 10(-5) at 15.0 MPa and 50 °C to 2.56 × 10(-5) at 30.0 MPa and 50 °C.

  14. Extraction and separation of mercury(II from succinate media with high molecular weight amine as an extractant

    Directory of Open Access Journals (Sweden)

    Chandrashekhar P. Mane

    2015-01-01

    Full Text Available The extraction of mercury(II from succinate solutions by 2-octylaminopyridine (2-OAP has been studied by metal distribution measurements. The optimum extraction conditions were determined from a critical study of effects of pH, sodium succinate concentration and 2-octylaminopyridine concentration. The probable composition of the species has been deduced from log–log plots. The extraction reaction proceeds with ion-pair formation and the stoichiometry of extracted species was found to be [(2OAPH+2 Hg(Succinate22−](org. The method has been used to separate mercury(II from commonly associated elements. The method has been further extended to separate and to estimate mercury in synthetic mixtures and real samples.

  15. Ternary solution of sodium chloride, succinic acid and water; surface tension and its influence on cloud droplet activation

    Directory of Open Access Journals (Sweden)

    J. Vanhanen

    2008-08-01

    Full Text Available Surface tension of ternary solution of sodium chloride, succinic acid and water was measured as a function of both composition and temperature by using the capillary rise technique. Both sodium chloride and succinic acid are found in atmospheric aerosols, the former being main constituent of marine aerosol. Succinic acid was found to decrease the surface tension of water already at very low concentrations. Sodium chloride increased the surface tension linearly as a function of the concentration. Surface tensions of both binary solutions agreed well with the previous measurements. Succinic acid was found to lower the surface tension even if sodium chloride is present, indicating that succinic acid, as a surface active compound, tends to concentrate to the surface. An equation based on thermodynamical relations was fitted to the data and extrapolated to the whole concentration range by using estimated surface tensions for pure compounds. As a result, we obtained an estimate of surface tensions beyond solubility limits in addition to a fit to the experimental data. The parameterization can safely be used at temperatures from 10 to 30°C. These kinds of parameterizations are important for example in atmospheric nucleation models. To investigate the influence of surface tension on cloud droplet activation, the surface tension parameterization was included in an adiabatic air parcel model. Usually in cloud models the surface tension of pure water is used. Simulations were done for characteristic marine aerosol size distributions consisting of the considered ternary mixture. We found that by using the surface tension of pure water, the amount of activated particles is underestimated up to 8% if particles contain succinic acid and overestimated it up to 8% if particles contain only sodium chloride. The surface tension effect was found to increase with increasing updraft velocity.

  16. Preparation, characterization and antibacterial activity of octenyl succinic anhydride modified inulin.

    Science.gov (United States)

    Zhang, Xiaoyun; Zhang, Ye-Wang; Zhang, Hongyin; Yang, Qiya; Wang, Haiying; Zhang, Guochao

    2015-01-01

    Octenyl succinic anhydride modified inulin (In-OSA) was synthesized via chemical modification of inulin with octenyl succinic anhydride (OSA). The esterification of inulin with OSA was confirmed by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and degree of substitution (DS) calculation. Antibacterial activity of In-OSA against Staphylococcus aureus and Escherichia coli was investigated by minimum inhibitory concentration (MIC) and inhibition rate determination. The results showed that inhibition rates against both E.coli and S. aureus increased with the increase of the In-OSA concentration. And the MICs against E. coli and S. aureus were 1% and 0.5% (w/v), respectively. The antibacterial mechanism was analyzed with the results of the proteins and nucleic acids leakage, SEM and negative staining transmission electron microscopy (TEM). Both the leakages of proteins and nucleic acids increased with the increase of the In-OSA concentration. The leakage occurred mainly in the early stage which indicated that cell membrane and wall were destroyed by In-OSA quickly. The images of SEM and negative staining TEM suggested that the cell membranes and cell walls of S. aureus were damaged more severely and even destroyed completely; but only pores appeared on the surface of E. coli.

  17. In-vitro characterization of buccal iontophoresis: the case of sumatriptan succinate.

    Science.gov (United States)

    Telò, Isabella; Tratta, Elena; Guasconi, Barbara; Nicoli, Sara; Pescina, Silvia; Govoni, Paolo; Santi, Patrizia; Padula, Cristina

    2016-06-15

    Buccal administration of sumatriptan succinate might be an interesting alternative to the present administration routes, due to its non-invasiveness and rapid onset of action, but because of its low permeability, a permeation enhancement strategy is required. The aim of this work was then to study, in-vitro, buccal iontophoresis of sumatriptan succinate. Permeation experiments were performed in-vitro across pig esophageal epithelium, a recently proposed model of human buccal mucosa, using vertical diffusion cells. The iontophoretic behavior of the tissue was characterized by measuring its isoelectric point (Na(+) transport number and the electroosmotic flow of acetaminophen determination) and by evaluating tissue integrity after current application. The results obtained confirm the usefulness of pig esophageal epithelium as an in-vitro model membrane for buccal drug delivery. The application of iontophoresis increased sumatriptan transport, proportionally to the current density applied, without tissue damage: electrotransport was the predominant mechanism. Integrating the results of the present work with literature data on the transport of other molecules across the buccal mucosa and across the skin, we can draw a general conclusion: the difference in passive transport across buccal mucosa and across the skin is influenced by permeant lipophilicity and by the penetration pathway. Finally, buccal iontophoretic administration of sumatriptan allows to administer 6mg of the drug in 1h, representing a promising alternative to the current administration routes.

  18. Succinate Functionalization of Hyperbranched Polyglycerol-Coated Magnetic Nanoparticles as a Draw Solute During Forward Osmosis.

    Science.gov (United States)

    Yang, Hee-Man; Choi, Hye Min; Jang, Sung-Chan; Han, Myeong Jin; Seo, Bum-Kyoung; Moon, Jei-Kwon; Lee, Kune-Woo

    2015-10-01

    Hyperbranched polyglycerol-coated magnetic nanoparticles (SHPG-MNPs) were functionalized with succinate groups to form a draw solute for use in a forward osmosis (FO). After the one-step synthesis of hyperbranched polyglycerol-coated magnetic nanoparticles (HPG-MNPs), the polyglycerol groups on the surfaces of the HPG-MNPs were functionalized with succinic anhydride moieties. The resulting SHPG-MNPs showed no change of size and magnetic property compared with HPG-MNPs and displayed excellent dispersibility in water up to the concentration of 400 g/L. SHPG-MNPs solution showed higher osmotic pressure than that of HPG-MNPs solution due to the presence of surface carboxyl groups in SHPG-MNPs and could draw water from a feed solution across an FO membrane without any reverse draw solute leakage during FO process. Moreover, the water flux remained nearly constant over several SHPG-MNP darw solute regeneration cycles applied to the ultrafiltration (UF) process. The SHPG-MNPs demonstrate strong potential for use as a draw solute in FO processes.

  19. α-Tocopherol succinate improves encapsulation and anticancer activity of doxorubicin loaded in solid lipid nanoparticles.

    Science.gov (United States)

    Oliveira, Mariana S; Mussi, Samuel V; Gomes, Dawidson A; Yoshida, Maria Irene; Frezard, Frederic; Carregal, Virgínia M; Ferreira, Lucas A M

    2016-04-01

    This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopheryl succinate (TS), a succinic acid ester of α-tocopherol that exhibits anticancer actions, evaluating the influence of TS on drug encapsulation efficiency. The SLN were characterized for size, zeta potential, entrapment efficiency (EE), and drug release. Studies of in vitro anticancer activity were also conducted. The EE was significantly improved from 30 ± 1% to 96 ± 2% for SLN without and with TS at 0.4%, respectively. In contrast, a reduction in particle size from 298 ± 1 to 79 ± 1 nm was observed for SLN without and with TS respectively. The doxorubicin release data show that SLN provide a controlled drug release. The in vitro studies showed higher cytotoxicity for doxorubicin-TS-loaded SLN than for free doxorubicin in breast cancer cells. These findings suggest that TS-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer.

  20. Guar gum succinate as a carrier for colon-specific drug delivery.

    Science.gov (United States)

    Seeli, D Sathya; Prabaharan, M

    2016-03-01

    A novel type of pH-sensitive colon-specific controlled drug delivery carrier based on guar gum succinate (GGS) was prepared by reacting guar gum (GG) with succinic anhydride (SA) in the presence of 4-dimethylaminopyridine (DMAP). The formation of GGS was confirmed by FT-IR and (1)H NMR and characterized using XRD techniques. GGS microparticles with 460-740 μm in size were prepared using sodium trimetaphosphate (STMP) as a cross-linking agent. The size and morphologies of GGS microparticles were assessed by scanning electron microscopy (SEM). The swelling degree of the GGS microparticles was found to be higher in pH 7.4 than in pH 1.2. In addition, GGS microparticles showed a pH dependent drug release profile when compared to the GG microparticles. The MTT assay revealed that there is no apparent cytotoxicity of GGS against a mouse mesenchymal stem cell line at a concentration range of 0-200 μg/ml. These results confirm that GGS could be used as a carrier for colon-specific drug delivery.

  1. Simultaneous derivative spectrophotometric analysis of doxylamine succinate, pyridoxine hydrochloride and folic Acid in combined dosage forms.

    Science.gov (United States)

    Pathak, A; Rajput, S J

    2008-01-01

    Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 mug/ml, 1-40 mug/ml and 1-30 mug/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.

  2. Simultaneous derivative spectrophotometric analysis of doxylamine succinate, pyridoxine hydrochloride and folic acid in combined dosage forms

    Directory of Open Access Journals (Sweden)

    Pathak A

    2008-01-01

    Full Text Available Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot′s method were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 µg/ml, 1-40 µg/ml and 1-30 µg/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.

  3. Microbial production of succinic acid using crude and purified glycerol from a Crotalaria juncea based biorefinery

    Directory of Open Access Journals (Sweden)

    Suvra Sadhukhan

    2016-06-01

    Full Text Available Microbial conversion of crude and purified glycerol obtained in the process of biorefining Crotalaria juncea is carried out to produce succinic acid using Escherichia coli. Batch tests are performed for nine different substrate concentrations of commercial, purified and crude glycerol, in order to observe cell growth and substrate utilization rate. Inhibitory (Halden-Andrew, Aiba-Edward, Tessier type and Andrews as well as non-inhibitory (Monod, Moser and Tessier models are fitted to the relationship between specific growth rate and substrate concentration obtained from the growth curves. Considering the inhibition effect, Aiba-Edward model ranked 1 out of 7 in case of two samples and Haldane-Andrew model ranked 1 in case of one sample. Aiba-Edward model gave the best fitment for a large range of concentrations of all the three types of glycerol, crude, purified and laboratory grade. Maximum production of succinic acid is obtained from commercial glycerol at pH 7 and 37.5 °C.

  4. Laminaria digitata as a potential carbon source for succinic acid and bioenergy production in a biorefinery perspective

    DEFF Research Database (Denmark)

    Alvarado-Morales, Merlin; Gunnarsson, Ingólfur Bragi; Fotidis, Ioannis

    2015-01-01

    A novel biorefinery concept utilizing macroalgae Laminaria digitata to produce succinic acid, and direct the process residues for feed and energy production, is investigated in the present study. Enzymatic hydrolysis was performed at high solid loading (25% w v− 1) resulting in solubilization...... of the carbohydrates to soluble sugars, which accumulated in the liquid hydrolysate. The overall sugar recovery in the macroalgae hydrolysate was 78.23%. Actinobacillus succinogenes 130Z was able to ferment macroalgae hydrolysate to succinic acid with a yield of 86.49% (g g− 1 of total sugars) and an overall...

  5. [Methods for the protection against counterfeit medications. Part 2. The assessment of interlot dispersion of the metoprolol succinate tablets fabricated by different manufacturers].

    Science.gov (United States)

    Iakushev, V A; Morozova, M A; Elizarova, T E; Fitilev, S B; Pletneva, T V

    2012-01-01

    This paper reports the results of analysis of the metoprolol succinate tablets fabricated by two different manufacturers, Akrikhin (Russia) and AstraZeneka (Sweden) by near-IR spectroscopy in the combination with the chemometric processing of the data obtained (discriminative analysis). It is concluded that this method is applicable for the assessment of interlot dispersion of the metoprolol succinate tablets.

  6. Kinetic analysis of bifidobacterial metabolism reveals a minor role for succinic acid in the regeneration of NAD+ through its growth-associated production.

    Science.gov (United States)

    Van der Meulen, Roel; Adriany, Tom; Verbrugghe, Kristof; De Vuyst, Luc

    2006-08-01

    Several strains belonging to the genus Bifidobacterium were tested to determine their abilities to produce succinic acid. Bifidobacterium longum strain BB536 and Bifidobacterium animalis subsp. lactis strain Bb 12 were kinetically analyzed in detail using in vitro fermentations to obtain more insight into the metabolism and production of succinic acid by bifidobacteria. Changes in end product formation in strains of Bifidobacterium could be related to the specific rate of sugar consumption. When the specific sugar consumption rate increased, relatively more lactic acid and less acetic acid, formic acid, and ethanol were produced, and vice versa. All Bifidobacterium strains tested produced small amounts of succinic acid; the concentrations were not more than a few millimolar. Succinic acid production was found to be associated with growth and stopped when the energy source was depleted. The production of succinic acid contributed to regeneration of a small part of the NAD+, in addition to the regeneration through the production of lactic acid and ethanol.

  7. Valorization of macroalga Saccharina latissima as novel feedstock for fermentation-based succinic acid production in a biorefinery approach and economic aspects

    DEFF Research Database (Denmark)

    Silva Marinho, Goncalo; Alvarado-Morales, Merlin; Angelidaki, Irini

    2016-01-01

    This study aimed to evaluate the potential of the macroalga Saccharina latissima as feedstock for fermentation-based succinic acid production in a biorefinery approach. Seasonal variations in the content of carbohydrates, and fermentable sugars, had a significant impact on the succinic acid yield...... and titer. A maximum succinic acid yield of 91.9% (g g-1 of total sugars) corresponding to 70.5% of the theoretical maximum yield was achieved when a blend of macroalgal biomass cultivated over two growing seasons and harvested in July and August was used as feedstock. A succinic acid titer of 36.8 g L-1...... co-production of antioxidants (i.e. phenolics) and fertilizer very attractive. Finally, a simplified economic assessment showed that for the analyzed scenarios the main product's selling price (succinic acid) can be lowered significantly by coproducing added value products (fertilizers) and high...

  8. The Audio Frequency Conductance Study of Some Metal Succinate Salts in Aqueous Medium at Different Temperatures (Part I: Magnesium, Manganese (II, Barium and Copper Succinates

    Directory of Open Access Journals (Sweden)

    Kosrat N. Kaka

    2013-01-01

    Full Text Available The audio electrical conductances of aqueous solutions of magnesium, manganese II, barium, and copper succinates have been measured at various temperatures in the range of 298.15 K to 313.15 K, using an audio frequency conductance bridge. The evaluation of conductance data was carried out by minimisation technique using the theoretical equations of the complete and modified forms of Pitts (P and Fuoss-Hsia (F-H, each a three-parameter equation, association constant (KA, molar conductance (Λm, and distance parameter (a. Quantitative results showed that these salts do not behave as “strong” electrolytes, and that their dissociations are far from complete. The abnormally low conductances of these electrolytes are not due to the presence of electrically neutral molecules but to the ion-pair formation. The Walden product values, as well as the standard thermodynamics functions (ΔH∘, ΔG∘, ΔS∘ for the association reaction at the four temperatures studied, have been evaluated.

  9. Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma

    NARCIS (Netherlands)

    H. Dannenberg (Hilde); W.N.M. Dinjens (Winand); M. Abbou; H. van Urk (Hero); B.K. Pauw; D. Mouwen; W.J. Mooi (Wolter); R.R. de Krijger (Ronald)

    2002-01-01

    textabstractPURPOSE: Recently, familial paraganglioma (PGL) was shown to be caused bymutations in the gene encoding succinate dehydrogenase subunit D (SDHD). However, the prevalence of SDHD mutations in apparently sporadic PGL is unknown. We studied the frequency and spectrum of ge

  10. Capture of carbon dioxide from ethanol fermentation by liquid absorption for use in biological production of succinic acid

    Science.gov (United States)

    Previously it was shown that the gas produced in an ethanol fermentor using either corn or barley as feedstock could be sparged directly into an adjacent fermentor using Escherichia coli AFP184 to provide the CO2 required for succinic acid production. In the present investigation it has been demons...

  11. A novel mutation in the succinate dehydrogenase subunit D gene in siblings with the hereditary paraganglioma-pheochromocytoma syndrome.

    Science.gov (United States)

    Prasad, Chaithra; Oakley, Gerard J; Yip, Linwah; Coyne, Christopher; Rangaswamy, Balasubramanya; Dixit, Sanjay B

    2014-01-01

    Germline mutations in the succinate dehydrogenase complex subunit D gene are now known to be associated with hereditary paraganglioma-pheochromocytoma syndromes. Since the initial succinate dehydrogenase complex subunit D gene mutation was identified about a decade ago, more than 131 unique variants have been reported. We report the case of two siblings presenting with multiple paragangliomas and pheochromocytomas; they were both found to carry a mutation in the succinate dehydrogenase complex subunit D gene involving a substitution of thymine to guanine at nucleotide 236 in exon 3. This particular mutation of the succinate dehydrogenase complex subunit D gene has only been reported in one previous patient in Japan; this is, therefore, the first report of this pathogenic mutation in siblings and the first report of this mutation in North America. With continued screening of more individuals, we will be able to create a robust mutation database that can help us understand disease patterns associated with particular variants and may be a starting point in the development of new therapies for familial paraganglioma syndromes.

  12. A novel mutation in the succinate dehydrogenase subunit D gene in siblings with the hereditary paraganglioma–pheochromocytoma syndrome

    Directory of Open Access Journals (Sweden)

    Chaithra Prasad

    2014-10-01

    Full Text Available Germline mutations in the succinate dehydrogenase complex subunit D gene are now known to be associated with hereditary paraganglioma–pheochromocytoma syndromes. Since the initial succinate dehydrogenase complex subunit D gene mutation was identified about a decade ago, more than 131 unique variants have been reported. We report the case of two siblings presenting with multiple paragangliomas and pheochromocytomas; they were both found to carry a mutation in the succinate dehydrogenase complex subunit D gene involving a substitution of thymine to guanine at nucleotide 236 in exon 3. This particular mutation of the succinate dehydrogenase complex subunit D gene has only been reported in one previous patient in Japan; this is, therefore, the first report of this pathogenic mutation in siblings and the first report of this mutation in North America. With continued screening of more individuals, we will be able to create a robust mutation database that can help us understand disease patterns associated with particular variants and may be a starting point in the development of new therapies for familial paraganglioma syndromes.

  13. A novel mutation in the succinate dehydrogenase subunit D gene in siblings with the hereditary paraganglioma–pheochromocytoma syndrome

    Science.gov (United States)

    Oakley, Gerard J; Yip, Linwah; Coyne, Christopher; Rangaswamy, Balasubramanya; Dixit, Sanjay B

    2014-01-01

    Germline mutations in the succinate dehydrogenase complex subunit D gene are now known to be associated with hereditary paraganglioma–pheochromocytoma syndromes. Since the initial succinate dehydrogenase complex subunit D gene mutation was identified about a decade ago, more than 131 unique variants have been reported. We report the case of two siblings presenting with multiple paragangliomas and pheochromocytomas; they were both found to carry a mutation in the succinate dehydrogenase complex subunit D gene involving a substitution of thymine to guanine at nucleotide 236 in exon 3. This particular mutation of the succinate dehydrogenase complex subunit D gene has only been reported in one previous patient in Japan; this is, therefore, the first report of this pathogenic mutation in siblings and the first report of this mutation in North America. With continued screening of more individuals, we will be able to create a robust mutation database that can help us understand disease patterns associated with particular variants and may be a starting point in the development of new therapies for familial paraganglioma syndromes. PMID:27489656

  14. Differential protonation and dynamic structure of doxylamine succinate in solution using 1H and 13C NMR.

    Science.gov (United States)

    Somashekar, B S; Nagana Gowda, G A; Ramesha, A R; Khetrapal, C L

    2004-07-01

    A protonation and dynamic structural study of doxylamine succinate, a 1:1 salt of succinic acid with dimethyl-[2-(1-phenyl-1-pyridin-2-yl-ethoxy)ethyl]amine, in solution using one- and two-dimensional 1H and 13C NMR experiments at variable temperature and concentration is presented. The two acidic protons of the salt doxylamine succinate are in 'intermediate' exchange at room temperature, as evidenced by the appearance of a broad signal. This signal evolves into two distinct signals below about -30 degrees C. A two-dimensional 1H-1H double quantum filtered correlation experiment carried out at -55 degrees C shows protonation of one of the acidic protons to the dimethylamine nitrogen. A two-dimensional rotating frame 1H-1H NOE experiment at the same temperature reveals that the other proton remains with the succinate moiety. Comparison of the 1H and 13C chemical shifts and the 13C T1 relaxation times of the salt with those of the free base further substantiate the findings.

  15. Capture of carbon dioxide from ethanol fermentation by liquid absorption for use in biological production of succinic acid.

    Science.gov (United States)

    Nghiem, Nhuan P; Senske, Gerard E

    2015-02-01

    Previously, it was shown that the gas produced in an ethanol fermentor using either corn or barley as feedstock could be sparged directly into an adjacent fermentor as a feedstock for succinic acid fermentation using Escherichia coli AFP184. In the present investigation, it was demonstrated that the CO2 produced in a corn ethanol fermentor could be absorbed in a base solution and the resultant carbonate solution used both for pH control and supply of the CO2 requirement in succinic acid fermentation. Thus, the CO2 produced in a 5-L corn mash containing 30 wt% total solids was absorbed in a packed column containing 2 L of either 5 M NaOH, 5 M KOH, or 15 wt% NH4OH, and the resultant carbonate solutions were used for pH control in a succinic acid fermentor. The results obtained indicated no significant differences between succinic acid production in these experiments and when 2.5 M solutions of Na2CO3, K2CO3, and (NH4)2CO3 from commercial sources were used. In a commercial setting, the demonstrated capture of CO2 in liquid form will allow transportation of the carbonate solutions to locations not in the immediate vicinity of the ethanol plant, and excess carbonate salts can also be recovered as value-added products.

  16. Hepatoprotective Activity of a Complex Compound of 5-Hydroxy-6-Methyluracil and Succinic Acid in Experimental Peritonitis

    Directory of Open Access Journals (Sweden)

    D. A. Yenikeyev

    2008-01-01

    Full Text Available Objective: to evaluate the hepatoprotective efficacy of a complex compound of 5-hydroxy-6-methyluracil and succinic acid in experimental peritonitis. Materials and methods. Experiments were carried out on 48 male albino rats in which peritonitis was simulated via intraperitoneal administration of 7% fecal suspension in a dose of 0.6 ml per 100 g bodyweight. The rate of free radical oxidation processes, the activity of antioxidative protection, the degree of endogenous intoxication and cytolytic syndrome, and the effect of the test compound on these parameters were estimated in the experiment. Results. With the development of an abdominal inflammatory process, there were increases in rates of endogenous intoxication and free radical oxidation (FRO, a change in the activity of antioxidative protection enzymes, and a reduction in the levels of ceruloplasmin and sulfahydryl groups. The complex compound, that comprised 5-hydroxy-6-methyluracil and succinic acid used as monotherapy, reduced the degree of endogenous intoxication, FRO, and lipid peroxidation-antioxidative defense system imbalance. Conclusion. The experimental data suggest that the use of the complex compound containing succinic acid and 5-hydroxy-6-methy-luracil is pathogenetically warranted. Key words: peritonitis, lipid peroxidation, antioxidants, succinic acid, pyrim-idine derivatives.

  17. Influence of salicylic and succinic acids on antioxidant enzymes activity, heat resistance and productivity of Panicum miliaceum L.

    Directory of Open Access Journals (Sweden)

    Miroshnichenko N.N.

    2011-05-01

    Full Text Available The influence of treatment of millet (Panicum miliaceum L. seeds with the solutions of salicylic and succinic acids on the heat resistance of plantlets and activity of antioxidant enzymes – superoxide dismutase (SOD, catalase and peroxidase – in them have been investigated. In the micro-field experiment the influence of these acids on the millet yield was estimated. The action of salicylic (10 μM and succinic (1 mM acids caused the increase of plantlets resistance to the damaging heating that expressed in the rise of relative quantity of survived plantlets in 5 days after heating at the temperature of 47°С and in the reduced content of lipid peroxidation product malonic dialdehyde during the poststress period. The increase of activity of SOD, catalase and peroxidase took place in millet plantlets under the influence of salicylic and succinic acids. The increase of productivity of millet grain under the action of salicylic and succinic acids on 13,3-52,0 and 6,4-38,8% respectively depending on weather conditions in the field experiments was noted.

  18. Preparation and structural characterisation of novel and versatile amphiphilic octenyl succinic anhydride-modified hyaluronic acid derivatives

    DEFF Research Database (Denmark)

    Eenschooten, Corinne Diane; Guillaumie, Fanny; Kontogeorgis, Georgios

    2010-01-01

    The purpose of the present study was to prepare amphiphilic hyaluronic acid (HA) derivatives and to study the influence of a selection of reaction parameters on the degree of substitution (DS) of the derivatives. Octenyl succinic anhydride (OSA)–modified HA (OSA–HA) derivatives were prepared...

  19. 双极膜电渗析制备琥珀酸%Production of succinic acid using bipolar membrane electrodialysis

    Institute of Scientific and Technical Information of China (English)

    范爱勇; 高学理; 付丽丽; 杨洋; 高从堦

    2013-01-01

    采用三室型双极膜电渗析从琥珀酸钠制备琥珀酸,考察了电流大小对电渗析过程中操作电压、琥珀酸浓度、电流效率和能耗等技术指标的影响.在2.0A的最佳操作电流下,对1L浓度为0.5 mol/L的琥珀酸钠进行处理.实验结果表明:产生的琥珀酸质量浓度可达52.55 g/L,平均能耗为3.24 kW.h/kg,电流效率可达88%.%Succinic acid is recovered from sodium succimte solution using bipolar membrane electrodialysis with three compartments.The influence of current for operating voltage,current efficiency,energy consumption and yield concentration of succinic acid are studied.The results showed that the yield concentration of succinic acid could exceed 52.55 g/L,the electric energy consumption is about 3.24 kWh/kg and the current efficiency is about 88% under the optimum operation current of 2.0 A for 1 L 0.5 mol/L sodium succinate solutions.

  20. Linear and cyclic ester Oligomers of succinic acid and 1,4-butanediol: Biocatalytic synthesis and characterization

    NARCIS (Netherlands)

    Habeych Narvaez, D.I.; Eggink, G.; Boeriu, C.G.

    2011-01-01

    The lipase-catalyzed synthesis of cyclic ester oligomers from non-activated succinic acid (A) and 1,4-butanediol (B) in the presence of immobilized Candida antarctica lipase B was investigated. Batch and pulse fed-batch systems were implemented to increase the formation of cyclic ester products. The

  1. Utilization of CO2 fixating bacterium Actinobacillus succinogenes 130Z for simultaneous biogas upgrading and bio-succinic acid production

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Alvarado-Morales, Merlin; Angelidaki, Irini

    2014-01-01

    acid using the bacterial strain Actinobacillus succinogenes 130Z, and simultaneously producing high purity CH4 (>95%). Results showed that when pressure during fermentation was increased from 101.325 to 140 kPa, higher CO2 solubility was achieved, thereby positively affecting final succinic acid yield...... and titre, CO2 consumption rate and CH4 purity. When using biogas as the only CO2 source at 140 kPa, the CO2 consumption rate corresponded to 2.59 L CO2 L-1 d-1 with a final succinic acid titre of 14.4 g L-1. Under this pressure condition the highest succinic acid yield and biogas quality reached...... corresponded to 0.635 g g-1 and 95.4% (v v-1) CH4 content respectively after 24 hours fermentation. This work represents the first successful attempt to develop a system capable of upgrading biogas to vehicle fuel/gas grid quality and simultaneously produce bio-succinic acid, a valuable building block...

  2. Ionic liquids as novel solvents for biosynthesis of octenyl succinic anhydride-modified waxy maize starch.

    Science.gov (United States)

    Li, Dandan; Zhang, Xiwen; Tian, Yaoqi

    2016-05-01

    Biosynthesis of octenyl succinic anhydride (OSA) starch was investigated using ionic liquids (ILs) as reaction media. Waxy maize starch was pretreated in 1-butyl-3-methylimidazolium chlorine and then esterified with OSA in 1-octyl-3-methylimidazolium nitrate by using Novozyme 435 as catalyst. The degree of substitution of OSA starch reached 0.0130 with 5 wt% starch concentration and 1 wt% lipase dosage based on ILs weight at 50 °C for 3h. The formation of OSA starch was confirmed by fourier transform infrared spectroscopy. Scanning electron microscopy and X-ray diffraction revealed that the morphology and crystal structure of starch were significantly destroyed. Thermogravimetric analysis showed that esterification decreased the thermal stability of starch. The successful lipase-catalyzed synthesis of OSA starch in ILs suggests that ILs are potential replacement of traditional organic solvents for starch ester biosynthesis.

  3. Structure of cis-1-([4-(1-imidazolylmethyl)cyclohexyl]methyl)imidazole- succinic acid complex.

    Science.gov (United States)

    Van Roey, P; Bullion, K A; Osawa, Y; Bowman, R M; Braun, D G

    1991-05-15

    CGS 14796C, C14H20N4.C4H6O4, Mr = 362.43, monoclinic, C2/c, a = 28.148 (4), b = 9.722 (1), c = 19.200 (2) A, beta = 133.06 (1) degree, V = 3838.88 A3, Z = 8, Dx = 1.26 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu 0.702 mm-1, F(000) = 1552, T = 294 K, R = 0.075 for all 3285 reflections. The structure is composed of linear chains of alternating CGS 14796C and succinic acid molecules. The CGS 14796C molecule is in an extended conformation.

  4. Core-in-cup tablet design of metoprolol succinate and its evaluation for controlled release.

    Science.gov (United States)

    Nagaraju, Ravouru; Meera, Durgumahanthi Sai; Kaza, Rajesh; Arvind, Vakati Venkata; Venkateswarlu, Vobalaboina

    2009-12-01

    The core-in-cup matrix tablets of Metoprolol succinate were prepared by wet granulation technique. Of all the investigated formulations, the optimized formulation of MS-09 followed zero-order kinetics of drug release. Trail on MS-09 was formulated using 7.5% hydrogenated castor-oil (HCO) and 4% of hydroxyl propyl methylcellulose (HPMC K15M) with an objective to achieve a linear release profile for 24 h. There is no initial burst release, with 16.17% of drug released during the first hour and release was extended up to 24 hrs. Study of drug release kinetics was performed by application of dissolution data to various kinetic equations like zero-order; first order, Higuchi and Korsmeyer-Peppas, from R(2) value (0.9975) it was concluded that the drug release followed zero order kinetics with both erosion and diffusion as the release mechanisms.

  5. Unsuspected task for an old team: succinate, fumarate and other Krebs cycle acids in metabolic remodeling.

    Science.gov (United States)

    Bénit, Paule; Letouzé, Eric; Rak, Malgorzata; Aubry, Laetitia; Burnichon, Nelly; Favier, Judith; Gimenez-Roqueplo, Anne-Paule; Rustin, Pierre

    2014-08-01

    Seventy years from the formalization of the Krebs cycle as the central metabolic turntable sustaining the cell respiratory process, key functions of several of its intermediates, especially succinate and fumarate, have been recently uncovered. The presumably immutable organization of the cycle has been challenged by a number of observations, and the variable subcellular location of a number of its constitutive protein components is now well recognized, although yet unexplained. Nonetheless, the most striking observations have been made in the recent period while investigating human diseases, especially a set of specific cancers, revealing the crucial role of Krebs cycle intermediates as factors affecting genes methylation and thus cell remodeling. We review here the recent advances and persisting incognita about the role of Krebs cycle acids in diverse aspects of cellular life and human pathology.

  6. Gadolinium(III)-hydroxy ladders trapped in succinate frameworks with optimized magnetocaloric effect.

    Science.gov (United States)

    Chen, Yan-Cong; Guo, Fu-Sheng; Zheng, Yan-Zhen; Liu, Jun-Liang; Leng, Ji-Dong; Tarasenko, Róbert; Orendáč, Martin; Prokleška, Jan; Sechovský, Vladimír; Tong, Ming-Liang

    2013-09-27

    Two kinds of inorganic gadolinium(III)-hydroxy "ladders", [2×n] and [3×n], were successfully trapped in succinate (suc) coordination polymers, [Gd2(OH)2(suc)2(H2O)]n·2nH2O (1) and [Gd6(OH)8(suc)5(H2O)2 ]n·4n H2O (2), respectively. Such coordination polymers could be regarded as alternating inorganic-organic hybrid materials with relatively high density. Magnetic and heat capacity studies reveal a large cryogenic magnetocaloric effect (MCE) in both compounds, namely (ΔH=70 kG) 42.8 J kg(-1) K(-1) for complex 1 and 48.0 J kg(-1) K(-1) for complex 2. The effect of the high density is evident, which gives very large volumetric MCEs up to 120 and 144 mJ cm(-3) K(-1) for complexes 1 and 2, respectively.

  7. Growth, characterization and dielectric property studies of gel grown barium succinate single crystals

    Indian Academy of Sciences (India)

    M P Binitha; P P Pradyumnan

    2014-05-01

    Single crystals of barium succinate (BaC4H4O4) were grown in silica gel medium using controlled chemical reaction method. Plate-like single crystals of size up to 3 × 2 × 0.2 mm3 was obtained. Single crystal X-ray diffraction (XRD) studies confirmed that structure of the title compound is tetragonal. Powder X-ray diffraction (PXRD) pattern of the grown crystal and the Fourier transform infrared (FT–IR) spectrum in the range 400–4000 cm-1 are recorded. The vibrational bands corresponding to different functional groups are assigned. Thermal stability of the grown crystals is confirmed by differential scanning calorimetry (DSC). Dielectric constant and dielectric loss have been calculated and discussed as a function of frequency at different temperatures.

  8. Biodegradable Poly(butylene succinate Composites Reinforced by Cotton Fiber with Silane Coupling Agent

    Directory of Open Access Journals (Sweden)

    Masahiro Funabashi

    2013-01-01

    Full Text Available In this study, the use of cotton fiber (CF as a filler in poly(butylene succinate (PBS and the effect of silane treatment on the mechanical properties, thermal stability, and biodegradability of PBS/CF composites are investigated. The results showed that the tensile strength of PBS was improved (15%–78% with the incorporation of CF (10–40 wt% and was further increased (25%–118% when CF was treated with a silane coupling agent. Scanning electron microscopy (SEM observation of the fracture surfaces of PBS/CF composites showed that there was slight improvement in fiber-matrix compatibility. Thermogravimetric (TG analysis showed that the thermal stability of the composites was lower than that of neat PBS and decreased with increasing filler loading. The biobased carbon content of the composites increased with increasing CF content. The incorporation of CF (with and without silane treatment in PBS significantly increased the biodegradation rate of the composites.

  9. Antimicrobial activity of electrospun poly(butylenes succinate) fiber mats containing PVP-capped silver nanoparticles.

    Science.gov (United States)

    Tian, Ligang; Wang, Pingli; Zhao, Zhiguo; Ji, Junhui

    2013-12-01

    In this study, biodegradable poly(butylenes succinate) (PBS) fiber mats containing silver nanoparticles (AgNPs) were prepared by the electrospinning process. Small AgNPs (fiber mats and the distribution of the AgNPs were well characterized by TEM and SEM. The release of Ag from the PBS fiber mats was quantitively determined by ICP. The PBS fiber mats with 0.29 % AgNPs content showed strong antimicrobial activity against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli with the efficacy as high as 99 %. The effective bactericidal activity on E. coli was demonstrated for a short contacting time with the PBS-AgNPs fiber mats. In addition, the long-term release performance of Ag from the fiber mats can keep inhibiting the bacterial growth in the mats over a long period of time.

  10. Synthesis and paste properties of octenyl succinic anhydride modified early Indica rice starch

    Institute of Scientific and Technical Information of China (English)

    SONG Xiao-yan; CHEN Qi-he; RUAN Hui; HE Guo-qing; XU Qiong

    2006-01-01

    Octenyl succinic anhydride (OSA) modified early Indica rice starch was prepared in aqueous slurry systems using response surface methodology. The paste properties of the OSA starch were also investigated. Results indicated that the suitable parameters for the preparation of OSA starch from early Indica rice starch were as follows: reaction period 4 h, reaction temperature 33.4 ℃, pH of reaction system 8.4, concentration of starch slurry 36.8% (in proportion to water, w/w), amount of OSA 3% (in proportion to starch, w/w). The degree of substitution was 0.0188 and the reaction efficiency was 81.0%. The results of paste properties showed that with increased OSA modification, the starch derivatives had higher paste clarity, decreased retrogradation and better freeze-thaw stability.

  11. Multi walled carbon nanotube nanocomposites with biodegradable poly(butylene succinate) and their physical characteristics.

    Science.gov (United States)

    Hong, M K; Ko, S W; Park, J H; Choi, H J; Kim, J H

    2011-06-01

    In order to examine the influence of multi walled carbon nanotube (MWNT) on physical properties of its biodegradable polymer nanocomposite, biodegradable poly(buthylene succinate) (PBS), which was synthesized from diols and dicarboxylic acids, and MWNT nanocomposites were prepared via a melt-mixing method using a co-rotating intermeshing twin screw extruder. Microstructure of the PBS/MWNT nanocomposites and MWNT were investigated via both scanning electron microscopy and transmission electron microscopy. Their rheological properties were also characterized via rotation and oscillation tests using a rotational rheometer with parallel-plate geometry. It was found that shear viscosity, storage modulus and loss modulus of the nanocomposites examined by a rotational rheometer increased with the MWNT content. Especially their sharp increase for MWNT content of ca. 2.0 wt% was observed, indicating its percolation threshold from the rheological viewpoint which was higher than its electrical percolation threshold (1.0 wt%).

  12. [Utility of challenge test in immediate hypersensitivity to hydrocortisone sodium succinate].

    Science.gov (United States)

    Amaya-Mejía, Adela Sisy; Galindo-Pacheco, Lucy Vania; O'Farrill-Romanillos, Patricia María; Rodríguez-Mireles, Karen Alicia; Campos-Romero, Freya Helena; del Rivero-Hernández, Leonel

    2014-01-01

    Corticosteroid hypersensitivity is a complex phenomenon in which many factors interact, such as idiosyncrasy, intolerance or allergic reactions. The prevalence of immediate hypersensitivity reactions to corticosteroids is 0.2%-0.5%. Corticosteroids have major therapeutic implications; thus, when hypersensitivity is suspected, in-vitro and/or in-vivo testing can be performed to confirm diagnosis, being the drug challenge the gold standard. After definitive diagnosis, cross-reactivity among the different corticosteroid groups should be considered, to choose wisely if corticosteroid therapy is still required. In Coopman classification, steroids belonging to groups A, B and D2 have high cross-reactivity, however, more studies are needed to determine the degree of cross-reaction among these drugs. This paper presents the case of a woman, in who hypersensitivity to hydrocortisone succinate was confirmed by drug challenge test.

  13. Synthesis and Crystal Structure of 2-(N-Cyclohexyl)-imino-1,4-succinic Acid Dihydrate

    Institute of Scientific and Technical Information of China (English)

    郭金波; 李森兰; 郁兆莲; 陈庆华

    2005-01-01

    The title compound, 2-(N-cyclohexyl)-imino-1,4-succinic acid dihydrate 4, has been prepared and structurally determined by X-ray diffraction analysis. Crystal data: monoclinic, space group Cc, a = 7.5790(15), b = 24.860(5), c = 7.1394(14)(A), β = 104.23(3)°, V = 1303.9(4) (A)3, C10H21NO6, Mr = 251.28, Z = 4, Dc = 1.280 g/cm3, μ = 0.105 mm-1, F(000) = 544, R = 0.0397 and wR = 0.0918 for 1212 observed reflections with I ≥ 2σ(I). X-ray structure analysis reveals that there exist two intramolecular and six intermolecular hydrogen-bonding interactions in the crystal lattice, which can stabilize the configuration of the α-imino acid dihydrate 4.

  14. Protonation Equilibria of L-Aspartic, Citric and Succinic Acids in Anionic Micellar Media

    Directory of Open Access Journals (Sweden)

    P. Srinivasa Rao

    2009-01-01

    Full Text Available The impact of sodium lauryl sulphate (SLS on the protonation equilibria of L-aspartic acid, citric acid and succinic acid has been studied in various concentrations (0.5-2.5% w/v of SLS solution maintaining an ionic strength of 0.16 mol dm-3 at 303 K. The protonation constants have been calculated with the computer program MINIQUAD75 and the best fit models have been calculated based on statistical parameters. The trend of log values of step-wise protonation constants with mole fraction of the medium has been explained based on electrostatic and non-electrostatic forces operating on the protonation equilibria. The effects of errors on the protonation constants have also been presented.

  15. 4-Chloro-6-methoxypyrimidin-2-amine–succinic acid (2/1

    Directory of Open Access Journals (Sweden)

    Kaliyaperumal Thanigaimani

    2012-12-01

    Full Text Available The asymmetric unit of the title compound, 2C5H6ClN3O·C4H6O4, consists of one 4-chloro-6-methoxypyrimidin-2-amine molecule and one half-molecule of succinic acid which lies about an inversion centre. In the crystal, the acid and base molecules are linked through N—H...O and O—H...N hydrogen bonds, forming a tape along [1-10] in which R22(8 and R42(8 hydrogen-bond motifs are observed. The tapes are further interlinked through a pair of C—H...O hydrogen bonds into a sheet parallel to (11-2.

  16. Development and validation of HPTLC method for simultaneous determination of amlodipine besylate and metoprolol succinate in bulk and tablets

    Directory of Open Access Journals (Sweden)

    P S Jain

    2012-01-01

    Full Text Available A simple, selective, precise high-performance thin-layer chromatographic method for simultaneous determination of amlodipine besylate and metoprolol succinate in bulk and pharmaceutical combined dosage form was developed and validated. The method employed HPTLC aluminum plates precoated with silica gel 60F-254 (10×10 as the stationary phase. The solvent system consisted of toluene:ethyl acetate:methanol:triethylamine (4:1:1:0.4 v/v/v. The system was found to give a compact spot for amlodipine besylate (R f = 0.39±0.02 and metoprolol succinate (R f = 0.59±0.02. Densitometric analysis of amlodipine besylate and metoprolol succinate was carried out in the absorbance mode at 254 nm. Linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.9990±0.0013 with respect to peak area in the concentration range 400-1400 ng per spot for amlodipine besylate and r2 = 0.9993±0.0013 with respect to peak area in the concentration range 3800-13300 ng per spot for metoprolol succinate. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 39.99 and 121.20 ng per spot for amlodipine besylate and 234.31 and 710.03 ng per spot for metoprolol succinate, respectively. Statistical analysis proved that the method is selective, precise and accurate for the estimation of amlodipine and metoprolol.

  17. Succinate overproduction: A case study of computational strain design using a comprehensive Escherichia coli kinetic model

    Directory of Open Access Journals (Sweden)

    Ali eKhodayari

    2015-01-01

    Full Text Available Computational strain design prediction accuracy has been the focus for many recent efforts through the selective integration of kinetic information into metabolic models. In general, kinetic model prediction quality is determined by the range and scope of genetic and/or environmental perturbations used during parameterization. In this effort, we apply the k-OptForce procedure on a kinetic model of E. coli core metabolism constructed using the Ensemble Modeling (EM method and parameterized using multiple mutant strains data under aerobic respiration with glucose as the carbon source. Minimal interventions are identified that improve succinate yield under both aerobic and anaerobic conditions to test the fidelity of model predictions under both genetic and environmental perturbations. Under aerobic condition, k-OptForce identifies interventions that match existing experimental strategies pointing at a number of unexplored flux redirections such as routing glyoxylate flux through the glycerate metabolism to improve succinate yield. Many of the identified interventions rely on the kinetic descriptions and would not be discoverable by a purely stoichiometric description. In contrast, under fermentative (anaerobic conditions, k-OptForce fails to identify key interventions including up-regulation of anaplerotic reactions and elimination of competitive fermentative products. This is due to the fact that the pathways activated under anaerobic conditions were not properly parameterized as only aerobic flux data were used in the model construction. This study shed light on the importance of condition-specific model parameterization and provides insight onto how to augment kinetic models so as to correctly respond to multiple environmental perturbations.

  18. Succinate Overproduction: A Case Study of Computational Strain Design Using a Comprehensive Escherichia coli Kinetic Model.

    Science.gov (United States)

    Khodayari, Ali; Chowdhury, Anupam; Maranas, Costas D

    2014-01-01

    Computational strain-design prediction accuracy has been the focus for many recent efforts through the selective integration of kinetic information into metabolic models. In general, kinetic model prediction quality is determined by the range and scope of genetic and/or environmental perturbations used during parameterization. In this effort, we apply the k-OptForce procedure on a kinetic model of E. coli core metabolism constructed using the Ensemble Modeling (EM) method and parameterized using multiple mutant strains data under aerobic respiration with glucose as the carbon source. Minimal interventions are identified that improve succinate yield under both aerobic and anaerobic conditions to test the fidelity of model predictions under both genetic and environmental perturbations. Under aerobic condition, k-OptForce identifies interventions that match existing experimental strategies while pointing at a number of unexplored flux re-directions such as routing glyoxylate flux through the glycerate metabolism to improve succinate yield. Many of the identified interventions rely on the kinetic descriptions that would not be discoverable by a purely stoichiometric description. In contrast, under fermentative (anaerobic) condition, k-OptForce fails to identify key interventions including up-regulation of anaplerotic reactions and elimination of competitive fermentative products. This is due to the fact that the pathways activated under anaerobic condition were not properly parameterized as only aerobic flux data were used in the model construction. This study shed light on the importance of condition-specific model parameterization and provides insight on how to augment kinetic models so as to correctly respond to multiple environmental perturbations.

  19. Metabolism of /sup 14/C-labeled doxylamine succinate (Bendectin) in the rhesus monkey (Macaca mulatta)

    Energy Technology Data Exchange (ETDEWEB)

    Slikker, W. Jr.; Holder, C.L.; Lipe, G.W.; Korfmacher, W.A.; Thompson, H.C. Jr.; Bailey, J.R.

    1986-05-01

    The time-course of the metabolic fate of (/sup 14/C)doxylamine was determined after the p.o. administration of 13 mg/kg doxylamine succinate as Bendectin plus (/sup 14/C)doxylamine succinate to the rhesus monkey. Urine and plasma samples were analyzed by reversed-phase high performance liquid chromatography (HPLC), chemical derivatization, and mass spectrometry. The cumulative 48-hr urinary metabolic profile contained 81% of the administered radiolabeled dose and consisted of at least six radiolabeled peaks. They were peak 1: unknown polar metabolites (8% of dose); peak 2: 2-(1-phenyl-1-(2-pyridinyl)ethoxy) acetic acid, 1-(1-phenyl-1(2-pyridinyl)ethoxy) methanol, and another minor metabolite(s) (31%); peak 3: doxylamine-N-oxide (1%); peak 4a: N,N-didesmethyldoxylamine (17%); peak 4b: doxylamine (4%); and peak 5: N-desmethyldoxylamine (20%). The plasma metabolic profile was the same as the urinary profile except for the absence of doxylamine-N-oxide. The maximum plasma concentrations and elapsed time to attain these concentrations were as follows. Peak 1: 540 ng/mL, 4 hr; peak 2: 1700 ng/mL, 1 hr; peak 4a: 430 ng/mL, 4 hr; peak 4b: 930 ng/mL, 2 hr; and peak 5: 790 ng/mL, 2 hr. These data suggest that in the monkey, doxylamine metabolism follows at least four pathways: a minor pathway to the N-oxide; a minor pathway to unknown polar metabolites; a major pathway to mono- and didesmethyldoxylamine via successive N-demethylation; and a major pathway to side-chain cleavage products (peak 2) via direct side-chain oxidation and/or deamination.

  20. Hygroscopic growth and droplet activation of soot particles: uncoated, succinic or sulfuric acid coated

    Science.gov (United States)

    Henning, S.; Ziese, M.; Kiselev, A.; Saathoff, H.; Möhler, O.; Mentel, T. F.; Buchholz, A.; Spindler, C.; Michaud, V.; Monier, M.; Sellegri, K.; Stratmann, F.

    2012-05-01

    The hygroscopic growth and droplet activation of uncoated soot particles and such coated with succinic acid and sulfuric acid were investigated during the IN-11 campaign at the Aerosol Interaction and Dynamics in the Atmosphere (AIDA) facility. A GFG-1000 soot generator applying either nitrogen or argon as carrier gas and a miniCAST soot generator were utilized to generate soot particles. Different organic carbon (OC) to black carbon (BC) ratios were adjusted for the CAST-soot by varying the fuel to air ratio. The hygroscopic growth was investigated by means of the mobile Leipzig Aerosol Cloud Interaction Simulator (LACIS-mobile) and two different Hygroscopicity Tandem Differential Mobility Analyzers (HTDMA, VHTDMA). Two Cloud Condensation Nucleus Counter (CCNC) were applied to measure the activation of the particles. For the untreated soot particles neither hygroscopic growth nor activation was observed at a supersaturation of 1%, with exception of a partial activation of GFG-soot generated with argon as carrier gas. Coatings of succinic acid lead to a detectable hygroscopic growth of GFG-soot and enhanced the activated fraction of GFG- (carrier gas: argon) and CAST-soot, whereas no hygroscopic growth of the coated CAST-soot was found. Sulfuric acid coatings led to an OC-content dependent hygroscopic growth of CAST-soot. Such a dependence was not observed for activation measurements. Coating with sulfuric acid decreased the amount of Polycyclic Aromatic Hydrocarbons (PAH), which were detected by AMS-measurements in the CAST-soot, and increased the amount of substances with lower molecular weight than the initial PAHs. We assume that these reaction products increased the hygroscopicity of the coated particles in addition to the coating substance itself.

  1. Hygroscopic growth and droplet activation of soot particles: uncoated, succinic or sulfuric acid coated

    Directory of Open Access Journals (Sweden)

    S. Henning

    2012-05-01

    Full Text Available The hygroscopic growth and droplet activation of uncoated soot particles and such coated with succinic acid and sulfuric acid were investigated during the IN-11 campaign at the Aerosol Interaction and Dynamics in the Atmosphere (AIDA facility. A GFG-1000 soot generator applying either nitrogen or argon as carrier gas and a miniCAST soot generator were utilized to generate soot particles. Different organic carbon (OC to black carbon (BC ratios were adjusted for the CAST-soot by varying the fuel to air ratio. The hygroscopic growth was investigated by means of the mobile Leipzig Aerosol Cloud Interaction Simulator (LACIS-mobile and two different Hygroscopicity Tandem Differential Mobility Analyzers (HTDMA, VHTDMA. Two Cloud Condensation Nucleus Counter (CCNC were applied to measure the activation of the particles. For the untreated soot particles neither hygroscopic growth nor activation was observed at a supersaturation of 1%, with exception of a partial activation of GFG-soot generated with argon as carrier gas. Coatings of succinic acid lead to a detectable hygroscopic growth of GFG-soot and enhanced the activated fraction of GFG- (carrier gas: argon and CAST-soot, whereas no hygroscopic growth of the coated CAST-soot was found. Sulfuric acid coatings led to an OC-content dependent hygroscopic growth of CAST-soot. Such a dependence was not observed for activation measurements. Coating with sulfuric acid decreased the amount of Polycyclic Aromatic Hydrocarbons (PAH, which were detected by AMS-measurements in the CAST-soot, and increased the amount of substances with lower molecular weight than the initial PAHs. We assume that these reaction products increased the hygroscopicity of the coated particles in addition to the coating substance itself.

  2. Hygroscopic growth and droplet activation of soot particles: uncoated, succinic or sulfuric acid coated

    Directory of Open Access Journals (Sweden)

    S. Henning

    2011-10-01

    Full Text Available The hygroscopic growth and droplet activation of uncoated soot particles and such coated with succinic acid and sulfuric acid were investigated during the IN-11 campaign at the Aerosol Interaction and Dynamics in the Atmosphere (AIDA facility. A GFG-1000 soot generator applying nitrogen, respectively argon as carrier gas and a miniCAST soot generator were utilized to generate soot particles. Different organic carbon (OC to black carbon (BC ratios were adjusted for the CAST-soot by varying the fuel to air ratio. The hygroscopic growth was investigated by means of the mobile Leipzig Aerosol Cloud Interaction Simulator (LACIS-mobile and two different Hygroscopicity Tandem Differential Mobility Analyzers (HTDMA, VHTDMA. Two Cloud Condensation Nucleus Counter (CCNC were applied to measure the activation of the particles. For the untreated soot particles neither hygroscopic growth nor activation was observed, with exception of a partial activation of GFG-soot generated with argon as carrier gas. Coatings of succinic acid lead to a detectable hygroscopic growth of GFG-soot and enhanced the activated fraction of GFG- (carrier gas: argon and CAST-soot, whereas no hygroscopic growth of the coated CAST-soot was found. Sulfuric acid coatings lead to an OC-content dependent hygroscopic growth of CAST-soot. Such a dependence was not observed for activation measurements. Coating with sulfuric acid decreased the amount of Polycyclic Aromatic Hydrocarbons (PAH, which were detected by AMS-measurements in the CAST-soot, and increased the amount of substances with lower molecular weight than the initial PAHs. We assume, that these reaction products increased the hygroscopicity of the coated particles in addition to the coating substance itself.

  3. Biodegradable mesoporous calcium–magnesium silicate-polybutylene succinate scaffolds for osseous tissue engineering

    Directory of Open Access Journals (Sweden)

    Zhang X

    2015-10-01

    Full Text Available Xinxin Zhang,1,2,* Chi Zhang,3,* Wei Xu,1,* Biao Zhong,3 Feng Lin,3 Jian Zhang,3 Quanxiang Wang,4 Jiajin Ji,4 Jie Wei,4 Yang Zhang1 1TongRen Hospital, School of Medicine, Shanghai Jiao Tong University, 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 3Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, 4Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The structural features of bone engineering scaffolds are expected to exhibit osteoinductive behavior and promote cell adhesion, proliferation, and differentiation. In the present study, we employed synthesized ordered mesoporous calcium–magnesium silicate (om-CMS and polybutylene succinate (PBSu to develop a novel scaffold with potential applications in osseous tissue engineering. The characteristics, in vitro bioactivity of om-CMS/PBSu scaffold, as well as the cellular responses of MC3T3-E1 cells to the composite were investigated. Our results showed that the om-CMS/PBSu scaffold possesses a large surface area and highly ordered channel pores, resulting in improved degradation and biocompatibility compared to the PBSu scaffold. Moreover, the om-CMS/PBSu scaffold exhibited significantly higher bioactivity and induced apatite formation on its surface after immersion in the simulated body fluid. In addition, the om-CMS/PBSu scaffold provided a high surface area for cell attachment and released Ca, Mg, and Si ions to stimulate osteoblast proliferation. The unique surface characteristics and higher biological efficacy of the om-CMS/PBSu scaffold suggest that it has great potential for being developed into a system that can be employed in osseous tissue engineering. Keywords: bone repair, polybutylene succinate, calcium–magnesium silicate, ordered mesoporous, proliferation

  4. 5-alpha-reductase type I (SRD5A1 is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosis

    Directory of Open Access Journals (Sweden)

    Kapp Friedrich G

    2012-01-01

    Full Text Available Abstract Background Non-small cell lung cancer (NSCLC is one of the most frequent malignancies and has a high mortality rate due to late detection and lack of efficient treatments. Identifying novel drug targets for this indication may open the way for new treatment strategies. Comparison of gene expression profiles of NSCLC and normal adjacent tissue (NAT allowed to determine that 5-alpha-reductase type I (SRD5A1 was up-regulated in NSCLC compared to NAT. This raised the question whether SRD5A1 was involved in sustained proliferation and survival of NSCLC. Methods siRNA-mediated silencing of SRD5A1 was performed in A549 and NCI-H460 lung cancer cell lines in order to determine the impact on proliferation, on distribution during the different phases of the cell cycle, and on apoptosis/necrosis. In addition, lung cancer cell lines were treated with 4-azasteroids, which specifically inhibit SRD5A1 activity, and the effects on proliferation were measured. Statistical analyses using ANOVA and post-hoc Tamhane-T2-test were performed. In the case of non-parametric data, the Kruskal-Wallis test and the post-hoc Mann-Whitney-U-test were used. Results The knock-down of SRDA51 expression was very efficient with the SRD5A1 transcripts being reduced to 10% of control levels. Knock-down efficiency was furthermore confirmed at the protein level. However, no effect of SRD5A1 silencing was observed in the proliferation assay, the cell cycle analysis, and the apoptosis/necrosis assay. Treatment of lung cancer cell lines with 4-azasteroids did not significantly inhibit proliferation. Conclusions In summary, the results suggest that SRD5A1 is not a crucial enzyme for the sustained proliferation of NSCLC cell lines.

  5. The gamma-aminobutyric acid shunt contributes to closing the tricarboxylic acid cycle in Synechocystis sp PCC 6803

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, W; Brune, D; Vermaas, WFJ

    2014-07-16

    A traditional 2-oxoglutarate dehydrogenase complex is missing in the cyanobacterial tricarboxylic acid cycle. To determine pathways that convert 2-oxoglutarate into succinate in the cyanobacterium Synechocystis sp. PCC 6803, a series of mutant strains, Delta sll1981, Delta slr0370, Delta slr1022 and combinations thereof, deficient in 2-oxoglutarate decarboxylase (Sll1981), succinate semialdehyde dehydrogenase (Slr0370), and/or in gamma-aminobutyrate metabolism (Slr1022) were constructed. Like in Pseudomonas aeruginosa, N-acetylornithine aminotransferase, encoded by slr1022, was shown to also function as gamma-aminobutyrate aminotransferase, catalysing gamma-aminobutyrate conversion to succinic semialdehyde. As succinic semialdehyde dehydrogenase converts succinic semialdehyde to succinate, an intact gamma-aminobutyrate shunt is present in Synechocystis. The Delta sll1981 strain, lacking 2-oxoglutarate decarboxylase, exhibited a succinate level that was 60% of that in wild type. However, the succinate level in the Delta slr1022 and Delta slr0370 strains and the Delta sll1981/Delta slr1022 and Delta sll1981/Delta slr0370 double mutants was reduced to 20-40% of that in wild type, suggesting that the gamma-aminobutyrate shunt has a larger impact on metabolite flux to succinate than the pathway via 2-oxoglutarate decarboxylase. C-13-stable isotope analysis indicated that the gamma-aminobutyrate shunt catalysed conversion of glutamate to succinate. Independent of the 2-oxoglutarate decarboxylase bypass, the gamma-aminobutyrate shunt is a major contributor to flux from 2-oxoglutarate and glutamate to succinate in Synechocystis sp. PCC 6803.

  6. 离子色谱法测定丁二酸合成电解液中马来酸和丁二酸%IC Determination of Maleic Acid and Succinic Acid in Electrolyte from Synthesis of Succinic Acid

    Institute of Scientific and Technical Information of China (English)

    马淳安; 邱志军; 颜飞; 赵峰鸣; 徐颖华; 褚有群

    2013-01-01

    采用离子色谱法测定丁二酸合成电解液中原料马来酸和产物丁二酸的含量.试样经Ion Pac AG19保护柱及Ion Pac AS19分析柱分离,以25 mmol·L-1氢氧化钾溶液为淋洗液,采用抑制电导器检测.马来酸和丁二酸的质量浓度在1.0~10 mg·L-1范围内与峰面积与峰高均呈线性关系.方法可用于测定合成丁二酸生产过程的不同时段溶液(起始、结束和母液)中马来酸和丁二酸的含量,有助于实现丁二酸的连续式电解合成工艺路线.%Contents of maleic acid (the raw material) and succinic acid (the products) in electrolyte from synthesis of succinic acid were determined by ion chromatography. Ion Pac AG19 protective column and Ion Pac AS19 separation column were used for separation and 25 mmol · L-1 KOH solution was used as eluant. Inhibitory conductivity detection was adopted in the determinatioa Linear relationships between values of peak area or peak height and mass concentration of maleic acid and succinic acid were kept in the range of 1. 0—10 mg · L-1. The proposed method could be used in the determination of the 2 acids in the electrolyte at different time interval (at starting and ending of electrolysis) and in the mother liquid in the synthetic process. The data obtained were helpful for the realization of synthetic technology of the continuous electrolytic production of succinic acid.

  7. Synthesis of Dimethyl Succinate by Continuous Catalytic Distillation%连续催化精馏合成丁二酸二甲酯

    Institute of Scientific and Technical Information of China (English)

    霍稳周; 魏晓霞; 田丹; 李花伊; 刘野

    2013-01-01

    以丁二酸和甲醇为原料、自主开发的耐温阳离子交换树脂为催化剂,采用无催化剂连续预酯化和连续催化精馏组合工艺合成了丁二酸二甲酯.考察了丁二酸进料液态空速、原料配比、反应温度等因素对丁二酸转化率和产物选择性的影响,并考察了催化剂的稳定性.实验结果表明,耐温阳离子交换树脂催化剂的稳定性好,在反应温度为110 ℃、甲醇与丁二酸的摩尔比为9、丁二酸进料液态空速为0.7 h-1的条件下连续运转2000h,丁二酸的平均转化率为99.96%,丁二酸二甲酯的平均选择性为99.93%.FTIR表征结果显示,反应产物的FTIR谱图与丁二酸二甲酯的标准谱图基本一致.该工艺具有良好的工业应用前景%Dimethyl succinate was synthesized from succinic acid and methanol over a proprietary heat-resistant cation exchange resin catalyst in a combined process containing continuous catalystfree pre-esterification and continuous catalytic distillation.The influences of succinic acid LHSV,mole ratio of methanol to succinic acid and reaction temperature on the conversion of succinic acid and the selectivity to the product dimethyl succinate were investigated.The experimental results show that the stability of the heat-resistant resin catalyst is good.Under the conditions of 110 ℃,mole ratio of methanol to succinic acid 9 and LHSV of succinic acid 0.7 h-1,the conversion of succinic acid and the selectivity to dimethyl succinate reached 99.96% and 99.93% after running 2000 h respectively.The structure of the product dimethyl succinate was verified by means of FTIR.

  8. Expression of the succinate dehydrogenase genes (sdhCAB) from the facultatively anaerobic paenibacillus macerans during aerobic growth

    Science.gov (United States)

    Schirawski; Hankeln; Unden

    1998-10-01

    Paenibacillus (formerly Bacillus) macerans is capable of succinate oxidation under oxic conditions and fumarate reduction under anoxic conditions. The reactions are catalyzed by different enzymes, succinate dehydrogenase (Sdh) and fumarate reductase (Frd). The genes encoding Sdh (sdhCAB) were analyzed. The gene products of sdhA and sdhB were similar to the subunits of known Sdh and Frd enzymes. The hydrophobic subunit SdhC showed close sequence similarity to the class of Sdh/Frd enzymes containing diheme cytochrome b. From the sdhCAB gene cluster two transcripts were produced, one comprising sdhCAB, the other sdhAB. The transcripts were found only during aerobic growth, and the amount was directly proportional to Sdh activity, but inversely proportional to Frd activity.

  9. Absorbance Correction Method for Simultaneous Estimation of Nifedipine and Metoprolol Succinate in Their Synthetic Mixture Using From Spectrophotometry

    Directory of Open Access Journals (Sweden)

    Sojitra Rajanit

    2015-03-01

    Full Text Available A new simple, economical, precise and accurate method are described for the simultaneous determination of Nifedipine (NIF and Metoprolol Succinate (MET in combined tablet dosage form. The proposed method was applied for the determination of Nifedipine and Metoprolol Succinate in synthetic mixture, for determination of sampling wavelength, 10μg/ml of each of NIF and MET were scanned in 200-400 nm range and sampling wavelengths were 313nm for NIF and 275.40nm for MET are selected for development and validation of absorption correction method. For this method linearity observed in the range of 5-25μg/ml for NIF and 25- 125μg/ml for MET, and in their pharmaceutical formulation with mean percentage recoveries 100.68 and 100.33, respectively. The method was validated according to ICH guidelines and can be applied for routine quality control testing.

  10. Leaf malate and succinate accumulation are out of phase throughout the development of the CAM plant Ananas comosus.

    Science.gov (United States)

    Rainha, N; Medeiros, V P; Ferreira, C; Raposo, A; Leite, J P; Cruz, C; Pacheco, C A; Ponte, D; Silva, A B

    2016-03-01

    In plants with Crassulacean Acid Metabolism (CAM), organic acids, mainly malate are crucial intermediates for carbon fixation. In this research we studied the circadian oscillations of three organic anions (malate, citrate, and succinate) in Ananas comosus, assessing the effect of season and plant development stage. Seasonal and plant development dependencies were observed. The circadian oscillations of malate and citrate were typical of CAM pathways reported in the literature. Citrate content was quite stable (25-30 μmol g(-1) FW) along the day, with a seasonal effect. Succinate was shown to have both diurnal and seasonal oscillations and also a correlation with malate, since it accumulated during the afternoon when malate content was normally at a minimum, suggesting a possible mechanistic effect between both anions in CAM and/or respiratory metabolisms.

  11. The H+/O ratio of proton translocation linked to the oxidation of succinate by mitochondria. Reply to a commentary.

    Science.gov (United States)

    Lehninger, A L; Reynafarje, B; Hendler, R W; Shrager, R I

    1985-11-18

    Costa, L.E., Reynafarje, B. and Lehninger, A.L. [(1984) J. Biol. Chem. 259, 4802-4811] have reported 'second-generation' measurements of the H+/O ratio approaching 8.0 for vectorial H+ translocation coupled to succinate oxidation by rat liver mitochondria. In a Commentary in this Journal [Krab, K., Soos, J. and Wikström, M. (1984) FEBS Lett. 178, 187-192] it was concluded that the measurements of Costa et al. significantly overestimated the true H+/O stoichiometry. It is shown here that the mathematical simulation on which Krab et al. based this claim is faulty and that data reported by Costa et al. had already excluded the criticism advanced by Krab et al. Also reported are new data, obtained under conditions in which the arguments of Krab et al. are irrelevant, which confirm that the H+/O ratio for succinate oxidation extrapolated to level flow is close to 8.

  12. A validity of the use of compositions on the basis of succinic acid in higher achievements sports.

    Directory of Open Access Journals (Sweden)

    Gunina L.М.

    2012-06-01

    Full Text Available A basic mechanism of influence on providing energy of muscular activity of succinic acid are analysed and the necessity of including in the complement of pharmacological facilities on her basis of other bioactive substances is reasonabled. In the 30 members of national team command of Ukraine on track-and-field at the level of cellular membranes at last 21 days a study of mechanisms of ergogenous action of dietary supplement "YantarIn-Sport" it was conducted and she's possesses a membranoprotective effect it was shown. In addition, a positive action of "YantarIn-Sport" on erythro- and leucopoiesis changes of bloods acid-base stat, as well as frequency of origin of sharp respiratory viral infections in sportsmen are well-proven. All of it is pre-conditions for including of facilities on the basis of succinic acid in the charts of the pharmacological providing of higher achievements sport.

  13. Identification of monomenthyl succinate, monomenthyl glutarate, and dimenthyl glutarate in nature by high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Hiserodt, Richard D; Adedeji, Jide; John, T V; Dewis, Mark L

    2004-06-01

    Menthol, menthone, and other natural compounds provide a cooling effect and a minty flavor and have found wide application in chewing gum and oral care products. Monomenthyl succinate, monomenthyl glutarate, and dimenthyl glutarate provide a cooling effect without the burning sensation associated with menthol. Additionally, because they do not have a distinct flavor, they can be used in applications other than mint flavors. Because these menthyl esters have not been reported in nature, we undertook to identify a natural source for these cooling compounds. Using high performance liquid chromatography-tandem mass spectrometry, monomenthyl succinate was identified in Lycium barbarum and Mentha piperita, and monomenthyl glutarate and dimenthyl glutarate were identified in Litchi chinesis. The identifications were based on the correlation of mass spectrometric and chromatographic retention time data for the menthyl esters in the extracts with authentic standards which resulted in a 99.980% confidence in the identifications.

  14. Mapping of Saccharomyces cerevisiae metabolites in fermenting wheat straight-dough reveals succinic acid as pH-determining factor.

    Science.gov (United States)

    Jayaram, Vinay B; Cuyvers, Sven; Lagrain, Bert; Verstrepen, Kevin J; Delcour, Jan A; Courtin, Christophe M

    2013-01-15

    Fermenting yeast does not merely cause dough leavening, but also contributes to the bread aroma and might alter dough rheology. Here, the yeast carbon metabolism was mapped during bread straight-dough fermentation. The concentration of most metabolites changed quasi linearly as a function of fermentation time. Ethanol and carbon dioxide concentrations reached up to 60 mmol/100g flour. Interestingly, high levels of glycerol (up to 10 mmol/100g flour) and succinic acid (up to 1.6 mmol/100g flour) were produced during dough fermentation. Further tests showed that, contrary to current belief, the pH decrease in fermenting dough is primarily caused by the production of succinic acid by the yeast instead of carbon dioxide dissolution or bacterial organic acids. Together, our results provide a comprehensive overview of metabolite production during dough fermentation and yield insight into the importance of some of these metabolites for dough properties.

  15. Contribution of the tricarboxylic acid (TCA) cycle and the glyoxylate shunt in Saccharomyces cerevisiae to succinic acid production during dough fermentation.

    Science.gov (United States)

    Rezaei, Mohammad N; Aslankoohi, Elham; Verstrepen, Kevin J; Courtin, Christophe M

    2015-07-02

    Succinic acid produced by yeast during bread dough fermentation can significantly affect the rheological properties of the dough. By introducing mutations in the model S288C yeast strain, we show that the oxidative pathway of the TCA cycle and the glyoxylate shunt contribute significantly to succinic acid production during dough fermentation. More specifically, deletion of ACO1 and double deletion of ACO1 and ICL1 resulted in a 36 and 77% decrease in succinic acid levels in fermented dough, respectively. Similarly, double deletion of IDH1 and IDP1 decreased succinic acid production by 85%, while also affecting the fermentation rate. By contrast, double deletion of SDH1 and SDH2 resulted in a two-fold higher succinic acid accumulation compared to the wild-type. Deletion of fumarate reductase activity (FRD1 and OSM1) in the reductive pathway of the TCA cycle did not affect the fermentation rate and succinic acid production. The changes in the levels of succinic acid produced by mutants Δidh1Δidp1 (low level) and Δsdh1Δsdh2 (high level) in fermented dough only resulted in small pH differences, reflecting the buffering capacity of dough at a pH of around 5.1. Moreover, Rheofermentometer analysis using these mutants revealed no difference in maximum dough height and gas retention capacity with the dough prepared with S288C. The impact of the changed succinic acid profile on the organoleptic or antimicrobial properties of bread remains to be demonstrated.

  16. 52. INHIBITORY EFFECTS OF VITAMIN E SUCCINATE ON BENZO(A) PYRENE-INDUCED FORESTOMACH CARCINOGENESIS IN FEMALE MICE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@This study is a part of an effort to develop effective chemoprevention for carcinogenesis of the forestomach. Vitamin E succinate(VES) administered by oral gavage and by intraperitioneal (IP) injections was used for the studies. Experimental design involved treating mice with Benzo(a) pyrene and VES(1.25 g/kg and 2.5 g/kg for gavage; 20 mg/kg for IP injections) for 4 weeks in order to study the

  17. Influence of cellulose derivatives and natural polymers on in vitro release kinetics of metoprolol succinate from extended release matrix tablets

    OpenAIRE

    Sunil, R.; Somagoni, Jagan M.; Panakanti, Pavan K.; Ega, Chandra M.; Yamsani, Madhusudan R.

    2011-01-01

    In the present investigation, extended release tablets of metoprolol succinate were developed using cellulose derivatives and natural gums as matrix formers and were evaluated for its extended release characteristics. The optimized formulation (F7) was obtained using cellulose derivatives in the ratio of 1:0.5:1drug, HPMC K 100M and Na CMC, respectively. Prepared tablets were subjected to all the Pharmacopeial quality tests and found to be in the limits. The in vitro release studies of prepar...

  18. Direct measurement of the initial proton extrusion to oxygen uptake ratio accompanying succinate oxidation by rat liver mitochondria.

    OpenAIRE

    Setty, O H; Shrager, R I; Bunow, B; Reynafarje, B; Lehninger, A L; Hendler, R W

    1986-01-01

    The problem of obtaining very early ratios for the H+/O stoichiometry accompanying succinate oxidation by rat liver mitochondria was attacked using new techniques for direct measurement rather than extrapolations based on data obtained after mixing and the recovery of the electrode from initial injection of O2. Respiration was quickly initiated in a thoroughly mixed O2-containing suspension of mitochondria under a CO atmosphere by photolysis of the CO-cytochrome c oxidase complex-. Fast respo...

  19. Poly(lactide)-g-poly(butylene succinate-co-adipate) with High Crystallization Capacity and Migration Resistance

    OpenAIRE

    Xi Yang; Huan Xu; Karin Odelius; Minna Hakkarainen

    2016-01-01

    Plasticized polylactide (PLA) with increased crystallization ability and prolonged life-span in practical applications due to the minimal plasticizer migration was prepared. Branched plasticized PLA was successfully obtained by coupling poly(butylene succinate-co-adipate) (PBSA) to crotonic acid (CA) functionalized PLA. The plasticization behavior of PBSA coupled PLA (PLA-CA-PBSA) and its counterpart PBSA blended PLA (PLA/PBSA) were fully elucidated. For both PLA-CA-PBSA and PLA/PBSA, a decre...

  20. Bagasse hydrolyzates from Agave tequilana as substrates for succinic acid production by Actinobacillus succinogenes in batch and repeated batch reactor.

    Science.gov (United States)

    Corona-González, Rosa Isela; Varela-Almanza, Karla María; Arriola-Guevara, Enrique; Martínez-Gómez, Álvaro de Jesús; Pelayo-Ortiz, Carlos; Toriz, Guillermo

    2016-04-01

    The aim of this work was to obtain fermentable sugars by enzymatic or acid hydrolyses of Agave tequilana Weber bagasse in order to produce succinic acid with Actinobacillus succinogenes. Hydrolyses were carried out with mineral acids (sulfuric and hydrochloric acids) or a commercial cellulolytic enzyme, and were optimized statistically by a response surface methodology, having as factors the concentration of acid/enzyme and time of hydrolysis. The concentration of sugars obtained at optimal conditions for each hydrolysis were 21.7, 22.4y 19.8g/L for H2SO4, HCl and the enzymatic preparation respectively. Concerning succinic acid production, the enzymatic hydrolyzates resulted in the highest yield (0.446g/g) and productivity (0.57g/Lh) using A. succinogenes in a batch reactor system. Repeated batch fermentation with immobilized A. succinogenes in agar and with the enzymatic hydrolyzates resulted in a maximum concentration of succinic acid of 33.6g/L from 87.2g/L monosaccharides after 5 cycles in 40h, obtaining a productivity of 1.32g/Lh.

  1. 琥珀酸的生产技术及应用初探%Production and application of succinic acid

    Institute of Scientific and Technical Information of China (English)

    盛晓晓; 周如金; 邱松山

    2012-01-01

    Succinic acid is an organic acid that occurs naturally in amber, and can be produced by chemical synthesis or fermentation. Succinic acid is highly reactive and has many derivatives, which makes it being extensively used in chemical, medical and food industries as an important industrial organic chemical and intermediate. The chemical synthesis and fermentation production of succinic acid were discussed, as well as its current and future application.%琥珀酸是从琥珀中分离的天然有机酸,可通过化学合成或微生物发酵得到,本身具有良好的反应活性,衍生物众多,是一种重要的有机化工原料及中间体,目前广泛应用于化工、医药、食品等行业,本文分别探讨了琥珀酸的化学合成及生物发酵的方法,并对其应用现状和前景进行了展望.

  2. Structural properties of pepsin-solubilized collagen acylated by lauroyl chloride along with succinic anhydride.

    Science.gov (United States)

    Li, Conghu; Tian, Zhenhua; Liu, Wentao; Li, Guoying

    2015-10-01

    The structural properties of pepsin-solubilized calf skin collagen acylated by lauroyl chloride along with succinic anhydride were investigated in this paper. Compared with native collagen, acylated collagen retained the unique triple helix conformation, as determined by amino acid analysis, circular dichroism and X-ray diffraction. Meanwhile, the thermostability of acylated collagen using thermogravimetric measurements was enhanced as the residual weight increased by 5%. With the temperature increased from 25 to 115 °C, the secondary structure of native and acylated collagens using Fourier transform infrared spectroscopy measurements was destroyed since the intensity of the major amide bands decreased and the positions of the major amide bands shifted to lower wavenumber, respectively. Meanwhile, two-dimensional correlation spectroscopy revealed that the most sensitive bands for acylated and native collagens were amide I and II bands, respectively. Additionally, the corresponding order of the groups between native and acylated collagens was different and the correlation degree for acylated collagen was weaker than that of native collagen, suggesting that temperature played a small influence on the conformation of acylated collagen, which might be concluded that the hydrophobic interaction improved the thermostability of collagen.

  3. Succinate dehydrogenase gene mutations are strongly associated with paraganglioma of the organ of Zuckerkandl.

    Science.gov (United States)

    Lodish, Maya B; Adams, Karen T; Huynh, Thanh T; Prodanov, Tamara; Ling, Alex; Chen, Clara; Shusterman, Suzanne; Jimenez, Camilo; Merino, Maria; Hughes, Marybeth; Cradic, Kendall W; Milosevic, Dragana; Singh, Ravinder J; Stratakis, Constantine A; Pacak, Karel

    2010-09-01

    Organ of Zuckerkandl paragangliomas (PGLs) are rare neuroendocrine tumors that are derived from chromaffin cells located around the origin of the inferior mesenteric artery extending to the level of the aortic bifurcation. Mutations in the genes encoding succinate dehydrogenase subunits (SDH) B, C, and D (SDHx) have been associated with PGLs, but their contribution to PGLs of the organ of Zuckerkandl PGLs is not known. We aimed to describe the clinical presentation of patients with PGLs of the organ of Zuckerkandl and investigate the prevalence of SDHx mutations and other genetic defects among them. The clinical characteristics of 14 patients with PGL of the organ of Zuckerkandl were analyzed retrospectively; their DNA was tested for SDHx mutations and deletions. Eleven out of 14 (79%) patients with PGLs of the organ of Zuckerkandl were found to have mutations in the SDHB (9) or SDHD (2) genes; one patient was found to have the Carney-Stratakis syndrome (CSS), and his PGL was discovered during surgery for gastrointestinal stromal tumor. Our results show that SDHx mutations are prevalent in pediatric and adult PGLs of the organ of Zuckerkandl. Patients with PGLs of the organ of Zuckerkandl should be screened for SDHx mutations and the CSS; in addition, asymptomatic carriers of an SDHx mutation among the relatives of affected patients may benefit from tumor screening for early PGL detection.

  4. RING OPENING COPOLYMERIZATION OF SUCCINIC ANHYDRIDE-ETHYLENE OXIDE BY Al (Ⅲ) ORGANOMETALLIC CATALYSTS

    Institute of Scientific and Technical Information of China (English)

    CHEN Xianhai; ZHANG Yifeng; SHEN Zhiquan

    1997-01-01

    Ring opening copolymerization of succinic anhydride (SA) with ethylene oxide (EO)was successfully carried out by using a series of aluminum-based catalyst in 1,4-dioxane at 62±2℃. The results showed that in-situ AlR3-H2O (R=ethyl, iso-butyl) catalysts gave higher molecular weight ((-M)w ~ 104), while Al(OR)3 catalysts gave the higher alternating copolymer structure with slightly lower molecular weight. The in-situ AlR3-H2O systems have been evaluated in more detail for the reaction which showed the optimum H2O/Al molar ratio to be 0.5. The copolymers with different composition (FSA/FEO = 36/64 to 45/55 mol/mol) were synthesized by using different monomer feed ratio. The melting point (Tm), glass transition temperature (Tg) and enthalpy of fusion (ΔHf) of these copolymers are depended on the copolymer composition and in the range of 87~ 102℃,-12 ~ -18℃, and 37 ~ 66J/g, respectively. The second heating scan of DSC also indicated that the higher alternating copolymer was more easily recrystallized. The onset decomposition temperature was more than 300℃ under nitrogen and influenced by the copolymer composition.

  5. Rheological, pasting, thermal and retrogradation properties of octenyl succinic anhydride modified potato starch

    Directory of Open Access Journals (Sweden)

    Chuin WON

    Full Text Available Abstract The objective of the present study was to investigate the rheological, pasting, and thermal properties of octenyl succinic anhydrate (OSA-modified potato starch. Potato starch was modified using different concentrations of OSA (0, 1, 3, and 5%, v/v. The degree of substitution (DS for the OSA-modified starch ranged from 0.0012 to 0.0055. The amylose leaching values of native and OSA-modified potato starch with different DS levels were in the range of 47.09-87.32%. The gel strength values of the OSA-modified starch were lower than those of native potato starch. Rapid Visco Analyzer data showed that peak, hot pasting, final and setback viscosities of the native starch decreased after OSA modification. Dynamic shear rheological tests, conducted at 4 °C, indicated that OSA-modified potato starch had weak gel-like behavior with the storage moduli (G' higher than the loss moduli (G” over most of the frequency ranges (0.63-63.8 rad·s-1.

  6. Stoichiometry of mitochondrial H+ translocation coupled to succinate oxidation at level flow.

    Science.gov (United States)

    Costa, L E; Reynafarje, B; Lehninger, A L

    1984-04-25

    The mechanistic stoichiometry of vectorial H+ translocation coupled to succinate oxidation by rat liver mitochondria in the presence of a permeant cation has been determined under level flow conditions with a membraneless fast responding O2 electrode kinetically matched with a glass pH electrode. The reactions were initiated by rapid injection of O2 into the anaerobically preincubated test system under conditions in which interfering H+ backflow was minimized. The rates of O2 uptake and H+ ejection, obtained from computer-fitted regression lines, were monotonic and first order over 75% of the course of O2 consumption. Extrapolation of the observed rates to zero time, at which zero delta mu H+ and thus level flow prevails, yielded vectorial H+/O flow ratios above 7 and closely approaching 8. The mitochondria undergo no irreversible change and give identical H+/O ratios on repeated tests. In a further refinement, the lower and upper limits of the mechanistic H+/O ratio were determined to be 7.55 and 8.56, respectively, from plots of the rates of O2 uptake versus H+ ejection at increasing malonate and increasing valinomycin concentrations, respectively. It is therefore concluded that the mechanistic H+/O ratio for energy-conserving sites 2 + 3 is 8, in confirmation of earlier measurements. KCl concentration is critical for maximal observed H+/O ratios. Optimum conditions and possible errors in determination of mechanistic H+/O translocation ratios are discussed.

  7. Sensitive Bromatometric Methods for the Determination of Sumatriptan Succinate in Pharmaceutical Formulations

    Directory of Open Access Journals (Sweden)

    K. V. V. Satyanarayana

    2011-01-01

    Full Text Available Two simple and sensitive spectrophotometric methods are described for the determination of sumatriptan succinate (STS in pure and tablets using bromate-bromide as the bromination reagent in acid medium and two dyes as subsidiary reagents. The two methods are based on the bromination of STS by a known excess of in situ generated bromine followed by determination of unreacted bromine by reacting with a fixed amount of methyl orange (Method A or indigo carmine (Method B and measuring the absorbance at 508 or 610 nm. In both methods, the amount of bromine reacted corresponds to the amount of STS. The experimental conditions for the assay have been optimized. In two methods, the absorbance was found to increase linearly with the concentration of STS at the respective wavelengths. Beer’s law was obeyed over the ranges 0.2-1.6 and 2.0-12.0 μg mL-1 for method A and method B respectively and the respective molar absorptivity values were 1.898×105 and 2.71×104 L mol-1 cm-1. The statistical analysis of the methods was validated according to the present ICH guidelines. The proposed methods were applied to the analysis of tablet form of STS and the results tallied well with the label claim.

  8. Bulk growth and characterization of novel organic piperazinium (bis) hydrogen succinate single crystals

    Science.gov (United States)

    Vizhi, R. Ezhil; Vijayalakshmi, M.

    2016-10-01

    The new organic nonlinear optical material piperazinium (bis) hydrogen succinate single crystal (PPHS) was synthesized by the slow evaporation method. The solubility of PPHS was determined by gravimetric analysis and the metastable zonewidth was assessed by polythermal method. The induction period was measured by isothermal method. The experimentally calculated values of the interfacial energies are in agreement with the theoretical values. As an outcome of studying the nucleation parameters, a bulk single crystal of PPHS was grown by slow cooling method. The structure of PPHS was estimated from single crystal X-ray diffraction analysis. FT NMR spectrum was analyzed. The cut - off wavelength and energy band gap values were found to be 254 nm and 4.85 eV respectively from the UV-vis-NIR spectrum analysis. The thermal stability of the grown crystal was studied. The mechanical strength and third order nonlinear optical susceptibility of the grown crystal were measured by Vicker's microhardness test and Z-scan technique respectively.

  9. Application of finite inverse gas chromatography in hypromellose acetate succinate-water-acetone systems.

    Science.gov (United States)

    Chiu, Sheng-Wei; Sturm, Derek R; Moser, Justin D; Danner, Ronald P

    2016-09-30

    A modification of a GC was developed to investigate both infinitely dilute and finite concentrations of solvents in polymers. Thermodynamic properties of hypromellose acetate succinate (HPMCAS-L)-acetone-water systems are important for the optimization of spray-drying processes used in pharmaceutical manufacturing of solid dispersion formulations. These properties, at temperatures below the glass transition temperature, were investigated using capillary column inverse gas chromatography (CCIGC). Water was much less soluble in the HPMCAS-L than acetone. Experiments were also conducted at infinitely dilute concentrations of one of the solvents in HPMCAS-L that was already saturated with the other solvent. Overall the partitioning of the water was not significantly affected by the presence of either water or acetone in the polymer. The acetone partition coefficient decreased as either acetone or water was added to the HPMCAS-L. A representation of the HPMCAS-L structure in terms of UNIFAC groups has been developed. With these groups, the UNIFAC-vdw-FV model did a reasonable job of predicting the phase equilibria in the binary and ternary systems. The Flory-Huggins correlation with fitted interaction parameters represented the data well.

  10. Solvent extraction separation of zirconium(IV from succinate media with N-n-octylaniline

    Directory of Open Access Journals (Sweden)

    M. M. RAJMANE

    2006-03-01

    Full Text Available The extraction behavior of zirconium(IV from succinate (0.01 – 0.03 M medium (25 mL with 10 mL 3 % N-n-octylaniline in xylene was investigated. The pH range 3.7 – 5.0 was effective for the quantitative extraction of zirconium(IV. Zirconium(IV was back extracted with 0.5 M HNO3 (3 × 5 mL. The method was free from interferences of a large number of cations and anions. Zirconium(IV was separated from associated elements in its binary mixture with Mo(VI, Nb(V, Re(VII, La(III, Ti(IV, Th(IV and Al(III. The proposed method was applied to synthetic mixtures. The results of analysis indicate that trace amounts of zirconium(IV could be separated effectively from higher amounts of other elements. The method is simple, selective, rapid and eco-friendly.

  11. The role of succinate dehydrogenase and oxaloacetate in metabolic suppression during hibernation and arousal.

    Science.gov (United States)

    Armstrong, Christopher; Staples, James F

    2010-06-01

    Hibernation elicits a major reduction in whole-animal O(2) consumption that corresponds with active suppression of liver mitochondrial electron transport capacity at, or downstream of, succinate dehydrogenase (SDH). During arousal from the torpor phase of hibernation this suppression is reversed and metabolic rates rise dramatically. In this study, we used the 13-lined ground squirrel (Ictidomys tridecemlineatus) to assess isolated liver mitochondrial respiration during the torpor phase of hibernation and various stages of arousal to elucidate a potential role of SDH in metabolic suppression. State 3 and state 4 respiration rates were seven- and threefold lower in torpor compared with the summer-active and interbout euthermic states. Respiration rates increased during arousal so that when body temperature reached 30 degrees C in late arousal, state 3 and state 4 respiration were 3.3- and 1.8-fold greater than during torpor, respectively. SDH activity was 72% higher in interbout euthermia than in torpor. Pre-incubating with isocitrate [to alleviate oxaloacetate (OAA) inhibition] increased state 3 respiration rate during torpor by 91%, but this rate was still fourfold lower than that measured in interbout euthermia. Isocitrate pre-incubation also eliminated differences in SDH activity among hibernation bout stages. OAA concentration correlated negatively with both respiration rates and SDH activity. These data suggest that OAA reversibly inhibits SDH in torpor, but cannot fully account for the drastic metabolic suppression observed during this hibernation phase.

  12. Aerogel Poly(butylene succinate) Biomaterial Substrate for RF and Microwave Applications

    Science.gov (United States)

    Habib Ullah, M.; Mahadi, W. N. L.; Latef, T. A.

    2015-08-01

    Polybutylene succinate (PBS) has become a potential candidate, similar to polypropylene (PP) and acrylonitrile butadiene styrene (ABS), for use as an organic plastic material due to its outstanding mechanical properties as well as high thermal deformation characteristics. A new composition of silica aerogel nanoparticles extracted from rice waste with PBS is proposed for use as a dielectric (ɛr = 4.5) substrate for microwave applications. A microstrip patch antenna was fabricated on the proposed dielectric substrate for multi-resonant ultra-wideband (UWB) applications. The performance characteristics of the proposed biomaterial-based antenna were investigated in a far-field measurement environment. The results indicate that the proposed biocompatible material-based antenna covered a bandwidth of 9.4 (2.3-11.7) GHz with stop bands from 5.5 GHz to 5.8 GHz and 7.0 GHz to 8.3 GHz. Peak gains of 9.82 dBi, 7.59 dBi, 8.0 dBi and 7.68 dBi were measured at resonant frequencies of 2.7 GHz, 4.6 GHz, 6.3 GHz and 9.5 GHz, respectively.

  13. Thermal and Mechanical Properties of Poly(butylene succinate Films Reinforced with Silica

    Directory of Open Access Journals (Sweden)

    Sangviroon Nanthaporn

    2015-01-01

    Full Text Available In recent year, bioplastics have become more popular resulting from the growing concerns on environmental issues and the rising fossil fuel price. However, their applications were limited by its mechanical and thermal properties. The aim of this research is thus to improve mechanical and thermal properties of PBS bioplastic films by reinforcing with silica. Due to the poor interfacial interaction between the PBS matrix and silica, glycidyl methacrylate grafted poly(butylene succinate (PBS-g-GMA was used as a compatibilizer in order to improve the interaction between bioplastic films and filler. PBS-g-GMA was prepared in a twin-screw extruder and analyzed by the FTIR spectrometer. PBS and silica were then mixed in a twin-screw extruder and processed into films by a chill-roll cast extruder. The effects of silica loading on thermal and mechanical properties of the prepared bioplastic films were investigated. It was found that the mechanical properties of PBS/silica composite films were improved when 1%wt of silica was added. However, the mechanical properties decreased with increasing silica loading due to the agglomeration of silica particles. The results also show that the silica/PBS films with PBS-g-GMA possessed improved mechanical properties over the films without the compatibilizer.

  14. DEVELOPMENT AND IN-VITRO EVALUATION OF METOPROLOL SUCCINATE CONTROLLED POROSITY OSMOTIC PUMP TABLETS

    Directory of Open Access Journals (Sweden)

    Veeramalla Anil Kumar

    2013-04-01

    Full Text Available In the present research work, attempts were made to develop and evaluate Sustained release formulation of Metoprolol succinate based on osmotic technology.As Metoprolol is a short acting drug, developed formulation provides the advantages of controlled release formulations. The developed formulation provides advantages of less steps of manufacturing procedure, no need of laser drilling, and economical. All of these made the procedure easily amenable to mass production using conventional tablet machines. Metoprolol 50mg core formulation was prepared using osmogents and coated with different coating formulae to optimize film former (cellulose acetate: pore former (sorbitol ratio. The effect of different formulation variables namely, membrane weight gain, and amount of pore former in the membrane, were studied. Metoprolol release was inversely proportional to the membrane weight (coating thickness but directly related to the initial amount of pore former (sorbitol in the membrane. All polymers and excipients used in optimized formula were found to be compatible with the drug and it was confirmed by FT-IR studies. Drug release from the developed formulations was independent of pH and agitational intensity. The drug release from formulation was proved as dependent on osmotic pressure only. The number of pores was directly proportional to the amount of pore former in the membrane. The manufactured formulations were stable after 45 days of accelerated stability studies.

  15. NONISOTHERMAL CRYSTALLIZATION AND MORPHOLOGY OF POLY(BUTYLENE SUCCINATE)/LAYERED DOUBLE HYDROXIDE NANOCOMPOSITES

    Institute of Scientific and Technical Information of China (English)

    Mei-qiu Zhan; Guang-yi Chen; Zhi-yong Wei; Yu-mei Shi; Wan-xi Zhang

    2013-01-01

    Biodegradable poly(butylene succinate) (PBS) and layered double hydroxide (LDH) nanocomposites were prepared via melt blending in a twin-screw extruder.The morphology and dispersion of LDH nanoparticles within PBS matrix were characterized by transmission electron microscopy (TEM),which showed that LDH nanoparticles were found to be well distributed at the nanometer level.The nonisothermal crystallization behavior of nanocomposites was extensively studied using differential scanning calorimetry (DSC) technique at various cooling rates.The crystallization rate of PBS was accelerated by the addition of LDH due to its heterogeneous nucleation effect; however,the crystallization mechanism and crystal structure of PBS remained almost unchanged.In kinetics analysis of nonisothermal crystallization,the Ozawa approach failed to describe the crystallization behavior of PBS/LDH nanocomposites,whereas both the modified Avrami model and the Mo method well represented the crystallization behavior of nanocomposites.The effective activation energy was estimated as a function of the relative degree of crystallinity using the isoconversional analysis.The subsequent melting behavior of PBS and PBS/LDH nanocomposites was observed to be dependent on the cooling rate.The POM showed that the small and less perfect crystals were formed in nanocomposites.

  16. Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

    Energy Technology Data Exchange (ETDEWEB)

    Milione, Massimo [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pusceddu, Sara [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Gasparini, Patrizia [Molecular Cytogenetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Melotti, Flavia [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Maisonneuve, Patrick [Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan 20141 (Italy); Mazzaferro, Vincenzo [Division of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Braud, Filippo G. de [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pelosi, Giuseppe, E-mail: giuseppe.pelosi@unimi.it [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Department of Medicine, Surgery and Dentistry, Università degli Studi, Facoltà di Medicina, Milan 20122 (Italy)

    2012-08-16

    Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.

  17. [Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].

    Science.gov (United States)

    Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

    2011-01-01

    Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

  18. Carob pod water extracts as feedstock for succinic acid production by Actinobacillus succinogenes 130Z.

    Science.gov (United States)

    Carvalho, Margarida; Roca, Christophe; Reis, Maria A M

    2014-10-01

    Carob pods are a by-product of locust bean gum industry containing more than 50% (w/w) sucrose, glucose and fructose. In this work, carob pod water extracts were used, for the first time, for succinic acid production by Actinobacillus succinogenes 130Z. Kinetic studies of glucose, fructose and sucrose consumption as individual carbon sources till 30g/L showed no inhibition on cell growth, sugar consumption and SA production rates. Sugar extraction from carob pods was optimized varying solid/liquid ratio and extraction time, maximizing sugar recovery while minimizing the extraction of polyphenols. Batch fermentations containing 10-15g/L total sugars resulted in a maximum specific SA production rate of 0.61Cmol/Cmol X.h, with a yield of 0.55Cmol SA/Cmol sugar and a volumetric productivity of 1.61g SA/L.h. Results demonstrate that carob pods can be a promising low cost feedstock for bio-based SA production.

  19. Effect of Rubberwood Content on Biodegradability of Poly(butylene succinate Biocomposites

    Directory of Open Access Journals (Sweden)

    Hemhong Anankaphong

    2015-01-01

    Full Text Available Poly(butylene succinate (PBS biocomposites incorporated with rubberwood powder (RWP were fabricated with various RWP weight fractions (i.e., 0 to 40% wt by injection moulding process. The soil burial test was employed to examine the biodegradability of such biocomposites under outdoor environment for 60 days. The physical appearance, percentage weight loss, chemical structure, and mechanical properties before and after the soil burial test were determined. Apparent changes in physical appearance of the biocomposites from optical micrographs were detected in terms of surface morphology and colour. The percentage of crystallinity of PBS/RWP biocomposites was studied by the X-ray diffraction (XRD technique, and the XRD pattern revealed a decrease in percentage of crystallinity due to enhancing RWP weight fractions. This may be attributed to a presence of rubberwood powders providing more disordered molecular chain arrangement of PBS matrix and also an agglomeration of the rubberwood powder content at greater concentration as seen in SEM micrographs. With increasing RWP weight fractions and burial time, the results exhibited a considerable change in chemical structure (essentially ester linkage due to biodegradation mechanism of PBS, relatively greater percentage weight loss, and a substantial decrease in flexural properties. Consequently, the results indicate that incorporating RWP enhances biodegradability of PBS/RWP biocomposites; that is, the biodegradation rate of biocomposites increases with increasing RWP weight fractions and burial time.

  20. Phase Transformation of Adefovir Dipivoxil/Succinic Acid Cocrystals Regulated by Polymeric Additives

    Directory of Open Access Journals (Sweden)

    Sungyup Jung

    2013-12-01

    Full Text Available The polymorphic phase transformation in the cocrystallization of adefovir dipivoxil (AD and succinic acid (SUC was investigated. Inspired by biological and biomimetic crystallization, polymeric additives were utilized to control the phase transformation. With addition of poly(acrylic acid, the metastable phase newly identified through the analysis of X-ray diffraction was clearly isolated from the previously reported stable form. Without additives, mixed phases were obtained even at the early stage of cocrystallization. Also, infrared spectroscopy analysis verified the alteration of the hydrogen bonding that was mainly responsible for the cocrystal formation between AD and SUC. The hydrogen bonding in the metastable phase was relatively stronger than that in the stable form, which indicated the locally strong AD/SUC coupling in the initial stage of cocrystallization followed by the overall stabilization during the phase transformation. The stronger hydrogen bonding could be responsible for the faster nucleation of the initially observed metastable phase. The present study demonstrated that the polymeric additives could function as effective regulators for the polymorph-selective cocrystallization.

  1. Analysis of Gas Permeability Characteristics of Poly(Lactic Acid/Poly(Butylene Succinate Nanocomposites

    Directory of Open Access Journals (Sweden)

    Amita Bhatia

    2012-01-01

    Full Text Available Gas permeability and morphological properties of nanocomposites prepared by the mixing of poly(lactic acid (PLA, poly(butylene succinate (PBS, and clay was investigated. While the composition of PLA and PBS polymers was fixed as 80% and 20% by weight, respectively, for all the nanocomposites, clay contents varied from 1 to 10 wt%. From the morphological studies using both wide angle X-ray diffraction and transmission electron microscopy, the nanocomposite having 1 wt% of clay was considered to have a mixed morphology of intercalated and delaminated structure, while some clusters or agglomerated particles were detected for nanocomposites having 3 and more than 3 wt% of clay content. However, the average particle size of the dispersed PBS phase was reduced significantly from 7 μm to 30–40 nm with the addition of clay in the blend. The oxygen barrier property was improved significantly as compared to the water vapor. A model based on gas barrier property was used for the validation of the oxygen relative permeabilities of PLA/PBS/clay nanocomposites. PLA/PBS/clay nanocomposites validated the Bharadwaj model up to 3 wt% of clay contents only, while for nanocomposites of higher clay contents the Bharadwaj model was invalid due to the clusters and agglomerates formed.

  2. Effect of hydrophilic and hydrophobic polymers on release kinetics of metoprolol succinate extended release tablets

    Directory of Open Access Journals (Sweden)

    Ramani Gade

    2011-01-01

    Full Text Available The purpose of the present work is to design and evaluate extended release matrix tablets of metoprolol succinate to reduce the dosing frequency and to improve patient compliance. The matrix tablets were prepared by the combination of hydrophilic and hydrophobic polymers, using methocel 10000 Cps in combination with ethyl cellulose 7 Cps, Eudragit® RS100, Eudragit® S100, and Eudragit® L100.The tablets were prepared by direct compression technique. Prepared formulations were evaluated for various parameters like weight variation, thickness, hardness, friability, and % drug content. Tablets were subjected to in vitro drug release studies. The formulations containing methocel 10000 Cps, Eudragit® L100 showed good release retardation. All the prepared formulations showed first-order release kinetics with matrix diffusion mechanism of release. The formulation containing 52.06% w/w of methocel 10000 Cps, 8.75% Eudragit® L100 offered the required release rate according to USP Pharmacopoeial guidelines. The combination of hydrophilic and hydrophobic polymers can effectively control the drug release for freely water-soluble drugs in case of extended release formulations which are the upcoming dosage forms for patient compliance in all aspects.

  3. γ-Glutamyl semialdehyde and 2-amino-adipic semialdehyde: biomarkers of oxidative damage to proteins

    DEFF Research Database (Denmark)

    Daneshvar, B.; Frandsen, H.; Autrup, Herman

    1997-01-01

    or Pro, while AAS is an oxidation product of Lys. When oxidative stress was induced in rats by treatments with t-butyl hydroperoxide or acrolein, rat plasma protein levels of GGS and AAS were found to be significantly higher compared with control rats. The AAS-content in serum albumin or in total plasma...

  4. Sugar-Based Ethanol Biorefinery: Ethanol, Succinic Acid and By-Product Production

    Energy Technology Data Exchange (ETDEWEB)

    Donal F. Day

    2009-03-31

    The work conducted in this project is an extension of the developments itemized in DE-FG-36-04GO14236. This program is designed to help the development of a biorefinery based around a raw sugar mill, which in Louisiana is an underutilized asset. Some technical questions were answered regarding the addition of a biomass to ethanol facility to existing sugar mills. The focus of this work is on developing technology to produce ethanol and valuable by-products from bagasse. Three major areas are addressed, feedstock storage, potential by-products and the technology for producing ethanol from dilute ammonia pre-treated bagasse. Sugar mills normally store bagasse in a simple pile. During the off season there is a natural degradation of the bagasse, due to the composting action of microorganisms in the pile. This has serious implications if bagasse must be stored to operate a bagasse/biorefinery for a 300+ day operating cycle. Deterioration of the fermentables in bagasse was found to be 6.5% per month, on pile storage. This indicates that long term storage of adequate amounts of bagasse for year-round operation is probably not feasible. Lignin from pretreatment seemed to offer a potential source of valuable by-products. Although a wide range of phenolic compounds were present in the effluent from dilute ammonia pretreatment, the concentrations of each (except for benzoic acid) were too low to consider for extraction. The cellulosic hydrolysis system was modified to produce commercially recoverable quantities of cellobiose, which has a small but growing market in the food process industries. A spin-off of this led to the production of a specific oligosaccharide which appears to have both medical and commercial implications as a fungal growth inhibitor. An alternate use of sugars produced from biomass hydrolysis would be to produce succinic acid as a chemical feedstock for other conversions. An organism was developed which can do this bioconversion, but the economics of

  5. Floating and bioadhesive delivery system of metoprolol succinate: Formulation, development and in vitro evaluation

    Directory of Open Access Journals (Sweden)

    Mohan Rathi

    2012-01-01

    Full Text Available Aim of this study was to develop gastroretentive sustained release floating and bioadhesive drug delivery system (FBDDS to prolong the gastric retention time of Metoprolol succinate. Tablets were prepared employing hydroxypropyl methylcellulose (HPMC K100M as hydrophilic gel material, sodium bicarbonate as gas-generating agent and Sodium CMC (SCMC as bioadhesive polymer. A 3 2 full factorial design and response surface methodology were used for designing of experiment, mapping change in responses and deriving optimum formulation. Selected independent variables were amounts HPMC K100M and SCMC polymer while floating lag time (FLT, bioadhesive strength, t 50 (time taken to release 50% of drug and t90 (time taken to release 90% of drug were selected as dependent variables. Investigation of functionality of individual polymer to predict effect on dependent variable were statistically analyzed using the RSM. Tablets were also evaluated for physical properties, swelling and matrix erosion. Increase in concentration of HPMC and decrease in concentration of SCMC resulted in retardation of drug release. Furthermore, combination of HPMC K100M and sodium bicarbonate along with SCMC was found to affect buoyancy, bioadhesion strength and drug release. Optimized formulation showed values of dependent variables close to predicted values. Optimized formulation follows Higuchi kinetics with short buoyancy lag time, total buoyancy time of more than 24 hours and could maintain drug release for 24 hours. Content uniformity, hardness, friability, weight variation were all lying within limits. Hence, FBDDS was found to be very promising and alternative approach to increase gastric retention of dosage form and may improve bioavailability.

  6. Pituitary Adenoma With Paraganglioma/Pheochromocytoma (3PAs) and Succinate Dehydrogenase Defects in Humans and Mice

    Science.gov (United States)

    Xekouki, Paraskevi; Szarek, Eva; Bullova, Petra; Giubellino, Alessio; Quezado, Martha; Mastroyannis, Spyridon A.; Mastorakos, Panagiotis; Wassif, Christopher A.; Raygada, Margarita; Rentia, Nadia; Dye, Louis; Cougnoux, Antony; Koziol, Deloris; Sierra, Maria de La Luz; Lyssikatos, Charalampos; Belyavskaya, Elena; Malchoff, Carl; Moline, Jessica; Eng, Charis; Maher, Louis James; Pacak, Karel; Lodish, Maya

    2015-01-01

    Context: Germline mutations in genes coding succinate dehydrogenase (SDH) subunits A, B, C, and D have been identified in familial paragangliomas (PGLs)/pheochromocytomas (PHEOs) and other tumors. We described a GH-secreting pituitary adenoma (PA) caused by SDHD mutation in a patient with familial PGLs. Additional patients with PAs and SDHx defects have since been reported. Design: We studied 168 patients with unselected sporadic PA and with the association of PAs, PGLs, and/or pheochromocytomas, a condition we named the 3P association (3PAs) for SDHx germline mutations. We also studied the pituitary gland and hormonal profile of Sdhb+/− mice and their wild-type littermates at different ages. Results: No SDHx mutations were detected among sporadic PA, whereas three of four familial cases were positive for a mutation (75%). Most of the SDHx-deficient PAs were either prolactinomas or somatotropinomas. Pituitaries of Sdhb+/− mice older than 12 months had an increased number mainly of prolactin-secreting cells and several ultrastructural abnormalities such as intranuclear inclusions, altered chromatin nuclear pattern, and abnormal mitochondria. Igf-1 levels of mutant mice tended to be higher across age groups, whereas Prl and Gh levels varied according to age and sex. Conclusion: The present study confirms the existence of a new association that we termed 3PAs. It is due mostly to germline SDHx defects, although sporadic cases of 3PAs without SDHx defects also exist. Using Sdhb+/− mice, we provide evidence that pituitary hyperplasia in SDHx-deficient cells may be the initial abnormality in the cascade of events leading to PA formation. PMID:25695889

  7. INVESTIGATION ON THE GELATION BEHAVIOR OF BIODEGRADABLE POLY(BUTYLENE SUCCINATE) DURING ISOTHERMAL CRYSTALLIZATION PROCESS

    Institute of Scientific and Technical Information of China (English)

    Fa-liang Luo; Xiu-qin Zhang; Wei Ning; Du-jin Wang

    2011-01-01

    The early stage of polymer crystallization may be viewed as physical gelation process, ie., the phase transition of polymer from liquid to solid. Determination of the gel point is of significance in polymer processing. In this work, the gelation behavior ofpoly(bntylene succinate) (PBS) at different temperatures has been investigated by theological method. It was found that during the isothermal crystallization process of PBS, both the storage modulus (G′) and the loss modulus (G")increase with time, and the theological response of the system varies from viscous-dominated (G′ < G") to elastic-dominated (G′ > G"), meaning the phase transition from liquid to solid. The physical gel point was determined by the intersection point of loss tangent curves measured under different frequencies. The gel time (tc) for PBS was found to increase with increasing crystallization temperature. The relative crystallinity of PBS at the gel point is very low (2.5%-8.5%) and increases with increasing the crystallization temperature. The low crystallinity of PBS at the gel point suggests that only a few junctions are necessary to form a spanning network, indicating that the network is “loosely” connected, in another word, the critical gel is soft. Due to the elevated crystallinity at gel point under higher crystallization temperature, the gel strength Sg increases,while the relaxation exponent n decreases with increasing the crystallization temperature. These experimental results suggest that rheological method is an effective tool for verifying the gel point of biodegradable semi-crystalline polymers.

  8. Successful chemotherapy of hepatic metastases in a case of succinate dehydrogenase subunit B-related paraganglioma.

    Science.gov (United States)

    He, J; Makey, D; Fojo, T; Adams, K T; Havekes, B; Eisenhofer, G; Sullivan, P; Lai, E W; Pacak, K

    2009-10-01

    Compared to other familial pheochromocytoma/paragangliomas (PHEO/PGLs), the succinate dehydrogenase subunit B (SDHB)-related PHEO/PGLs often present with aggressive and rapidly growing metastatic lesions. Currently, there is no proven effective treatment for malignant PHEO/PGLs. Here, we present a 35-year-old white man with primary malignant abdominal extra-adrenal 11 cm paraganglioma underwent surgical successful resection. But 6 months later, he developed extensive bone, liver, and lymph nodes metastasis, which were demonstrated by computed tomography scan and the (18)F-fluorodeoxyglucose positron emission tomography. However, his (123)I-metaiodobenzylguanidine scintigraphy was negative; therefore, the cyclophosphamide, vincristine, and dacarbazine (CVD) combination chemotherapy was initiated. The combination chemotherapy was very effective showing 80% overall reduction in the liver lesions and 75% overall reduction in the retroperitoneal mass and adenopathy, and normalization of plasma catecholamine and metanephrine levels. However, plasma levels of dopamine (DA) and methoxytyramine (MTY) were only partially affected and remained consistently elevated throughout the remaining period of follow-up evaluation. Genetic testing revealed an SDHB gene mutation. Here, we present an SDHB-related PHEO/PGL patient with extensive tumor burden, numerous organ lesions, and rapidly growing tumors, which responded extremely well to CVD therapy. We conclude patients with SDHB-related PHEO/PGLs can be particularly sensitive to CVD chemotherapy and may have an excellent outcome if this therapy is used and continued on periodic basis. The data in this patient also illustrate the importance of measuring plasma levels of DA and MTY to provide a more complete and accurate assessment of the biochemical response to therapy than provided by measurements restricted to other catecholamines and O-methylated metabolites.

  9. CRISPR-Cas9 for the genome engineering of cyanobacteria and succinate production.

    Science.gov (United States)

    Li, Hung; Shen, Claire R; Huang, Chun-Hung; Sung, Li-Yu; Wu, Meng-Ying; Hu, Yu-Chen

    2016-11-01

    Cyanobacteria hold promise as a cell factory for producing biofuels and bio-derived chemicals, but genome engineering of cyanobacteria such as Synechococcus elongatus PCC 7942 poses challenges because of their oligoploidy nature and long-term instability of the introduced gene. CRISPR-Cas9 is a newly developed RNA-guided genome editing system, yet its application for cyanobacteria engineering has yet to be reported. Here we demonstrated that CRISPR-Cas9 system can effectively trigger programmable double strand break (DSB) at the chromosome of PCC 7942 and provoke cell death. With the co-transformation of template plasmid harboring the gene cassette and flanking homology arms, CRISPR-Cas9-mediated DSB enabled precise gene integration, ameliorated the homologous recombination efficiency and allowed the use of lower amount of template DNA and shorter homology arms. The CRISPR-Cas9-induced cell death imposed selective pressure and enhanced the chance of concomitant integration of gene cassettes into all chromosomes of PCC 7942, hence accelerating the process of obtaining homogeneous and stable recombinant strains. We further explored the feasibility of engineering cyanobacteria by CRISPR-Cas9-assisted simultaneous glgc knock-out and gltA/ppc knock-in, which improved the succinate titer to 435.0±35.0μg/L, an ≈11-fold increase when compared with that of the wild-type cells. These data altogether justify the use of CRISPR-Cas9 for genome engineering and manipulation of metabolic pathways in cyanobacteria.

  10. Chiral separation of (d- and (l-enantiomers of doxylamine succinate in rat plasma

    Directory of Open Access Journals (Sweden)

    Tadiboyina Sirisha

    2015-12-01

    Full Text Available A selective chiral ultra fast liquid chromatography (UFLC-DAD method was developed and validated to separate and quantify the (d- and (l-enantiomers of doxylamine in rat plasma. After extraction of the plasma samples with acetonitrile, the separation of doxylamine succinate enantiomers and internal standard (I.S., diphenhydramine hydrochloride was achieved on a cellulose Tris (4-chloro,3-methylphenylcarbamate column with a mobile phase of 20 mM ammonium bicarbonate buffer–acetonitrile (65:35 v/v with 0.15% diethylamine in the buffer at a flow rate of 1.0 mL/min. The diode array (DAD detection wavelength was set at 220 nm. The peaks obtained were identified as (d and (l by injecting the pure (d form into the liquid chromatography and comparing the chromatograms. The effect of column oven temperature on the retention of doxylamine and mobile phase variables which have an effect on the enantiomers separation like ionic strength, type and concentration of organic modifier was studied. Linear calibration curves were obtained over the range of 100–1400 ng/mL in plasma for both enantiomers (R2 > 0.995. The mean extraction recoveries were 94.5–104.7% of rat plasma. The mean relative standard deviation (RSD% of accuracy and intra-day and inter-day precision for both enantiomers were ⩽10%. The method can be further applied to determine the pharmacokinetics of (d- and (l-enantiomers in rat plasma.

  11. Novel bioactive polyester scaffolds prepared from unsaturated resins based on isosorbide and succinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Śmiga-Matuszowicz, Monika, E-mail: monika.smiga-matuszowicz@polsl.pl [Silesian University of Technology, Department of Physical Chemistry and Technology of Polymers, M. Strzody Street 9, 44-100 Gliwice (Poland); Janicki, Bartosz; Jaszcz, Katarzyna; Łukaszczyk, Jan [Silesian University of Technology, Department of Physical Chemistry and Technology of Polymers, M. Strzody Street 9, 44-100 Gliwice (Poland); Kaczmarek, Marcin [Silesian University of Technology, Department of Biomaterials and Medical Devices Engineering, de Gaulle' a Street 66, 41-800 Zabrze (Poland); Lesiak, Marta; Sieroń, Aleksander L. [Medical University of Silesia, Department of General and Molecular Biology and Genetics, Medyków Street 18, 40-752 Katowice (Poland); Simka, Wojciech [Silesian University of Technology, Department of Chemistry, Inorganic Technology and Fuels, B. Krzywoustego Street 6, 44-100 Gliwice (Poland); Mierzwiński, Maciej; Kusz, Damian [Medical University of Silesia, Department of Orthopedics and Traumatology, Ziołowa Street 45, 40-635 Katowice (Poland)

    2014-12-01

    In this study new biodegradable materials obtained by crosslinking poly(3-allyloxy-1,2-propylene succinate) (PSAGE) with oligo(isosorbide maleate) (OMIS) and small amount of methyl methacrylate were investigated. The porous scaffolds were obtained in the presence of a foaming system consisted of calcium carbonate/carboxylic acid mixture, creating in situ porous structure during crosslinking of liquid formulations. The maximum crosslinking temperature and setting time, the cured porous materials morphology as well as the effect of their porosity on mechanical properties and hydrolytic degradation process were evaluated. It was found that the kind of carboxylic acid used in the foaming system influenced compressive strength and compressive modulus of porous scaffolds. The MTS cytotoxicity assay was carried out for OMIS using hFOB1.19 cell line. OMIS resin was found to be non-toxic in wide range of concentrations. On the ground of scanning electron microscopy (SEM) observations and energy X-ray dispersive analysis (EDX) it was found that hydroxyapatite (HA) formation at the scaffolds surfaces within short period of soaking in phosphate buffer solution occurs. After 3 h immersion a compact layer of HA was observed at the surface of the samples. The obtained results suggest potential applicability of resulted new porous crosslinked polymeric materials as temporary bone void fillers. - Highlights: • Isosorbide-based resin was used as a component of biodegradable scaffolds. • CAC/carboxylic acid system was proven as facile method to obtain porous scaffolds. • Porous scaffolds displayed the formation of hydroxyapatite at their surfaces.

  12. Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae

    Institute of Scientific and Technical Information of China (English)

    YANG Wei-ping; HU Bo-hua; SUN Jian-he; ZHAI Suo-qiang; Donald Henderson

    2010-01-01

    Background Our previous studies have shown that both apoptosis and necrosis are involved in hair cell (HC) pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae.Methods The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy.Results Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs.Conclusions In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results suggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.

  13. Structural properties of pepsin-solubilized collagen acylated by lauroyl chloride along with succinic anhydride

    Energy Technology Data Exchange (ETDEWEB)

    Li, Conghu [The Key Laboratory of Leather Chemistry and Engineering of Ministry of Education, Sichuan University, Chengdu 610065 (China); College of Life Sciences, Anqing Normal University, Anqing 246011 (China); Tian, Zhenhua; Liu, Wentao [The Key Laboratory of Leather Chemistry and Engineering of Ministry of Education, Sichuan University, Chengdu 610065 (China); Li, Guoying, E-mail: liguoyings@163.com [The Key Laboratory of Leather Chemistry and Engineering of Ministry of Education, Sichuan University, Chengdu 610065 (China)

    2015-10-01

    The structural properties of pepsin-solubilized calf skin collagen acylated by lauroyl chloride along with succinic anhydride were investigated in this paper. Compared with native collagen, acylated collagen retained the unique triple helix conformation, as determined by amino acid analysis, circular dichroism and X-ray diffraction. Meanwhile, the thermostability of acylated collagen using thermogravimetric measurements was enhanced as the residual weight increased by 5%. With the temperature increased from 25 to 115 °C, the secondary structure of native and acylated collagens using Fourier transform infrared spectroscopy measurements was destroyed since the intensity of the major amide bands decreased and the positions of the major amide bands shifted to lower wavenumber, respectively. Meanwhile, two-dimensional correlation spectroscopy revealed that the most sensitive bands for acylated and native collagens were amide I and II bands, respectively. Additionally, the corresponding order of the groups between native and acylated collagens was different and the correlation degree for acylated collagen was weaker than that of native collagen, suggesting that temperature played a small influence on the conformation of acylated collagen, which might be concluded that the hydrophobic interaction improved the thermostability of collagen. - Highlights: • Acylated collagen retained the unique triple helix conformation. • Acylated collagen had stronger thermostability than native collagen. • Amide I was the most sensitive band to the temperature for acylated collagen. • Amide II was the most sensitive band to the temperature for native collagen. • Auto-peak at 1680 cm{sup −1} for acylated collagen disappeared at higher temperature.

  14. Influences of hyperbranched poly(amide-ester) on the properties of poly(butylene succinate)

    Energy Technology Data Exchange (ETDEWEB)

    Run, Mingtao, E-mail: lhbx@hbu.cn [Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002 (China); Wang, Jian; Yao, Meng; Guo, Lijie; Wang, Hai-jun [Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002 (China); Ba, Xinwu, E-mail: baxw@hbu.cn [Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002 (China)

    2013-05-15

    The polymer blends of hyperbranched poly(amide-ester) and poly(butylene succinate) (HBP/PBS) were prepared by melt-blending method. The molecular interaction within the blends, phase morphology, crystal morphology, mechanical, rheological and dynamic mechanical properties were investigated by using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), tensile machine, polarized optical microscopy, rotational rheometer and dynamic mechanical analyzer (DMA), respectively. The results suggest that PBS and HBP have a certain compatibility at amorphous state. A certain number of H-bonding was detected between PBS and HBP phases and it influences the material properties. HBP not only serves partially as a nucleating agent for the crystallization of PBS but also plays a role of plasticizer for the rheology of PBS. The glass transition temperatures of the blends slightly decrease with increasing HBP content. The proper amount of HBP (4–6%) has a reinforcement effect on the PBS matrix at glassy state. However, the blend with 10%HBP content has an improved impact strength mainly due to the plasticization effect or H-bonding effect of HBP on PBS matrix. The storage modulus is increased with increasing HBP contents, and the loss modulus is much smaller than the storage modulus in each blend at glassy state. At rubbery state the storage modulus of different samples is independent of HBP content. The complex viscosity of the melt decreases with increasing HBP content; however, the blend with 10%HBP is a special sample because of its abnormal larger complex viscosity at low shear frequencies. In addition, the melt’s elasticity behavior increases slightly with increasing HBP content. - Highlights: ► H-bonding was detected between PBS and HBP phases by FTIR. ► HBP serves partly as a nucleating agent for the crystallization of PBS. ► HBP plays a role of plasticizer for PBS. ► The blend with 10%HBP has abnormal larger complex viscosity.

  15. Mutagenesis and functional studies with succinate dehydrogenase inhibitors in the wheat pathogen Mycosphaerella graminicola.

    Science.gov (United States)

    Scalliet, Gabriel; Bowler, Judith; Luksch, Torsten; Kirchhofer-Allan, Lucy; Steinhauer, Diana; Ward, Keith; Niklaus, Michael; Verras, Andreas; Csukai, Michael; Daina, Antoine; Fonné-Pfister, Raymonde

    2012-01-01

    A range of novel carboxamide fungicides, inhibitors of the succinate dehydrogenase enzyme (SDH, EC 1.3.5.1) is currently being introduced to the crop protection market. The aim of this study was to explore the impact of structurally distinct carboxamides on target site resistance development and to assess possible impact on fitness. We used a UV mutagenesis approach in Mycosphaerella graminicola, a key pathogen of wheat to compare the nature, frequencies and impact of target mutations towards five subclasses of carboxamides. From this screen we identified 27 amino acid substitutions occurring at 18 different positions on the 3 subunits constituting the ubiquinone binding (Qp) site of the enzyme. The nature of substitutions and cross resistance profiles indicated significant differences in the binding interaction to the enzyme across the different inhibitors. Pharmacophore elucidation followed by docking studies in a tridimensional SDH model allowed us to propose rational hypotheses explaining some of the differential behaviors for the first time. Interestingly all the characterized substitutions had a negative impact on enzyme efficiency, however very low levels of enzyme activity appeared to be sufficient for cell survival. In order to explore the impact of mutations on pathogen fitness in vivo and in planta, homologous recombinants were generated for a selection of mutation types. In vivo, in contrast to previous studies performed in yeast and other organisms, SDH mutations did not result in a major increase of reactive oxygen species levels and did not display any significant fitness penalty. However, a number of Qp site mutations affecting enzyme efficiency were shown to have a biological impact in planta.Using the combined approaches described here, we have significantly improved our understanding of possible resistance mechanisms to carboxamides and performed preliminary fitness penalty assessment in an economically important plant pathogen years ahead of

  16. Mutagenesis and functional studies with succinate dehydrogenase inhibitors in the wheat pathogen Mycosphaerella graminicola.

    Directory of Open Access Journals (Sweden)

    Gabriel Scalliet

    Full Text Available A range of novel carboxamide fungicides, inhibitors of the succinate dehydrogenase enzyme (SDH, EC 1.3.5.1 is currently being introduced to the crop protection market. The aim of this study was to explore the impact of structurally distinct carboxamides on target site resistance development and to assess possible impact on fitness. We used a UV mutagenesis approach in Mycosphaerella graminicola, a key pathogen of wheat to compare the nature, frequencies and impact of target mutations towards five subclasses of carboxamides. From this screen we identified 27 amino acid substitutions occurring at 18 different positions on the 3 subunits constituting the ubiquinone binding (Qp site of the enzyme. The nature of substitutions and cross resistance profiles indicated significant differences in the binding interaction to the enzyme across the different inhibitors. Pharmacophore elucidation followed by docking studies in a tridimensional SDH model allowed us to propose rational hypotheses explaining some of the differential behaviors for the first time. Interestingly all the characterized substitutions had a negative impact on enzyme efficiency, however very low levels of enzyme activity appeared to be sufficient for cell survival. In order to explore the impact of mutations on pathogen fitness in vivo and in planta, homologous recombinants were generated for a selection of mutation types. In vivo, in contrast to previous studies performed in yeast and other organisms, SDH mutations did not result in a major increase of reactive oxygen species levels and did not display any significant fitness penalty. However, a number of Qp site mutations affecting enzyme efficiency were shown to have a biological impact in planta.Using the combined approaches described here, we have significantly improved our understanding of possible resistance mechanisms to carboxamides and performed preliminary fitness penalty assessment in an economically important plant pathogen

  17. Activite succino-deshydrogenasique des microsomes et mode d'incorporation du succinate 2,3-(14)C dans les acides gras des microsomes de foie de rat in vitro.

    Science.gov (United States)

    Rous, S; Aubry, L; Bonini, F

    1970-03-16

    The incorporations of 2,3-(14)C-succinate 2-(14)C-acetate into fatty acids of different cellular fractions of rat liver were studied. Acetate was incorporated mainly into supernatant and succinate into microsomal fatty acids. Mitochondria only could intensively decarboxylate pyruvate. Avidine inhibited fatty acid synthesis from succinate mainly in the supernatant. It is suggested that succinate is an important physiological precursor of fatty acids in the liver and that an active succino-dehydrogenase is present in microsomes.

  18. A review of current knowledge of resistance aspects for the next-generation succinate dehydrogenase inhibitor fungicides.

    Science.gov (United States)

    Sierotzki, Helge; Scalliet, Gabriel

    2013-09-01

    The new broad-spectrum fungicides from the succinate dehydrogenase inhibitor (SDHI) class have been quickly adopted by the market, which may lead to a high selection pressure on various pathogens. Cases of resistance have been observed in 14 fungal pathogens to date and are caused by different mutations in genes encoding the molecular target of SDHIs, which is the mitochondrial succinate dehydrogenase (SDH) enzyme. All of the 17 marketed SDHI fungicides bind to the same ubiquinone binding site of the SDH enzyme. Their primary biochemical mode of action is the blockage of the TCA cycle at the level of succinate to fumarate oxidation, leading to an inhibition of respiration. Homology models and docking simulations explain binding behaviors and some peculiarities of the cross-resistance profiles displayed by different members of this class of fungicides. Furthermore, cross-resistance patterns among SDHIs is complex because many mutations confer full cross resistance while others do not. The nature of the mutations found in pathogen populations varies with species and the selection compound used but cross resistance between all SDHIs has to be assumed at the population level. In most of the cases where resistance has been reported, the frequency is still too low to impact field performance. However, the Fungicide Resistance Action Committee has developed resistance management recommendations for pathogens of different crops in order to reduce the risk for resistance development to this class of fungicides. These recommendations include preventative usage, mixture with partner fungicides active against the current pathogen population, alternation in the mode of action of products used in a spray program, and limitations in the total number of applications per season or per crop.

  19. Cationic lipids bearing succinic-based, acyclic and macrocyclic hydrophobic domains: Synthetic studies and in vitro gene transfer.

    Science.gov (United States)

    Jubeli, Emile; Maginty, Amanda B; Khalique, Nada Abdul; Raju, Liji; Nicholson, David G; Larsen, Helge; Pungente, Michael D; Goldring, William P D

    2017-01-05

    In this communication we describe the construction of four succinic-based cationic lipids, their formulation with plasmid DNA (pDNA), and an evaluation of their in vitro gene delivery into Chinese hamster ovarian (CHO-K1) cells. The cationic lipids employed in this work possess either a dimethylamine or trimethylamine headgroup, and a macrocyclic or an acyclic hydrophobic domain composed of, or derived from two 16-atom, succinic-based acyl chains. The synthesized lipids and a co-lipid of neutral charge, either cholesterol or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), were formulated in an overall 3:2 cationic-to-neutral lipid molar ratio, then complexed with plasmid DNA (pDNA). The relative transfection performance was evaluated via a comparison between matched versus mismatched formulations defined by the rigidity relationship between the lipids employed. Gel electrophoresis was used to characterize the binding of the lipid formulations with plasmid DNA and the relative degree of plasmid degradation using a DNase I degradation assay. Small angle X-ray diffraction (SAXD) was employed to characterize the packing morphology of the lipid-DNA complexes. In general, the succinic unit embedded within the hydrophobic domain of the cationic lipids was found to improve lipid hydration. The transfection assays revealed a general trend in which mismatched formulations that employed a rigid lipid combined with a non-rigid (or flexible) lipid, outperformed the matched formulations. The results from this work suggest that the design of the cationic lipid structure and the composition of the lipoplex formulation play key roles in governing the transfection performance of nonviral gene delivery agents.

  20. Cationic lipids bearing succinic-based, acyclic and macrocyclic hydrophobic domains: synthetic studies and in vitro gene transfer

    DEFF Research Database (Denmark)

    Jubeli, Emile; Maginty, A. B.; Khalique, N. A.;

    2016-01-01

    a dimethylamine or trimethylamine headgroup, and a macrocyclic or an acyclic hydrophobic domain composed of, or derived from two 16-atom, succinic-based acyl chains. The synthesized lipids and a co-lipid of neutral charge, either cholesterol or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), were formulated...... within the hydrophobic domain of the cationic lipids was found to improve lipid hydration. The transfection assays revealed a general trend in which mismatched formulations that employed a rigid lipid combined with a non-rigid (or flexible) lipid, outperformed the matched formulations. The results from...

  1. Occurrence of single-electron phenomenon in CdS nanoclusters in Langmuir-Blodgett films of -octadecyl succinic acid

    Indian Academy of Sciences (India)

    G Hemakanthi; Aruna Dhathathreyan

    2002-10-01

    Cadmium complex of -octadecyl succinic acid (ODSA) in Langmuir films at air/water interface has been studied using surface pressure-molecular area ( - ) and surface potential-molecular area ( - ) isotherms. The metal complex formed, transferred as LB film onto solid substrates, was analysed using FT-IR and was subjected to sulphidation reaction. Antisymmetric and symmetric carboxylate stretching vibrations have been used to determine the nature of the ODSA/cation complexes. CdS formed after sulphidation of the cadmium complex (ODSACd) showed possible single-electron phenomenon indicating the nanosized nature of clusters formed. Atomic Force Microscopy (AFM) measurements carried out confirmed the size of these CdS clusters.

  2. FORMULATION, OPTIMIZATION AND EVALUATION OF BILAYERED TABLETS OF AMLODIPINE BESILATE AS IMMEDIATE RELEASE AND METOPROLOL SUCCINATE AS SUSTAINED RELEASE

    OpenAIRE

    Arup Ratan Deb; Vivek Keshri; Padmakana Malakar

    2013-01-01

    The purpose of the study was to develop a bilayer tablet of Amlodipine besilate (IR) and Metoprolol succinate (SR) having different release pattern, which is indicated for the management of hypertension. The study was planned in three stages. In the first stage six batches (A1, A2, A3, A4, A5 and A6) of immediate release tables of Amlodipine besilate was prepared by direct compression method using sodium starch glycolate and pre-gelatinised starch as super disintegrant. In the second stage, s...

  3. Speciation study on the interaction of some divalent transition metal ions with succinic acid dihydrazide in aqueous medium.

    Science.gov (United States)

    Satyanarayana, Atreyapurapu; Kenie, Dunkana Negussa; Shyamala, Pulipaka

    2013-01-01

    The interaction of succinic acid dihydrazide with Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) was investigated in aqueous medium at 303K and ionic strength of 0.1 mol dm-3. The speciation and stability constants of the metal complexes formed were determined by pH-metric method. Mononuclear and homo binuclear species in different protonation and deprotonation states were identified, the corresponding formation constants calculated using MINIQUAD-75 computer program, and species distribution diagrams produced using the HYSS computer program. Selection of the best-fit chemical models was based on statistical parameters.

  4. Two transgenic mouse models for β-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations

    DEFF Research Database (Denmark)

    Kacso, Gergely; Ravasz, Dora; Doczi, Judit;

    2016-01-01

    -forming activity. Bioenergetic parameters including substrate-level phosphorylation (SLP) were not different between wild-type and Sucla2 heterozygote mice unless a submaximal pharmacological inhibition of SUCL was concomitantly present. mtDNA contents were moderately decreased, but blood carnitine esters were...... expression, yielding double heterozygote mice with no alterations in GTP-forming activity or SLP, but more pronounced changes in mtDNA content and blood carnitine esters, and an increase in succinate dehydrogenase activity. We conclude that a partial reduction in Sucla2 elicits rebound increases in Suclg2...

  5. Production of succinic acid in basket and mobile bed bioreactors-Comparative analysis of substrate mass transfer aspects☆

    Institute of Scientific and Technical Information of China (English)

    Anca-Irina Galaction; Dan Cacaval; Ramona-Mihaela Matran; Alexandra Tucaliuc

    2016-01-01

    The glucose mass transfer in the biosynthesis of succinic acid with immobilized Actinobacil us succinogenes cel s has been comparatively analyzed for a bioreactor with mobile bed vs. a stationary basket bioreactor. The process has been considered to occur under substrate and product inhibitory effects. The results indicated that the biore-actor with mobile bed is more efficient for biocatalyst particles with a diameter over 3 mm, while the basket bio-reactor is more efficient for smal er biocatalyst particles and basket bed thickness below 5 mm. The performances of both configurations of immobilized A. succinogenes cell beds were found to be superior to the column packed bed bioreactor.

  6. 丁二酸生产工艺技术进展%Research progress of production technology on succinic acid

    Institute of Scientific and Technical Information of China (English)

    杨如惠; 杨效军

    2015-01-01

    The present development of succic acid were introduced,and the main methods of production were reviewed,including the electrochemical process,the catalytic hydrogenation of maleic anhydride process and the biological fermentation process.It was pointed out the research direction of succinic acid.%简述了丁二酸的发展现状,介绍了目前丁二酸的主要生产方法,包括电化学法、顺酐催化加氢法和生物发酵法,并指出丁二酸的发展前景。

  7. Changes in succinate dehydrogenase activity in various parts of the brain during combined exposure to vibration and licorice root.

    Science.gov (United States)

    Oganisyan, A O; Oganesyan, K R; Minasyan, S M

    2005-06-01

    Data obtained in the studies reported here provide evidence that during exposure to vibration for 30 days, feeding with licorice root significantly increases the activity of the anaerobic respiration enzyme succinate dehydrogenase (SDH) in the cerebral cortex, while activity in the subcortex, conversely, decreases. Combined treatment for 30 days with licorice root and vibration after a preliminary 30-day period of feeding with licorice root resulted in high SDH activity in all the structures studied, improving brain energy supply and metabolism and ameliorating the effect of vibration.

  8. Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate

    Directory of Open Access Journals (Sweden)

    Emri Zsuzsa

    2011-10-01

    Full Text Available Abstract Background Accumulating evidence suggests that glial signalling is activated by different brain functions. However, knowledge regarding molecular mechanisms of activation or their relation to neuronal activity is limited. The purpose of the present study is to identify the characteristics of ATP-evoked glial signalling in the brain reward area, the nucleus accumbens (NAc, and thereby to explore the action of citric acid cycle intermediate succinate (SUC. Results We described the burst-like propagation of Ca2+ transients evoked by ATP in acute NAc slices from rat brain. Co-localization of the ATP-evoked Ca2+ signalling with immunoreactivities of the astroglia-specific gap junction forming channel protein connexin43 (Cx43 and the glial fibrillary acidic protein (GFAP indicated that the responsive cells were a subpopulation of Cx43 and GFAP immunoreactive astrocytes. The ATP-evoked Ca2+ transients were present under the blockade of neuronal activity, but were inhibited by Ca2+ store depletion and antagonism of the G protein coupled purinergic P2Y1 receptor subtype-specific antagonist MRS2179. Similarly, Ca2+ transients evoked by the P2Y1 receptor subtype-specific agonist 2-(Methylthioadenosine 5'-diphosphate were also blocked by MRS2179. These characteristics implied that intercellular Ca2+ signalling originated from the release of Ca2+ from internal stores, triggered by the activation of P2Y1 receptors. Inhibition by the gap junction blockers carbenoxolone and flufenamic acid and by an antibody raised against the gating-associated segment of Cx43 suggested that intercellular Ca2+ signalling proceeded through gap junctions. We demonstrated for the first time that extracellular SUC also evoked Ca2+ transients (EC50 = 50-60 μM in about 15% of the ATP-responsive NAc astrocytes. By contrast to glial cells, electrophysiologically identified NAc neurons surrounded by ATP-responsive astrocytes were not activated simultaneously. Conclusions We

  9. Effects of doxylamine succinate on thyroid hormone balance and enzyme induction in mice.

    Science.gov (United States)

    Bookstaff, R C; Murphy, V A; Skare, J A; Minnema, D; Sanzgiri, U; Parkinson, A

    1996-12-01

    The effects of doxylamine (as the succinate salt) on microsomal enzyme activity and serum thyroid hormone levels were examined in B6C3F1 mice following dietary exposure for 7 or 15 days (0, 40, 375, 750, or 1500 ppm in diet, expressed as free base doxylamine). In addition, the hepatic P450 enzyme inducer sodium phenobarbital (375 ppm, expressed as free acid phenobarbital) was used as a positive control for CYP2B induction. Exposure of mice to doxylamine produced dose-related increases in liver weight at both time points. Liver weights were also increased in the phenobarbital-treated mice. Doxylamine treatment caused a dose-dependent increase (up to 2.6-fold) in liver microsomal cytochrome P450 in both male and female mice, at both time points. Analyses of the activities of various hepatic microsomal cytochromes P450 indicated that doxylamine caused a marked induction of CYP2B enzymes. This was demonstrated by a large increase in the O-dealkylation of 7-pentoxyresorufin (up to 38-fold) and the 16beta-hydroxylation of testosterone (up to 6.9-fold), both of which are indicative of CYP2B induction. In addition, like phenobarbital, doxylamine treatment resulted in a modest induction of CYP3A and CYP2A enzymes and approximately a 50% increase in thyroxine-glucuronosyltransferase activity. Doxylamine did not appear to induce P450 enzymes in the CYP1A, CYP2E, or CYP4A enzyme subfamilies. None of the enzyme-inducing effects of doxylamine could be distinguished from those of phenobarbital. These results suggest that doxylamine is a phenobarbital-type inducer of liver microsomal cytochrome P450 in B6C3F1 mice. Exposure to either doxylamine or phenobarbital also resulted in decreases in serum thyroxine (T4) levels (approximately 80% of control) with compensatory increases in serum thyroid-stimulating hormone levels (approximately 4-fold). No clear changes in serum triiodothyronine levels were apparent. These findings are consistent with the hypothesis that doxylamine increases

  10. Efficient carbon dioxide utilization and simultaneous hydrogen enrichment from off-gas of acetone-butanol-ethanol fermentation by succinic acid producing Escherichia coli.

    Science.gov (United States)

    He, Aiyong; Kong, Xiangping; Wang, Chao; Wu, Hao; Jiang, Min; Ma, Jiangfeng; Ouyang, Pingkai

    2016-08-01

    The off-gas from acetone-butanol-ethanol (ABE) fermentation was firstly used to be CO2 source (co-substrate) for succinic acid production. The optimum ratio of H2/CO2 indicated higher CO2 partial pressures with presence of H2 could enhance C4 pathway flux and reductive product productivity. Moreover, when an inner recycling bioreactor was used for CO2 recycling at a high total pressure (0.2Mpa), a maximum succinic acid concentration of 65.7g·L(-1) was obtained, and a productivity of 0.76g·L(-1)·h(-1) and a high yield of 0.86g·g(-1) glucose were achieved. Furthermore, the hydrogen content was simultaneously enriched to 92.7%. These results showed one successful attempt to reuse the off-gas of ABE fermentation which can be an attractive CO2 source for succinic acid production.

  11. 琥珀酸对中性粒细胞的抑制作用%Succinic acid inhibits polymorphonuclear leukocyte's function

    Institute of Scientific and Technical Information of China (English)

    任利成; 黄晓元; 龙剑虹

    2004-01-01

    Objective:To examine the effect of succinic acid on the function of human polymorphonuclear(PMN)leukocyte and it's special function as a virulent factor of Bacteroides Fragilis.Methods:PMN wasseperated from the blood of healthy donors,incubated with succinic acid at the concentration of 5,10,20 and 30 mmol/L for 20 min or at the concentration of 20 mmol/L for 5,10 15 and 20 min.Tested PMN's power of adherence and deoxidizing NBT.Results:Succinic acid can inhibit PMN's power of adherence and deoxidization,the inhibitory action was related to the time of incubation and succinic acid's concentration.Conclusions:Succinic acid can inhibit PMN's function and it may be an important virulent factor to Bacteroides Fragilis.%目的探讨脆弱类杆菌代谢产物琥珀酸(succinic acid)对中性粒细胞(polymorphonuclear,PMN)功能的影响及其在脆弱类杆菌(bacteroides fragilis)发病中的作用.方法体外分离外周血PMN,以5,10,20,30 nmol/L四种浓度的琥珀酸分别孵育20 min,或以20 mmol/L浓度的琥珀酸孵育5,10,15和20 min,测定对PMN粘附率(adherencerate)及硝基蓝四氮唑(NBT)还原能力的影响.结果琥珀酸能显著抑制PMN粘附率及NBT还原能力,且呈浓度,时间依赖关系.结论琥珀酸能抑制PMN的功能,在脆弱类杆菌的发病中占有重要的作用.

  12. 丁二酸酐性能及各种生产工艺介绍%The Properties and Various Production Technology of Succinic Anhydride

    Institute of Scientific and Technical Information of China (English)

    潘玉莹; 李江; 胡利娜; 肖鹏飞

    2014-01-01

    Succinic anhydride was a kind of widely used and important fine chemical raw materials , especially its derivatives of high value -added fine chemical products , succinic anhydride production process in all the world mainly divided into succinic acid dehydration and maleic anhydride hydrogenated to succinic anhydride .The properties, the application and production technology of succinic anhydride , and comparison of production technology , maleic anhydride melting catalytic hydrogenated to succinic anhydride were mainly introduced , which was one of the most competitive and promising development method due to the cost of production and the comprehensive energy consumption was low .%丁二酸酐是一种重要的精细化工原料,用途广泛,尤其它的衍生物更是附加值高的精细化工产品,全球丁二酸酐的生产工艺主要有丁二酸脱水法、顺丁烯二酸酐催化加氢法。本文章主要介绍了丁二酸酐的性能、用途和生产工艺技术,并对生产工艺技术进行了比较,顺丁烯二酸酐熔融催化加氢法由于生产成本和综合能耗较低,是最具竞争力,发展前景看好的一种方法。

  13. Liquid-liquid equilibrium of poly(ethylene glycol) 6000 + sodium succinate + water system at different temperatures.

    Science.gov (United States)

    Raja, Selvaraj; Murty, Vytla Ramachandra

    2013-01-01

    Phase diagrams and the compositions of coexisting phases of poly(ethylene glycol) (PEG) 6000 + sodium succinate + water system have been determined experimentally at 298.15, 308.15, and 318.15 K. The effects of temperature on the binodal curve and tie lines have been studied. The binodal curves were successfully fitted to a nonlinear equation relating the concentrations of PEG 6000 and sodium succinate, and the coefficients were estimated for the formentioned systems (low AARD, high R(2), and low SD). Tie-line compositions were estimated and correlated using Othmer-Tobias and Bancroft equations, and the parameters were reported. The effect of temperature on the phase-forming ability has been studied by fitting the binodal data to a Setschenow-type equation for each temperature. The effective excluded volume (EEV) values were also calculated from the binodal data, and it was found out that the values increased with an increase in the temperature. Furthermore, the effect of MW of PEG on the phase diagram has been studied and verified.

  14. Development of an Ion Chromatography Method for Analysis of Organic Anions (Fumarate, Oxalate, Succinate, and Tartrate) in Single Chromatographic Conditions.

    Science.gov (United States)

    Kaviraj, Yarbagi; Srikanth, B; Moses Babu, J; Venkateswara Rao, B; Paul Douglas, S

    2015-01-01

    A single organic counterion analysis method was developed by using an ion chromatography separation technique and conductivity detector. This allows the rapid characterization of an API to support clinical studies and to fulfil the regulatory requirements for the quantitation of fumarate, oxalate, succinate, and tartrate counterions in active pharmaceutical ingredients (quetiapine fumarate, escitalopram oxalate, sumatriptan succinate, and tolterodine tartrate). The method was developed by using the Metrohm Metrosep A Supp 1 (250 × 4.0 mm, 5.0 µm particle size) column with a mobile phase containing an isocratic mixture of solution A: 7.5 mM sodium carbonate and 2.0 mM sodium bicarbonate in Milli-Q water and solution B: acetonitrile. The flow rate was set at 1.0 mL/min and the run time was 25 minutes. The developed method was validated as per ICH guidelines, and the method parameters were chosen to ensure the spontaneous quantitation of all four anions. The method was validated for all four anions to demonstrate the applicability of this method to common anions present in various APIs.

  15. Effect of peroxide and chain extender on mechanical properties and morphology of poly (butylene succinate)/poly (lactic acid) blends

    Science.gov (United States)

    Cherykhunthod, W.; Seadan, M.; Suttiruengwong, S.

    2015-07-01

    Poly (butylene succinate) (PBS) and poly (lactic acid) (PLA) are biodegradable polymers with high potential to replace commodity fossil-based polymers in a wide range of applications. However, these two polymers are immiscible in most ratios, but partially miscible when one of the two is a major phase. In this study, a one-step process in a twin-screw extruder was used to prepare the blends between poly (butylene succinate) (PBS) as a matrix and poly (lactic acid) (PLA) as a dispersed phase. To improve mechanical properties and morphology of blends, two reactive agents, peroxide (Perkadox) and multifunctional epoxide chain extender (Joncryl) were selected and compared. All samples were characterized for melt flow index (MFI), morphology, tensile, and impact properties. The results showed that the mechanical properties and morphology of PBS/PLA blends were improved when using both reactive agents. It was demonstrated that the increased mechanical properties resulted from good interfacial adhesion between PBS and finely dispersed PLA particles. The addition of 0.075 phr Perkadox to PBS/PLA (75:25 and 80:20) blends increased elongation at break by 7.2% and 38.4%, respectively compared with the blends without reactive agents. The results from gel content also revealed the graft copolymer existed at the interface when reactive agents were added. In the case of using multifunctional epoxide chain extender, the impact strength of the blends increased.

  16. Physical Stability of Octenyl Succinate-Modified Polysaccharides and Whey Proteins for Potential Use as Bioactive Carriers in Food Systems.

    Science.gov (United States)

    Puerta-Gomez, Alex F; Castell-Perez, M Elena

    2015-06-01

    The high cost and potential toxicity of biodegradable polymers like poly(lactic-co-glycolic)acid (PLGA) has increased the interest in natural and modified biopolymers as bioactive carriers. This study characterized the physical stability (water sorption and state transition behavior) of selected starch and proteins: octenyl succinate-modified depolymerized waxy corn starch (DWxCn), waxy rice starch (DWxRc), phytoglycogen, whey protein concentrate (80%, WPC), whey protein isolate (WPI), and α-lactalbumin (α-L) to determine their potential as carriers of bioactive compounds under different environmental conditions. After enzyme modification and particle size characterization, glass transition temperature and moisture isotherms were used to characterize the systems. DWxCn and DWxRc had increased water sorption compared to native starch. The level of octenyl succinate anhydrate (OSA) modification (3% and 7%) did not reduce the water sorption of the DWxCn and phytoglycogen samples. The Guggenheim-Andersen-de Boer model indicated that native waxy corn had significantly (P whey proteins had higher glass transition temperature (Tg) values. On the other hand, depolymerized waxy starches at 7%-OSA modification had a "melted" appearance when exposed to environments with high relative humidity (above 70%) after 10 days at 23 °C. The use of depolymerized and OSA-modified polysaccharides blended with proteins created more stable blends of biopolymers. Hence, this biopolymer would be suitable for materials exposed to high humidity environments in food applications.

  17. Preparation of modified SiO2 colloidal spheres with succinic acid and the assembly of colloidal crystals

    Institute of Scientific and Technical Information of China (English)

    FANG Jun; WANG XiuFeng; WANG LieSong; CHENG Bing; WU YuanTing; ZHU WanLin

    2007-01-01

    SiO2 colloidal spheres were synthesized by St(o)ber method. In order to enhance surface charge of the SiO2 spheres, they were modified with succinic acid. Scanning electron microscope (SEM) shows that the average size of modified SiO2 spheres is 473 nm, and its distribution standard deviation is less than 5%; Fourier-transform infrared spectra (FT-IR) and X-ray photoelectron spectrometer (XPS) results indicate that one end of succinic acid is chemically bonded to the SiO2 spheres through esterification; Zeta potential of the modified SiO2 spheres in water solution is improved from -53.72 to -67.46 mV, and surface charge density of the modified SiO2 spheres is enhanced from 0.19 to 0.94 μC/cm2. SiO2 colloidal crystal was fabricated from aqueous colloidal solution by the vertical deposition method at 40℃ and 60% relative humidity. SEM images show that the sample of SiO2 colloidal crystal is face-centered cubic (fcc) structure with its (111) planes parallel to the substrate. Transmission measurement shows the existence of photonic band gap at 1047 nm.

  18. Roles of Fas signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yao Li; Yan Zhao; Yu-Juan Shan; Wei Xia; Wei-Ping Yu; Lan Zhao

    2002-01-01

    AIM: To investigate the roles of Fas signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS: Human gastric cancer SGC-7901 cells were treated with VES at 5, 10, 20 mg@L-1, succinic acid and vitamin E as vehicle control and condition media only as untreated (UT) control. Apoptotic morphology was observed by DAPI staining. Western blot analysis was applied to measure the expression of Fas, FADD and caspase-8 proteins. After the cells were transiently transfected with Fas and FADD antisense oligonucleotides, respectively, caspase-8 activity was determined by flurometric method.RESULTS: The morphologically apoptotic changes were observed after VES treatment by DAPI staining. 23.7 % and 89.6 % apoptosis occurred after 24 h and 48 h of 20 mg@L-1 VES treatment, respectively. The protein levels of Fas, FADD and caspase-8 were evidently increased in a dose-dependent manner after 24 h of VES treatment. The blockage of Fas by transfection with Fas antisense oligonucleotides obviously inhibited the expression of FADD protein. After SGC-7901 cells were transfected with Fas and FADD antisense oligonucleotides, caspase-8 activity was obviously decreased (P<0.01), whereas Fas blocked more than FADD.CONCLUSION: VES-induced apoptosis in human gastric cancer SGC-7901 cells involves Fas signaling pathway including the interaction of Fas, FADD and caspase-8.

  19. Influence of the course prescription of sodium succinate on functional state and general physical working ability of footballers organism during the training sessions

    Directory of Open Access Journals (Sweden)

    Олексій Володимирович Чернєв

    2015-09-01

    Full Text Available Pharmacological purpose of metabotropic preparations including burshtin acid and its derivative succinate sodium copes with the number of tasks the main of which is an activation of alternative ways of energoproduction at the work of submaximal and maximal force and preliminary training of the separate links of metabolism.The task of research is to ascertain changes that take place in functional state of sportsmen during long physical loadings and optimization of the work of cardiovascular system (CVS and prophylaxis of psychical strains with the help of succinate sodium.Methods and organization of research. There were examined 84 sportsmen to ascertain changes that take place in the functional state of sportsmen during the long physical loadings and optimization of the work of CVS with the help of succinate sodium. Examinations took place during the training sessions (TS in January, February and July 2012-2013 years.Results of research and its discussion. There was studied an efficiency of the course use of succinate sodium in footballers 100 mg 3 times a day during 14 days. Energetic supply of processes of intracellular homeostasis in erythrocytes realizes by means of ATP that is created in the process of glycolysis. According to the results of research after course prescription of succinate sodium in sportsmen the content of ATP in erythrocytes increased and an amount of ADP and AMP decreased. An improvement of general metabolic situation under an influence of succinate sodium was proved by the decrease of products of reactions of peroxidation in blood plasma of footballers.These results indicated an essential antiacidotic effect of the course use of succinate sodium by footballers after loading in anaerobic and glycolytic zone of intensity. At the same time there was ascertain in our research that the use of succinate sodium had a positive effect on the dynamics of lactate content during the processes of renewal after training in aerobic

  20. Enzyme-catalyzed Synthesis of Vitamin E Succinate Using a Chemically Modified Novozym-435%化学修饰Novozym-435酶催化合成维生素E琥珀酸酯的研究

    Institute of Scientific and Technical Information of China (English)

    尹春华; 张聪; 高明

    2011-01-01

    Vitamin E succinate was synthesized in organic solvents using a modified Novozym-435 as catalyst. In order to improve the catalytic performance of Novozym-435, the enzyme was modified using acetic anhydride, propionic anhydride and succinic anhydride separately. We found that both the hydrolytic activity and the thermal stability of the modified Novozym-435 were enhanced compared with the unmodified enzyme. The modified Novozym-435 catalysts were used to synthesize the succinate derivative of vitamin E. Compared with the native Novozym-435, the catalytic activity of the modified novozym-435 in promoting the synthesis of vitamin E succinate was dramatically increased, with the novozym-435 modified with succinic anhydride (N435-S) as the most active catalyst. Conditions for the synthesis of vitamin E succinate were also optimized. A mixture of tert-butanol and DMSO (volume ratio of 2: 3) was the most suitable medium for the reaction, whereas the appropriate molar ratio of vitamin E to succinic anhydride and reaction temperature were 1: 5 and 40 ℃, respectively. Under these reaction conditions, the yield of vitamin E succinate reached 94.4%. N435-S could be reused for five batches.

  1. Characterization of the myelotoxicity of chloramphenicol succinate in the B6C3F1 mouse.

    Science.gov (United States)

    Turton, John A; Fagg, Rajni; Sones, William R; Williams, Thomas C; Andrews, C Michael

    2006-04-01

    Chloramphenicol (CAP) is haemotoxic in man, inducing two types of toxicity. First, a dose-related, reversible anaemia with reticulocytopenia, sometimes seen in conjunction with leucopenia and thrombocytopenia; this form of toxicity develops during drug treatment. The second haemotoxicity is aplastic anaemia (AA) which is evident in the blood as severe pancytopenia. AA development is not dose-related and occurs weeks or months after treatment. We wish, in the longer term, to investigate CAP-induced AA in the busulphan-pretreated mouse. However, as a prelude to that study, we wanted to characterize in detail the reversible haemotoxicity of CAP succinate (CAPS), administered at high dose levels in the mouse, and follow the recovery of the bone marrow in the post-dosing period. Female B6C3F1 mice were gavaged with CAPS at 0, 2500 and 3500 mg/kg, daily, for 5 days and sampled (n = 5) at 1, 7, 14 and 21 days post-dosing. Blood, bone marrow and spleen samples were analysed and clonogenic assays carried out. At day 1 post-dosing, at both CAPS dose levels, decreases were seen in erythrocytes and erythrocyte precursors; marrow erythroid cells were reduced. Reductions were also evident in splenic nucleated cell counts, blood high fluorescence ratio (HFR) reticulocyte counts and total reticulocyte counts; burst-forming units-erythroid and colony-forming units-erythroid showed decreases. At day 7 post-dosing (2500 mg/kg CAPS), there was regeneration of erythrocyte production, with marked splenic erythropoietic activity, and raised blood HFR reticulocytes. At day 7, at 3500 mg/kg CAPS, erythrocyte and reticulocyte parameters remained depressed. At 14 days post-dosing (2500 mg/kg CAPS), many erythrocyte parameters had returned to normal; at 3500 mg/kg CAPS, there was erythroid regeneration. By 21 days post-dosing, at both CAPS dose levels, most erythrocytic parameters were equivalent to control values. For leucocyte parameters, there was some depression at day 1 post-dosing (at

  2. Artificial primary marine aerosol production: a laboratory study with varying water temperature, salinity and succinic acid concentration

    Directory of Open Access Journals (Sweden)

    J. Zábori

    2012-08-01

    Full Text Available Primary marine aerosols are an important component of the climate system, especially in the remote marine environment. With diminishing sea-ice cover, better understanding of the role of sea spray aerosol on climate in the polar regions is required. As for Arctic Ocean water, laboratory experiments with NaCl water confirm that a few degrees change in the water temperature (Tw gives a large change in the number of primary particles. Smaller particles with a dry diameter between 0.01 μm and 0.25 μm dominate the aerosol number density, but their relative dominance decreases with increasing water temperature from 0 °C where they represent 85–90% of the total aerosol number to 60–70% of the total aerosol number at 10 °C water temperature. This effect is most likely related to a change in physical properties and not to modification of sea water chemistry. A change of salinity between 15 g kg−1 and 35 g kg−1 showed no influence on the relative shape of a particle number size distribution, nor did a change in water temperature between 0 °C and 16 °C. An experiment where succinic acid was added to a NaCl water solution showed, that the number concentration of particles with Dp < 0.312 μm decreased by 43% when the succinic acid concentration in NaCl water at Tw = 0 °C was increased from 0 μmol l−1 to 2446 μmol l−1. Different organic constituents and perhaps inorganic substances resulted in a particle number shift towards larger particle sizes, when comparing a size distribution resulting from pure NaCl water to size distributions resulting from Arctic Ocean water and resulting from NaCl water with a succinic acid concentration of 2446 μmol l−1.

  3. Silica gel modified with ethylenediamine and succinic acid-adsorption and calorimetry of cations in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Arakaki, L.N.H.; Filha, V.L.S. Augusto; Germano, A.F.S.; Santos, S.S.G. [Department of Chemistry, Federal University of Paraíba, 58051-900 João Pessoa, Paraíba (Brazil); Fonseca, M.G., E-mail: mgardennia@quimica.ufpb.br [Department of Chemistry, Federal University of Paraíba, 58051-900 João Pessoa, Paraíba (Brazil); Sousa, K.S.; Espínola, J.G.P. [Department of Chemistry, Federal University of Paraíba, 58051-900 João Pessoa, Paraíba (Brazil); Arakaki, T. [Department of Food Engineering, CT, Federal University of Paraíba, 58059-900 João Pessoa, Paraíba (Brazil)

    2013-03-20

    Highlights: ► Succinic acid-modified silica acted as an adsorbent for Cu (II), Ni (II), and Co (II) from aqueous solutions. ► Modified silica adsorbed metallic cations in the order Cu{sup 2+} > Co{sup 2+} > Ni{sup 2+}. ► Succinic acid-modified silica could be employed as low-cost material for the removal of cations from aqueous solution. ► Thermodynamic data for these systems are favorable at the solid/liquid interface. - Abstract: Ethylenediamine molecules were covalently immobilized onto silica gel previously functionalized with 3-chlorosilylpropyltrimethoxysilane (Sil–Cl), producing a Sil–N surface. The Sil–N surface reacted with succinic acid, yielding a Sil–NSuc surface. This new synthesized silica gel surface was used to adsorb divalent cations from aqueous solutions at room temperature. The adsorption isotherms were fit to a modified Langmuir equation using the data obtained by suspending the solid in MCl{sub 2} (M = Cu, Ni, and Co) aqueous solutions, yielding the maximum number of moles adsorbed as 1.04 ± 0.01, 1.89 ± 0.02 and 1.85 ± 0.02 mmol g{sup −1} for divalent copper, nickel and cobalt, respectively. The metal-basic center ratio for complexes on the surfaces varied with the nature of the metal. The spontaneity of these systems was reflected in the negative values of the Gibbs free energy calculated using calorimetric data. The net thermal effects obtained from the calorimetric titration measurements were adjusted to a modified Langmuir equation, and the calculation of the enthalpies of the interaction for the complexation with Sil–NSuc yielded the following exothermic values: 2.81 ± 0.08, 0.35 ± 0.04 ± and 0.69 ± 0.05 kJ mol{sup −1} for Cu{sup 2+}, Co{sup 2+} and Ni{sup 2+}, respectively. Based on these values, the metals are preferentially adsorbed in the order Cu{sup 2+} > Co{sup 2+} > Ni{sup 2+}. The other thermodynamic data for these systems are favorable at the solid/liquid interface, suggesting the efficacy of this

  4. An association study between polymorphisms in five genes in glutamate and GABA pathway and paranoid schizophrenia.

    Science.gov (United States)

    Zhang, Boyu; Yuan, Yanbo; Jia, Yanbin; Yu, Xin; Xu, Qi; Shen, Yucun; Shen, Yan

    2005-01-01

    Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.

  5. Unprecedented Catalytic Wet Oxidation of Glucose to Succinic Acid Induced by the Addition of n-Butylamine to a Ru(III) Catalyst.

    Science.gov (United States)

    Podolean, Iunia; Rizescu, Cristina; Bala, Camelia; Rotariu, Lucian; Parvulescu, Vasile I; Coman, Simona M; Garcia, Hermenegildo

    2016-09-08

    A new pathway for the catalytic wet oxidation (CWO) of glucose is described. Employing a cationic Ru@MNP catalyst, succinic acid is obtained in unprecedently high yield (87.5 %) for a >99.9 % conversion of glucose, most probably through a free radical mechanism combined with catalytic didehydroxylation of vicinal diols and hydrogenation of the resulted unsaturated intermediate.

  6. Production of fermentable sugars from corn fiber using soaking in aqueous ammonia (saa) pretreatment and fermentation to succinic acid by Escherichia coli afp184

    Science.gov (United States)

    Conversion of corn fiber (CF), a by-product from the corn-to-ethanol conversion process, into fermentable sugar and succinic acid was investigated using soaking in aqueous ammonia (SAA) pretreatment followed by biological conversions including enzymatic hydrolysis and fermentation using genetically ...

  7. Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Kozupa, A.; Eisenhofer, G.; Raygada, M.; Adams, K.T.; Solis, D.; Lenders, J.W.M.; Pacak, K.

    2007-01-01

    CONTEXT: Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in apparently sporadic PGL directs appropriate treatment and family screening. OBJECTIVE: The objective of the study was to assess mutation-

  8. Polystyrene/TiO2 composite electrospun fibers as fillers for poly(butylene succinate-co-adipate): Structure, morphology and properties

    NARCIS (Netherlands)

    Neppalli, Ramesh; Causin, Valerio; Benetti, Edmondo M.; Ray, Suprakas Sinha; Esposito, Antonella; Wanjale, Santosh; Birajdar, Mallinath; Saiter, Jean-Marc; Marigo, Antonio

    2014-01-01

    In this work, composite polystyrene/titanium dioxide (PS/TiO2) electrospun fibers were used as a reinforcement for a poly(butylene succinate-co-adipate) (PBSA) matrix. The structure, morphology, mechanical properties and degradation behavior of such materials were investigated, finding that, as a fu

  9. STUDY ON THE PHOTOLYSIS MECHANISM OF POLYESTER FROM SUCCINIC ACID AND N-β-HYDROXYETHYL 2,2,6,6-TETRAMETHYL-4-HYDROXY PIPERIDINE (TINUVIN-622)

    Institute of Scientific and Technical Information of China (English)

    PAN Jiangqing; CUI Song

    1988-01-01

    The photolysis mechanism of polyester of succinic acid with N-β-hydroxyethyl 2,2,6,6-tetramethyl-4-hydroxy piperidine (Tinuvin-622) has been studied by instrumental analysis. The results show that Tinuvin-622 can be easily photolysed. Based on the results of IR, NMR, ESR, GPC, GC, MS, the photolysis mechanism of Tinuvin-622 has been proposed.

  10. Butanol Alcoholysis of Succinic Anhydride Under Neutral Condition%中性条件下丁二酸酐的丁醇解

    Institute of Scientific and Technical Information of China (English)

    高艳萍; 张利萍

    2011-01-01

    Alcoholysis of succinic anhydride and n - butyl alcohol takes place without catalysts and the monobutyl succinie forms. The IR and MS spectra of the products are measured respectively. The factors such as the molar radio between succinic anhydride and n - butanol, raction time are discussed. The radio of succinic acid to n - butanol is 1:3 ,the reaction time is 2h, alcoholysis radio is up to 95.8% ;the reaction time is over 2.5h,succinic anhydride has been alcoholyzed and a little amount of dibutyl has formed.%丁二酸酐和正丁醇在无催化剂参与下,直接醇解生成丁二酸正丁单酯。用IR谱和MS谱分别对产物进行了结构表征。反应讨论了物质的量比、反应时间对醇解反应的影响。当酸酐与醇的物质的量比为1:3,反应2h时,酸酐醇解率已达到95.8%;反应2.5h以上时,酸酐完全醇解,并且有少量丁二酸二丁酯生成。

  11. Succinic acid production derived from carbohydrates: An energy and greenhouse gas assessment of a platform chemical toward a bio-based economy

    NARCIS (Netherlands)

    Cok, B.; Tsiropoulos, I.; Roes, A.L.; Patel, M.K.

    2014-01-01

    Bio-based succinic acid has the potential to become a platform chemical, i.e. a key building block for deriving both commodity and high-value chemicals, which makes it an attractive compound in a bio-based economy. A few companies and industrial consortia have begun to develop its industrial product

  12. Selective separation of succinic acid from simulated fermentation broth by nanofiltration%纳滤选择性分离丁二酸模拟发酵液

    Institute of Scientific and Technical Information of China (English)

    吴昊; 姜岷; 韦萍; 高超; 杨高; 雷丹

    2011-01-01

    生物法制备的丁二酸发酵液中含有残留的底物(葡萄糖)、甲酸、乙酸及二价无机离子(Mg2+、SO42-)等杂质,不利于分离纯化.采用截留相对分子质量为160的纳滤膜LNG-NF-016对丁二酸模拟发酵液进行分离,考察了pH、操作压力、MgSO4浓度、丁二酸浓度、葡萄糖浓度、料液体积流量、操作温度等因素对纳滤分离性能的影响.纳滤分离的选择性由丁二酸的解离状态决定:模拟发酵液调节至pH3.0,丁二酸未解离,可将其与葡萄糖、MgSO4分离,丁二酸的透过率达98%,葡萄糖、MgSO4的截留率均>85%.随后将透过液调节至pH 6.0,丁二酸形成二价阴离子,可将其与单价的甲酸盐、乙酸盐分离,丁二酸截留率达90%,丁二酸被浓缩至121 g/L,而膜截留液中的甲酸、乙酸浓度均<5 g/L.同一型号纳滤膜可实现模拟发酵液中丁二酸与副产一元有机酸、底物及多价无机离子的选择性分离.%Many impurities existed in succinic acid fermentation broth, such as by-product organic acids (formic acid, acetic acid), residual substrate (glucose) and divalent ion (Mg2+, SO42-) , which was unfavorable to purification. Separation of succinic acid from simulated fermentation broth by nanofiltration membrane LNG-NF-016(MWCO 160) was studied, For this purpose, the effect of operating parameters such as pH in the feed solution, operation pressure, MgSO4 concentration, succinic acid concentration, glucose concentration, cross-flow rate and operation temperature on nanofiltration was investigated using an experimental design technique. The selectivity of nanofiltration depended on the degree of dissociation of succinic acid. At pH about 3. 0, undissociated succinic acid could be separated from glucose, and MgSCX with succinic acid permeation of 98% and glucose and MgSCX with rejection more than 85%. The divalent succinate could be separated from acetate and formate at pH about 6. 0, succinic acid rejection of

  13. Effects of synthetic detergents on in vivo activity of tissue phosphatases and succinic dehydrogenase from Mystus vittatus.

    Science.gov (United States)

    Mohan, D; Verma, S R

    1981-05-01

    African catfish (Mystus vittatus) were exposed to three sub-lethal concentrations of Swascofix E45 (13.8, 9.2 and 4.6 mg/l) and Swascol 3L (69.3, 46.2 and 23.1 mg/l) for 15 and 30 days, and their effects on alkaline and acid phosphatase, and succinic dehydrogenase in liver, kidney and intestine were measured. The enzymes were found to be inhibited in all the tissues. Maximum inhibition (38.44%) was observed in liver alkaline phosphatase activity after 30 days with the highest concentration of Swascofix E45 and the lowest inhibition (0.118%) was found in kidney acid phosphatase activity with the lowest concentration of Swascol 3L after 15 days. Insignificant enzyme stimulation in some cases was also observed.

  14. Effects of synthetic detergents on in vivo activity of tissue phosphatases and succinic dehydrogenase from Mystus vittatus

    Energy Technology Data Exchange (ETDEWEB)

    Mohan, D.; Verma, S.R.

    1981-05-01

    African catfish (Mystus vittatus) were exposed to three sub-lethal concentrations of Swascofix E45 (13.8, 9.2 and 4.6 mg/l) and Swascol 3L (69.3, 46.2 and 23.1 mg/l) for 15 and 30 days, and their effects on alkaline and acid phosphatase, and succinic dehydrogenase in liver, kidney and intestine were measured. The enzymes were found to be inhibited in all the tissues. Maximum inhibition (38.44%) was observed in liver alkaline phosphatase activity after 30 days with the highest concentration of Swascofix E45 and the lowest inhibition (0.118%) was found in kidney acid phosphatase activity with the lowest concentration of Swascol 3L after 15 days. Insignificant enzyme stimulation in some cases was also observed.

  15. Anti-diabetic activity of cassava cross-linked octenyl succinic maltodextrin in STZ-induced diabetic mice.

    Science.gov (United States)

    Wang, Li; Zheng, Maoqiang; Wang, Yingyao; Zhang, Ying; Qian, Haifeng; Zhang, Hui; Qi, Xiguang

    2014-03-01

    The effect of cassava cross-linked octenyl succinic maltodextrin (CCOMD) on diabetic mice was investigated in this study. For CCOMD-L (low dose) and CCOMD-H (high dose) groups, the body weights were recovered by 14.9% and 18.5%, respectively, which were significantly higher than that of model control group. It was also found that the blood glucose and insulin levels were ameliorated in the diabetic mice by the CCOMD diet. Moreover, the CCOMD diet decreased the plasma total cholesterol level (8.1-9.1%) and LDL cholesterol level (28.9-39.4%), and improved the plasma HDL cholesterol level (13.8-15.3%) and intestine short chain fatty acid content. The results indicated that CCOMD administration may be helpful for treating and preventing hyperlipidemia and hyperglycemia in diabetes.

  16. Long-distance inter-hydrogen bond coupling effects in the polarized IR spectra of succinic acid crystals

    Science.gov (United States)

    Flakus, Henryk T.; Hachuła, Barbara; Hołaj-Krzak, Jakub T.

    2015-05-01

    The spectral properties of four different crystalline succinic acid (HOOC-(CH2)2-COOH) (SAC) isotopomer systems, h6, d2, d4 and d6, were examined by means of the IR spectroscopy in polarized light aided by numerical simulations of the νO-H and νO-D band contour shapes on utilizing the "strong-coupling" model. The abnormal IR spectral properties of SAC crystals in relation to the corresponding properties of glutaric, pimelic and adipic acid crystals were ascribed to the hyperconjugation electronic effects in the acid associated molecules. A vibronic coupling mechanism involving the proton stretching vibrations in the (COOH)2 cycles and the electronic motions in the molecular skeletons, the isotopic "H/D self-organization" mechanisms and a long-distance vibrational exciton coupling between the adjacent (COOH)2 cycles in the molecular chains are mainly responsible for the generation of the temperature effects in the crystalline IR spectra.

  17. Crystal Structure of Diethyl [2,3-Di(Ethoxycarbonyl)-2, 3-di(p-nitrophenyl)l Succinate

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new conformational carbon-carbon bond free radical initiator diethyl [2,3- di(ethoxycarbonyl)-2,3-di(p-nitrophenyl)] succinate (EMNPS) was synthesized and identified by elemental analysis, FAB-MS, IR and 1H NMR spectroscopy. The analytical results of single crystal X-ray show the conforma-tion of EMNPS tends to be a stagger gauche form, and torsion angle of the two gauche phenyls is smaller than 60°. There is obvious elongation in central car bon-carbon bond length (0.161 nm). EMNPS can be decomposed into two relatively stable free radicals measured by ESR. By initiating bulk polymeriza-tion of methyl methacrylate (MMA), EMNPS shows the ability of controlling the molecular weight of polymers.

  18. [Effect of citrate, tartrate, succinate and phosphate ions on the penetration of phosphorus-labelled anions into erythrocytes].

    Science.gov (United States)

    Gomulkievich, Ia; Popdimitrova, N; Kunchev, N; Zlatarev, G

    1980-01-01

    Membrane permeability for different ions may successfully be evaluated under conditions of ionic equilibrium, which provides osmotic equilibrium in the cell and steadiness of its volume. The present investigation was promoted on red cells of experimental animals under conditions of ionic equilibrium, using P32 with up to 30 microCi activity. Unidirectional penetration of ions in the red cells was studied. The speed constant K0 was derived from the graphic relation InA=f(t) as an angular coefficient at the starting moment. The type of ions was shown to influence K0 value, which was maximal in the presence of tartarate ions in the suspension medium and minimal in the presence of succinate ions. This study demonstrated that the activation energy does not depend on the ions in the solution. The results are highly suggestive of the existence of differences in the mechanism of penetration of different ions through the red cell membrane.

  19. Structural Elucidation of α-Cyclodextrin-Succinic Acid Pseudo Dodecahydrate: Expanding the Packing Types of α-Cyclodextrin Inclusion Complexes

    Directory of Open Access Journals (Sweden)

    Sofiane Saouane

    2015-12-01

    Full Text Available This paper reports a new packing type of α-cyclodextrin inclusion complexes, obtained here with succinic acid under low-temperature crystallization conditions. The structure of the 1:1 complex is characterized by heavy disorder of the guest, the solvent, and part of the host. The crystal packing belongs to the known channel-type structure; the basic structural unit is composed of cyclodextrin trimers, as opposed to the known isolated molecular or dimeric constructs, packed along the c-axis. Each trimer is made of crystallographically independent molecules assembled in a stacked vase-like cluster. A multi-temperature single-crystal X-ray diffraction analysis reveals the presence of dynamic disorder.

  20. Acylation Modification of Antheraea pernyi Silk Fibroin Using Succinic Anhydride and Its Effects on Enzymatic Degradation Behavior

    Directory of Open Access Journals (Sweden)

    Xiufang Li

    2013-01-01

    Full Text Available The degradation rate of tissue engineering scaffolds should match the regeneration rate of new tissues. Controlling the degradation behavior of silk fibroin is an important subject for silk-based tissue engineering scaffolds. In this study, Antheraea pernyi silk fibroin was successfully modified with succinic anhydride and then characterized by zeta potential, ninhydrin method, and FTIR. In vitro, three-dimensional scaffolds prepared with modified silk fibroin were incubated in collagenase IA solution for 18 days to evaluate the impact of acylation on the degradation behavior. The results demonstrated that the degradation rate of modified silk fibroin scaffolds was more rapid than unmodified ones. The content of the β-sheet structure in silk fibroin obviously decreased after acylation, resulting in a high degradation rate. Above all, the degradation behavior of silk fibroin scaffolds could be regulated by acylation to match the requirements of various tissues regeneration.

  1. DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR SIMULTANEOUS ESTIMATION OF METOPROLOL SUCCINATE AND TELMISARTAN IN COMBINED PHARMACEUTICAL FORMULATION

    Directory of Open Access Journals (Sweden)

    Mayur Modi*, Rikin Shah and R.C. Mashru

    2012-05-01

    Full Text Available Four simple, rapid, precise, economical and accurate spectrophotometric methods have been developed for simultaneous analysis of Metoprolol succinate and Telmisartan in their combined dosage form. Method 1, First derivative simultaneous equation method (Vierodt’s method. It employs formation and solving of simultaneous equation using two wavelengths 230.2 nm (λmax of Metoprolol succinate and 237 nm (λmax of Telmisartan in first derivative spectra. Method 2, First derivative Q-Absorbance equation method. It involves, formation of Q-absorbance equation at 231.8 nm (isoabsorptive point and 237 nm (λmax of Telmisartan in first derivative spectra. Method 3, Absorbance correction method, involves measurement of absorbance at 296.6 nm for estimation of TEL and measurement of corrected absorbance at 223 nm for estimation of MET. Method 4, Combination of First derivative dual wavelength ,which uses the difference in absorbance at 282.4 nm and 284.6 nm for estimation of MET and zero crossing first derivative spectrophotometry involves measurement of amplitudes at 330 nm for estimation of TEL in first derivative spectra. Developed methods were validated according to ICH guidelines. The calibration graph follows Beer’s law in the range of 3-20 µg/ml for MET and 4-16 µg/ml for TEL with R square value greater than 0.999. Accuracy of all methods was determined by recovery studies and showed % recovery between 99 to 101%. Intraday and interday precision was checked for all methods and mean %RSD was found to be less than 2 for all the methods. The methods were successfully applied for estimation of MET and TEL in marketed formulation.

  2. Amberlite XAD-4 functionalized with succinic acid for the solid phase extractive preconcentration and separation of uranium(VI).

    Science.gov (United States)

    Metilda, P; Sanghamitra, K; Mary Gladis, J; Naidu, G R K; Prasada Rao, T

    2005-01-15

    Amberlite XAD-4 resin has been functionalized with succinic acid by coupling it with dibromosuccinic acid after acetylation. The resulting resin has been characterized by FT-IR, elemental analysis and TGA and has been used for preconcentrative separation of uranium(VI) from host of other inorganic species prior to its determination by spectrophotometry. The optimum pH value for quantitative sorption of uranium(VI) in both batch and column modes is 4.5-8.0 and desorption can be achieved by using 5.0ml of 1.0moll(-1) HCl. The sorption capacity of functionalized resin is 12.3mgg(-1). Calibration graphs were rectilinear over the uranium(VI) concentrations in the range 5-200mugl(-1). Five replicate determinations of 50mug of uranium(VI) present in 1000ml of solution gave a mean absorbance of 0.10 with a relative standard deviation of 2.56%. The detection limit corresponding to three times the standard deviation of the blank was found to be 2mugl(-1). Various cationic and anionic species at 200-fold amounts do not interfere during the preconcentration of 5.0mug of uranium(VI) present in 1000ml (batch) or 100ml (column) of sample solution. Further, adsorption kinetic and isotherm studies were also carried out by a batch method to understand the nature of sorption of uranium(VI) with the succinic acid functionalized resin. The accuracy of the developed solid phase extractive preconcentration method in conjunction with Arsenazo III procedure was tested by analyzing marine sediment (MESS-3) and soil (IAEA soil-7) reference material. Further, the above procedure has been successfully employed for the analysis of soil and sediment samples.

  3. [The methods for the protection against counterfeit medications. Part 1. The estimation of the quality of metoprolol succinate substance and tablets from different manufacturers in terms of "identity" and "active ingredient content"].

    Science.gov (United States)

    Iakushev, V A; Morozova, M A; Elizarova, T E; Fitilev, S B; Pletneva, T V

    2012-01-01

    This paper was designed to report the results of analysis of metoprolol succinate substance and tablets obtained from two manufacturers, Akrikhin (Russia) and AstraZeneca (Sweden). The analysis was performed by spectroscopy in the near IR region and followed by the chemometric treatment of the data obtained. The method was used to confirm the "identity" of metoprolol succinate tablets. The approach to distinguishing the differences between pharmaceutical dosage forms produced by different manufacturers is proposed. Also, the method for the qualitative determination of metoprolol succinate in the pharmaceutical formulations has been developed.

  4. New insight into the central benzodiazepine receptor-ligand interactions: design, synthesis, biological evaluation, and molecular modeling of 3-substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds.

    Science.gov (United States)

    Anzini, Maurizio; Valenti, Salvatore; Braile, Carlo; Cappelli, Andrea; Vomero, Salvatore; Alcaro, Stefano; Ortuso, Francesco; Marinelli, Luciana; Limongelli, Vittorio; Novellino, Ettore; Betti, Laura; Giannaccini, Gino; Lucacchini, Antonio; Daniele, Simona; Martini, Claudia; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Giorgi, Gianluca; Mascia, Maria Paola; Biggio, Giovanni

    2011-08-25

    3-Substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds were synthesized as central benzodiazepine receptor (CBR) ligands. Most of the compounds showed high affinity for bovine and human CBR, their K(i) values spanning from the low nanomolar to the submicromolar range. In particular, imidazoester 5f was able to promote a massive flow of (36)Cl(-) in rat cerebrocortical synaptoneurosomes overlapping its efficacy profile with that of a typical full agonist. Compound 5f was then examined in mice for its pharmacological effects where it proved to be a safe anxiolytic agent devoid of the unpleasant myorelaxant and amnesic effects of the classical 1,4-benzodiazepines. Moreover, the selectivity of some selected compounds has been assessed in recombinant α(1)β(2)γ(2)L, α(2)β(1)γ(2)L, and α(5)β(2)γ(2)L human GABA(A) receptors. Finally, some compounds were submitted to molecular docking calculations along with molecular dynamics simulations in the Cromer's GABA(A) homology model.

  5. Localization and physical mapping of a plasmid-borne 23-kb nif gene cluster from Enterobacter agglomerans showing homology to the entire nif gene cluster of Klebsiella pneumoniae M5a1.

    Science.gov (United States)

    Singh, M; Kreutzer, R; Acker, G; Klingmüller, W

    1988-01-01

    A physical and genetical map of the plasmid pEA3 indigenous to Enterobacter agglomerans is presented. pEA3 is a 111-kb large plasmid containing a 23-kb large cluster of nif genes which shows extensive homology (Southern hybridization and heteroduplex analysis) to the entire nif gene cluster of Klebsiella pneumoniae (Kp) M5a1. All the nif genes on pEA3 are organized in the same manner as in K. pneumoniae, except nifJ, which is located on the left end of pEA3 nif gene cluster (near nifQB). A BamHI restriction map of pEA3 and a detailed restriction map of the 23-kb nif region on pEA3 is also presented. The nif genes of pEA3 showed a low level of acetylene reduction in Escherichia coli, demonstrating that these genes are functional and contain the whole genetic information required to fix nitrogen. The origin of vegetative replication (OriV) of pEA3 was localized about 5.5 kb from the right end of the nif gene cluster. In addition to pEA3, large plasmids from four other strains of E. agglomerans showed homology to all the Kp nif genes tested, indicating that in diazotrophic strains of E. agglomerans nif genes are usually located on plasmids. In contrast, in most of the free-living, nitrogen-fixing bacteria the nif genes are on chromosome.

  6. Synthesis Technology of Octenyl Succinic Acid Cross - Link Starch Esters%辛烯基琥珀酸交联淀粉酯合成工艺研究

    Institute of Scientific and Technical Information of China (English)

    石海信; 谢新玲; 张友全; 童张法

    2009-01-01

    以木薯淀粉为原料,用环氧氯丙烷作交联剂,辛烯基琥珀酸酐作酯化剂,采用湿法工艺合成辛烯基琥珀酸交联淀粉酯.探讨了淀粉乳浓度、反应温度、反应时间、pH和沉降积对辛烯基琥珀酸交联淀粉酯取代度的影响,确定制备辛烯基琥珀酸交联淀粉酯的最佳工艺参数为:淀粉乳浓度35%,酯化pH 8.0,酯化温度35℃,酯化时间3 h.交联淀粉的沉降积对酯化取代度影响较小,在生产中可根据最终产品的用途选用合适沉降积的交联淀粉进行酯化复合变性.复合变性淀粉符合食品行业标准,可以在食品工业中应用.扫描电镜对其结构进行观察显示淀粉中受侵蚀颗粒增多,颗粒表面的小凹痕数量增加.%Octenyl succinic acid cross - link starch esters were prepared by wet process with cassava starch as raw material, epichlorohydrin as cross - link agent and octenyl succinic anhydride as esterifying agent. The effects of starch slurry concentration, reaction temperature, reaction time, pH and sediment volume on the substitution degree of octenyl succinic acid cross - link starch esters were studied. Results; The optimal conditions for preparing octenyl succinic acid cross -link starch esters are starch slurry concentration 35% , esterification pH 8.0, esterification temperature 35 ℃ and esterification time 3 h. The sediment volume of cross - link starch has little effect on the substitution degree. Thus, a proper sediment volume can be determined according to the usage of final octenyl succinic acid cross - link starch esters. The produced octenyl succinic acid cross - link starch esters are identified safe to be used in food industry. The result of scanning electron microscope observation shows that the number of dents and splits in the granule surface of the prepared starch increases.

  7. Research advances in metabolic control of succinic acid fermentation%代谢控制发酵产琥珀酸研究进展

    Institute of Scientific and Technical Information of China (English)

    王乐; 倪子富; 惠明; 王金水

    2015-01-01

    As an important chemical raw material, succinic acid is widely used in many fields of modern industry with a huge market demand. Recently, the biological method for succinic acid fermentation has become a hot topic in research, since it has the advantages of renewable utilization of resources and environmental friendly production. From the perspective of metabolic control, the methods and strategies for succinic acid production with some strains, especially the recombinant E. coli, are summarized in this paper. Regulation of key enzyme gene in metabolism branch and the key factors in fermentation of succinic acid, such as regulation of redox force, carbon dioxide control, and metabolic pathways transforming are introduced. The progress of metabolic control of succinic acid fermentation is presented, and development of succinic acid fermentation in the future is proposed.%琥珀酸作为一种重要的化工原料被广泛应用于现代工业的各个领域,具有庞大的市场需求。利用生物法发酵生产琥珀酸因具有资源可再生利用、绿色清洁节能等方面不可替代的优势而成为当今研究的热点。本文从代谢调控的角度出发分析总结了一些产琥珀酸菌株,尤其是重组大肠杆菌在发酵生产琥珀酸中所应用到的方法和策略,如对代谢途径中关键酶的调控以及发酵生产中的关键因素(如氧化还原回复力调控、CO2调节、代谢途径改造等),着重突出了代谢控制发酵生产方面的研究进展,并对今后的发展方向提出了一些设想。

  8. Synthesis of poly ( butylene succinate)%聚丁二酸丁二醇酯的合成

    Institute of Scientific and Technical Information of China (English)

    郑文俊; 黄关葆

    2011-01-01

    A poly(butylene succinate) (PBS) with higher relative molecular weight was synthesized by direct esterification-polycondensation of succinic acid(SA) and 1,4-butanediol( BD), and it was the first time to investigate the side reaction of esterification in PBS by using refractometric analysis. The results showed that the esterification rate was significantly affected by SA/BD ratio, temperature and catalysts. The side reaction increased with the increase of the amount of BD and rising of the temperature. The viscosity- average molecular weight of the synthesized PBS was from 5. 7 x 104 g/mol to 8. 0 x 104 g/mol, and the highest molecular weight PBS was obtained when the esterification temperature was 150 ℃ , SA/ BD ratio was 1: 1. 2, the amount of titanium catalyst was 0. 1% of SA( mole ratio) , and the temperature of polycondensation was 220 ℃.%通过直接酯化-缩聚法,以丁二酸、丁二醇为原料,合成了相对分子质量较高的聚丁二酸丁二醇酯(PBS),并首次采用折光率法研究了PBS酯化反应中的副反应.结果表明:酯化反应中,酸醇比、反应温度及催化剂对酯化率的影响较大;随着丁二醇加入量的增加,酯化反应中的副反应增强,随着反应温度的升高也增强;缩聚反应所合成PBS的黏均摩尔质量在5.7 ×104~8.0×104 g/mol之间,且在酯化反应温度为150℃,酸醇比为1∶1.2,采用钛系催化剂,其用量为所加入丁二酸的0.1%(物质的量比),缩聚反应温度为220℃时,所得产物分子质量最高.

  9. Artificial primary marine aerosol production: a laboratory study with varying water temperature, salinity, and succinic acid concentration

    Directory of Open Access Journals (Sweden)

    J. Zábori

    2012-11-01

    Full Text Available Primary marine aerosols are an important component of the climate system, especially in the remote marine environment. With diminishing sea-ice cover, better understanding of the role of sea spray aerosol on climate in the polar regions is required. As for Arctic Ocean water, laboratory experiments with NaCl water confirm that a few degrees change in the water temperature (Tw gives a large change in the number of primary particles. Small particles with a dry diameter between 0.01 μm and 0.25 μm dominate the aerosol number density, but their relative dominance decreases with increasing water temperature from 0 °C where they represent 85–90% of the total aerosol number to 10 °C, where they represent 60–70% of the total aerosol number. This effect is most likely related to a change in physical properties and not to modification of sea water chemistry. A change of salinity between 15 g kg−1 and 35 g kg−1 did not influence the shape of a particle number size distribution. Although the magnitude of the size distribution for a water temperature change between 0 °C and 16 °C changed, the shape did not. An experiment where succinic acid was added to a NaCl water solution showed, that the number concentration of particles with 0.010 μm < Dp < 4.5 μm decreased on average by 10% when the succinic acid concentration in NaCl water at a water temperature of 0 °C was increased from 0 μmol L−1 to 94 μmol L−1. A shift to larger sizes in the particle number size distribution is observed from pure NaCl water to Arctic Ocean water. This is likely a consequence of organics and different inorganic salts present in Arctic Ocean water in addition to the NaCl.

  10. 生物降解PBS聚醋的改性研究进展%Advances in Modification of Biodegradable Poly(Butylene Succinate)

    Institute of Scientific and Technical Information of China (English)

    孙桂香; 罗勇; 陆平晔

    2011-01-01

    聚丁二酸丁二醇酯(PBS)是一种具有良好生物降解性的聚酯,本文简述了PBS的基础物性和力学性能,综述了各种改善PBS生物降解性、生物相容性、热学和力学性能的方法,重点介绍了通过共聚、共混等方法对PBS进行改性的研究进展.%Poly(butylene succinate) (PBS) are polyesters with outstanding biodegradability. The basic physical and mechanical properties of PBS were introduced briefly in this article. Advances in modification research of biodegradation, biocompatibility, thermal and mechanical properties of poly (butylene succinate) were reviewed and the modification methods including copolymerization, blending,and so on, were presented emphatically.

  11. Degradation studies of 1, 6-diisocyanatohexane-extended poly (1, 4-butylene succinate) - bioactive glass scaffolds for bone tissue repair applications

    Science.gov (United States)

    Kaur, Kulwinder; Singh, K. J.; Anand, Vikas

    2016-05-01

    Bio composite scaffolds prepared from polymer and bio glass provide necessary sites for bone tissue regeneration. In the presented work, bioactive glass scaffolds have been prepared from 1, 6-diisocyanatohexane-extended poly (1, 4-butylene succinate) with different amount of bioactive glass powder by solvent casting method. Prepared scaffolds have been characterized by XRD, FTIR and FESEM techniques. Effect of content of bioactive glass on biodegradability has been investigated in detail.

  12. c-Jun N-terminal kinase is required for vitamin E succinate-induced apoptosis in human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yan Zhao; Gui-Chang Li; Wei-Ping Yu

    2004-01-01

    AIM: To investigate the roles of c-Jun N-terminal kinase (JNK)signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS: Human gastric cancer cell lines (SGC-7901)were treated with vitamin E succinate (VES) at 5, 10, 20 mg/L.Succinic acid and vitamin E were used as vehicle controls and condition medium only as an untreated (UT) control.Apoptosis was observed by 4′, 6-diamidine-2′-phenylindole dihydrochloride (DAPI) staining for morphological changes and by DNA fragmentation for biochemical alterations.Western blot analysis was applied to measure the expression ofJNK and phosphorylated JNK. After the cells were transiently transfected with dominant negative mutant of JNK (DNJNK) followed by treatment of VES, the expression of JNK and c-Jun protein was determined.RESULTS: The apoptotic changes were observed after VES treatment by DNA fragmentation. DNA ladder in the 20 mg/L VES group was more clearly seen than that in 10 mg/L VES group and was not detected following treatment of UT control, succinate and vitamin E. VES at 5, 10 and 20 mg/L increased the expression of p-JNK by 2.5-, 2.8- and 4.2-fold, respectively. VES induced the phosphorylation of JNK beginning at 1.5 h and produced a sustained increase for 24 h with the peak level at 12 h. Transient transfection of DN-JNK blocked VES-triggered apoptosis by 52%. DN-JNK significantly increased the level of JNK, while decreasing the expression of VES-induced c-Jun protein.CONCLUSION: VES-induced apoptosis in human gastric cancer SGC-7901 cells involves JNK signaling pathway via c-Jun and its downstream transcription factor.

  13. Synthesis of high molecular weight polylactic acid from aqueous lactic acid co-catalyzed by tin(II)chloride dihydrate and succinic anhydride

    Institute of Scientific and Technical Information of China (English)

    LEI Ziqiang; BAI Yanbin; WANG Shoufeng

    2005-01-01

    Polylactic acid was synthesized from commercial available cheap aqueous lactic acid (85%―90% w/w) using succinic anhydride and SnCl2·2H2O as catalyst in the absence of organic solvents. As a result, polylactic acid with a molecular weight of 60000 was prepared in 10 h. The new procedure is much simple, cheap and outstanding in that the start material is aqueous lactic acid; the catalytic system is environmentally benign.

  14. Screening and Breeding of a Strain for High Yield of Succinic Acid%一株丁二酸高产菌株的筛选与选育

    Institute of Scientific and Technical Information of China (English)

    王乐; 宇光海; 杨硕晔; 王为为; 惠明

    2015-01-01

    旨在提高丁二酸发酵生产水平,通过初筛、复筛从土壤中分离得到了高产丁二酸菌株,发酵结束后利用高效液相色谱法检测丁二酸的产率为34.45%。对菌株进行紫外诱变选育,结果表明,在底物葡萄糖的浓度为100 g/L时,丁二酸的产率提高了46%,达到了50.30%,残糖低于10 g/L。经形态学特征、生理生化指标测定以及16S rDNA序列分析等,鉴定该菌株为放线杆菌。%It was to improve the production of succinic acid. After the primary and secondary screening, a strain with high-yield of succinic acid was isolated from the soil. The succinic acid production of 34.45% was determined by the high performance liquid chromatography (HPLC)after the fermentation. Later, the UV mutagenic breeding of strains has been performed, resulting in the succinic acid production of 50.30% which increased by 46% in the substrate of glucose concentration of 100 g/L with the residual sugar lower than 10 g/L. After the determinations of morphological characteristics, physiological and biochemical index and 16S rDNA sequence analysis, the strain was identified asactinobacillus.

  15. A simple sample preparation for simultaneous determination of chloramphenicol and its succinate esters in food products using high-performance liquid chromatography/high-resolution mass spectrometry.

    Science.gov (United States)

    Amelin, Vasiliy; Korotkov, Anton

    2017-02-01

    A simple method is described for the determination of chloramphenicol and its succinate esters in food products. Examination of food products using high-performance liquid chromatography/high-resolution mass spectrometry showed the presence not only of chloramphenicol but also of its succinate forms. A scheme is proposed for determining chloramphenicol and its succinate esters (calculated as chloramphenicol) in meat (beef, pork, poultry), milk, liver, kidney, eggs, fish and honey. Analytes are extracted from a 1.0 g sample with 5 ml acetonitrile. It was found that using the method of standard addition and diluting the extract with water leads to the elimination of matrix effects and also eliminates errors associated with peak splitting due to the separate elution of the differing forms of the analyte. Validation results were satisfactory, with recoveries from 85% to 111% (meat, milk, liver, kidney, eggs, fish and honey) and a relative standard deviation (RSD) lower than 13% for spiked levels of 0.3, 1.0 and 5 µg kg(-)(1). The limits of detection and quantification (calculated as chloramphenicol for all forms) were 0.1 and 0.3 µg kg(-)(1), respectively. The RSD of the results of the analysis was < 10%. The duration of the analysis was less than 1 h.

  16. EFFECT OF SUBSTITUTION POSITION OF HYDROXY GROUP AT BENZOIC ACID ON THE LUMINESCENT AND DEGRADATION PROPERTIES OF POLY[DI(CARBOXYPHENYL) SUCCINATE-co-SEBACIC ANHYDRIDE]S

    Institute of Scientific and Technical Information of China (English)

    Jun Fan; Hong-liang Jiang; Kang-jie Zhu

    2007-01-01

    In this work, two new diacids, di(m-carboxyphenyl) succinate (m-dCPS) and di(o-carboxyphenyl) succinate (o-dCPS), were synthesized by reaction of m-, o-hydroxy benzoic acid with succinic chloride, respectively. Their corresponding copolymers with sebacic acid (SA), P(m-dCPS:SA) and P(o-dCPS:SA), were prepared by melt copolycondensation and characterized by NMR, UV and DSC methods. Compared with inherently fluorescent poly[di(p-carboxyphenyl) succinateco-sebacic anhydride] (P(p-dCPS:SA)), P(m-dCPS:SA) and P(o-dCPS:SA) displayed different luminescent properties. P(m-dCPS:SA) could emit fluorescence under the excitation of both visible and UV light, while P(o-dCPS:SA) could only emit fluorescence when excited with UV light. Degradation rate of the two new copolyanhydrides increased with the increase of SA fraction in the copolymers. In addition, P(o-dCPS:SA) degraded more rapidly than P(m-dCPS:SA) with the same composition. Typical surface-degradation characteristics of these copolyanhydrides were observed.

  17. Development and Validation of a Specific Stability Indicating High Performance Liquid Chromatographic Methods for Related Compounds and Assay of Solifenacin Succinate

    Directory of Open Access Journals (Sweden)

    B. V. Rami Reddy

    2013-01-01

    Full Text Available Gradient, reverse phase liquid chromatographic methods were developed separately for the related compounds and solifenacin succinate, an active pharmaceutical ingredient used for the treatment of overactive bladder. Gradient LC method was employed for related compounds. The mobile phase-A contains a 0.01 M phosphate buffer pH: 3.5±0.05 with orthophosphoric acid (88% and mobile phase-B contains a mixture of acetonitrile and water in the ratio of 90 : 10(v/v. The flow rate was 1.0 mL/minute, column temperature was kept at 35°C, and detection was monitored at 220 nm. In the developed HPLC method the resolution between solifenacin succinate and its closely eluting impurity, that is, solifenacin N-oxide was found to be greater than 3.0. The drug was subjected to stress conditions such as hydrolysis, oxidation, photolysis, and thermal degradation. Considerable degradation was found to occur in only oxidative stress condition. Degradation product formed during oxidative stress condition was found to be impurity-C and it can be identified by LC-MS. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP-LC method was validated as per ICH guidelines. We also developed LC-MS/MS method for determination and identification of these impurities in solifenacin succinate.

  18. Electrosynthesis of succinic acid in non-membrane electrolyzer%无隔膜电化学合成丁二酸清洁工艺研究

    Institute of Scientific and Technical Information of China (English)

    孙洋洲

    2013-01-01

    通过对合成丁二酸新电化学体系的研究,设计了无隔膜电解装置,开发出了低能耗、高收率、无污染的丁二酸电化学合成高效清洁工艺.产品总收率可达98.5%,吨产品直流耗电量小于1 500 kW·h,母液可循环利用.%On the basis of the study on new electrochemical systems for synthesizing succinic acid,a new nonmembrane electrolyzer is designed.A new effective and clean electrosynthesis process with advantages such as energysaving,high yield and non-pollution is developed to prepare succinic acid.The total yield of the succinic acid reaches 98.5%.DC power consumption is less than 1 500 kwh/t and the mother liquor can be recycled.

  19. Oxygen and water vapor barrier properties of MMT nanocomposites from low density polyethylene or EPM with grafted succinic groups.

    Science.gov (United States)

    Passaglia, Elisa; Bertoldo, Monica; Ceriegi, Silvia; Sulcis, Roberta; Narducci, Piero; Conzatti, Lucia

    2008-04-01

    LDPE, EPM and their derivatives containing a moderate amount (0.08-1.8 by mol) of diethylsuccinate or succinic anhydryde groups were used as matrices in blending with different amount of organophilic montmorillonites and the resulting composite morphology and structure (by XRD, SEM, TEM microscopy, DSC analysis and selective solvent extraction) were studied with reference to the polar groups/MMT ratio. Exfoliated, intercalated and mixed morphologies were achieved. High concentrations of polar groups grafted to the polyolefin and montmorillonite loading not larger than 5% wt were favourable for obtaining high exfoliation degree. Particularly in the exfoliated MMT composite LDPE had lower crystallinity degree, while EPM showed increased glass transition temperature and reduced solubility in hot toluene. Moreover, oxygen and water vapor barrier property improvement was observed in films where MMT exhibits either exfoliated or intercalated morphologies. Strong interactions with the montmorillonite particle surface through the polar groups grafted to the polyolefin seems to be the basic effect responsible for the morphology and peculiar properties. A model based on the reduced mobility of the polymer located near the particle surface or inside the MMT gallery (confined phase) was proposed to explain the observed oxygen permeability reduction, the T(g) increase and solubility of poly(ethylene-ran-propylene)/MMT nanocomposites.

  20. Regenerable Subnanometer Pd Clusters on Zirconia for Highly Selective Hydrogenation of Biomass-Derived Succinic Acid in Water

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    2016-07-01

    Full Text Available The size of metal particles is an important factor to determine the performance of the supported metal catalysts. In this work, we report subnanometer Pd clusters supported on zirconia by the microwave-assisted hydrothermal method. The presence of subnanometer Pd clusters on the zirconia surface was confirmed by two-dimensional Gaussian-function fits of the aberration-corrected high-angle annual dark-field images. These subnanometer Pd catalysts exhibit high catalytic performance for the hydrogenation of biomass-derived succinic acid to γ-butyrolactone in water and avoid the formation of overhydrogenated products, such as 1,4-butanediol and tetrahydrofuran. The catalyst with an ultra-low Pd loading of 0.2 wt. % demonstrated high selectivity (95% for γ-butyrolactone using water as a solvent at 473 K and 10 MPa. Moreover, it can be reused at least six times without the loss of catalytic activity, illustrating high performance of the small Pd clusters.

  1. Simultaneous ammonia and nitrate removal in an airlift reactor using poly(butylene succinate) as carbon source and biofilm carrier.

    Science.gov (United States)

    Ruan, Yun-Jie; Deng, Ya-Le; Guo, Xi-Shan; Timmons, Michael B; Lu, Hui-Feng; Han, Zhi-Ying; Ye, Zhang-Ying; Shi, Ming-Ming; Zhu, Song-Ming

    2016-09-01

    In this study, an airlift inner-loop sequencing batch reactor using poly(butylene succinate) as the biofilm carrier and carbon source was operated under an alternant aerobic/anoxic strategy for nitrogen removal in recirculating aquaculture system. The average TAN and nitrate removal rates of 47.35±15.62gNH4-Nm(-3)d(-1) and 0.64±0.14kgNO3-Nm(-3)d(-1) were achieved with no obvious nitrite accumulation (0.70±0.76mg/L) and the dissolved organic carbon in effluents was maintained at 148.38±39.06mg/L. Besides, the activities of dissimilatory nitrate reduction to ammonium and sulfate reduction activities were successfully inhibited. The proteome KEGG analysis illustrated that ammonia might be removed through heterotrophic nitrification, while the activities of nitrate and nitrite reductases were enhanced through aeration treatment. The microbial community analysis revealed that denitrifiers of Azoarcus and Simplicispira occupied the dominate abundance which accounted for the high nitrate removal performance. Overall, this study broadened our understanding of simultaneous nitrification and denitrification using biodegradable material as biofilm carrier.

  2. Solution viscosity – molar mass relationships for poly(butylene succinate and discussion on molar mass analysis

    Directory of Open Access Journals (Sweden)

    Q. Charlier

    2015-05-01

    Full Text Available Poly(butylene succinate (PBS is currently developing due to its biodegradability and the similarity of its mechanical properties to those of polyolefins. Relationships between the number average molar mass, Mn, and solution viscosity such as [η] and ηred were derived for this aliphatic polyester. Mn values were determined by end-group analysis and size exclusion chromatography (SEC. Mark-Houwink-Sakurada (MHS parameters were proposed in two solvents and for the different molar masses and viscosity measurement methods. As an example, the MHS equations were respectively, [η] =6.4•10–4•Mn0.67 in chloroform and [η] = 7.1•10–4•Mn0.69 in 50/50 wt% 1,2-dichlorobenzene/phenol at 25°C for molar masses measured by SEC in hexafluoro isopropanol (HFIP with poly(methyl methacrylate (PMMA standards. Empirical relationships were also suggested to derive Mn directly from reduced viscosity, ηred, which is much easier to determine than intrinsic viscosity. With these data, the number average molar mass of PBS can be conveniently estimated from a single viscosity measurement. In addition, it was shown that PBS contains 1–2 wt% of cyclic oligomers produced during esterification and that molar masses determined by taking this fraction into account or not were significantly different, especially for long chains.

  3. The Combination of α-Tocopheryl Succinate and Sodium Selenite on Breast Cancer: A Merit or a Demerit?

    Directory of Open Access Journals (Sweden)

    Doaa M. Badr

    2016-01-01

    Full Text Available α-Tocopheryl succinate (α-TOS, a mitochondria-targeting agent, induces apoptosis in malignant cells in vitro and in vivo. Selenite is a nutritional supplement that has been shown to stimulate apoptosis in cancer cells. This study was designed to investigate the cytotoxic effect of combined treatment of α-TOS and sodium selenite (SSe in vitro and in vivo and to explore their effect on apoptosis and autophagy in breast cancer. The type of interaction between α-TOS and SSe was evaluated and levels of oxidative stress and apoptotic and autophagic markers were determined. SSe alone showed varying degrees of cytotoxicity on all the tested cell lines. Its combination with α-TOS was antagonistic in vitro in MCF7 and in vivo in mice bearing Ehrlich tumor compared to α-TOS-treated one. Combination of TOS with 2 μM of SSe increased the level of glutathione without changes in antiapoptotic markers Bcl-2 and Mcl-1 at 16 and 48 hrs. SSe decreased caspase 3 activity and protein level of caspases 7 and 9, while it increased autophagic markers beclin-1 and LC3B protein levels of MCF7 cells treated with α-TOS. In conclusion, SSe antagonizes α-TOS-induced apoptosis via inhibition of oxidative stress and promoting prosurvival machinery of autophagy.

  4. Inhibition mechanism of hydroxypropyl methylcellulose acetate succinate on drug crystallization in gastrointestinal fluid and drug permeability from a supersaturated solution.

    Science.gov (United States)

    Ueda, Keisuke; Higashi, Kenjirou; Kataoka, Makoto; Yamashita, Shinji; Yamamoto, Keiji; Moribe, Kunikazu

    2014-10-01

    The effects of drug-crystallization inhibitor in bile acid/lipid micelles solution on drug permeation was evaluated during the drug crystallization process. Hydroxypropyl methylcellulose acetate succinate (HPMC-AS) was used as a drug-crystallization inhibitor, which efficiently suppressed dexamethasone (DEX) crystallization in a gastrointestinal fluid model containing sodium taurocholate (NaTC) and egg-phosphatidylcholine (egg-PC). Changes of molecular state of supersaturated DEX during the DEX crystallization process was monitored in real time using proton nuclear magnetic resonance (1H NMR). It revealed that DEX distribution to bulk water and micellar phases formed by NaTC and egg-PC was not changed during the DEX crystallization process even in the presence of HPMC-AS. DEX permeation during DEX crystallization was evaluated using dissolution/permeability system. The combination of crystallization inhibition by HPMC-AS and micellar encapsulation by NaTC and egg-PC led to considerably higher DEX concentrations and improvement of DEX permeation at the beginning of the DEX crystallization process. Crystallization inhibition by HPMC-AS can efficiently work even in the micellar solution, where NaTC/egg-PC micelles encapsulates some DEX. It was concluded that a crystallization inhibitor contributed to improvement of permeation of a poorly water-soluble drug in gastrointestinal fluid.

  5. Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

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    Sachiko Fukui

    2017-03-01

    Full Text Available The purpose of this study was to develop an extended-release (ER matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS and hydroxypropylcellulose (HPC were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet. Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method, dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin. Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

  6. FORMULATION AND IN VITRO EVALUATION OF METOPROLOL SUCCINATE FLOATING TABLETS BY USING TWO VISCOSITY GRADE OF HPMC

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    Shubhrajit Mantry et al

    2012-09-01

    Full Text Available Metoprolol is a beta1-selective (cardio selective adrenergic receptor blocking agent used in the treatment of Hypertension. The purpose of this investigation is to improve bioavailability by preparing a gastroretentive drug delivery system. Floating tablets of Metoprolol Succinate were prepared by employing two different grades of HPMC K4M and HPMC E15M in different concentrations by effervescent granulation technique. These grades of HPMC K4M and HPMC E15M were evaluated for their gel forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy and dissolution studies. The prepared tablets exhibited satisfactory physicochemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 6-8 hours. A combination of 5:1 sodium bicarbonate and magnesium stearate was found to achieve optimum in vitro buoyancy. The tablets with HPMC K4M and HPMC E15M with drug in the ratio of 1:1:2 were found to float for longer duration and released found to be 98.98%. FTIR show that there is no interaction with drug and other excipients. Selected Formulation F4 were subjected to FTIR that shows that is compatible and release was found superior to marketed conventional tablets with respect to floating and found to be stable.

  7. Dynamics of three organic acids (malic, acetic and succinic acid) in sunflower exposed to cadmium and lead.

    Science.gov (United States)

    Niu, Zhixin; Li, Xiaodong; Sun, Lina; Sun, Tieheng

    2013-01-01

    Sunflower (Helianthus annuus L.) has been considered as a good candidate for bioaccumulation of heavy metals. In the present study, sunflower was used to enrich the cadmium and lead in sand culture during 90 days. Biomass, Cd and Pb uptake, three organic acids and pH in cultures were investigated. Results showed that the existence of Cd and Pb showed different interactions on the organic acids exudation. In single Cd treatments, malic and acetic acids in Cd10 showed an incremental tendency with time. In the mixed treatments of Cd and Pb, malic acids increased when 10 and 40 mg x L(-1) Cd were added into Pb50, but acetic acids in Pb50 were inhibited by Cd addition. The Cd10 supplied in Pb10 stimulated the secretion of malic and succinic acids. Moreover, the Cd or Pb uptake in sunflower showed various correlations with pH and some organic acids, which might be due to the fact that the Cd and Pb interfere with the organic acids secretion in rhizosphere of sunflower, and the changes of organic acids altered the form and bioavailability of Cd and Pb in cultures conversely.

  8. Sedaxane, Isopyrazam and Solatenol™: Novel Broad-spectrum Fungicides Inhibiting Succinate Dehydrogenase (SDH) - Synthesis Challenges and Biological Aspects.

    Science.gov (United States)

    Walter, Harald; Tobler, Hans; Gribkov, Denis; Corsi, Camilla

    2015-01-01

    Sedaxane (SDX) 1, isopyrazam (IZM) 2 and Solatenol™ (STL) 3 are broad-spectrum pyrazole carboxamides, which originate from novel chemical classes of fungicides. Their mode of action (MoA) is inhibition of succinate dehydrogenase (SDH), which was recognized for a long time to deliver only compounds with a narrow biological spectrum. This view changed with the market introduction of BASF's boscalid in 2003. All major agro-companies subsequently worked in parallel on this MoA successfully and recently introduced new compounds to the market. Syngenta entered the SDHI area in 1998 and was able to introduce three complementary compounds to the market between 2010 and 2012. In this short review some synthesis challenges and biological effects of SDX 1, IZM 2 and STL 3 will be covered. New cost-efficient synthesis strategies for the preparation of o-biscyclopropyl-aniline, new benzonorbornene intermediates and the key pyrazole carboxylic acid intermediate which is essential for all three Syngenta SDHIs, will be in the focus of this review.

  9. Controlled-release fertilizer prepared using a biodegradable aliphatic copolyester of poly(butylene succinate) and dimerized fatty acid.

    Science.gov (United States)

    Lubkowski, Krzysztof; Smorowska, Aleksandra; Grzmil, Barbara; Kozłowska, Agnieszka

    2015-03-18

    The preparation and characterization of a controlled-release multicomponent (NPK) fertilizer with the coating layer consisting of a biodegradable copolymer of poly(butylene succinate) and a butylene ester of dilinoleic acid (PBS/DLA) is reported. The morphology and structure of the resulting polymer-coated materials and the thickness of the covering layers were examined using X-ray diffraction and scanning electron microscopy coupled with energy dispersive X-ray analysis. The mechanical properties of these materials were determined with a strength-testing machine. Nutrient release was measured in water using spectrophotometry, potentiometry, and conductivity methods. The results of the nutrient release experiments from these polymer-coated materials were compared with the requirements for controlled-release fertilizers. A conceptual model is presented describing the mechanism of nutrient release from the materials prepared in this study. This model is based on the concentrations of mineral components inside the water-penetrated fertilizer granules, the diffusion properties of the nutrients in water, and a diffusion coefficient through the polymer layer. The experimental kinetic data on nutrient release were interpreted using the sigmoidal model equation developed in this study.

  10. Doxylamine succinate-pyridoxine hydrochloride (Diclegis) for the management of nausea and vomiting in pregnancy: an overview.

    Science.gov (United States)

    Nuangchamnong, Nina; Niebyl, Jennifer

    2014-01-01

    Nausea and vomiting in pregnancy (NVP) is common and often undertreated, in part due to fears of adverse effects of medications on the fetus during early pregnancy. In April 2013, the US Food and Drug Administration (FDA) approved doxylamine succinate 10 mg and pyridoxine hydrochloride (a vitamin B6 analog) 10 mg as a delayed-release combination pill called Diclegis for the treatment of NVP. Diclegis is currently the only medication that is FDA-approved for the indication of NVP. This review addresses the historical context, safety, efficacy, pharmacology, and practical role of doxylamine and pyridoxine for the management of NVP. The reintroduction of this doxylamine-pyridoxine combination pill into the American market fills a therapeutic gap in the management of NVP left by the removal of the same active drugs marketed over 30 years ago in the form of Bendectin. The substantial amount of safety data accumulated over the years makes it one of the few drugs that qualify for FDA Pregnancy Category A status. In the hierarchical approach to pharmacological treatment of NVP, the combination of doxylamine and pyridoxine should thus be first-tier.

  11. Crystallization behavior and thermal stability of poly(butylene succinate)/poly(propylene carbonate) blends prepared by novel vane extruder

    Science.gov (United States)

    Chen, Rongyuan; Zou, Wei; Zhang, Haichen; Zhang, Guizhen; Qu, Jinping

    2016-03-01

    This work focused on the study of crystallization behavior and thermal stability of degradable poly(butylene succinate) (PBS) and poly(propylene carbonate) (PPC) blends prepared by vane extruder based on elongation force field, which is novel equipment for polymer processing. Dicumyl peroxide (DCP) was applied in this work as compatibilizer for PBS/PPC blend. Crystallization behavior and melting behavior of the blends were investigated by differential scanning calorimetry (DSC) testing. Thermal stability of the blends was studied by thermogravimetric (TG) testing. Furthermore, the melt flow indices (MFI) of the blends were examined by a MFI instrument. The results showed that the crystallization temperature of PBS decreased with the addition of PPC and DCP. The glass transition temperature of PPC increased and the melting temperature of the blend increased with the addition of PPC and DCP, which indicated that the entanglement between the molecular chains of PBS and PPC was enhanced. Thermogravimetric analysis showed that a two-step decomposition process of the blend occurred due to the different thermal resistance of PBS and PPC, and the addition of PBS reduced the decomposition rate of PPC. Moreover, the addition of PBS improved the melt flow property of PPC.

  12. Preparation and optimization of sustained release matrix tablets of metoprolol succinate and taro gum using response surface methodology

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    M. Soumya

    2014-01-01

    Full Text Available In the present study, an effort was made to formulate and evaluate matrix tablets of tarogum utilizing metaprolol succinate as the model drug. 3 2 full optimization procedure was adopted where two factors are studied at three levels. The amount of taro gum (X1 and polyvinylpyrrolidone (PVP K30 (X2 were selected as independent variables. The time required for 90% of drug release was selected as the dependent variable. Tablets were prepared by direct compression and were evaluated for various post compression parameters such as tablet hardness, friability, weight variation, drug content and in vitro dissolution. The results were found to be within the acceptable limits. The release exponent (n lies between 0.416 and 0.584 indicating drug release from the matrix tablets may be fickian or non-fickian (anomalous depending upon the concentration of natural polymer. T90 was 10.70, 11.20, 12.05, 12.66 h for B6, B7, B8 and B9 batches respectively showing overriding potential of taro gum, but still the effect of PVP K 30 is noteworthy. PVP K 30 has an indirect effect on all the factors by increasing tensile strength and making the tablet firm and intact.

  13. Effect of organo-modified montmorillonite on poly(butylene succinate/poly(butylene adipate-co-terephthalate nanocomposites

    Directory of Open Access Journals (Sweden)

    2010-07-01

    Full Text Available The composite material based on poly(butylene succinate (PBS, poly(butylene adipate-co-terephthalate (PBAT and organo-modified montmorillonite (OMMT were prepared by melt blending technique and characterized. Sodium montmorillonite (Na-MMT was successfully modified by octadecylammonium (ODA and dimethyldioctadecylammonium (DDOA salts to become OMMT through cation exchange technique which is shown by the increase of basal spacing of clay by XRD. The addition of the OMMT to the PBS/PBAT blends produced nanocomposites which is proved by XRD and TEM. Tensile tests showed increase in tensile strength and modulus which is attributed to the existence of strong interactions between PBS/PBAT and clay, particularly with OMMT. Highest tensile strength of nanocomposite was observed at 1 wt% of OMMT incorporated. TGA study showed that the thermal stability of the blend increased after the addition of clays. SEM micrographs of the fracture surfaces show that the morphology of the blend becomes homogeneous and smoother with presence of OMMT.

  14. Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney.

    Science.gov (United States)

    Toma, Ildikó; Kang, Jung Julie; Sipos, Arnold; Vargas, Sarah; Bansal, Eric; Hanner, Fiona; Meer, Elliott; Peti-Peterdi, János

    2008-07-01

    Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein-coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products through renal hyperfiltration, and it could also link metabolic diseases, such as diabetes, or metabolic syndrome with RAS overactivation, systemic hypertension, and organ injury.

  15. A split and rearranged nuclear gene encoding the iron-sulfur subunit of mitochondrial succinate dehydrogenase in Euglenozoa

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    Gray Michael W

    2009-02-01

    Full Text Available Abstract Background Analyses based on phylogenetic and ultrastructural data have suggested that euglenids (such as Euglena gracilis, trypanosomatids and diplonemids are members of a monophyletic lineage termed Euglenozoa. However, many uncertainties are associated with phylogenetic reconstructions for ancient and rapidly evolving groups; thus, rare genomic characters become increasingly important in reinforcing inferred phylogenetic relationships. Findings We discovered that the iron-sulfur subunit (SdhB of mitochondrial succinate dehydrogenase is encoded by a split and rearranged nuclear gene in Euglena gracilis and trypanosomatids, an example of a rare genomic character. The two subgenic modules are transcribed independently and the resulting mRNAs appear to be independently translated, with the two protein products imported into mitochondria, based on the presence of predicted mitochondrial targeting peptides. Although the inferred protein sequences are in general very divergent from those of other organisms, all of the required iron-sulfur cluster-coordinating residues are present. Moreover, the discontinuity in the euglenozoan SdhB sequence occurs between the two domains of a typical, covalently continuous SdhB, consistent with the inference that the euglenozoan 'half' proteins are functional. Conclusion The discovery of this unique molecular marker provides evidence for the monophyly of Euglenozoa that is independent of evolutionary models. Our results pose questions about the origin and timing of this novel gene arrangement and the structure and function of euglenozoan SdhB.

  16. Toughening of biodegradable polylactide/poly(butylene succinate-co-adipate) blends via in situ reactive compatibilization.

    Science.gov (United States)

    Ojijo, Vincent; Ray, Suprakas Sinha; Sadiku, Rotimi

    2013-05-22

    Polylactide and poly(butylene succinate-co-adipate) (PLA/PBSA) were melt-blended in the presence of triphenyl phosphite (TPP). An increase in the torque during melt mixing was used to monitor the changes in viscosity as compatibilization of the blends occurred. Scanning electron micrographs showed not only a reduction in the dispersed-phase size with increased TPP content but also fibrillated links between the PLA and PBSA phases, signifying compatibilization. Moreover, optimization of parameters such as the mixing sequence and time, TPP content, and PBSA concentration revealed that blends containing 30 and 10 wt % PBSA and 2 wt % TPP, which were processed for 30 min, were optimal in terms of thermomechanical properties. The impact strength increased from 6 kJ/m(2) for PLA to 11 and 16 kJ/m(2) for blends containing 30 and 10 wt % PBSA, respectively, whereas the elongation-at-break increased from 6% for PLA to 20 and 37% for blends containing 30 and 10 wt % PBSA, respectively. Upon compatibilization, the failure mode shifted from the brittle fracture of PLA to ductile deformation, effected by the debonding between the two phases. With improved phase adhesion, compatibilized blends not only were toughened but also did not significantly lose tensile strength and thermal stability.

  17. Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

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    Majeed Ullah

    2015-01-01

    Full Text Available The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25 in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS. At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

  18. Effect of succinic acid monoethyl ester on hemoglobin glycation and tail tendon collagen properties in type 2 diabetic rats.

    Science.gov (United States)

    Saravanan, Ramalingam; Pari, Leelavinothan

    2008-06-01

    Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of type 2 diabetes. The aim of the study was to investigate the effect of EMS and metformin administration on tail collagen content and its characteristics in streptozotocin-nicotinamide-induced type 2 diabetic rats. EMS was administered intraperitoneally for 30 days to normal and diabetic rats. In the diabetic rats, a significant increase in the levels of glucose, glycated hemoglobin, hydroxyproline, collagen content, extent glycation, fluorescence, neutral salt, acid and pepsin soluble collagen content was absorbed with a significant decrease in the level of insulin, hemoglobin in streptozotocin-nicotinamide diabetic rats. Moreover, a daily administration of nonglucidic nutrient EMS and metformin significantly decreased the levels of glucose, glycated hemoglobin, hydroxyproline, collagen content, extent glycation, fluorescence, neutral salt, acid and pepsin soluble collagen content, whereas it increased insulin, hemoglobin levels in diabetic rats. The positive influence of nonglucidic nutrient on both collagen content and its properties suggests a potential mechanism for the ability of EMS to delay diabetic complications.

  19. Succinic acid in levels produced by yeast (Saccharomyces cerevisiae) during fermentation strongly impacts wheat bread dough properties.

    Science.gov (United States)

    Jayaram, Vinay B; Cuyvers, Sven; Verstrepen, Kevin J; Delcour, Jan A; Courtin, Christophe M

    2014-05-15

    Succinic acid (SA) was recently shown to be the major pH determining metabolite produced by yeast during straight-dough fermentation (Jayaram et al., 2013), reaching levels as high as 1.6 mmol/100 g of flour. Here, the impact of such levels of SA (0.8, 1.6 and 2.4 mmol/100 g flour) on yeastless dough properties was investigated. SA decreased the development time and stability of dough significantly. Uniaxial extension tests showed a consistent decrease in dough extensibility upon increasing SA addition. Upon biaxial extension in the presence of 2.4 mmol SA/100 g flour, a dough extensibility decrease of 47-65% and a dough strength increase of 25-40% were seen. While the SA solvent retention capacity of flour increased with increasing SA concentration in the solvent, gluten agglomeration decreased with gluten yield reductions of over 50%. The results suggest that SA leads to swelling and unfolding of gluten proteins, thereby increasing their interaction potential and dough strength, but simultaneously increasing intermolecular electrostatic repulsive forces. These phenomena lead to the reported changes in dough properties. Together, our results establish SA as an important yeast metabolite for dough rheology.

  20. Biodegradability and mechanical properties of poly(butylene succinate) composites with finely dispersed hydrophilic poly(acrylic acid)

    Science.gov (United States)

    Mizuno, Sawako; Hotta, Atsushi

    2014-03-01

    Biodegradability and mechanical properties of aliphatic poly(butylene succinate) (PBS) films with finely dispersed hydrophilic poly(acrylic acid) (PAA) were investigated. First, 3.5 wt% of PAA was chemically grafted onto the surface of the PBS films (surface-grafted PBS) by photo grafting polymerization, and then the grafted PAA was homogeneously and finely dispersed into PBS by dissolving the surface-grafted PBS into chloroform before mixing and drying to get solid PAA-dispersed PBS. Degradation of these modified PBS was investigated using gel permeation chromatography (GPC) and tensile testing. According to the GPC results, it was found that the PAA-dispersed PBS had intermediate biodegradability with the intermediate water intake, and the reaction constant of PAA-dispersed PBS was in between those of untreated PBS and surface-grafted PBS, in fact 25% higher and 17% lower, respectively. The experimental results presented that the biodegradability of PBS could be well controlled by the dispersion of PAA, possibly leading to the widespread use of PBS for biodegradable polymers.

  1. Molecular characterization and detection of mutations associated with resistance to succinate dehydrogenase-inhibiting fungicides in Alternaria solani.

    Science.gov (United States)

    Mallik, I; Arabiat, S; Pasche, J S; Bolton, M D; Patel, J S; Gudmestad, N C

    2014-01-01

    Early blight, caused by Alternaria solani, is an economically important foliar disease of potato in several production areas of the United States. Few potato cultivars possess resistance to early blight; therefore, the application of fungicides is the primary means of achieving disease control. Previous work in our laboratory reported resistance to the succinate dehydrogenase-inhibiting (SDHI) fungicide boscalid in this plant pathogen with a concomitant loss of disease control. Two phenotypes were detected, one in which A. solani isolates were moderately resistant to boscalid, the other in which isolates were highly resistant to the fungicide. Resistance in other fungal plant pathogens to SDHI fungicides is known to occur due to amino acid exchanges in the soluble subunit succinate dehydrogenase B (SdhB), C (SdhC), and D (SdhD) proteins. In this study, the AsSdhB, AsSdhC, and AsSdhD genes were analyzed and compared in sensitive (50% effective concentration [EC50] resistant (EC50 = 5.1 to 20 μg ml(-1)), highly resistant (EC50 = 20.1 to 100 μg ml(-1)), and very highly resistant (EC50 > 100 μg ml(-1)) A. solani isolates. In total, five mutations were detected, two in each of the AsSdhB and AsSdhD genes and one in the AsSdhC gene. The sequencing of AsSdhB elucidated point mutations cytosine (C) to thymine (T) at nucleotide 990 and adenine (A) to guanine (G) at nucleotide 991, leading to an exchange from histidine to tyrosine (H278Y) or arginine (H278R), respectively, at codon 278. The H278R exchange was detected in 4 of 10 A. solani isolates moderately resistant to boscalid, exhibiting EC50 values of 6 to 8 μg ml(-1). Further genetic analysis also confirmed this mutation in isolates with high and very high EC50 values for boscalid of 28 to 500 μg ml(-1). Subsequent sequencing of AsSdhC and AsSdhD genes confirmed the presence of additional mutations from A to G at nucleotide position 490 in AsSdhC and at nucleotide position 398 in the AsSdhD, conferring H134R and H

  2. Targeted drug delivery nanosystems based on copolymer poly(lactide)-tocopheryl polyethylene glycol succinate for cancer treatment

    Science.gov (United States)

    Thu Ha, Phuong; Nguyen, Hoai Nam; Doan Do, Hai; Thong Phan, Quoc; Nguyet Tran Thi, Minh; Phuc Nguyen, Xuan; Nhung Hoang Thi, My; Huong Le, Mai; Nguyen, Linh Toan; Quang Bui, Thuc; Hieu Phan, Van

    2016-03-01

    Along with the development of nanotechnology, drug delivery nanosystems (DDNSs) have attracted a great deal of concern among scientists over the world, especially in cancer treatment. DDNSs not only improve water solubility of anticancer drugs but also increase therapeutic efficacy and minimize the side effects of treatment methods through targeting mechanisms including passive and active targeting. Passive targeting is based on the nano-size of drug delivery systems while active targeting is based on the specific bindings between targeting ligands attached on the drug delivery systems and the unique receptors on the cancer cell surface. In this article we present some of our results in the synthesis and testing of DDNSs prepared from copolymer poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS), which carry anticancer drugs including curcumin, paclitaxel and doxorubicin. In order to increase the targeting effect to cancer cells, active targeting ligand folate was attached to the DDNSs. The results showed copolymer PLA-TPGS to be an excellent carrier for loading hydrophobic drugs (curcumin and paclitaxel). The fabricated DDNSs had a very small size (50-100 nm) and enhanced the cellular uptake and cytotoxicity of drugs. Most notably, folate-decorated paclitaxel-loaded copolymer PLA-TPGS nanoparticles (Fol/PTX/PLA-TPGS NPs) were tested on tumor-bearing nude mice. During the treatment time, Fol/PTX/PLA-TPGS NPs always exhibited the best tumor growth inhibition compared to free paclitaxel and paclitaxel-loaded copolymer PLA-TPGS nanoparticles. All results evidenced the promising potential of copolymer PLA-TPGS in fabricating targeted DDNSs for cancer treatment.

  3. Probing the mechanism of interaction of metoprolol succinate with human serum albumin by spectroscopic and molecular docking analysis.

    Science.gov (United States)

    Pawar, Suma K; Jaldappagari, Seetharamappa

    2017-02-24

    In the present work, the mechanism of the interaction between a β1 receptor blocker, metoprolol succinate (MS) and human serum albumin (HSA) under physiological conditions was investigated by spectroscopic techniques, namely fluorescence, Fourier transform infra-red spectroscopy (FT-IR), fluorescence lifetime decay and circular dichroism (CD) as well as molecular docking and cyclic voltammetric methods. The fluorescence and lifetime decay results indicated that MS quenched the intrinsic intensity of HSA through a static quenching mechanism. The Stern-Volmer quenching constants and binding constants for the MS-HSA system at 293, 298 and 303 K were obtained from the Stern-Volmer plot. Thermodynamic parameters for the interaction of MS with HSA were evaluated; negative values of entropy change (ΔG°) indicated the spontaneity of the MS and HSA interaction. Thermodynamic parameters such as negative ΔH° and positive ΔS° values revealed that hydrogen bonding and hydrophobic forces played a major role in MS-HSA interaction and stabilized the complex. The binding site for MS in HSA was identified by competitive site probe experiments and molecular docking studies. These results indicated that MS was bound to HSA at Sudlow's site I. The efficiency of energy transfer and the distance between the donor (HSA) and acceptor (MS) was calculated based on the theory of Fosters' resonance energy transfer (FRET). Three-dimensional fluorescence spectra and CD results revealed that the binding of MS to HSA resulted in an obvious change in the conformation of HSA. Cyclic voltammograms of the MS-HSA system also confirmed the interaction between MS and HSA. Furthermore, the effects of metal ions on the binding of MS to HSA were also studied.

  4. Biocompatibility and drug release behavior of scaffolds prepared by coaxial electrospinning of poly(butylene succinate) and polyethylene glycol

    Energy Technology Data Exchange (ETDEWEB)

    Llorens, E.; Ibañez, H. [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Valle, L.J. del, E-mail: luis.javier.del.valle@upc.edu [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Puiggalí, J. [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Center for Research in Nano-Engineering (CrNE), Universitat Politècnica de Catalunya, Edifici C, C/Pasqual i Vila s/n, Barcelona E-08028 (Spain)

    2015-04-01

    Scaffolds constituted by electrospun microfibers of poly(ethylene glycol) (PEG) and poly(butylene succinate) (PBS) were studied. Specifically, coaxial microfibers having different core–shell distributions and compositions were considered as well as uniaxial micro/nanofibers prepared from mixtures of both polymers. Processing conditions were optimized for all geometries and compositions and resulting morphologies (i.e. diameter and surface texture) characterized by scanning electron microscopy. Chemical composition, molecular interactions and thermal properties were evaluated by FTIR, NMR, XPS and differential scanning calorimetry. The PEG component of electrospun fibers could be solubilized by immersion of scaffolds in aqueous medium, giving rise to high porosity and hydrophobic samples. Nevertheless, a small amount of PEG was retained in the PBS matrix, suggesting some degree of mixing. Solubilization was slightly dependent on fiber structure; specifically, the distribution of PEG in the core or shell of coaxial fibers led to higher or lower retention levels, respectively. Scaffolds could be effectively loaded with hydrophobic drugs having antibacterial and anticarcinogenic activities like triclosan and curcumin, respectively. Their release was highly dependent on their chemical structure and medium composition. Thus, low and high release rates were observed in phosphate buffer saline (SS) and SS/ethanol (30:70 v/v), respectively. Slight differences in the release of triclosan were found depending on fiber distribution and composition. Antibacterial activity and biocompatibility were evaluated for both loaded and unloaded scaffolds. - Highlights: • Coaxial microfibers with different hydrophobicities were studied. • The surface morphology of the coaxial fiber shows the distribution of polymers. • Coaxial fiber microstructure favors the polymer molecular orientation. • These hybrid materials have greater advantages for loading and drug release. • PEG

  5. Reinforcement effect of poly(butylene succinate) (PBS)-grafted cellulose nanocrystal on toughened PBS/polylactic acid blends.

    Science.gov (United States)

    Zhang, Xuzhen; Zhang, Yong

    2016-04-20

    Poly(butylene succinate) (PBS)/polylactic acid (PLA) blends modified with dicumyl peroxide (DCP) were reinforced by PBS-g-cellulose nanocrystal (CNC) through melt mixing. PBS-g-CNC was prepared through in situ polymerization and its structure was confirmed by FTIR, (13)C NMR, XPS and GPC analysis after saponification. The morphological analysis of PBS/PLA/PBS-g-CNC composites before and after etched by CH2Cl2 shows that the addition of DCP and PBS-g-CNC could decrease the size of PBS as a dispersed phase in PLA matrix and improve the dispersion of PBS-g-CNC in both PBS and PLA phases, which could affect the crystallization and mechanical properties of composites. The crystallinity of PLA α'-phase crystal in PBS/PLA/PBS-g-CNC composites is increased obviously by the addition of PBS-g-CNC, leading to an increase of the crystallinity of the composites. PBS/PLA blends modified by DCP have high Notched Izod impact strength and moduli, and the values are increased by the addition of PBS-g-CNC. Both storage modulus and glass translation temperature of PBS/PLA blend are increased by DCP and PBS-g-CNC, which is proved by DMA results, showing a weak molecular segment mobility of PBS/PLA matrix. The addition of DCP decreases the crystallization temperature and crystallinity of PBS/PLA composite, but increases the thermal stability of composites, mostly because of the crosslink effect of DCP on PBS/PLA matrix.

  6. Molecular alterations and expression of succinate dehydrogenase complex in wild-type KIT/PDGFRA/BRAF gastrointestinal stromal tumors.

    Science.gov (United States)

    Celestino, Ricardo; Lima, Jorge; Faustino, Alexandra; Vinagre, João; Máximo, Valdemar; Gouveia, António; Soares, Paula; Lopes, José Manuel

    2013-05-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, disclosing somatic KIT, PDGFRA and BRAF mutations. Loss of function of succinate dehydrogenase (SDH) complex is an alternative molecular mechanism in GISTs, namely in carriers of germline mutations of the SDH complex that develop Carney-Stratakis dyad characterized by multifocal GISTs and multicentric paragangliomas (PGLs). We studied a series of 25 apparently sporadic primary wild-type (WT) KIT/PDGFRA/BRAF GISTs occurring in patients without personal or familial history of PGLs, re-evaluated clinicopathological features and analyzed molecular alterations and immunohistochemistry expression of SDH complex. As control, we used a series of well characterized 49 KIT/PDGFRA/BRAF-mutated GISTs. SDHB expression was absent in 20% and SDHB germline mutations were detected in 12% of WT GISTs. Germline SDHB mutations were significantly associated to younger age at diagnosis. A significant reduction in SDHB expression in WT GISTs was found when compared with KIT/PDGFRA/BRAF-mutated GISTs. No significant differences were found when comparing DOG-1 and c-KIT expression in WT, SDHB-mutated and KIT/PDGFRA/BRAF-mutated GISTs. Our results confirm the occurrence of germline SDH genes mutations in isolated, apparently sporadic WT GISTs. WT KIT/PDGFRA/BRAF GISTs without SDHB or SDHA/SDHB expression may correspond to Carney-Stratakis dyad or Carney triad. Most importantly, the possibility of PGLs (Carney-Stratakis dyad) and/or pulmonary chondroma (Carney triad) should be addressed in these patients and their kindred.

  7. MexiB 6 AS A RESULT OF FORTIFICATION OF ETHYLMETHYLHYDROXYPYRIDINE SUCCINATE WITH MAGNESIUM AND PYRIDOXINE: PROTEOME EFFECTS

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2016-01-01

    Full Text Available The efficacy of ethylmethylhydroxypyridine succinate (EMHPS  depends on the concentration and activity of proteomic proteins. To provide the body with magnesium and pyridoxine is an important condition for the efficacy of EMHPS because these micronutrients are essential for maintaining neuronal function.Objective: to analyze the biological effects of pyridoxineand magnesium-dependent proteins providing the molecular mechanisms of multi-targeted action of EMHPS,  pyridoxine, and magnesium.Material and methods. Proteins that interact with both pyridoxine and magnesium were found in the genomic and proteomic databases. A list of 78 vitamin B6-dependent proteins, which is based on the available human genome records in NCBIPROTEIN, EMBL,  UNIPROT,  and HumanProteomeMap databases, was analyzed using a functional binding assay. The same assay was also applied to analyze a list 720 magnesium-dependent proteins.Results. The analysis has shown that 78 pyridoxine-dependent proteomic proteins are necessary for: 1 the synthesis and processing of amino acids; 2 cell energy metabolism (ATP synthesis, and 3 the synthesis of neurotransmitters and neuronal membranes. MexiB 6 has numerous synergistic interactions between the molecules of EMHPS,  pyridoxine, and magnesium. The combination of the components of EMHPS,  pyridoxine and magnesium in MexiB 6 (triple synergism allows prediction that the drug has more pronounced clinical effects than the molecules of EMHPS,  which emerges in its antihypoxic and antioxidant activities, the improvement of synaptic transmission of a signal, the neutralization of homocysteine, and the regulation of lipid and carbohydrate metabolism (restoration of cell sensitivity to insulin and carbohydrates in patients with atherosclerosis and in those at risk for diabetes mellitus or obesity. Pyridoxineand magnesium-induced potentiation of the effects of EMHPS may enhance its activity.

  8. Inhibitory effect of hydroxypropyl methylcellulose acetate succinate on drug recrystallization from a supersaturated solution assessed using nuclear magnetic resonance measurements.

    Science.gov (United States)

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2013-10-07

    We examined the inhibitory effect of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) on drug recrystallization from a supersaturated solution using carbamazepine (CBZ) and phenytoin (PHT) as model drugs. HPMC-AS HF grade (HF) inhibited the recrystallization of CBZ more strongly than that by HPMC-AS LF grade (LF). 1D-1H NMR measurements showed that the molecular mobility of CBZ was clearly suppressed in the HF solution compared to that in the LF solution. Interaction between CBZ and HF in a supersaturated solution was directly detected using nuclear Overhauser effect spectroscopy (NOESY). The cross-peak intensity obtained using NOESY of HF protons with CBZ aromatic protons was greater than that with the amide proton, which indicated that CBZ had hydrophobic interactions with HF in a supersaturated solution. In contrast, no interaction was observed between CBZ and LF in the LF solution. Saturation transfer difference NMR measurement was used to determine the interaction sites between CBZ and HF. Strong interaction with CBZ was observed with the acetyl substituent of HPMC-AS although the interaction with the succinoyl substituent was quite small. The acetyl groups played an important role in the hydrophobic interaction between HF and CBZ. In addition, HF appeared to be more hydrophobic than LF because of the smaller ratio of the succinoyl substituent. This might be responsible for the strong hydrophobic interaction between HF and CBZ. The intermolecular interactions between CBZ and HPMC-AS shown by using NMR spectroscopy clearly explained the strength of inhibition of HPMC-AS on drug recrystallization.

  9. Poly(glycerol sebacate)/poly(butylene succinate-butylene dilinoleate) fibrous scaffolds for cardiac tissue engineering.

    Science.gov (United States)

    Tallawi, Marwa; Zebrowski, David C; Rai, Ranjana; Roether, Judith A; Schubert, Dirk W; El Fray, Miroslawa; Engel, Felix B; Aifantis, Katerina E; Boccaccini, Aldo R

    2015-06-01

    The present article investigates the use of a novel electrospun fibrous blend of poly(glycerol sebacate) (PGS) and poly(butylene succinate-butylene dilinoleate) (PBS-DLA) as a candidate for cardiac tissue engineering. Random electrospun fibers with various PGS/PBS-DLA compositions (70/30, 60/40, 50/50, and 0/100) were fabricated. To examine the suitability of these fiber blends for heart patches, their morphology, as well as their physical, chemical, and mechanical properties were measured before examining their biocompatibility through cell adhesion. The fabricated fibers were bead-free and exhibited a relatively narrow diameter distribution. The addition of PBS-DLA to PGS resulted in an increase of the average fiber diameter, whereas increasing the amount of PBS-DLA decreased the hydrophilicity and the water uptake of the nanofibrous scaffolds to values that approached those of neat PBS-DLA nanofibers. Moreover, the addition of PBS-DLA significantly increased the elastic modulus. Initial toxicity studies with C2C12 myoblast cells up to 72 h confirmed nontoxic behavior of the blends. Immunofluorescence analyses and scanning electron microscopy analyses confirmed that C2C12 cells showed better cell attachment and proliferation on electrospun mats with higher PBS-DLA content. However, immunofluorescence analyses of the 3-day-old rat cardiomyocytes cultured for 2 and 5 days demonstrated better attachment on the 70/30 fibers containing well-aligned sarcomeres and expressing high amounts of connexin 43 in cellular junctions indicating efficient cell-to-cell communication. It can be concluded, therefore, that fibrous PGS/PBS-DLA scaffolds exhibit promising characteristics as a biomaterial for cardiac patch applications.

  10. Risk assessment studies on succinate dehydrogenase inhibitors, the new weapons in the battle to control Septoria leaf blotch in wheat.

    Science.gov (United States)

    Fraaije, Bart A; Bayon, Carlos; Atkins, Sarah; Cools, Hans J; Lucas, John A; Fraaije, Marco W

    2012-04-01

    Chemical control of Septoria leaf blotch, caused by Mycosphaerella graminicola, is essential to ensure wheat yield and food security in most European countries. Mycosphaerella graminicola has developed resistance to several classes of fungicide and, with the efficacy of azoles gradually declining over time, new modes of action and/or improvements in host varietal resistance are urgently needed to ensure future sustainable disease control. Several new-generation carboxamide fungicides with broad-spectrum activity have recently been introduced into the cereal market. Carboxamides inhibit succinate dehydrogenase (Sdh) of the mitochondrial respiratory chain (complex II) but, because of their single-site specificity, these fungicides may be prone to resistance development. The objective of this study was to assess the risk of resistance development to different Sdh inhibitor (SDHI) fungicides in M. graminicola. UV mutagenesis was conducted to obtain a library of carboxin-resistant mutants. A range of SDHI resistance-conferring mutations was found in Sdh subunits B, C and D. Pathogenicity studies with a range of Sdh variants did not detect any fitness costs associated with these mutations. Most of the amino acid residues identified (e.g. B-S221P/T, B-H267F/L/N/Y, B-I269V and D-D129E/G/T) are directly involved in forming the cavity in which SDHI fungicides bind. Docking studies of SDHI fungicides in structural models of wild-type and mutated Sdh complexes also indicated which residues were important for the binding of different SDHI fungicides and showed a different binding for fluopyram. The predictive power of the model was also shown. Further diagnostic development, enabling the detection of resistant alleles at low frequencies, and cross-resistance studies will aid the implementation of anti-resistance strategies to prolong the cost-effectiveness and lifetime of SDHI fungicides.

  11. Inhibition of Krebs cycle and activation of glyoxylate cycle in the course of chronological aging of Saccharomyces cerevisiae. Compensatory role of succinate oxidation.

    Science.gov (United States)

    Samokhvalov, V; Ignatov, V; Kondrashova, M

    2004-01-01

    We investigated oxidative processes in mitochondria of Saccharomyces cerevisiae grown on ethanol in the course of chronological aging. We elaborated a model of chronological aging that avoids the influence of exhaustion of medium, as well as the accumulation of toxic metabolites during aging. A decrease in total respiration of cells and, even more, of the contribution of respiration coupled with ATP-synthesis was observed during aging. Aging is also related with the decrease of the contribution of malonate-insensitive respiration. Activities of citrate-synthase (CS), alpha-ketoglutarate dehydrogenase (KGDH) and malate dehydrogenase (MDH) were threefold decreased. The activity of NADP-dependent isocitrate dehydrogenase (NADP-ICDH) decreased more significantly, while the activity of NAD-dependent isocitrate dehydrogenase (NAD-ICDH) fell even greater, being completely inactivated on the third week of aging. In contrast, succinate dehydrogenase (SDH), enzymes of glyoxylate cycle (GCL) (isocitrate lyase (ICL) and malate synthase (MLS)), and enzymes of ethanol oxidation (alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ACDH)), were activated by 50% or more. The behavior of oxidative enzymes and metabolic pathways are apparently inherent to a more viable, long-lived cells in population, selected in the course of chronological aging. This selection allows cells to reveal the mechanism of their higher viability as caused by shunting of complete Krebs cycle by glyoxylate cycle, with a concomitant increased rate of the most efficient energy source, namely succinate formation and oxidation. Thiobarbituric-reactive species (TAR species) increased during aging. We supposed that to be the immediate cause of damage of a part of yeast population. These data show that a greater succinate contribution to respiration in more active cells is a general property of yeast and animal tissues.

  12. Cybernetic Model Application in Succinate Fermentation%控制论模型在丁二酸发酵过程中的应用

    Institute of Scientific and Technical Information of China (English)

    苗大龙; 张湜; 焦敏; 王玲玲; 姜岷; 周春红

    2011-01-01

    The cybernetic model was taken to replace kinetic model so as to establish an excellent model for succinate fermentation and then to have its parameters optimized with PSO. The application in practice proves the good reliability of cybernetic model in fitting result.%使用控制论模型来代替国内现有的动力学模型,对丁二酸发酵过程进行建模,然后使用粒子群算法进行参数优化.结果表明控制论模型拟合结果具有较好的可靠性.

  13. Novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s bearing functionalizable carbonate building blocks: II. Enzymatic biodegradation and in vitro biocompatibility assay.

    Science.gov (United States)

    Yang, Jing; Tian, Weisheng; Li, Qiaobo; Li, Yang; Cao, Amin

    2004-01-01

    In a previous study, we have reported chemical synthesis of novel aliphatic poly(butylene succinate-co-cyclic carbonate) P(BS-co-CC)s bearing various functionalizable carbonate building blocks, and this work will continue to present our new studies on their enzymatic degradation and in vitro cell biocompatibility assay. First, enzymatic degradation of the novel P(BS-co-CC) film samples was investigated with two enzymes of lipase B Candida Antartic (Novozyme 435) and lipase Porcine Pancreas PPL, and it was revealed that copolymerizing linear poly(butylene succinate) PBS with a functionalizable carbonate building block could remarkably accelerate the enzymatic degradation of a synthesized product P(BS-co-CC), and its biodegradation behavior was found to strongly depend on the overall impacts of several important factors as the cyclic carbonate (CC) comonomer structure and molar content, molar mass, thermal characteristics, morphology, the enzyme-substrate specificity, and so forth. Further, the biodegraded residual film samples and water-soluble enzymatic degradation products were allowed to be analyzed by means of proton nuclear magnetic resonance (1H NMR), gel permeation chromatograph (GPC), differential scanning calorimeter (DSC), attenuated total reflection FTIR (ATR-FTIR), scanning electron microscope (SEM), and liquid chromatograph-mass spectrometry (LC-MS). On the experimental evidences, an exo-type mechanism of enzymatic chain hydrolysis preferentially occurring in the noncrystalline domains was suggested for the synthesized new P(BS-co-CC) film samples. With regard to their cell biocompatibilities, an assay with NIH 3T3 mouse fibroblast cell was conducted using the novel synthesized P(BS-co-CC) films as substrates with respect to the cell adhesion and proliferation, and these new biodegradable P(BS-co-CC) samples were found to exhibit as low cell toxicity as the PLLA control, particularly the two samples of poly(butylene succinate-co-18.7 mol % dimethyl

  14. The effect of epoxidized soybean oil on mechanical and rheological properties of poly(butylene succinate)/lignin via vane extruder

    Science.gov (United States)

    Liu, Huanyu; Huang, Zhaoxia; Qu, Jinping; Meng, Cong

    2016-03-01

    Epoxidized Soybean Oil (ESO) have been used as the compatilizer in the Poly (butylene succinate)/lignin (PBS/lignin) composites. Compatibilized composites were fabricated by a novel vane extruder (VE) which can generate global and dynamic elongational flow. The effects of ESO on the mechanical, rheological properties and morphology of PBS/lignin were studied. The results indicated that the use of ESO had plasticizing effect on the matrix PBS while the addition reduced tensile strength. From SEM micrographs it could be clearly observed that there was a better interfacial adhesion between lignin and matrix. Meanwhile, rheological tests showed the incorporation of ESO improved its Newtonian behavior and can enhance PBS's flexibility.

  15. THERMAL PROPERTY, MISCIBILITY AND CRYSTALLIZATION BEHAVIOR OF POLY(3-HYDROXYBUTYRATE-co 3-YDROXYHEXANOATE) AND POLY(BUTYLENE SUCCINATE-ADIPATE) (PHBHHX/PBSA) BLENDS

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Blends of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and poly(butylene succinate-adipate) (PBSA), both biodegradable semicrystalline polyesters, were prepared with the ratio of PHBHHx/PBSA ranging from 80/20 to 20/80 by melt mixing method. Differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), dynamic mechanical thermal analysis (DMA), polarizing optical microscopy (POM) and wide angle X-ray diffractometer (WAXD) were used to study the miscibility and crystallization behavior of PHBHHx/PBSA blends. Experimental results indicate that PHBHHx is immiscible with PBSA as shown by the almost unchanged glass transition temperature and the biphasic melt.

  16. Recovery of Succinate from Fermentation Broth Based on Complexation Extraction Process%络合萃取法提取发酵液中丁二酸铵

    Institute of Scientific and Technical Information of China (English)

    古博华; 郑璞

    2013-01-01

    To improve the extraction yield of succinic acid produced by microbial fermentation,trioctylamine/octanol was used as extraction agent to extract succinate from fermentation broth.The pre-treatment of fermentation broth as well as the preparation of succinic acid ammonium using ammonia in the re-extraction were investigated.The results show that the rate of succinic acid extraction from fermentation broth pre-treated by cation exchange resin reached 91.3%,which was higher than that by sulfuric acid.Ammonia was an excellent re-extraction agent and the extractant (trioctylamine /octano) could be reused.When the extractant was recycled five times,the average rate of extraction and that of re-extraction were 90.4% and 94.9%,respectively,showing no obvious decline.%为提高微生物发酵法生产丁二酸的产品提取收率,用三辛胺/正辛醇体系对发酵液进行络合萃取.比较硫酸和阳离子交换树脂两种前处理发酵液方式对络合萃取丁二酸的影响以及用氨水反萃制备丁二酸铵.结果表明,通过阳离子交换树脂前处理发酵液,三辛胺/正辛醇体系对丁二酸的萃取率高于硫酸前处理,达到91.3%;氨水是一种优良反萃剂;萃取剂重复使用5次,平均萃取率为90.4%,平均反萃率为94.9%,且萃取率和反萃率未见明显下降.

  17. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yan Zhao; Bai-He Liu; Yao Li; Fang Liu; Jian Guo; Wei-Ping Yu

    2002-01-01

    AIM: To investigate the effects of growth inhibition ofhuman gastric cancer SGC-7901 cell with RRR-α-tocopherylsuccinate (VES), a derivative of natural Vitamin E, viainducing apoptosis and DNA synthesis arrest.METHODS: Human gastric cancer SGC-7901 cells wereregularly incubated in the presence of VES at 5, 10 and20mg@ L 1(VES was dissolved in absolute ethanol anddiluted in RPMI 1640 complete condition mediacorrespondingly to a final concentration of VES and 1mL@L-1 ethanol), succinic acid and ethanol equivalents asvehicle (VEH) control andcondition media only asuntreated (UT) control. Trypan blue dye exclusionanalysis and MTT assay were applied to detect the cellproliferation. 37kBq of tritiated thymidine was added tocells and [3H] TdR uptake was measured to observe DNAsynthesis. Apoptotic morphology was observed byelectron microscopy and DAPI staining. Flow cytometryand terminal deoxynucleotidyl transferase-mediated dUTPnick end labeling (TUNEL) assay were performed to detectVES-triggered apoptosis.RESULTS: VES inhibited SGC-7901 cell growth in a dose-dependent manner. The growth curve showed suppressionby 24.7%, 49.2% and 68.7% following 24h of VEStreatment at 5, 10 and 20 mg@L 1, respectively, similar tothe findings from MTT assay. DNA synthesis wasevidently reduced by 35%, 45% and 98% after 24h VEStreatment at 20 mg@ L-1 and 48h at 10 and 20 mg@ L 1,respectively. VES induced SGC-7901 cells to undergoapoptosis with typically apoptotic characteristics,including morphological changes of chromatincondensation, chromatin crescent formation/margination,nucleus fragmentation and apoptotic body formation,typical apoptotic sub-G1 peak by flow cytometry andincrease of apoptotic cells by TUNEL assay in which 90%of cells underwent apoptosis after 48h of VES treatment at20 mcg@L-1.CONCLUSION: VES can inhibit human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesisarrest. Inhibition of SGC-7901 cell growth by VES is dose-and time

  18. Preparation and characterization of new succinic anhydride grafted Posidonia for the removal of organic and inorganic pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Chadlia, Aguir, E-mail: aguirc@yahoo.ca [Unite de Recherche de Chimie Appliquee et Environnement, Faculte des Sciences de Monastir, 5000 (Tunisia); Mohamed, Khalfaoui [Unite de Recherche de Physique Quantique, Faculte des Sciences de Monastir, 5000 (Tunisia); Najah, Laribi; Farouk, M' henni Mohamed [Unite de Recherche de Chimie Appliquee et Environnement, Faculte des Sciences de Monastir, 5000 (Tunisia)

    2009-12-30

    The present work describes the preparation of new chelating materials derived from Posidonia for adsorption of heavy metal ions and dye in aqueous solution. The first part of this report deals with the chemical modification of Posidonia with succinic anhydride. Thus, we have obtained materials with various succinyl groups contents (from 29.8 to 39.2%). The obtained materials were characterized by infrared and CP/MAS {sup 13}C-RMN spectroscopy. The rate of succinyl content of the modified Posidonia was determined by saponification. The second part is devoted to the evaluation of the adsorption capacity of metal ions such as Pb{sup 2+} and dye such as direct red 75 (DR75) for raw and modified Posidonia materials. Two possible ways for the adsorption of these pollutants are studied: adsorption of each pollutant alone onto these supports, and cumulative adsorption of both metal ions and dye on the same supports. In the last case, the pollutant is adsorbed successively from two different solutions. The effects of pollutants concentration, support dose, pH, contact time and temperature on adsorption of each pollutant were evaluated. The results showed that the raw and modified Posidonia show a high capacity for Pb{sup 2+} adsorption. The capacity of modified Posidonia saturated with Pb{sup 2+} to adsorb DR75 was found 147.12 mg g{sup -1}. While the adsorption capacity of the nonsaturated modified Posidonia was equal to 81.63 mg g{sup -1}. The pseudo-second-order model was the best to represent adsorption kinetics of DR75. The pseudo-first-order model would be better for fitting the adsorption kinetic process of Pb{sup 2+} onto raw and modified Posidonia. The adsorption isotherms of Pb{sup 2+} could be described by the Jossens equation model. Any of the tested models can describe the adsorption of DR75 onto the studied materials. These results confirm that the adsorption of DR75 from aqueous solution was multilayer.

  19. Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D-α-tocopheryl polyethylene glycol 1000 succinate nanoemulsions

    Directory of Open Access Journals (Sweden)

    Sun DQ

    2014-07-01

    Full Text Available Deqing Sun,1,2 Xinbing Wei,1 Xia Xue,2 Zengjun Fang,3 Manru Ren,1 Haiyan Lou,1 Xiumei Zhang11Department of Pharmacology, School of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Pharmacy, 3Department of Clinical Pharmacology, Second Hospital of Shandong University, Jinan, People’s Republic of ChinaBackground: Acetylpuerarin (AP, because of its lower water solubility, shows poor absorption that hinders its therapeutic application. Thus, the aim of this study was to prepare nanoemulsions for AP, enhance its oral bioavailability, and thus improve the therapeutic effect.Methods: The nanoemulsions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS were prepared by high-pressure homogenization and characterized in terms of particle size, drug loading, morphology, and in vitro drug release. A lipid digestion model was used to predict in vivo drug solubilization in the gastrointestinal environment. The pharmacokinetics of AP formulations were performed in rats; meanwhile, a chylomicron flow-blocking rat model was used to evaluate the lymphatic drug transport. Moreover, the therapeutic effects of AP nanoemulsions on the model of focal cerebral ischemia-reperfusion for brain injury were also assessed.Results: The nanoemulsions with a droplet size of 150 nm were well stabilized by TPGS and showed a high loading capacity for AP. In the digestion model, the distribution of AP in aqueous phase/pellet phase was about 90%/10% for nanoemulsions and 5%/95% for oil solution, indicating that the drug encapsulated in nanoemulsions would present in solubilized form after transportation into the gastrointestinal tract, whereas drug precipitation would occur as the oil solution was orally administered. The area under the curve value of AP nanoemulsions was 5.76±0.56 µg·hour·mL-1, or was about 2.6 and 1.7 times as great as that of suspension and oil solution, respectively, indicating enhanced drug

  20. Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Tünde eMolnár

    2011-12-01

    Full Text Available Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signalling. Recently, astroglial Ca2+ transients evoked by the major citric acid cycle metabolite succinate (SUC and gamma-hydroxybutyrate (GHB that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc. Cells responding to SUC by Ca2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca2+ transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca2+ dynamics evoked by GHB suggested that Ca2+ was released from internal stores. Similarly to SUC, the GHB-response was also characterized by an effective concentration of 50 µM. We observed that the number of ATP-responsive cells decreased with increasing concentration of either SUC or GHB. Moreover, the concentration dependence of the number of ATP-responsive cells were highly identical as a function of both [SUC] and [GHB], suggesting a mutual receptor for SUC and GHB, therefore implying the existence of a distinct GHB-recognizing astroglial SUC receptor in the brain. The SUC-evoked Ca2+ signal remained in mice lacking GABAB receptor type 1 subunit in the presence and absence of the N-Methyl-D-Aspartate (NMDA receptor antagonist (2R-amino-5-phosphonovaleric acid (APV, indicating action mechanisms independent of the GABAB or NMDA receptor subtypes. By molecular docking calculations we found that residues R99, H103, R252 and R281 of the binding crevice of the kidney SUC-responsive membrane receptor SUCNR1 (GPCR91 also predict interaction with GHB, further implying similar GHB and SUC action mechanisms. We conclude that the astroglial action of SUC and GHB may represent a link between brain energy states and Ca2+ signalling in astrocytic networks.

  1. D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery

    Directory of Open Access Journals (Sweden)

    Wu YP

    2015-08-01

    Full Text Available Yupei Wu,1,* Qian Chu,2,* Songwei Tan,1 Xiangting Zhuang,1 Yuling Bao,1 Tingting Wu,1 Zhiping Zhang1,3,41Tongji School of Pharmacy, 2Department of Oncology, Tongji Hospital, Tongji Medical School, 3Hubei Engineering Research Center for NDDS, 4National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workAbstract: Paclitaxel (PTX is one of the most effective antineoplastic drugs. Its current clinical administration Taxol® is formulated in Cremophor EL, which causes serious side effects. Nanoparticles (NP with lower systemic toxicity and enhanced therapeutic efficiency may be an alternative formulation of the Cremophor EL-based vehicle for PTX delivery. In this study, novel amphipathic 4-arm-PEG-TPGS derivatives, the conjugation of D-α-tocopherol polyethylene glycol succinate (TPGS and 4-arm-polyethylene glycol (4-arm-PEG with different molecular weights, have been successfully synthesized and used as carriers for the delivery of PTX. These 4-arm-PEG-TPGS derivatives were able to self-assemble to form uniform NP with PTX encapsulation. Among them, 4-arm-PEG5K-TPGS NP exhibited the smallest particle size, highest drug-loading efficiency, negligible hemolysis rate, and high physiologic stability. Therefore, it was chosen for further in vitro and in vivo investigations. Facilitated by the effective uptake of the NP, the PTX-loaded 4-arm-PEG5K-TPGS NP showed greater cytotoxicity compared with free PTX against human ovarian cancer (A2780, non-small cell lung cancer (A549, and breast adenocarcinoma cancer (MCF-7 cells, as well as a higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M phase in A2780 cells. More importantly, PTX-loaded 4-arm-PEG5K-TPGS NP resulted in a significantly improved tumor growth inhibitory effect in comparison to Taxol® in S180 sarcoma-bearing mice models. This study suggested

  2. Synthesis and characterization of polyester copolymers based on poly(butylene succinate) and poly(ethylene glycol)

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiao-Ming, E-mail: xiaomingzhou@tust.edu.cn

    2012-12-01

    A series of polyester copolymers was synthesized from 1,4-succinic acid with 1,4-butanediol and poly(ethylene glycol) through a two-step process of esterification and polycondensation in this article. The composition and physical properties of copolyesters were investigated via GPC, {sup 1}HNMR, DSC and PLM. The copolymer composition was in good agreement with that expected from the feed composition of the reactants. The melting temperature (T{sub m}), crystallization temperature (T{sub c}), and crystallinity (X{sub c}) of these copolyesters decreased gradually as the content of PEG unit increased. Otherwise, experimental results also showed that the contents of PEG in copolymers had an effect on the molecular weight, distribution, thermal properties, hydrolysis degradation properties, and crystalline morphology of polyester copolymers. - Graphical abstract: The composition of polyester copolymer was determined from the {sup 1}H NMR spectra using the relative intensities of the proton peaks. As a sample, the {sup 1}H NMR spectrum of polyester copolymer with 10 mol% of PEG is shown in Fig. 2: CO-(CH{sub 2}){sub 2}-CO; O-CH{sub 2}- and C-(CH{sub 2}){sub 2}-C from the SA and BD unit at {delta}2.59; {delta} 4.08 and {delta}1.67; O-(CH{sub 2}CH{sub 2}){sub n}-O from the PEG unit at {delta} 3.61. The molar composition of polyester copolymer was measured as the area ratio of {delta}3.61/({delta}4.08 + {delta}1.67) peak. The PEG unit is incorporated into the copolymers in an amount of about 9.12mol% less than that of the feed proportion. These results showed that the composition of the copolymers is in good agreement with that expected from the feed proportion. Highlights: Black-Right-Pointing-Pointer The introduction of PEG unit changed the flexibility of PBS main chain. Black-Right-Pointing-Pointer PEG unit did not alter the crystal form of PBS in copolymers. Black-Right-Pointing-Pointer PEG unit hindered the formation of ring-banded spherulite morphology in copolymers

  3. 维生素E丁二酸单酯的合成及其在卷烟中的应用%Synthesis of Monovitamin E Succinate and its Application in Cigarettes

    Institute of Scientific and Technical Information of China (English)

    汤建国; 乔丹娜; 刘悍; 孟昭宇; 牟定荣

    2011-01-01

    为了提高卷烟主流烟气中维生素E(VE)释放量,改善卷烟口味,以VE和丁二酸酐为原料合成了VE丁二酸单酯,进行了HPLC纯度分析和1H NMR,13C NMR和EI-MS结构确证,并对添加了合成产物的卷烟进行了烟气分析和感官评吸试验.结果表明:①合成产物为目标产物——VE丁二酸单酯,纯度达98%;②添加VE丁二酸单酯的卷烟主流烟气中VE释放量增大;③添加VE丁二酸单酯的卷烟烟气刺激性小,吸味品质好.VE丁二酸单酯具有增大卷烟主流烟气VE释放量,降低刺激性,改善卷烟吸味的效果.%Abstract: In order to increase the delivery of vitamin E (VE) in mainstream cigarette smoke and improve smoking taste, monovitamin E succinate was synthesized from Ve and succinic anhydride, the synthetic was analyzed by HPLC, and identified by 'H NMR, 13C NMR and El - MS. The smoke analysis and sensory evaluation of the cigarettes spiked with the synthetic were carried out. The results showed that: 1) The synthetic was the target product, monovitamin E succinate, with the purity of 98%. 2) The delivery of Ve increased in mainstream smoke of the cigarette spiked with monovitamin E succinate. 3) The smoke irritation of the cigarette containing monovitamin E succinate decreased, and smoking taste improved, monovitamin E succinate has the functions of increasing VE delivery in mainstream cigarette smoke, reducing smoke irritation, and improving cigarette smoking taste.

  4. The influence of antioxidant and post-synthetic treatment on the properties of biodegradable poly(butylene succinates modified with poly(propylene oxide

    Directory of Open Access Journals (Sweden)

    DRAGANA PEPIC

    2007-12-01

    Full Text Available Novel poly(ester–ethers based on poly(butylene succinate (PBS as the hard segments and 30 mass % of poly(propylene oxide (PPO as the soft segments were synthesized with varying amount of the antioxidant (N,N'-diphenyl-p-phenylenediamine, DPPD. The influences of the addition of DPPD and the impact of post-synthetic treatment by precipitation on the molecular structure, thermal and physical properties, as well as on the storage stability of the biodegradable aliphatic copolyesters, were investigated. The structure and composition of the copolymers were determined by means of 1H-NMR spectroscopy. The molecular weight and polydispersity of the poly(ester–ethers were evaluated from solution viscosity and GPC measurements. The thermal properties and stability were evaluated, respecttively, by means of DSC and non-isothermal thermogravimetry in an inert nitrogen atmosphere. The biodegradability potential of the polymers was studied in hydrolytic and enzymatic degradation tests with Candida cylindracea lipase by monitoring the weight loss of polymer films after incubation. The weight losses of the samples increased with time and were in the range from 1 to 5 mass % after 4 weeks. GPC analysis confirmed that there were changes in the molecular weight of the copolyesters during both hydrolytic and enzymatic degradation tests, leading to the conclusion that the degradation mechanism of poly(butylenes succinate modified with PPO occurred through surface erosion and bulk degradation.

  5. Purification of d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by a temperature-modulated silica gel column chromatography: use of Taguchi method to optimize purification conditions.

    Science.gov (United States)

    Chang, Yinzi; Cao, Yucheng; Zhang, Jin; Wen, Yangyi; Ren, Qilong

    2011-12-05

    The demand for high purity d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) is increasing with the exploitation of TPGS-related products. Previously, we synthesized a TPGS mixture by esterifying vitamin E succinate with polyethyleneglycol 1000. In this study, a temperature-modulated silica gel chromatographic column was used to purify the synthesized TPGS. Taguchi method was used to optimize purification conditions associated with column temperature, loading amount, feedstock concentration and flow rate of mobile phases. Purification efficacy under the Taguchi optimized conditions was predicted theoretically and the predicted results were verified experimentally. High-performance liquid chromatography was used to quantify the unpurified and purified TPGS. The Taguchi-based analysis separately produced an optimum combination of purification conditions for TPGS purity and recovery. Under the optimized conditions, both the theoretical prediction and the confirmatory experiment yielded TPGS purity and recovery approximating to 98% each. Impressively, the study also found that column temperature had a considerable effect on purification efficacy, in particular on TPGS purity, although it was a less influential factor compared to loading amount and feedstock concentration.

  6. Modification of wheat starch with succinic acid/acetic anhydride and azelaic acid/acetic anhydride mixtures I. Thermophysical and pasting properties.

    Science.gov (United States)

    Subarić, Drago; Ačkar, Durđica; Babić, Jurislav; Sakač, Nikola; Jozinović, Antun

    2014-10-01

    The aim of this research was to investigate the influence of modification with succinic acid/acetic anhydride and azelaic acid/acetic anhydride mixtures on thermophysical and pasting properties of wheat starch. Starch was isolated from two wheat varieties and modified with mixtures of succinic acid and acetic anhydride, and azelaic acid and acetic anhydride in 4, 6 and 8 % (w/w). Thermophysical, pasting properties, swelling power, solubility and amylose content of modified starches were determined. The results showed that modifications with mixtures of afore mentioned dicarboxylic acids with acetic anhydride decreased gelatinisation and pasting temperatures. Gelatinisation enthalpy of Golubica starch increased, while of Srpanjka starch decreased by modifications. Retrogradation after 7 and 14 day-storage at 4 °C decreased after modifications of both starches. Maximum, hot and cold paste viscosity of both starches increased, while stability during shearing at high temperatures decreased. % setback of starches modified with azelaic acid/acetic anhydride mixture decreased. Swelling power and solubility of both starches increased by both modifications.

  7. Trace analysis of doxylamine succinate in animal feed, human urine, and wastewater by GC using a rubidium-sensitized nitrogen detector

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, H.C. Jr.; Holder, C.L.; Bowman, M.C.

    1982-08-01

    Doxylamine succinate, a drug used as a sleep-inducing agent, an antihistamine, and in a therapeutic formulation taken by pregnant women as an antinauseant, was scheduled for toxicological evaluation as part of a structure activity relationship study, with rats and mice, because a deficiency of such data exists with regard to many antihistamines. Analytical chemical procedures that ensure proper concentration, homogeneity, and stability of the drug in dosed feed, as well as the safety of personnel and the environment, were prerequisites for the toxicological tests. GC methods using a rubidium-sensitized nitrogen detector were developed for analysis of doxylamine succinate in animal feed, human urine, and wastewater at levels as low as 1 ppm, 100 ppb, and 100 ppb, respectively. Sample extracts were cleaned up by liquid-liquid partitioning, followed by additional cleanup on a column of silica gel. Data are presented concerning the stability of the drug in animal feed, extraction efficiencies, and the use of the silica gel cleanup column to separate the caffeine interference from doxylamine in extracts of human urine. Partition values and ancillary data concerning analysis of the drug in feed, by HPLC at levels as low as 10 ppm, are also reported.

  8. Enhancement of malate-production and increase in sensitivity to dimethyl succinate by mutation of the VID24 gene in Saccharomyces cerevisiae.

    Science.gov (United States)

    Negoro, Hiroaki; Kotaka, Atsushi; Matsumura, Kengo; Tsutsumi, Hiroko; Hata, Yoji

    2016-06-01

    Malate in sake (a Japanese alcoholic beverage) is an important component for taste that is produced by yeasts during alcoholic fermentation. To date, many researchers have developed methods for breeding high-malate-producing yeasts; however, genes responsible for the high-acidity phenotype are not known. We determined the mutated gene involved in high malate production in yeast, isolated as a sensitive mutant to dimethyl succinate. In the comparative whole genome analysis between high-malate-producing strain and its parent strain, one of the non-synonymous substitutions was identified in the VID24 gene. The mutation of VID24 resulted in enhancement of malate-productivity and sensitivity to dimethyl succinate. The mutation appeared to lead to a deficiency in Vid24p function. Furthermore, disruption of cytoplasmic malate dehydrogenase (Mdh2p) gene in the VID24 mutant inhibited the high-malate-producing phenotype. Vid24p is known as a component of the multisubunit ubiquitin ligase and participates in the degradation of gluconeogenic enzymes such as Mdh2p. We suggest that the enhancement of malate-productivity results from an accumulation of Mdh2p due to the loss of Vid24p function. These findings propose a novel mechanism for the regulation of organic acid production in yeast cells by the component of ubiquitin ligase, Vid24p.

  9. Synthesis, characterization and magnetic property of a succinate bridged 1D coordination polymer of cobalt(II) containing benzidine as end-capping ligand

    Science.gov (United States)

    Roy, Subhasis; Choubey, Somnath; Khan, Sumitava; Bhar, Kishalay; Ribas, Joan; Ghosh, Barindra Kumar

    2014-03-01

    A new bis(monodentate) succinate bridged 1D coordination polymer [Co(bnzd)2(μ-suc)(OH2)2]nṡ(H2O)n (1) (bnzd = benzidine; suc = succinate dianion) has been isolated using a one-pot reaction of the building components, and characterized structurally and magneto-structurally. Single crystal X-ray diffraction measurement reveals that each cobalt(II) center adopts an octahedral geometry with a CoN2O4 chromophore coordinated by two N atoms of two bnzd ligands, two O atoms of two water molecules and two O atoms of two suc units. In crystalline state, individual units of 1 self-assemble through cooperative N-H⋯O, O-H⋯O and C-H⋯O hydrogen bonds and C-H⋯π interactions affording a 3D network structure. Variable-temperature magnetic susceptibility measurement of 1 in the 2-300 K temperature range shows weak antiferromagnetic coupling among the adjacent cobalt(II) centers presumably due to long bridging arm of the dicarboxylate.

  10. The solubility measurements of sodium dicarboxylate salts; sodium oxalate, malonate, succinate, glutarate, and adipate in water from T = (279.15 to 358.15) K

    Energy Technology Data Exchange (ETDEWEB)

    Rozaini, Mohd Zul Helmi [School of Environmental Science, University of East Anglia, Norwich, Norfolk NR4 7TJ (United Kingdom); Department of Chemical Sciences, Faculty of Science and Technology, University Malaysia Terengganu, 21030 Kuala Terengganu (Malaysia)], E-mail: zulhelmi@umt.edu.my; Brimblecombe, Peter [School of Environmental Science, University of East Anglia, Norwich, Norfolk NR4 7TJ (United Kingdom)

    2009-09-15

    The solubility measurements of sodium dicarboxylate salts; sodium oxalate, malonate, succinate, glutarate, and adipate in water at temperatures from (278.15 to 358.15 K) were determined. The molar enthalpies of solution at T = 298.15 K were derived: {delta}{sub sol}H{sub m} (m = 2.11 mol . kg{sup -1}) = 13.86 kJ . mol{sup -1} for sodium oxalate; {delta}{sub sol}H{sub m} (m = 3.99 mol . kg{sup -1}) = 14.83 kJ . mol{sup -1} for sodium malonate; {delta}{sub sol}H{sub m} (m = 2.45 mol . kg{sup -1}) = 14.83 kJ . mol{sup -1} for sodium succinate; {delta}{sub sol}H{sub m} (m = 4.53 mol . kg{sup -1}) = 16.55 kJ . mol{sup -1} for sodium glutarate, and {delta}{sub sol}H{sub m} (m = 3.52 mol . kg{sup -1}) = 15.70 kJ . mol{sup -1} for sodium adipate. The solubility value exhibits a prominent odd-even effect with respect to terms with odd number of sodium dicarboxylate carbon numbers showing much higher solubility. This odd-even effect may have implications for the relative abundance of these compounds in industrial applications and also in the atmospheric aerosols.

  11. Investigating the stability of the nonionic surfactants tocopheryl polyethylene glycol succinate and sucrose laurate by HPLC-MS, DAD, and CAD.

    Science.gov (United States)

    Christiansen, Anne; Backensfeld, Thomas; Kühn, Silke; Weitschies, Werner

    2011-05-01

    High-performance liquid chromatography (HPLC) methods using a charged aerosol detector (CAD), a mass selective detector (MSD), and a diode array detector (DAD) were developed to characterize the nonionic surfactants d-α-tocopheryl polyethylene glycol (1000) succinate (TPGS) and Surfhope sugar ester D-1216 (sucrose laurate). The molecular structure and the heterogeneous composition resulting from different isomers and various lengths of polyethylene glycol (PEG) chains make it difficult to develop sensitive and specific analytical methods for both surfactants. Hence, there is lack of knowledge about the stability and grade of impurity of these compounds. Sucrose laurate does not possess any chromophore, thus UV detection is not applicable. Therefore, CAD and MSD have been used for determination. The aim of the study was to characterize these nonionic surfactants and to examine chemical stability at pH 1.0 and 37 °C, simulating harsh gastric conditions. It was shown that both compounds are liable to degradation under these conditions. Sucrose monolaurate exhibited a massive degradation within 8 h incubation due to cleavage of the glycosidic bondage. About 50% of sucrose monolaurate broke down, whereas a marginal amount of 3.4% (± 0.4%) of TPGS degraded into d-α-tocopheryl succinate and the associated PEG chain.

  12. Supramolecular micellar nanoaggregates based on a novel chitosan/vitamin E succinate copolymer for paclitaxel selective delivery

    Directory of Open Access Journals (Sweden)

    Lian H

    2011-12-01

    Full Text Available He Lian1, Jin Sun1, Yan Ping Yu1, Yan Hua Liu2, Wen Cao1, Yong Jun Wang1, Ying Hua Sun1, Si Ling Wang1, Zhong Gui He11School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Ningxia, People's Republic of ChinaBackground: Nowadays, many cytotoxic anticancer drugs exhibit low solubility and poor tumor selectivity, which means that the drug formulation is very important. For example, in the case of paclitaxel (PTX, Cremophor EL® (BASF, Ludwigshafen, Germany needs to be used as a solubilizer in its clinical formulation (Taxol®, Bristol-Myers Squibb, New York, NY, although it can cause serious side effects. Nanomicellar systems are promising carriers to resolve the above problems, and the polymer chosen is the key element.Methods: In this study, a novel amphiphilic chitosan/vitamin E succinate (CS-VES copolymer was successfully synthesized for self-assembling polymeric micelles. Proton nuclear magnetic resonance spectroscopy and infrared were used to characterize the molecular structure of the copolymer. The PTX-loaded CS-VES polymeric micelles (PTX-micelles were characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, and differential scanning calorimetry.Results: The critical micelle concentration of CS-VES was about 12.6 µg/mL, with the degree of amino group substitution being 20.4%. PTX-micelles were prepared by a nanoprecipitation/dispersion technique without any surfactant being involved. PTX-micelles exhibited a drug loading as high as 21.37% and an encapsulation efficiency of 81.12%, with a particle size ranging from 326.3 to 380.8 nm and a zeta potential of +20 mV. In vitro release study showed a near zero-order sustained release, with 51.06%, 50.88%, and 44.35% of the PTX in the micelles being released up to 168 hours at three drug loadings of 7.52%, 14.09%, and 21.37%, respectively. The cellular uptake

  13. 炎琥宁治疗毛细支气管炎疗效观察%Efficacy obseruatim of Dehydroandrographolide Succinate in treating capillary bronchitis

    Institute of Scientific and Technical Information of China (English)

    唐军

    2012-01-01

    Objective To analyze the therapeutic effect of Dehydroandrographolide Succinate in the treatment of capillary bronchitis. Methods 91 cases of capillary bronchitis were randomly divided into two groups: the treatment group with 52 cases and the control group with 39 cases. On the basis of the comprehensive treatment of the two groups, the control group was given intravenous ribavirin. The treatment group was treated with Dehydroandrographolide Succinate in addition with the control group. The differences in the total effective rate, the time of improvement of symptoms and physical signs between the patients of two groups were analyzed and compared. Results The total effective rate of treatment group (98.08 %) was higher than the control group (84.62 %) and the difference was statistically significant (P < 0. 05). The time when signs and symptoms such as cough, pulmonary rales and wheezing sound disappeared in treatment group were shorter than in control group, the difference was statistically significant (P < 0. 05). Conclusion The treatment of children with capillary bronchitis is more effective with additional Dehydroandrographolide Succinate.%目的 观察炎琥宁治疗毛细支气管炎的临床疗效.方法 将91例临床确诊毛细支气管炎的患儿随机分为两组,在综合治疗基础上,对照组39例加用病毒唑治疗,治疗组52例在对照组基础上加用炎琥宁,观察两组总有效率及症状、体征改善的时间并进行比较.结果 治疗组与对照组总有效率分别为98.08%和84.62%,差异具有统计学意义(P < 0.05);治疗组咳嗽、肺部啰音、肺部哮鸣音等的消失时间均明显短于对照组,差异具有统计学意义(P < 0.05).结论 炎琥宁治疗毛细支气管炎可提高疗效.

  14. Gel Reaction Checking The Bacteria Endotoxin of Potassium Dehydroandrograpolide Succinate Injection%凝胶法检查穿琥宁注射液细菌内毒素

    Institute of Scientific and Technical Information of China (English)

    孟军

    2015-01-01

    建立凝胶法检查穿琥宁注射液细菌内毒素的方法.本实验细菌内毒素检查应用鲎试剂与内毒素产生凝集反应的原理进行.选用灵敏度为0.5 EUmL-1的鲎试剂,并用细菌内毒素检查用水将穿琥宁注射液稀释成1:10浓度的稀释液,进行凝胶法反应实验,结果表明该注射液中所含细菌内毒素对鲎试剂反应无干扰作用.同时将细菌内毒素检查法与家兔法检测结果进行比较,两种方法测定结果相符.以上结果证明细菌内毒素检测方法可以代替家兔法检测穿琥宁注射液的热原.%The method of the determination about the bacteria endotoxin has been established for Potassium Dehydroandrograpolide Succinate injection.The checking of bacteria endotoxin was carried out based on the principle of agglomerate reaction between limulus reagent and bacteria endotoxin.In this experiment,Limulus reagent was selected at sensitivity 0.5EU mL-1,and Potassium Dehydroandrograpolide Succinate injection was diluted to ten times with the water used for the checking of bacteria endotoxin, then the gel reaction was performed. The results of the experiments indicate that the bacteria endotoxin contained in the injection have no observed interfering with Limulus reagent.Compared with the results determined by cattle rabbit method, the two methods show same results.These results verify that the method of the bacteria endotoxin determination may replace cattle rabbit method to check Potassium Dehydroandrograpolide Succinate injection heating source.

  15. Syntheses and physical characterization of new aliphatic triblock poly(L-lactide-b-butylene succinate-b-L-lactide)s bearing soft and hard biodegradable building blocks.

    Science.gov (United States)

    Ba, Chaoyi; Yang, Jing; Hao, Qinghui; Liu, Xiaoyun; Cao, Amin

    2003-01-01

    This study presents chemical syntheses and physical characterization of a new aliphatic poly(L-lactide-b-butylene succinate-b-L-lactide) triblock copolyester with soft and hard biodegradable building blocks. First, poly(butylene succinate) (PBS) prepolymers terminated with hydroxyl functional groups were synthesized through melt polycondensation from succinic acid and 1,4-butanediol. Further, a series of new PLLA-b-PBS-b-PLLA triblock copolyesters bearing various average PLLA block lengths were prepared via ring opening polymerization of L-lactide with the synthesized hydroxyl capped PBS prepolymer (Mn = 4.9 KDa) and stannous octanoate as the macroinitiator and catalyst, respectively. By means of GPC, NMR, FTIR, DSC, TGA, and wide-angle X-ray diffractometer (WAXD), the macromolecular structures and physical properties were intensively studied for these synthesized PBS prepolymer and PLLA-b-PBS-b-PLLA triblock copolyesters. 13C NMR and GPC experimental results confirmed the formation of sequential block structures without any detectable transesterification under the present experimental conditions, and the molecular weights of triblock copolyesters could be readily regulated by adjusting the feeding molar ratio of L-lactide monomer to the PBS macroinitiator. DSC measurements showed all single glass transitions, and their glass transition temperatures were found to be between those of PLLA and PBS, depending on the lengths of PLLA blocks. It was noteworthy that the segmental flexibilities of the hard PLLA blocks were found to be remarkably enhanced by the more flexible PBS block partner, and the PBS and PLLA building blocks were well mixed in the amorphous regions. Results of TGA analyses indicated that thermal degradation and stabilities of the PLLA blocks strongly depended on the average PLLA block lengths of triblock copolyesters. In addition, FTIR and WAXD results showed the coexistence of the assembled PLLA and PBS crystal structures when the average PLLA block

  16. Inhibitory effects of RRR-α-tocopheryl succinate on benzo(a) pyrene (B (a ) P)-induced forestomach carcinogenesis in female mice

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yu Juan Shan; Yan Zhao; Jian Wu Yu; Bai He Liu

    2001-01-01

    AIM To study the inhibitory effects of VES( RRR-α-tocopheryl Succinate, VES ), aderivative of natural Vitamin E, on benzo (a)pyrene (B (a) P)-induced forestomach tumor infemale mice.METHODS The model of B (a)P-inducedforestomach tumor was established according tothe methods of Wattenberg with slightmodifications. One hundred and eighty femalemice (6 weeks old) were divided into six groupsequally; negative control (Succinic acid),vehicle control ( Succinate + B (a) P), positivecontrol(B(a) P), high VES(2.5g/kg. b. w + B(a)P), Iow VES(1 .25 g/kg. b. w + B(a) P) ig as wellas VES by ip (20 mg/kg, b. w + B(a) P). Exceptthe negative control group, the mice wereadministrated with B(a)P ig. and correspondingtreatments for 4 weeks to study the anti-carcinogenetic effect of VES during the initiationperiod. The experiment lasted 29 weeks, inwhich the inhibitory effects of VES both ontumor incidence and tumor size were tested.RESULTS The models of B (a)P-inducedforestomach tumor in female mice wereestablished successfully. Some werecauliflower-like, others looked like papilla, evena few were formed into the ulcer cavities. VES at1.25 g/kg. b. w, 2.5 g/kg. b.w. by ig and 20 mg/kg. b. w. via ip could decrease the number oftumors per mouse (1.7 ± 0. 41, 1.6 ± 0.34 and 1.1±0.43), being lower than that of B(a)P group(5.4 ± 0.32, P<0.05). The tumor incidence wasinhibited by 18.2%, 23.1% and 50.0%. VES at1.25g/kg.b.w., 2.5 g/ kg.b.w. by ig and20 mg/kg. b.w. via ip reduced the total volumeof tumors per mouse (54.8 ± 8.84, 28.4 ± 8.32and 23.9± 16.05), being significantly lower thanthat of B(a)P group (150.2±20.93, P<0.01).The inhibitory rates were 63.5%, 81.1% and84.1%, respectively.CONCLUSION VES has inhibitory effects on B(a) P-induced forestomach carcinogenesis infemale mice, especially by ip and it may be apotential anti-cancer agent in vivo.

  17. Effect of temperature on formation of two new lanthanide metal-organic frameworks: Synthesis, characterization and theoretical studies of Tm(III)-succinate

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Carlos Alberto F. de; Silva, Fausthon Fred da; Malvestiti, Ivani [Department of Fundamental Chemistry, UFPE, 50590-470 Recife, PE (Brazil); Malta, Valeria Rodrigues dos S. [Institute of Chemistry and Biotechnology, UFAL, 57062-970 Maceio, AL (Brazil); Dutra, Jose Diogo L.; Costa, Nivan B. da; Freire, Ricardo O. [Department of Chemistry, UFS, 49100-000 Sao Cristovao, SE (Brazil); Junior, Severino A., E-mail: salvesjr@ufpe.br [Department of Fundamental Chemistry, UFPE, 50590-470 Recife, PE (Brazil)

    2013-01-15

    Two new metal-organic frameworks (MOFs) have been synthesized under different hydrothermal conditions and characterized by single-crystal X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and elemental analysis. Compound 1, crystallized in space group P1-bar with the formula [Tm{sub 2}(L){sub 3}(H{sub 2}O){sub 2}]{center_dot}H{sub 2}O, (H{sub 2}L=succinic acid), has triclinic cell parameters of a=7.61780(10), b=10.58050(10), c=12.71030(10), {alpha}=95.3130(10), {beta}=107.4370(10), {gamma}=111.0960(10) and a cell volume of 888.446(16) A{sup 3}. Compound 2, crystallized in space group I2/a with the same formula, is monoclinic, with cell parameters of a=13.77020(10), b=7.63170(10), c=17.2410(2), {beta}=101.303(10) and a cell volume of 1776.72(3) A{sup 3}. The results of this work indicate that a flexible succinate ligand that provides several modes of coordination can lead to different conformations, depending on the temperature used in the reaction. In the theoretical part of this study, semiempirical quantum chemistry methods using AM1, PM3 and PM6 models are employed to predict the structure of MOFs, calculate the geometric and crystallographic parameters, and make comparisons with experimental data. - Graphical abstract: Scheme of obtaining [Tm{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 2}]H{sub 2}O in two different crystalline phases under the influence of reaction temperature. Highlights: Black-Right-Pointing-Pointer Was synthesized new MOFs based on Tm{sup 3+} ions and succinic acid in different temperature. Black-Right-Pointing-Pointer The change in the temperature leads to two compounds with different crystalline systems. Black-Right-Pointing-Pointer The Sparkle AM1, PM3 and PM6 models were used to comparison of the theoretical and experimental cell.

  18. Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations.

    NARCIS (Netherlands)

    Zelinka, T.; Timmers, H.J.L.M.; Kozupa, A.; Chen, C.C.; Carrasquillo, J.A.; Reynolds, J.C.; Ling, A.; Eisenhofer, G.; Lazurova, I.; Adams, K.T.; Whatley, M.A.; Widimsky, J.Jr.; Pacak, K.

    2008-01-01

    We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%),

  19. Application of comb-like weak base resin for concentrating succinic acid by circulating desorption%梳状弱碱性树脂对丁二酸高浓度循环解吸

    Institute of Scientific and Technical Information of China (English)

    方芳; 刘晓宁; 王楠; 王舒雅; 姜岷; 魏荣卿; 郑涛

    2014-01-01

    An effective and low energy consumption method was established for absorption and circulating desorption of succinic acid using a comb-like weak base polystyrene resin. The behavior of the comblike weak base resin (MKF-D30X) in adsorption and desorption of succinic acid was studied in terms of volume of desorption reagent, stages of desorption, desorption temperature and recycle desorption. MKF-D30X resin had good adsorption effect on succinic acid. And the maximum adsorption capacity could be up to 425 mg succinic acid·(g dry resin)-1. The desorption process for 3 g resin with saturated succinic acid was divided into two stages at 50℃ of each stage of 10 ml, 1.0 mol·L-1 HCl as desorption reagent. In the first stage, the concentration of succinic acid in desorption solution could be up to 52.4 mg·ml-1, and the concentration of succinic acid increased to 209.6% of original concentration (original concentration of 25 mg·ml-1). Recycle desorption not only maintained high concentration of succinic acid in the first stage of desorption, but also obtained twice concentration in the second stage. On the other hand, the concentration of succinic acid in the first desorption stage, as desorption reagent, had no obvious effect on desorption of succinic acid in next stage.%建立了一种有效的、低能耗的从梳状弱碱性(MKF-D30X)树脂上解吸丁二酸的工艺。考察了解吸剂用量(体积)、解吸温度、分段解吸及分段循环解吸对MKF-D30X树脂解吸附丁二酸的影响。结果表明,MKF-D30X树脂对溶液中的丁二酸(25 mg·ml-1)有很好的吸附作用,吸附量高达425 mg·(g干树脂)-1。当解吸温度为50℃,每个阶段用10 ml、1.0 mol·L-1 HCl解吸剂,两阶段解吸3 g吸附饱和的树脂,第1阶段解吸得到的丁二酸浓度可高达52.4 mg·ml-1,将丁二酸浓度提高到原液浓度的209.6%;在此基础上再进行分段循环解吸,不仅可以维持第1阶段获得的高浓度丁

  20. 以白酒酒糟为原料发酵产丁二酸%Study on fermentative production of succinic acid from spirit-based distillers' grains

    Institute of Scientific and Technical Information of China (English)

    周小兵; 郑璞

    2013-01-01

    Spirit-based ditillers' grains ( SDG) treated with enzyme hydrolysis was used as a stuff for fermentative production of succinic acid by Actinobacillus succinogenes.When the hydrolysis reaction was solely catalyzed by cellulase or amylase under its optimum temperature and pH, the corresponding hydrolysis rates of cellulose in SDG and starch in SDG were 44.04% and 92.26% , respectively.While hydrolysis using cellulase and amylase step by step ( HSS) , the later hydrolysis reaction could be restrained.Otherwise, the yield of reducing sugar in hydrolysis u-sing cellulase and amylase simultaneously was about 150 mg/g SDG, the same as that of HSS.Using hydrolysis and fermentation separated process, 58.4 g/L reducing sugar was obtained, which resulted in 28.8 g/L succinic acid with a yield of 72 mg/g SDG.However, using the procedure that firstly SDG was hydrolyzed with cellulase and then starch in SDG was simultaneously saccharified and fermented, 32 g/L succinic acid was achieved with a yield of 133 mg/g SDG.This study provided a new economical stuff for fermentative production of succinic acid in the future.%以白酒酒糟为原料,经酶法糖化,由Actinobacillus succinogenes发酵生产丁二酸.纤维素酶或糖化酶分别水解白酒糟,在酶反应的最适温度和pH条件下,酒糟中的纤维素和淀粉的水解率分别为44.04%和92.26%,相应还原糖对酒糟的得率分别为110 mg/g和126 mg/g酒糟;但2种酶以分步或同步方式水解白酒糟时,酶水解反应受到产物抑制作用,总还原糖得率仅约为150 mg/g酒糟.采用分步糖化发酵工艺,400g/L白酒糟经两种酶水解后,得到还原糖58.4 g/L,该水解液发酵产丁二酸28.8g/L,丁二酸产率72 mg/g酒糟;而采用先用纤维素酶水解白酒糟,再用糖化酶和A.succinogenes同步糖化发酵的工艺,240 g/L白酒糟产丁二酸浓度为32 g/L,产率133 mg/g酒糟.以白酒酒糟为原料发酵生产丁二酸,利用了废弃物,无需外源添加氮源,

  1. Large pore volume mesoporous copper particles and scaffold microporous carbon material obtained from an inorganic-organic nanohybrid material, copper-succinate-layered hydroxide.

    Science.gov (United States)

    Ghotbi, Mohammad Yeganeh; Bagheri, Narjes; Sadrnezhaad, S K

    2011-10-01

    Copper-succinate-layered hydroxide (CSLH), a new nanohybrid material, was synthesized as an inorganic-organic nanohybrid, in which organic moiety was intercalated between the layers of a single cation layered material, copper hydroxide nitrate. Microporous scaffold carbon material was obtained by thermal decomposition of the nanohybrid at 500 °C under argon atmosphere followed by acid washing process. Furthermore, the heat-treated product of the nanohybrid at 600 °C was ultrafine mesoporous metallic copper particles. The results of this study confirmed the great potential of CSLH to produce the carbon material with large surface area (580 m(2)/g) and high pore volume copper powder (2.04 cm(3)/g).

  2. 气相色谱法测定丁二酸酯化液中有机组分的含量%Determination of organic components in succinic acid esterification solution by gas chromatography

    Institute of Scientific and Technical Information of China (English)

    唐建兴; 张军

    2013-01-01

      针对丁二酸酯化液的特点,选择强极性毛细管柱作为分析柱,优化得到了分析测试条件,利用气相色谱建立了丁二酸二甲酯、丁二酸单甲酯和甲醇的标准曲线。在测试确认模拟混合样品的分析精度的基础上,分析了丁二酸酯化反应液样品中有机组分浓度。分析结果表明,该方法快速、准确、灵敏度高、重复性好,相对标准偏差( RSDs,n=7)在2%以内,能满足丁二酸酯化反应过程特性研究的分析要求。%Referring to the features of succinic acid esterification solution , three standard curves of dimethyl succinate ,mono-Methyl hydrogen succinate and methanol were established by gas chromatography with strong polar capillary column under the optimized test conditions .Organic components in succinic acid esterification solution were tested on the basis of the confirmed accuracy&precision obtained from the determination of the mixed simula -tion solution .The results showed that the method is rapid ,accurate ,sensitive and reliable with relative standard de-viations (RSDs,n=7) less than 2%,and could satisfy the requirements for analysis on the process of succinic acid esterification .

  3. Anaphylactic shock induced by potassium sodium dehydroandroan drographolide succinate for injection%注射用炎琥宁致过敏性休克

    Institute of Scientific and Technical Information of China (English)

    黄黎明; 马金强; 张伟

    2013-01-01

    1例2岁男性患儿,因疱疹性咽峡炎、发热入院。给予注射用炎琥宁(80 mg,qd)静脉滴注,并联合头孢美唑钠(1.0 g,qd)抗感染治疗。在应用上述药物第4天,头孢美唑静滴完毕,给予炎琥宁滴注3 min后,患儿出现过敏性休克,伴躯干、下肢大面积皮疹,立即停药,给予肾上腺素和异丙嗪,并吸氧治疗处理,10 min后呼吸和心率好转,40 min后皮疹开始消退,第2天晨随访,患儿皮疹全部消失,生命体征平稳。病情好转于下午出院。%One 2-year-old male patient was hospitalized for herpangina and fever. The patient was intravenously given potassium sodium dehydroandroan drographolide succinate 80 mg and cefmetazole sodium 1.0 g, once a day. At the fourth day, the patient ifnished the infusion of cefmetazole sodium, and suffered allergic shock with rash in body and lower limbs during the infusion of potassium sodium dehydroandroan drographolide succinate for 3 minutes. Then the medication was stopped immediately, adrenaline, promethazine and the inhalation of oxygen were given. Ten minutes later, the symptoms relieved, and rash abated gradually forty minutes later. In the next morning, the rash disappeared completely and the life signs were stable. The patient was discharged in the afternoon.

  4. The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency

    Directory of Open Access Journals (Sweden)

    Devilee Peter

    2005-11-01

    Full Text Available Abstract Background The SDHA, SDHB, SDHC and SDHD genes encode the subunits of succinate dehydrogenase (succinate: ubiquinone oxidoreductase, a component of both the Krebs cycle and the mitochondrial respiratory chain. SDHA, a flavoprotein and SDHB, an iron-sulfur protein together constitute the catalytic domain, while SDHC and SDHD encode membrane anchors that allow the complex to participate in the respiratory chain as complex II. Germline mutations of SDHD and SDHB are a major cause of the hereditary forms of the tumors paraganglioma and pheochromocytoma. The largest subunit, SDHA, is mutated in patients with Leigh syndrome and late-onset optic atrophy, but has not as yet been identified as a factor in hereditary cancer. Description The SDH mutation database is based on the recently described Leiden Open (source Variation Database (LOVD system. The variants currently described in the database were extracted from the published literature and in some cases annotated to conform to current mutation nomenclature. Researchers can also directly submit new sequence variants online. Since the identification of SDHD, SDHC, and SDHB as classic tumor suppressor genes in 2000 and 2001, studies from research groups around the world have identified a total of 120 variants. Here we introduce all reported paraganglioma and pheochromocytoma related sequence variations in these genes, in addition to all reported mutations of SDHA. The database is now accessible online. Conclusion The SDH mutation database offers a valuable tool and resource for clinicians involved in the treatment of patients with paraganglioma-pheochromocytoma, clinical geneticists needing an overview of current knowledge, and geneticists and other researchers needing a solid foundation for further exploration of both these tumor syndromes and SDHA-related phenotypes.

  5. Development and evaluation of vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate-mixed polymeric phospholipid micelles of berberine as an anticancer nanopharmaceutical.

    Science.gov (United States)

    Shen, Roger; Kim, Jane J; Yao, Mingyi; Elbayoumi, Tamer A

    2016-01-01

    Berberine (Brb) is an active alkaloid occurring in various common plant species, with well-recognized potential for cancer therapy. Brb not only augments the efficacy of antineoplastic chemotherapy and radiotherapy but also exhibits direct antimitotic and proapoptotic actions, along with distinct antiangiogenic and antimetastatic activities in a variety of tumors. Despite its low systemic toxicity, several pharmaceutical challenges limit the application of Brb in cancer therapy (ie, extremely low solubility and permeability, very poor pharmacokinetics (PKs), and oral bioavailability). Among lipid-based nanocarriers investigated recently for Brb, stealth amphiphilic micelles of polymeric phospholipid conjugates were studied here as a promising strategy to improve Brb delivery to tumors. Specifically, physicochemically stable micelles made of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (PEG-PE) mixed with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) (PEG-succinate ester of vitamin E), in a 3:1 M ratio, increased Brb solubilization by 300%. Our PEG-PE/TPGS-mixed micelles firmly retained the incorporated Brb, displaying extended-release profile in simulated media, with up to 30-fold projected improvement in simulated PKs of Brb. Owing to the markedly better uptake of Brb-containing mixed micelles in vitro, our Brb-mixed micelles nanoformulation significantly amplified apoptosis and overall cytotoxic effectiveness against monolayer and spheroid cultures of human prostate carcinomas (16- to 18-fold lower half-maximal inhibitory concentration values in PC3 and LNPaC, respectively), compared to free Brb. Mixed PEG-PE/TPGS micelles represent a promising delivery platform for the sparingly soluble anticancer agent, Brb, encouraging further pharmaceutical development of this drug for cancer therapy.

  6. Ablation of succinate production from glucose metabolism in the procyclic trypanosomes induces metabolic switches to the glycerol 3-phosphate/dihydroxyacetone phosphate shuttle and to proline metabolism.

    Science.gov (United States)

    Ebikeme, Charles; Hubert, Jane; Biran, Marc; Gouspillou, Gilles; Morand, Pauline; Plazolles, Nicolas; Guegan, Fabien; Diolez, Philippe; Franconi, Jean-Michel; Portais, Jean-Charles; Bringaud, Frédéric

    2010-10-15

    Trypanosoma brucei is a parasitic protist that undergoes a complex life cycle during transmission from its mammalian host (bloodstream forms) to the midgut of its insect vector (procyclic form). In both parasitic forms, most glycolytic steps take place within specialized peroxisomes, called glycosomes. Here, we studied metabolic adaptations in procyclic trypanosome mutants affected in their maintenance of the glycosomal redox balance. T. brucei can theoretically use three strategies to maintain the glycosomal NAD(+)/NADH balance as follows: (i) the glycosomal succinic fermentation branch; (ii) the glycerol 3-phosphate (Gly-3-P)/dihydroxyacetone phosphate (DHAP) shuttle that transfers reducing equivalents to the mitochondrion; and (iii) the glycosomal glycerol production pathway. We showed a hierarchy in the use of these glycosomal NADH-consuming pathways by determining metabolic perturbations and adaptations in single and double mutant cell lines using a combination of NMR, ion chromatography-MS/MS, and HPLC approaches. Although functional, the Gly-3-P/DHAP shuttle is primarily used when the preferred succinate fermentation pathway is abolished in the Δpepck knock-out mutant cell line. In the absence of these two pathways (Δpepck/(RNAi)FAD-GPDH.i mutant), glycerol production is used but with a 16-fold reduced glycolytic flux. In addition, the Δpepck mutant cell line shows a 3.3-fold reduced glycolytic flux compensated by an increase of proline metabolism. The inability of the Δpepck mutant to maintain a high glycolytic flux demonstrates that the Gly-3-P/DHAP shuttle is not adapted to the procyclic trypanosome context. In contrast, this shuttle was shown earlier to be the only way used by the bloodstream forms of T. brucei to sustain their high glycolytic flux.

  7. Utilization of α-olefins obtained by pyrolysis of waste high density polyethylene to synthesize α-olefin-succinic-anhydride based cold flow improvers

    Institute of Scientific and Technical Information of China (English)

    Norbert MISKOLCZI; Richard SAGI; László BARTHA; Lívia FORCEK

    2009-01-01

    A new route of utilization of α-olefin rich hydrocarbon fractions obtained by waste polymer pyrolysis was investigated. α-olefin-succinic-anhydride intermediate-based pour point depressant additives for diesel fuel were synthesized, in which reactions needed α-olefins were obtained by pyrolysis of waste high-density polyethylene (HDPE). Fraction of α-olefins was produced by the de-polymerization of plastic waste in a tube reactor at 500℃ in the absence of catalysts and air. C17~22 range of mixtures of olefins and paraffins were separated for synthesis and then, these hydrocarbons were reacted with maleic-anhydride (MA) for formation of α-olefin-succinic-anhydride intermediates. The olefin-rich hydrocarbon fraction contained approximately 60% of olefins, including 90%~95% α-olefins. Other intermediates were produced in the same way by using commercial C20 α-olefin instead of C17~22 olefin mixture. The two different experimental intermediates with number average molecular weights of 1850g/mol and 1760g/mol were reacted with different alcohols: 1-butanol, 1-hexanol, 1-octanol, i-butanol, and c-hexanol to produce their ester derivatives. The synthesized ten experimental pour point depressants were added in different concentrations to conventional diesel fuel, which had no other additive content before. The structure and efficiency of experimental additives were followed by different standardized and non-standardized methods. Results showed that the experimental additives on the basis of the product of waste pyrolysis were able to decrease not only the pour but also the cloud point and cold filter plugging point (CFPP) of diesel fuel, whose effects could be observed even if the concentration of additives was low. Furthermore, all additives had anti-wear and anti-friction effects in diesel fuel.

  8. Enhancement of Mechanical and Thermal Properties of Oil Palm Empty Fruit Bunch Fiber Poly(butylene adipate-co-terephtalate Biocomposites by Matrix Esterification Using Succinic Anhydride

    Directory of Open Access Journals (Sweden)

    Samira Siyamak

    2012-02-01

    Full Text Available In this work, the oil palm empty fruit bunch (EFB fiber was used as a source of lignocellulosic filler to fabricate a novel type of cost effective biodegradable composite, based on the aliphatic aromatic co-polyester poly(butylene adipate-co-terephtalate PBAT (EcoflexTM, as a fully biodegradable thermoplastic polymer matrix. The aim of this research was to improve the new biocomposites’ performance by chemical modification using succinic anhydride (SAH as a coupling agent in the presence and absence of dicumyl peroxide (DCP and benzoyl peroxide (BPO as initiators. For the composite preparation, several blends were prepared with varying ratios of filler and matrix using the melt blending technique. The composites were prepared at various fiber contents of 10, 20, 30, 40 and 50 (wt % and characterized. The effects of fiber loading and coupling agent loading on the thermal properties of biodegradable polymer composites were evaluated using thermal gravimetric analysis (TGA. Scanning Electron Microscopy (SEM was used for morphological studies. The chemical structure of the new biocomposites was also analyzed using the Fourier Transform Infrared (FTIR spectroscopy technique. The PBAT biocomposite reinforced with 40 (wt % of EFB fiber showed the best mechanical properties compared to the other PBAT/EFB fiber biocomposites. Biocomposite treatment with 4 (wt % succinic anhydride (SAH and 1 (wt % dicumyl peroxide (DCP improved both tensile and flexural strength as well as tensile and flexural modulus. The FTIR analyses proved the mechanical test results by presenting the evidence of successful esterification using SAH/DCP in the biocomposites’ spectra. The SEM micrograph of the tensile fractured surfaces showed the improvement of fiber-matrix adhesion after using SAH. The TGA results showed that chemical modification using SAH/DCP improved the thermal stability of the PBAT/EFB biocomposite.

  9. Enhancement of mechanical and thermal properties of oil palm empty fruit bunch fiber poly(butylene adipate-co-terephtalate) biocomposites by matrix esterification using succinic anhydride.

    Science.gov (United States)

    Siyamak, Samira; Ibrahim, Nor Azowa; Abdolmohammadi, Sanaz; Yunus, Wan Md Zin Bin Wan; Rahman, Mohamad Zaki Ab

    2012-02-16

    In this work, the oil palm empty fruit bunch (EFB) fiber was used as a source of lignocellulosic filler to fabricate a novel type of cost effective biodegradable composite, based on the aliphatic aromatic co-polyester poly(butylene adipate-co-terephtalate) PBAT (Ecoflex™), as a fully biodegradable thermoplastic polymer matrix. The aim of this research was to improve the new biocomposites' performance by chemical modification using succinic anhydride (SAH) as a coupling agent in the presence and absence of dicumyl peroxide (DCP) and benzoyl peroxide (BPO) as initiators. For the composite preparation, several blends were prepared with varying ratios of filler and matrix using the melt blending technique. The composites were prepared at various fiber contents of 10, 20, 30, 40 and 50 (wt %) and characterized. The effects of fiber loading and coupling agent loading on the thermal properties of biodegradable polymer composites were evaluated using thermal gravimetric analysis (TGA). Scanning Electron Microscopy (SEM) was used for morphological studies. The chemical structure of the new biocomposites was also analyzed using the Fourier Transform Infrared (FTIR) spectroscopy technique. The PBAT biocomposite reinforced with 40 (wt %) of EFB fiber showed the best mechanical properties compared to the other PBAT/EFB fiber biocomposites. Biocomposite treatment with 4 (wt %) succinic anhydride (SAH) and 1 (wt %) dicumyl peroxide (DCP) improved both tensile and flexural strength as well as tensile and flexural modulus. The FTIR analyses proved the mechanical test results by presenting the evidence of successful esterification using SAH/DCP in the biocomposites' spectra. The SEM micrograph of the tensile fractured surfaces showed the improvement of fiber-matrix adhesion after using SAH. The TGA results showed that chemical modification using SAH/DCP improved the thermal stability of the PBAT/EFB biocomposite.

  10. Sequence Classification: 389262 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31793773|ref|NP_856266.1| 4-AMINOBUTYRATE AMI...NOTRANSFERASE GABT (GAMMA-AMINO-N-BUTYRATE TRANSAMINASE) (GABA TRANSAMINASE) (GLUTAMATE:SUCCINIC SEMIALDEHYDE TRANSAMI...NASE) (GABA AMINOTRANSFERASE) (GABA-AT) || http://www.ncbi.nlm.nih.gov/protein/31793773 ...

  11. Sequence Classification: 399013 [

    Lifescience Database Archive (English)

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|15609726|ref|NP_217105.1| 4-AMINOBUTYRATE AMI...NOTRANSFERASE GABT (GAMMA-AMINO-N-BUTYRATE TRANSAMINASE) (GABA TRANSAMINASE) (GLUTAMATE:SUCCINIC SEMIALDEHYDE TRANSAMI...NASE) (GABA AMINOTRANSFERASE) (GABA-AT) || http://www.ncbi.nlm.nih.gov/protein/15609726 ...

  12. HPLC测定穿琥宁中的聚合物%Research of polymer in potassium dehydroandrogapholide succinate

    Institute of Scientific and Technical Information of China (English)

    陈启立; 付平; 赵子翰; 宋艳霞; 李直; 袁军; 李波

    2013-01-01

    OBJECTIVE To establish an HPLC method for determination of polymer in potassium dehydroandrographolide succinate (PDS) ,and study the nature and the causes of polymer. METHODS An optimal HPLC method was set up. The samples were separated by Elite Sephadex G-10column(10 mm × 150 mm, 40-120 μm) with 0. 05 mol·L-1 , phosphate buffer [ 0. 05 mol·L-1 disodium hydrogen phosphate - 0.05 mol·L-1 sodium dihydrogen phosphate(61 : 39) ] at pH 7. 0 as mobile phase A, water as mobile phase B, and detected with UV 251 nm with a flow rate of 1.0 mL·min-1. The effect of temperature,pH,humidity,and sterilization time on poly- mer was analyzed by HPLC. RESULTS The calibration curve of the control solution was linear in the range of 0. 011 - 22. 20 μg( r = 0. 9999)and the calibration curve of the test solution was linear in the range of 0. 0163 - 2. 98 mg( r = 0. 9988 ). LOD was 2. 2 ng (S/N =3) and LOQ was 11 ng( S/N = 10). The RSD of injection precision was 1. 13% and the RSD of intra - day precision was 0. 56%. The control solution was stable within 10 h,but the test solution was not stable. After polymerization,the polarity of PDS was increased. The content of polymer was increased with high temperature, high humidity, high pH and long sterilization time. CONCLUSION The method is good at the aspect of simplicity, sensitivity, reproducibility and it is applicable for determination of the content of polmyer in PDS. Seriously control of temperature, humidity, pH and sterilization time through pharmaceutical production is important.%目的 采用HPLC法测定穿琥宁聚合物的含量,并研究聚合物的性质及成因.方法 采用依利特Sephadex G-10色谱柱(10 mm×300 mm,40 ~120 μm),流动相A为pH7 0.05 mol· L-1磷酸盐缓冲液[0.05 mol·L-1磷酸氢二钠溶液-0.05 mol·L-1磷酸二氢钠溶液(61∶39)],流动相B为水,流速1.0 mL· min-1,检测波长251 nm.用HPLC法分析温度、pH、湿度、灭菌时间对聚合物产生的影响.结果 对照品、

  13. 响应面分析优化菊粉的十二烯基琥珀酸酐改性工艺研究%Study on dodecenly succinic anhydride-modified inulin

    Institute of Scientific and Technical Information of China (English)

    李丹丹; 曹威; 周杰; 李静鹏

    2013-01-01

    为了研究菊糖的十二烯基琥珀酸酐改性工艺条件,以菊糖、硼氢化钠及十二烯基琥珀酸酐用量、反应时间、反应pH以及反应温度为影响因素,以十二烯基琥珀酸酐的取代度为考察指标,运用Plackett-Burman设计筛选出3个对菊糖的十二烯基琥珀酸酐取代度影响显著因素,即十二烯基琥珀酸酐用量、反应pH和反应时间.用响应面分析实验优化十二烯基琥珀酸菊糖酯改性工艺.十二烯基琥珀酸菊糖酯改性最优工艺:菊糖4g,硼氢化钠0.015g,十二烯基琥珀酸酐0.94g,反应时间为6.8h,反应pH8.5,反应温度35℃,菊糖的十二烯基琥珀酸酐取代度为0.0140±3.33E-05.%In order to study optimum conditions for dodecenly succinic anhydride-modified inulin,effects of the amount of inulin,the dosage of sodium borohydride and dodecenly succinic anhydride (DDSA),pH,time and temperature used on the degree of substitution of dodecenly succinic anhydride-modified inulin were investigated.Plackett-Burman was adopted to screen out the important factors,which were the dosage of dodecenly succinic anhydride,pH and time used.The optimum reaction conditions were obtained by response surface analysis..inulin 4g,sodium borohydride 0.015g,dodecenly succinic anhydride 0.94g,time 6.8h,pH8.5,temperature 35℃,and the degree of substitution of dodecenly succinic anhydride-modified inulin is 0.0140± 3.33E-05.

  14. Fermentation of succinic acid using cellobiose from cellulose hydrolysates%利用纤维素水解液中的纤维二糖发酵制备丁二酸

    Institute of Scientific and Technical Information of China (English)

    徐蓉; 奚永兰; 张九花; 戴文宇; 万月佳; 陈可泉; 姜岷

    2013-01-01

    Cellobiose was often found in cellulose hydrolysates. In this study, the ability to use cellobiose to produce succinic acid by A.succinogenes NJ113 and using cellobiose prepared from sugarcane bagasse cellulose hydrolysates as a carbon source to produce succinic acid were investigated. A final succinic acid concentration of 23.51 g/L with a yield of 67.17% was achieved from an initial cellobiose concentration of 35 g/L via batch fermentation. In batch fermentation with 18 g/L of cellobiose and 17 g/L of other sugars from sugarcane bagasse cellulose hydrolysates, a succinic acid concentration of 20.00 g/L was obtained, with a yield of 64.73%. This study suggested that A. succinogenes had a strong ability to convert cellobiose into succinic acid and cellobiose from cellulose hydrolysate could be a potential carbon source for economical and efficient succinic acid production by A. succinogenes.%纤维素水解液中通常含有纤维二糖.本文考察了Actinobacillus succinogenes NJ 113利用纤维二糖厌氧发酵生产丁二酸的能力,并利用蔗渣纤维素制备纤维二糖作为碳源用于厌氧发酵生产丁二酸.3L发酵罐厌氧发酵结果显示:以35 g/L纤维二糖作为碳源发酵制备丁二酸,其产量为23.51 g/L,产率达到67.17%;用含有18g/L纤维二糖和17 g/L其它糖类的蔗渣纤维素水解液作为碳源发酵制备丁二酸,丁二酸的产量和产率分别为20.00 g/L和64.73%.因此,Actinobacillus succinogenes NJ 113具有较强的利用纤维二糖生产丁二酸的能力,而且利用废弃的纤维素制备纤维二糖作为碳源高效、经济地发酵制备丁二酸具有可行性.

  15. 顺酐加氢产物精制丁二酸的工艺研究%Purifying Technology of Succinic Acid from Product of M aleic Anhydride Hydrogenation

    Institute of Scientific and Technical Information of China (English)

    田丹; 霍稳周; 吕清林; 乔凯; 孟宪革; 李守田

    2013-01-01

    The process of succinic acid purifying from product of maleic anhydride hydrogenation was studied .The effects of distillation pressure ,temperature and reflux ratio on the process of vacuum distillation were investigated ;it also discussed the effects of reaction time and molar ratio of water to succinic anhydride on hydrolysis ;meanwhile ,the effect of temperature on the crystallization was concerned . The pure succinic acid was acquired through vacuum distillation , hydrolyzation and crystallization .The process conditions of purifying technology of succinic acid were detemined .The results show that the yield of succinic acid is more than 70% and purity of the product can reach 99 .5% even more under the conditions of vaccum distillation temperature 75~85 ℃ ,distillation pressure 200~300 Pa ,hydrolysis temperature 100 ℃ ,molar ratio of water to succinic anhydride 4~5 ,reaction time 2 h .%对顺酐加氢产物精制丁二酸的工艺进行了研究。考察了蒸馏压力、蒸馏温度及回流比对减压蒸馏过程的影响;考察了水解时间、水与酸酐物质的量比对水解过程的影响;考察了结晶温度对结晶过程的影响。确定了顺酐加氢产物减压蒸馏后水解结晶精制丁二酸的方法及工艺条件。结果表明,在减压蒸馏温度为75~85℃,蒸馏压力为200~300 Pa ,水解温度为100℃,水与丁二酸酐物质的量比为4~5,水解时间为2 h的条件下,得到的丁二酸产品收率≥70%,纯度≥99.5%。

  16. Lewis酸性离子液体催化合成丁二酸二异丙酯%Synthesis of succinic acid diisopropyl ester catalyzed by Lewis acid ionic liquids

    Institute of Scientific and Technical Information of China (English)

    赵地顺; 葛京京; 翟建华; 张娟; 刘猛帅; 李俊盼

    2014-01-01

    采用两步法制备了9种不同的Lewis酸性离子液体,采用1H NMR、FT-IR对离子液体的结构进行了表征,并系统地考察了其对丁二酸和异丙醇酯化反应的催化性能。结果表明,离子液体随着卤化物用量增加表现出更强的酸性。其中[Bmim]Br-Fe2Cl6催化合成丁二酸二异丙酯效果良好,催化剂用量为丁二酸质量的10.0%,反应温度100℃,反应时间4 h,酸醇摩尔比为1:5,丁二酸二异丙酯收率为88.9%,酯化率达92.7%。离子液体重复使用6次后,产品收率下降1.7%。%Nine kinds of different Lewis acid ionic liquids were synthesized by two-step process and their structures were characterized with 1H NMR and FT-IR. Lewis acid ionic liquids prepared were used to catalyze the esterification reaction of succinic acid and isopropyl alcohol. With the increase of dosage of halide, the ionic liquids showed stronger acidity. [Bmim]Br-Fe2Cl6 had the best catalytic performance, and optimal conditions for the synthesis of succinic acid diisopropyl ester were obtained as follows, amount of catalyst 10.0%(g/g)of succinic acid, reaction temperature 100℃ and reaction time 4 h, succinic acid and isopropyl alcohol ratio 1:5. Under the optimal conditions, the yield of succinic acid diisopropyl ester was up to 88.9%, esterification rate was 92.7%.The catalyst was recycled 6 times, and the yield of succinic acid diisopropyl ester only decreased by 1.7%.

  17. Synthesis of diethyl succinate catalyzed by functional ionic liquids%功能化离子液体催化合成丁二酸二乙酯

    Institute of Scientific and Technical Information of China (English)

    胡晶晶; 赵地顺; 李静静; 胡甜甜; 翟建华

    2016-01-01

    Four kinds of functional ionic liquids,1-methyl-3-(3-sulfopropyl)imidazolium hydrogen sulfate ([C3 SO3 Hmim]HSO4 ),1-ethyl-3-(3-sulfopropyl)imidazolium hydrogen sulfate ([C3 SO3 Emim]HSO4 ), 1-propyl-3-(3-sulfopropyl)imidazolium hydrogen sulfate ([C3 SO3 Pmim]HSO4 ),1-butyl-3-(3-sulfoprop-yl)imidazolium hydrogen sulfate ([C3 SO3 Bmim]HSO4 ),were designed and synthesized.The properties of samples were characterized by FTIR,1 H NMR and TG.The catalytic activities of the functional ionic liquid were investigated by the esterification of succinic anhydride with ethanol.The results showed that under the optimized conditions n(succinic anhydride)∶n(ethanol)=1∶2.5,catalyst dosage 9%,water carrying agent dosage 35%,reaction temperature 90 ℃ and reaction time 5 h,the yield of diethyl succi-nate was up to 92.28%.The ionic liquids dried in vacuum till remained high activity after reused for 8 times.Moreover,compared to conventional industrial catalysts,ionic liquid catalyst needed less,and had the superiorities of less by-product,mild reaction conditions,high yield and the catalyst could be recy-cled,and has the potential of replacing the traditional sulfuric acid in catalytic esterification reaction.%采用两步法合成了4种不同阳离子的功能化离子液体:1-甲基-3-(3-磺丙基)咪唑硫酸氢盐([C3 SO3 Hmim] HSO4)、1-乙基-3-(3-磺丙基)咪唑硫酸氢盐([C3SO3Emim]HSO4)、1-丙基-3-(3-磺丙基)咪唑硫酸氢盐([C3SO3-Pmim]HSO4)、1-丁基-3-(3-磺丙基)咪唑硫酸氢盐([C3 SO3 Bmim]HSO4)。通过FTIR、1 H NMR和TG分析了离子液体的结构和热稳定性。并将其应用于催化丁二酸酐和乙醇的酯化反应中,考察了4种离子液体的催化活性。结果表明,离子液体[C3SO3Bmim]HSO4的催化效果较好,在n(丁二酸酐)∶n(乙醇)=1∶2.5,催化剂用量9%,环己烷用量35%,反应温度90℃的条件下反应5 h后,丁二酸二乙酯的收率可达92

  18. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    Directory of Open Access Journals (Sweden)

    Chu QC

    2016-01-01

    Full Text Available Qiuchen Chu,1,* Hong Xu,2,* Meng Gao,1 Xin Guan,1 Hongyan Liu,1 Sa Deng,1 Xiaokui Huo,1 Kexin Liu,1 Yan Tian,1 Xiaochi Ma1 1College of Pharmacy, 2College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer remains a major problem around the world. Resibufogenin (RBG is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison, which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid (PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN, and RBG/coumarin-6-loaded PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS, and 5-fluorouracil solution (used as the negative controls, as assayed using flow cytometry. LD50 (median lethal dose values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in

  19. Development and evaluation of vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate-mixed polymeric phospholipid micelles of berberine as an anticancer nanopharmaceutical

    Directory of Open Access Journals (Sweden)

    Shen R

    2016-04-01

    Full Text Available Roger Shen,1 Jane J Kim,2 Mingyi Yao,2,3 Tamer A Elbayoumi2,3 1Department of Family Medicine, Northeastern Health Systems-Tahlequah City Hospital, Tahlequah, OK, USA; 2Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, 3Nanomedicine Center of Excellence in Translational Nanomedicine, Midwestern University, Glendale, AZ, USA Abstract: Berberine (Brb is an active alkaloid occurring in various common plant species, with well-recognized potential for cancer therapy. Brb not only augments the efficacy of antineoplastic chemotherapy and radiotherapy but also exhibits direct antimitotic and proapoptotic actions, along with distinct antiangiogenic and antimetastatic activities in a variety of tumors. Despite its low systemic toxicity, several pharmaceutical challenges limit the application of Brb in cancer therapy (ie, extremely low solubility and permeability, very poor pharmacokinetics (PKs, and oral bioavailability. Among lipid-based nanocarriers investigated recently for Brb, stealth amphiphilic micelles of polymeric phospholipid conjugates were studied here as a promising strategy to improve Brb delivery to tumors. Specifically, physicochemically stable micelles made of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol-2000] (PEG-PE mixed with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS (PEG-succinate ester of vitamin E, in a 3:1 M ratio, increased Brb solubilization by 300%. Our PEG-PE/TPGS-mixed micelles firmly retained the incorporated Brb, displaying extended-release profile in simulated media, with up to 30-fold projected improvement in simulated PKs of Brb. Owing to the markedly better uptake of Brb-containing mixed micelles in vitro, our Brb-mixed micelles nanoformulation significantly amplified apoptosis and overall cytotoxic effectiveness against monolayer and spheroid cultures of human prostate carcinomas (16- to 18-fold lower half-maximal inhibitory

  20. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    Science.gov (United States)

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  1. Novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s with functional carbonate building blocks. 1. Chemical synthesis and their structural and physical characterization.

    Science.gov (United States)

    Yang, Jing; Hao, Qinghui; Liu, Xiaoyun; Ba, Chaoyi; Cao, Amin

    2004-01-01

    This study presents chemical synthesis, structural, and physical characterization of novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s P(BS-co-CC) bearing functional carbonate building blocks. First, five kinds of six-membered cyclic carbonate monomers, namely, trimethylene carbonate (TMC), 1-methyl-1,3-trimethylene carbonate (MTMC), 2,2-dimethyl-1,3-trimethylene carbonate (DMTMC), 5-benzyloxytrimethylene carbonate (BTMC), and 5-ethyl-5-benzyloxymethyl trimethylene carbonate (EBTMC), were well prepared from ethyl chloroformate and corresponding diols at 0 degrees C in THF solution with our modified synthetic strategies. Then, a series of new P(BS-co-CC)s were synthesized at 210 degrees C through a simple combination of poly-condensation and ring-opening-polymerization (ROP) of hydroxyl capped PBS macromers and the prepared carbonate monomers, and titanium tetra-isopropoxide Ti(i-OPr)4 was used as a more suitable catalyst of 5 candidate catalysts which could concurrently catalyze poly-condensation and ROP. By means of NMR, GPC, FTIR, and thermal analytical instruments, macromolecular structures and physical properties have been characterized for these aliphatic poly(ester carbonate)s. The experimental results indicated that novel biodegradable P(BS-co-CC)s were successfully synthesized with number average molecular weight Mn ranging from 24.3 to 99.6 KDa and various CC molar contents without any detectable decarboxylation and that the more bulky side group was attached to a cyclic carbonate monomer, the lower reactivity for its copolymerization would be observed. The occurrences of 13C NMR signal splitting of succinyl carbonyl attributed to the BS building blocks could be proposed due to the randomized sequences of BS and CC building blocks. FTIR characterization indicated two distinct absorption bands at 1716 and 1733 approximately 1735 cm(-1), respectively, stemming from carbonyl stretching modes for corresponding BS and CC units. With

  2. 谷氨酸棒状杆菌厌氧产丁二酸的发酵条件%Influence of lactate dehydrogenase gene knockout on anaerobic production of succinic acid by Corynebacterium glutamicum

    Institute of Scientific and Technical Information of China (English)

    贾全栋; 刘学胜; 郭燕风; 徐建中; 张伟国

    2014-01-01

    考察谷氨酸棒状杆菌ATCC13032Δldh厌氧产丁二酸的发酵条件。结果发现:补加NaHCO3的效果最好,并且考察了NaHCO3浓度对葡萄糖转化速率及丁二酸生成速率的影响。运用代谢流分析方法分析了乳酸脱氢酶基因敲除对谷氨酸棒状杆菌厌氧代谢的影响,发现乳酸脱氢酶基因敲除导致磷酸烯醇式丙酮酸生成丁二酸的流量提高了214�3%,流向乳酸的流量变为0;分批厌氧转化36 h生成41�2 g/L丁二酸,产率45�0%。%The conversion conditions of Corynebacterium glutamicum ATCC13032Δldh under anaerobic condition were investigated.The optimal carbonates were bicarbonate,and the rate of sugar consumption and succinic acid production were influenced by bicarbonate concentration�The effects of lactate dehydrogenase deletion in Corynebacterium glutamicum under anaerobic metabolism were investigated by the metabolic flux analysis and the metabolic flux to the succinic acid synthesis pathway increased by 214�3%, while the metabolic flux to lactic acid synthesis pathway became zero�Succinic acid concentration reached 41�2 g/L within 36 h and the yield of succinic acid was 45.0%.

  3. Development and Validation of a Rapid Chemometrics Assisted RP-HPLC with PDA Detection Method for the Simultaneous Estimation of Pyridoxine HCl and Doxylamine Succinate in Bulk and Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    P. Giriraj

    2014-01-01

    Full Text Available Simple, rapid, precise, and accurate RP-HPLC method was developed and optimized with the help of chemometric tool for the simultaneous estimation of pyridoxine HCl and doxylamine succinate in bulk and pharmaceutical dosage form. Optimization was done by central composite design in response surface methodology. Based on the trial and error, percentage of organic phase (methanol in mobile phase, flow rate, and molarity of the buffer were selected as factors. Resolution and retention time were used for the estimation of system response during the optimization procedure. The optimized condition was used and the separation was carried out on phenomenex C18 column (150 × 4.6 mm; i.d, 5 μ particle size using the mobile phase containing 49.37% of methanol and 50.63% of phosphate buffer (45.14 mM at a flow rate of 1 mL/min. Retention time was found to be 1.884 minutes for pyridoxine HCl and 3.959 minutes for doxylamine succinate. The calibration curves were found to be linear from 10 to 70 μg/mL and 10 to 90 μg/mL for pyridoxine HCl and doxylamine succinate with their correlation coefficient values 0.9995 and 0.9997. LOD and LOQ were found to be 23.5 ng/mL and 71.1 ng/mL for pyridoxine HCl and 99.9 ng/mL and 302.6 ng/mL for doxylamine succinate.

  4. Optimization of Fermentation Medium for Succinic Acid Production Using Canna edulis ker Syrup%芭蕉芋糖浆发酵生产丁二酸培养基的优化

    Institute of Scientific and Technical Information of China (English)

    刘宇鹏; 陈万河; 陈梁; 方晨; 白彦兵; 孙志浩

    2011-01-01

    Canna edulis Ker syrup was firstly used to product succinic acid by Actinobacillus succinogenes CGMCC1593. It was found that the total sugar, corn steep liquid and phosphate significantly improved the production of succinic acid. The Response Surface Methodology (RSM) based on a three-factor Box-Behnken design of experiments was used to build an analytical model and finally employed as a constraint in an obvious optimization process. The optimized parameters were total sugar of 89.66 g/L, corn steep liquid of 38.55 g/L, and phosphate of 4.46 g/L. Under those optimization conditions, it was predicted that the the highest concentation of succinic acid recached 62.92 g/L.After optimization, the succinic acid production increased by 22. 7% , and the experimental data basically in line with the predicted values.%以芭蕉芋糖浆为主要原料,利用琥珀酸放线杆菌(Actinobacillus succinogenes)CCMCC1593发酵生产丁二酸.单因素试验表明,培养基中总糖、玉米浆和磷酸盐对发酵有显著影响,利用响应面分析法(RSM)对培养基成分进行优化,并建立了各因素与丁二酸产量之间的数学模型.当各参数取值分别为总糖89.66 g/L,磷酸盐4.46g/L,玉米浆38.55 g/L,丁二酸最大估计值为62.92 g/L.优化后丁二酸产量比优化前提高了22.7 %,与响应面预测极值基本相符.

  5. Development and Validation of Stability-Indicating RP-UPLC Method for Simultaneous Determination of Related Substances of S(−Amlodipine and S(−Metoprolol Succinate in Fixed Dose Combination Tablet Dosage Form

    Directory of Open Access Journals (Sweden)

    Suresh Shitole

    2014-01-01

    Full Text Available A novel, rapid, accurate, sensitive, precise, and stability-indicating reverse-phase ultra-performance liquid chromatographic (RP-UPLC method was developed and validated for determination of related substances of S(−Amlodipine and S(−Metoprolol Succinate in fixed dose combination tablet dosage form. The chromatographic separation was achieved with the use of Acquity UPLC HSS T3, 1.8 μm, 2.1 × 100 mm analytical column at 45°C employing a gradient elution. Mobile phase consisting of mobile phase-A (solution containing 5.0 gm of sodium dihydrogen phosphate monohydrate per liter of water and Acetonitrile in the ratio of 95 : 5 and mobile phase-B (Acetonitrile was used at a flow rate of 0.5 mL min−1 with injection volume of 10 μL and the detection was done at 232 nm using UV detector. The retention times of S(−Metoprolol Succinate and S(−Amlodipine were found to be 2.8 minutes and 8.1 minutes, respectively. During method validation all the parameters were evaluated as per ICH guidelines, which remained well within acceptable limits. This method can be used for the estimation of related substances of S(−Amlodipine and S(−Metoprolol Succinate in fixed dose combination tablet dosage form.

  6. Equilibrium of Extraction of Succinic, Malic, Maleic and Fumaric Acids with Trioctylamine%三辛胺萃取丁二酸、苹果酸、马来酸、富马酸特性的研究

    Institute of Scientific and Technical Information of China (English)

    李振宇; 秦炜; 汪敏; 黄焱; 戴猷元

    2002-01-01

    Extraction equilibrium features of succinic acid, malic acid, maleic acid and fumaric acid were investigated systematically with trioctylamine (TOA) in chloroform, 4-methyl-2-pentanone (MIBK) and 1-octanol. Fourier transform-infrared (FTIR) spectroscopic analysis of organic samples loaded with the acid shows that amine forms 1:1 complex of ion-pair association with succinic acid, malic acid and maleic acid, and 1:1, 2:1 complex of ion-pair association with fumaric acid. It is proposed that the complex forms depend on the second dissociation constant of the dibasic acid, pKa2. Results of equilibrium experiments show that diluents affect extraction behavior, and depend on the solute concentration. Protic diluents, chloroform and 1-octanol, are more effective than the others when the equilibrium solute concentration is lower than 1:1 stoichiometry of TOA to acid, otherwise the extraction ability shows that MIBK>l-octanol>chloroform for malic and maleic acids, and 1-octanol>MIBK>chloroform for succinic acid. Overloading (solute concentration in organic phase is lager than TOA concentration) appears for all of the studied acids, and the sequence of overloading amount is the same as that of distribution constant of diluent. The results show that the sequence of extraction ability of different acid is the same as that of acidity at low equilibrium solute concentrations, while it is the same as the sequence of hydrophobicity at high equilibrium concentrations.

  7. Exploring details about structure requirements based on novel CGRP receptor antagonists urethanamide, aspartate, succinate and pyridine derivatives by in silico methods

    Science.gov (United States)

    Li, Yan; He, Haoran; Wang, Jinghui; Han, Chunxiao; Feng, Jiaqi; Zhang, Shuwei; Yang, Ling

    2014-09-01

    The migraine never fails to afflict individuals in the world that knows no lack of such cases. CGRP (calcitonin gene-related peptide) is found closely related to migraine and olcegepant (BIBN4096) is effective in alleviating the pain. In our work, the combination of ligand- and receptor-based three-dimensional quantitative structure-activity relationship (3D-QSAR) studies along with molecular docking was applied to provide us insights about how urethanamide, pyridine and aspartate and succinate derivatives (novel CGRP receptor antagonists) play a part in inhibiting the activity of CGRP receptor. The optimal CoMSIA model shows the Q2 of 0.505, R2ncv of 0.992 and its accurate predictive ability was confirmed by checking out an independent test set which gave R2pred value of 0.885. Besides, the 3D contour maps help us identify how different groups affect the antagonist activity while connecting to some key positions. In addition, the docking analysis shows the binding site emerging as the distorted “V” shape and including two binding pockets: one of them is hydrophobic, fixing the structural part 3 of compound 80, the other anchors the part 1 of compound 80. The docking analysis also shows the interaction mechanism between compound 80 and CGRP receptor, similar to the interaction between olcegepant and CGRP receptor. The findings derived from this work reveal the mechanism of related antagonists and facilitate the future rational design of novel antagonists with higher potency.

  8. SPHERULITIC STRUCTURE AND MORPHOLOGY OF POLY(ETHYLENE SUCCINATE)/POLY(ETHYLENE OXIDE) (PES/PEO) BLENDS WITH ONE-STEP CRYSTALLIZATION

    Institute of Scientific and Technical Information of China (English)

    Jie-ping Liu; Shuan-gai He; Xiao-ping Qiao

    2008-01-01

    The spherlitic structure and morphology development of poly(ethylene succinate)/poly(ethylene oxide) (PES/PEO) blends with one-step crystallization behavior were observed by means of polarizing optical microscope.It was found that the pure PES spherulite in which the adequate quantity of PEO melt existed in the interlamellar regions,and the blending spherulite formed by both PES and PEO lamellae could form simultaneously.When the two types of spherulites contacted with each other the front of the blending spherulite could penetrate into the pure PES spherulite to grow continually.This penetration growth behavior was also observed when the mini-crystal particles of the PES component were formed at lower crystallization temperatures.The kinetics analysis showed that the penetration growth rate was faster than that in the original melt.It was evidenced that the increasing of growth rate and the formation of new growth site should be the typical characteristics of interpenetrated growth in binary crystalline polymer blends.

  9. Highly dispersed ruthenium nanoparticle-embedded mesoporous silica as a catalyst for the production of gamma-butyrolactone from succinic anhydride.

    Science.gov (United States)

    Chung, Sang-Ho; Eom, Hee-Jun; Kim, Min-Sung; Lee, Myung Suk; Lee, Kwan-Young

    2013-11-01

    In this study, a novel, strategic method was developed for the synthesis of a mesoporous silica catalyst embedded with ruthenium nanoparticles (RuNPs/SiO2) by combining the polyol and modified sol-gel methods. By applying this new procedure, uniformly synthesized ruthenium nanoparticles with an average size of 3.8 nm and 95% spherical shape were highly dispersed in the mesoporous silica support material. Coordinated carbonyl groups of PVP remaining from the synthesis of the RuNPs were effectively removed by the thermal treatment (calcined at 573 K for 4 h) and the sythesized RuNPs/SiO2 catalysts were reduced under hydrogen at 20 bar for 2 h. These catalysts were analyzed using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), N2 adsorption-desorption, and X-ray diffraction (XRD). After the thermal treatment and the reduction procedure, the size and shape of the embedded RuNPs were nearly unchanged, and the catalyst was active in the liquid-phase hydrogenation of succinic anhydride (SAN) to selectively form y-butyrolactone (GBL) with a maximum yield of 90.1%. This novel catalyst preparation is a potentially useful method for the synthesis of metal nanoparticles as heterogeneous catalysts.

  10. Succinate dehydrogenase (SDHx) mutations in pituitary tumors: could this be a new role for mitochondrial complex II and/or Krebs cycle defects?

    Science.gov (United States)

    Xekouki, Paraskevi; Stratakis, Constantine A

    2012-12-01

    Succinate dehydrogenase (SDH) or mitochondrial complex II is a multimeric enzyme that is bound to the inner membrane of mitochondria and has a dual role as it serves both as a critical step of the tricarboxylic acid or Krebs cycle and as a member of the respiratory chain that transfers electrons directly to the ubiquinone pool. Mutations in SDH subunits have been implicated in the formation of familial paragangliomas (PGLs) and/or pheochromocytomas (PHEOs) and in Carney-Stratakis syndrome. More recently, SDH defects were associated with predisposition to a Cowden disease phenotype, renal, and thyroid cancer. We recently described a kindred with the coexistence of familial PGLs and an aggressive GH-secreting pituitary adenoma, harboring an SDHD mutation. The pituitary tumor showed loss of heterozygosity at the SDHD locus, indicating the possibility that SDHD's loss was causatively linked to the development of the neoplasm. In total, 29 cases of pituitary adenomas presenting in association with PHEOs and/or extra-adrenal PGLs have been reported in the literature since 1952. Although a number of other genetic defects are possible in these cases, we speculate that the association of PHEOs and/or PGLs with pituitary tumors is a new syndromic association and a novel phenotype for SDH defects.

  11. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate

    Directory of Open Access Journals (Sweden)

    João P. Costa-Nunes

    2015-01-01

    Full Text Available Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day and dicholine succinate (50 mg/kg/day, against standard antidepressants, imipramine (7 mg/kg/day and citalopram (15 mg/kg/day, utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies.

  12. Preparation of Octenyl Succinic Anhydride Modified Broken Rice Starch%辛烯基琥珀酸碎米淀粉酯的制备

    Institute of Scientific and Technical Information of China (English)

    苟林; 王泽南; 韩堂健; 蒋艳; 徐春泽

    2011-01-01

    Broken rice starch was modified with octenyl succinic anhydride in aqueous slurry system.The modification process was optimized by one-factor-at-a-time and orthogonal array design methods to achieve maximum degree of substitution(DS).The results showed that the optimal process conditions were found to be: starch slurry concentration 30%,pH 8.5,reaction time 5 h,and reaction temperature 35 ℃.Under the optimal conditions,the degree of substitution was 0.01445.%以碎米淀粉为原料,采用湿法制备辛烯基琥珀酸碎米淀粉酯,以取代度为评价指标,确定辛烯基琥珀酸酐添加量为3%,通过单因素与正交试验确定辛烯基琥珀酸碎米淀粉酯的最佳制备工艺。结果显示:淀粉乳质量分数30%、pH8.5、反应时间5h、反应温度35℃为最佳工艺条件,在此条件下所得产品取代度可达0.01445。

  13. Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by d-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

    Science.gov (United States)

    Qiao, Hongzhi; Chen, Lihua; Rui, Tianqi; Wang, Jingxian; Chen, Ting; Fu, Tingming; Li, Junsong; Di, Liuqing

    2017-01-01

    Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box–Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3), respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability (Papp) of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS (Pnanosuspensions could act as an effective delivery device for ADG to enhance its oral bioavailability and biological efficacy. PMID:28223797

  14. Formulation and in vitro evaluation of quercetin loaded polymeric micelles composed of pluronic P123 and D-a-tocopheryl polyethylene glycol succinate.

    Science.gov (United States)

    Zhao, Liyan; Shi, Yikang; Zou, Shaohua; Sun, Min; Lil, Lingbing; Zhail, Guangxi

    2011-06-01

    The objective of this study was to develop a polymeric delivery system to improve the solubility and biological activity of Quercetin (QT). QT loaded mixed micelles, composed of Pluronic P123 (P123) and D-a-tocopheryl polyethylene glycol succinate (TPGS) with proportion of 7:3 (QT-P/T), were prepared by thin-film hydration method. The average size of the mixed micelles was 18.43 nm, and the encapsulating efficiency for QT was 88.94 +/- 3.71%, drug-loading was 10.59 +/- 0.38%. The solubility of QT in QT-P/T was 5.56 mg/mL, which was about 2738-fold that of crude QT in water. Compared with the QT propylene glycol solution, the in vitro release of QT from QT-P/T presented the sustained-release property. The in vitro cytotoxicity assay showed that the IC50 values on MCF-7 cells for QT-P/T and QT loaded P123 micelles (QT-P123) were 7.13 microg/mL and 10.73 microg/mL, respectively, while 7.23 microg/mL and 14.47 microg/mL on MCF-7/ADR cells. From the results, it can be concluded that, P123/TPGS mixed micelles may serve as a pharmaceutical nano carrier with improved solubility and biological activity for QT.

  15. 3-nitropropionic acid inhibition of succinate dehydrogenase (complex II) activity in cultured Chinese hamster ovary cells: antagonism by L-carnitine.

    Science.gov (United States)

    Scallet, Andrew C; Haley, Raney L; Scallet, Dori M; Duhart, Helen M; Binienda, Zbigniew K

    2003-05-01

    3-Nitropropionic acid (3-NPA) is an inhibitor of the mitochondrial enzyme succinate dehydrogenase (SDH, a part of complex II) that links the tricarboxylic acid (TCA) cycle to the respiratory electron transport chain. 3-NPA inactivates SDH by covalently and irreversibly binding to its active site. We previously examined the effects of 3-NPA on the histochemical activity of SDH in vivo, by using the reduction of a yellow tetrazolium dye (nitro blue tetrazolium) to a blue formazan as an indicator. In studies of cultured cells, the related dye methylthiazoletetrazolium (MTT) has commonly been used as an indicator of the presence and number of viable cells; that is cells that are capable of producing energy via the TCA cycle. Here we observed that doses of 3-NPA as low as 10(-8) M inhibited formazan production in an in vitro model system using CHO cells. This effect was antagonized by l-carnitine, which greatly increased the production of formazan, indicating a considerable improvement in energy production by the cultured cells. CHO cells appear to be a convenient model for the evaluation of therapeutic compounds that may modulate cellular bioenergetics.

  16. Growth, optical, thermal, mechanical and dielectric studies of sodium succinate hexahydrate (β phase) single crystal: A promising third order NLO material

    Science.gov (United States)

    Mageshwari, P. S. Latha; Priya, R.; Krishnan, S.; Joseph, V.; Das, S. Jerome

    2016-11-01

    A third order nonlinear optical (NLO)single crystals of sodium succinate hexahydrate (SSH) (β phase) has been grown by a slow evaporation growth technique using aqueous solution at ambient temperature. The lattice parameters and morphology of SSH were determined by single crystal X-ray diffraction analysis. SSH crystallizes in centrosymmetric monoclinic system with space group P 21 / c and the crystalline purity was analyzed by powder X-ray diffraction analysis. The UV-vis-NIR spectrum reveals that the crystal is transparent in the entire visible region. The recorded FT-IR spectrum verified the presence of various functional groups in the material. NMR analysis of the grown crystal confirms the structural elucidation and detects the major and minor functional groups present in the title compound. ICP-OES analysis proved the presence of sodium in SSH. TG-DTA/DSCanalysis was used to investigate the thermal stability of the material. The dielectric permittivity and dielectric loss of SSH were carried out as a function of frequency for different temperatures and the results were discussed. The mechanical stability was evaluated from Vicker's microhardness test. The third order nonlinear optical properties of SSH has been investigated employing Z-scan technique with He-Ne laser operating at 632.8 nm wavelength.

  17. SUBSTITUTION OF HIGH-YIELD-PULP FOR HARDWOOD BLEACHED KRAFT PULP IN PAPER PRODUCTION AND ITS EFFECT ON ALKENYL SUCCINIC ANHYDRIDE SIZING

    Directory of Open Access Journals (Sweden)

    Qijie Chen,

    2012-02-01

    Full Text Available In recent years there has been an increasing interest in using high-yield pulp (HYP as a partial replacement for hardwood bleached kraft pulp (HWBKP in the production of high-quality fine papers as a cost-effective way of improving the product performance. This study investigated the substitution of HYP for HWBKP and its effect on the Alkenyl Succinic Anhydride (ASA sizing performance. The results showed that the substitution of an aspen HYP for HWBKP can increase the ASA sizing performance at a HYP substitution as high as 15 to 20%. The ASA addition sequence has an influence on the ASA sizing performance and first adding ASA to the HYP followed by mixing with kraft pulps was the preferred method. Using precipitated calcium carbonate (PCC as a paper filler at a dosage of less than 20% can increase the ASA sizing performance due to the contribution of the calcium soap of the hydrolysed ASA. A PCC dosage greater than 20% resulted in a negative impact on the sizing performance. It was also found that different PCC loading sequences can also affect the ASA sizing performance.

  18. Simultaneous Estimation of Phenylephrine HCl, Doxylamine Succinate and Dextromethorphan HBr in Soft Gelatin Capsule (Cough and Cold Preparation by RP-HPLC

    Directory of Open Access Journals (Sweden)

    Mo.Salauddin A Shaikh

    2014-05-01

    Full Text Available A RP-HPLC methods were developed and validated for simultaneous estimation of Phenylephrine HCl (PE, Doxylamine Succinate (DOX and Dextromethorphan HBr (DEX. The separation was achieved on a Princestone ODS C18 (250mm X 4.6 mm i.d., 10 μm particle size with an Isocratic system of Phosphate Buffer (10 mM : Methanol : Acetonitrile (pH 4 in the ratio of 70:25:5 v/v/v. The retention time for PE, DOX and DEX was obtained as 5.125 min, 10.419 min and 2.661 min respectively with a flow rate of 1.0 ml/min at detection wavelength 215 nm. The linearity of the proposed method was investigated in the range of 25 -125 μg/ml, 31.25 - 156.25 μg/ml and 50 - 250 μg/ml for PE, DOX and DEX respectively. The developed method was validated as per ICH guideline and found to be satisfactory.

  19. Simultaneous determination of pyridoxine hydrochloride and doxylamine succinate from tablets by ion pair reversed-phase high-performance liquid chromatography (RP-HPLC).

    Science.gov (United States)

    Argekar, A P; Sawant, J G

    1999-08-01

    A new, simple, precise, and rapid ion pair reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed for the simultaneous determination of pyridoxine hydrochloride (PYR) and doxylamine succinate (DOX) in tablets. The stationary phase was a Microbondapak C18 column (10 mu, 300 mm x 3.9 mm i.d.). The mobile phase was water:methanol (60:40) containing 10 mM heptanesulfonic acid and 0.25% triethylamine and adjusted to pH 2.2 with orthophosphoric acid. Detection was carried out at 263 nm using an ultraviolet (UV) detector. The flow rate was 1.0 ml/min, and retention times were 3.65 min and 7.32 min for PYR and DOX, respectively. The linearity was obtained in the concentration range 0.5-500 micrograms/ml for PYR and DOX. Mean percentage recoveries were 100.20% and 101.20% for PYR and DOX, respectively.

  20. Enhanced oral delivery of paclitaxel using acetylcysteine functionalized chitosan-vitamin E succinate nanomicelles based on a mucus bioadhesion and penetration mechanism.

    Science.gov (United States)

    Lian, He; Zhang, Tianhong; Sun, Jin; Liu, Xiaohong; Ren, Guolian; Kou, Longfa; Zhang, Youxi; Han, Xiaopeng; Ding, Wenya; Ai, Xiaoyu; Wu, Chunnuan; Li, Lin; Wang, Yongjun; Sun, Yinghua; Wang, Siling; He, Zhonggui

    2013-09-03

    In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min(-1), Papp = 0.059 cm · min(-1)) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0-t (586.37 ng/mL · h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.

  1. Role of specific interfacial area in controlling properties of immiscible blends of biodegradable polylactide and poly[(butylene succinate)-co-adipate].

    Science.gov (United States)

    Ojijo, Vincent; Sinha Ray, Suprakas; Sadiku, Rotimi

    2012-12-01

    Binary blends of two biodegradable polymers: polylactide (PLA), which has high modulus and strength but is brittle, and poly[(butylene succinate)-co-adipate] (PBSA), which is flexible and tough, were prepared through batch melt mixing. The PLA/PBSA compositions were 100/0, 90/10, 70/30, 60/40, 50/50, 40/60, 30/70, 10/90, and 0/100. Fourier-transform infrared measurements revealed the absence of any chemical interaction between the two polymers, resulting in a phase-separated morphology as shown by scanning electron microscopy (SEM). SEM micrographs showed that PLA-rich blends had smaller droplet sizes when compared to the PBSA-rich blends, which got smaller with the reduction in PBSA content due to the differences in their melt viscosities. The interfacial area of PBSA droplets per unit volume of the blend reached a maximum in the 70PLA/30PBSA blend. Thermal stability and mechanical properties were not only affected by the composition of the blend, but also by the interfacial area between the two polymers. Through differential scanning calorimetry, it was shown that molten PBSA enhanced crystallization of PLA while the stiff PLA hindered cold crystallization of PBSA. Optimal synergies of properties between the two polymers were found in the 70PLA/30PBSA blend because of the maximum specific interfacial area of the PBSA droplets.

  2. Effect of nanoclay loading on the thermal and mechanical properties of biodegradable polylactide/poly[(butylene succinate)-co-adipate] blend composites.

    Science.gov (United States)

    Ojijo, Vincent; Sinha Ray, Suprakas; Sadiku, Rotimi

    2012-05-01

    Polylactide/poly[(butylene succinate)-co-adipate] (PLA/PBSA)-organoclay composites were prepared via melt compounding in a batch mixer. The weight ratio of PLA to PBSA was kept at 70:30, while the weight fraction of the organoclay was varied from 0 to 9%. Small angle X-ray scattering patterns showed slightly better dispersion in PBSA than PLA, and there was a tendency of the silicate layers to delaminate in PBSA at low clay content. Thermal analysis revealed that crystallinity was dependent on the clay content as well its localization within the composite. On the other hand, thermal stability marginally improved for composites with 2 wt %. Tensile properties showed dependence on clay content and localization. Composite with 2 wt % clay content showed slight improvement in elongation at break. Overall, the optimum property was found for a composite with 2 wt % of the organoclay. This paper therefore has demonstrated the significance of the clay content and localization on the properties of the PLA/PBSA blends.

  3. Characterization and expression of a cDNA, AmphiSDHD,encoding the amphioxus cytochrome b small subunit in mitochondrial succinate-ubiquinone oxidoreductase

    Institute of Scientific and Technical Information of China (English)

    MA Lifang; ZHANG Shicui; ZHUANG Zhimeng; LIU Zhenhui; LI Hongyan; XIA Jianjun

    2005-01-01

    In this study, an amphioxus cDNA, AmphiSDHD, encoding the cytochrome b small subunit in mitochondrial succinate-ubiquinone oxidoreductase, was isolated from the gut cDNA library of amphioxus Branchiostoma belcheri tsingtauense. It is 1429 bp in length, with an open reading frame of 465 bp coding for a protein of 154 amino acids. The deduced protein contains a mitochondrial targeting presequence of 65 amino acids rich in basic residues like arginine and hydroxy residues such as serine and threonine. Alignment of the amino acid sequences of AmphiSDHD and other eukaryotic SDHD proteins showed that AmphiSDHD has three transmembrane segments, and includes two histidine residues in the second transmembrane segment that are the putative binding sites for the heme b molecule. The phylogenetic tree constructed suggests that AmphiSDHD appears more closely related to vertebrate SDHD proteins than invertebrate ones. Northern blotting demonstrated that AmphiSDHD is ubiquitously expressed in amphioxus, being in line with the fact that SDHD is a house-keeping protein.

  4. The conserved RGxxE motif of the bacterial FAD assembly factor SdhE is required for succinate dehydrogenase flavinylation and activity.

    Science.gov (United States)

    McNeil, Matthew B; Fineran, Peter C

    2013-10-29

    Succinate dehydrogenase (SDH) is an important respiratory enzyme that plays a critical role in the generation of energy in the majority of eukaryotes, bacteria, and archaea. The activity of SDH is dependent on the covalent attachment of the redox cofactor FAD to the flavoprotein subunit SdhA. In the Gram-negative bacteria Escherichia coli and Serratia sp. ATCC 39006, the covalent attachment of FAD to SdhA is dependent on the FAD assembly factor SdhE (YgfY). Although mechanisms have been proposed, experimental evidence that elucidates the molecular details of SdhE-mediated flavinylation are scarce. In this study, truncation and alanine swap mutagenesis of SdhE identified a highly conserved RGxxE motif that was important for SdhE function. Interestingly, RGxxE site-directed variants were not impaired in terms of protein folding or interactions with SdhA. Purification and analysis of SdhA from different mutant backgrounds demonstrated that SdhE interacts with and flavinylates folded SdhA without a requirement for the assembly of the entire SDH complex. SdhA was also partially active in the absence of SdhE, suggesting that SdhA is able to attach FAD through an inefficient autocatalytic mechanism. The results presented are of widespread relevance because SdhE and SDH are required for bacterial pathogenesis and mutations in the eukaryotic homologues of SdhE and SDH are associated with cancer in humans.

  5. 碳酸乙烯酯与丁二酸二甲酯耦合反应制备聚丁二酸乙二醇酯预聚体的热力学分析%Thermodynamic analysis of coupling reaction of ethylene carbonate and dimethyl succinate to poly(ethylene glycol succinate) oligomers

    Institute of Scientific and Technical Information of China (English)

    王丽苹

    2015-01-01

    采用基团贡献法在433K~533K温度范围对碳酸乙烯酯与丁二酸二甲酯耦合制聚丁二酸乙二醇酯反应体系的4个可能的反应进行了反应焓变、反应熵变、反应吉布斯自由能变(ΔrGθ)及平衡常数(Kp)的计算。结果表明,反应(2)和(4)为放热反应,其ΔrGθ<0可自发进行,升高温度不利于反应的进行,而反应(1)和(3)为吸热反应,其ΔrGθ>0,反应不能自发进行。与反应(3)相比,反应(2)的平衡常数较大,反应更易进行。%The reaction enthalpy change, reaction entropy change, Gibbs free energy change(ΔrGθ) and equilibrium constants(Kp) of the four possible reactions for coupling of ethylene carbonate and dimethyl succinate to poly (ethylene glycol succinate) oligomers in the temperature range of 433 to 533K were calculated by using the group contribution method. Results showed that for reaction (2) and (4), they were exothermic, and their ΔrGθwere less than zero, so both of the reactions were spontaneous and high temperature was unfavorable. However, for reaction (1) and (3), they were endothermic, and their ΔrGθ were greater than zero, so both of the reactions were not spontaneous. The Kp for reaction (2) was greater than that for reaction (3), which indicated that the reaction (2) could be carried out more easily.

  6. 2-Phenyl-7-(4-pyridylmethylamino-1,2,4-triazolo[1,5-a][1,3,5]triazin-5(4H-oneFused heterocyclic systems with s-triazine ring. Part 17. For part 16, see Dolzhenko et al. (2011.

    Directory of Open Access Journals (Sweden)

    Lip Lin Koh

    2011-01-01

    Full Text Available In the title compound, C16H13N7O, the 1,2,4-triazolo[1,5-a][1,3,5]triazine heterocyclic system is essentially planar (r.m.s. deviation = 0.0375 Å. The attached benzene ring lies almost in the mean plane of 1,2,4-triazolo[1,5-a][1,3,5]triazine [dihedral angle = 1.36 (23°], while the pyridine ring is turned out of this plane by the aminomethyl bridge [dihedral angle = 69.22 (9°]. The amino group H atom is involved in intramolecular hydrogen bonding with a triazole N atom. In the crystal, molecules are connected via C(=ONH...N hydrogen bonds into C(11 chains parallel to [100]. The amino group H atom acts as a hydrogen-bond donor, forming an NH...O=C hydrogen bond with the carbonyl O atom, which links the molecules into C(6 chains running along [011] and [01overline{1}].

  7. Hyperproduction of poly(4-hydroxybutyrate) from glucose by recombinant Escherichia coli

    DEFF Research Database (Denmark)

    Zhou, Xiao-Yun; Yuan, Xiao-Xi; Shi, Zhen-Yu

    2012-01-01

    -hydroxybutyrate) [poly(4HB)] using glucose as a sole carbon source. An engineering pathway was established in E. coli containing genes encoding succinate degradation of Clostridium kluyveri and PHB synthase of Ralstonia eutropha. Native succinate semialdehyde dehydrogenase genes sad and gabD in E. coli were both......) biosynthesis from glucose can be achieved in sad and gabD genes deficient strain of E. coli JM109 harboring an engineering pathway encoding succinate degradation genes and PHB synthase gene, together with expression of four PHA binding proteins PhaP or phasins, respectively. Over 68% poly(4HB) was produced...

  8. Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

    Directory of Open Access Journals (Sweden)

    Qiao H

    2017-02-01

    Full Text Available Hongzhi Qiao,1,2,* Lihua Chen,3,* Tianqi Rui,1,2 Jingxian Wang,1,2 Ting Chen,1,2 Tingming Fu,1,2 Junsong Li,1,2 Liuqing Di1,2 1College of Pharmacy, Nanjing University of Chinese Medicine, 2Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, 3Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China *These authors contributed equally to this work Abstract: Andrographolide (ADG is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS were prepared using a wet media milling technique followed by freeze drying. D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box–Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3, respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability (Papp of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS (P<0.01. Compared to the ADG coarse powder, a physical mixture, commercial dripping pills and ADG-NS without TPGS, ADG-NS exhibited significantly higher plasma exposure with significant enhancements in Cmax

  9. The effects of vitamin E succinate on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells

    Institute of Scientific and Technical Information of China (English)

    Yan Zhao; Kun Wu; Wei Xia; Yu-Juan Shan; Li-Jie Wu; Wei-Ping Yu

    2002-01-01

    AIM: To investigate the effects of vitamin E succinate (VES) on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells.METHODS: After SGC-7901 cells were treated with VES at different doses (5,10,20 mg@L-1) at different time, reverse transcription-PCR technique was used to detect the level of c-jun mRNA; Western Blot was applied to measure the expression of c-jun protei n/RESULTS: After the cells were treated with VES at 20 mg@L-1 for 3 h, the expression rapidly reached its maximum that was 3.5 times of UT control (P<0.01). The level of c-jun mRNA was also increased following treatment of VES for 6 h.However, the expression after treatment of VES at 5 mg@L-1for 24 h was 1.6 times compared with UT control (P<0.01).Western blot analysis showed that the level of c-jun protein was obviously elevated in VES-treated SGC-7901 cells at 20 mg@L-1 for 3 h. The expression of c-jun protein was gradually increased after treatment of VES at 20 mg@L-1 for 3, 6, 12 and 24 h, respectively, with an evident time-effect relationship. CONCLUSION: The levels of c-jun mRNA and protein in VES-treated SGC-7901 cells were increased in a dose- and time-dependent manner; the expression of c-jun was prolonged by VES, indicating that c-jun is involved in VESinduced apoptosis in SGC-7901 cells.

  10. Effects of vitamin E succinate on the expression of Fas and PCNA proteins in human gastric carcinoma cells and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Lan Zhao; Yao Li; Yu-Juan Shan; Li-Jie Wu

    2004-01-01

    AIM: To investigate the effects of vitamin E succinate (VES) on the expression of Fas and PCNA proteins as well as its clinical significance in human gastric carcinoma, and to explore the mechanism of VES-induced inhibition of gastric carcinoma cell growth.METHODS: Immunohistochemical methods were used to detect Fas and PCNA expression both in human gastric cancer SGC-7901 cells treated with VES at different doses and in human gastric carcinoma tissues.RESULTS: After the SGC-7901 cells were treated with VES at 5, 10, 20 mg/L for 48 h, the positive rates of Fas expression were 16%, 27% and 48%, respectively, significantly increased compared to that of control group (P<0.05); while the positive rates of PCNA expression in groups treated with different doses of VES were 20%, 18% and 7%, respectively, which were significantly decreased compared to that of the control group (P<0.05). In human gastric carcinoma tissues, the Fas positive expression rate was 42.4%(25/59), which declined with the decrease in the degree of tumor differentiation (P<0.05) and with the existence of lymph node metastasis (P<0.001). While the PCNA positive expression rate was 91.5%(54/59), no relationship was observed between PCNA expression and clinicopathologic parameters.CONCLUSION: VES inhibited the growth of gastric cancer cells by inducing Fas expression and inhibiting PCNA expression.It is, therefore, considered that the expression of Fas and PCNA genes, through tumor cell apoptosis and proliferation,respectively, may be useful as a clinical predictive index in the application of VES to gastric carcinoma therapy, where as Fas may be of more value than PCNA.

  11. Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol

    Directory of Open Access Journals (Sweden)

    Im-Sook Song

    2016-10-01

    Full Text Available The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 (w/w/w. The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion formulation within 10 min. After administering the formulation orally to rats, higher plasma concentrations of curcumin were observed, with increases in the maximum plasma concentration (Cmax and area under the plasma concentration-time curve (AUC of 86- and 65-fold, respectively, compared with those of curcumin powder. The solid dispersion formulation effectively increased intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion formulation of curcumin with TPGS and mannitol could be a promising option for enhancing the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate, cell permeability, and P-gp modulation.

  12. A novel artemisinin derivative, 3-(12-β-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Wen-liang ZHOU; Yu ZHANG; Ying LI; Jian-ping ZUO; Jin-ming WU; Qing-li WU; Jun-xia WANG; Yu ZHOU; Ru ZHOU; Pei-lan HE; Xiao-yu LI; Yi-fu YANG

    2005-01-01

    Aim: To study the immunosuppressive activity of SM735 { [3-(12-β-artemisininoxy)]phenoxyl succinic acid }, a synthetic artemisinin derivative with nonsteroidal anti-inflammatory drug structure, with the aim of finding potential immunosuppressiveagents. Methods: Concanavalin A (ConA), lipopolysaccharide (LPS), and mixedlymphocyte reaction (MLR), were used to induce the proliferation of splenocytes,and [3H]-thymidine incorporation was used to evaluate the proliferation ofsplenocytes. Cytokine production was promoted with ConA, LPS, or PMA plusionomycin, and was detected with the enzyme-linked immunosorbent assay.Dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC) were used toinduce delayed-type hypersensitivity and quantitative hemolysis of SRBC (QHS)mouse models, as criteria for the evaluation of in vivo immune activity. Results:SM735 strongly inhibited the proliferation of splenocytes induced by ConA, LPS,or MLR, with IC50 values of 0.33 μmol/L, 0.27 μmol/L, and 0.51 μmol/L, respectively.When compared with a CC50 value of 53.1 μmol/L, SM735 had a favorable safetyrange. SM735 dose-dependently inhibited proinflammatory cytokine production[including interleukins (IL)-12, interferon (IFN)-γ and IL-6] induced by LPS orPMA plus ionomycin. Upon ConA stimulation, SM735 suppressed IFN-γ in adose-dependent manner, but did not affect IL-2 secretion. SM735 also stronglysuppressed both T-cell-mediated delayed-type hypersensitivity (DTH) and B-cell-mediated QHS reactions. Conclusion: SM735 had strong immunosuppres-sive activity in vitro and in vivo, suggesting a potential role for SM735 as animmunosuppressive agent, and established the groundwork for further researchon SM735.

  13. Effect of a novel insulinotropic agent, succinic acid monoethyl ester, on lipids and lipoproteins levels in rats with streptozotocin-nicotinamideinduced type 2 diabetes

    Indian Academy of Sciences (India)

    Ramalingam Saravanan; Leelavinothan Pari

    2006-12-01

    In the present study, the effect of succinic acid monoethyl ester (EMS) on the pattern of lipids and lipoproteins in streptozotocin-nicotinamide induced type 2 diabetes was investigated. Type 2 diabetes was induced in male Wistar rats by single intraperitoneal injection (i.p.) of 45 mg/kg streptozotocin, 15 min after the i.p administration of 110 mg/kg body weight of nicotinamide. The carboxylic nutrient EMS was administered intraperitonially at a dose of 8 mol/g body weight for 30 days. At the end of experimental period, the effect of EMS on plasma glucose, insulin, thiobarbituric acid reactive substances (TBARS) and hydroperoxide (HP) and serum triglycerides (TG), phospholipids (PL), free fatty acids (FFA), total cholesterol (TC), very low density lipoprotein-cholesterol (VLDL-C) and low density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and the percentage of antiatherogenic index (AAI) (ratio of HDL-C to total cholesterol) were studied. Administration of EMS to diabetic rats resulted in a significant reduction in the elevated levels of plasma glucose, TBARS and hydroperoxides as well as TG, PL, FFA, TC, VLDL-C and LDC-C levels. The decreased plasma insulin and serum HDL-C and percentage of AAI in diabetic rats were also reversed towards near normal. The effect produced by EMS was compared with metformin, a reference drug. The results indicates that the administration of EMS and metformin to nicotinamide-streptozotocin diabetic rats normalized plasma glucose, insulin concentrations and caused marked improvement in altered lipids, lipoprotein and lipid peroxidation markers during diabetes. Our results show the antihyperlipidemic properties of EMS and metformin in addition to its antidiabetic action. Moreover, the antihyperlipidemic effect could represent a protective mechanism against the development of atherosclerosis.

  14. pH-sensitive nanoparticles of poly(L-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate for anti-tumor drug delivery.

    Science.gov (United States)

    Li, Zhen; Qiu, Lipeng; Chen, Qing; Hao, Tangna; Qiao, Mingxi; Zhao, Haixia; Zhang, Jie; Hu, Haiyang; Zhao, Xiuli; Chen, Dawei; Mei, Lin

    2015-01-01

    A novel pH-sensitive polymer, poly(L-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate (PLH-PLGA-TPGS), was synthesized to design a biocompatible drug delivery system for cancer chemotherapy. The structure of the PLH-PLGA-TPGS copolymer was confirmed by (1)H-NMR, FTIR and GPC. The apparent pKa of the PLH-PLGA-TPGS copolymer was calculated to be 6.33 according to the acid-base titration curve. The doxorubicin (DOX)-loaded nanoparticles (PLH-PLGA-TPGS nanoparticles and PLGA-TPGS nanoparticles) and corresponding blank nanoparticles were prepared by a co-solvent evaporation method. The blank PLH-PLGA-TPGS nanoparticles showed an acidic pH-induced increase in particle size. The DOX-loaded nanoparticles based on PLH-PLGA-TPGS showed a pH-triggered drug-release behavior under acidic conditions. The results of in vitro cytotoxicity experiment on MCF-7 and MCF-7/ADR cells showed that the DOX-loaded PLH-PLGA-TPGS nanoparticles resulted in lower cell viability versus the PLGA-TPGS nanoparticles and free DOX solution. Confocal laser scanning microscopy images showed that DOX-loaded PLH-PLGA-TPGS nanoparticles were internalized by MCF-7/ADR cells after 1 and 4h incubation and most of them accumulated in lysosomes to accelerate DOX release under acidic conditions. In summary, the PLH-PLGA-TPGS nanoparticles have great potential to be used as carriers for anti-tumor drug delivery.

  15. Characterization of mutations in the iron-sulphur subunit of succinate dehydrogenase correlating with Boscalid resistance in Alternaria alternata from California pistachio.

    Science.gov (United States)

    Avenot, H F; Sellam, A; Karaoglanidis, G; Michailides, T J

    2008-06-01

    Thirty-eight isolates of Alternaria alternata from pistachio orchards with a history of Pristine (pyraclostrobin + boscalid) applications and displaying high levels of resistance to boscalid fungicide (mean EC(50) values >500 microg/ml) were identified following mycelial growth tests. A cross-resistance study revealed that the same isolates were also resistant to carboxin, a known inhibitor of succinate dehydrogenase (Sdh). To determine the genetic basis of boscalid resistance in A. alternata the entire iron sulphur gene (AaSdhB) was isolated from a fungicide-sensitive isolate. The deduced amino-acid sequence showed high similarity with iron sulphur proteins (Ip) from other organisms. Comparison of AaSdhB full sequences from sensitive and resistant isolates revealed that a highly conserved histidine residue (codon CAC in sensitive isolates) was converted to either tyrosine (codon TAC, type I mutants) or arginine (codon CGC, type II mutants) at position 277. In other fungal species this residue is involved in carboxamide resistance. In this study, 10 and 5 mutants were of type I and type II respectively, while 23 other resistant isolates (type III mutants) had no mutation in the histidine codon. The point mutation detected in type I mutants was used to design a pair of allele-specific polymerase chain reaction (PCR) primers to facilitate rapid detection. A PCR-restriction fragment length polymorphism (RFLP) assay in which amplified gene fragments were digested with AciI was successfully employed for the diagnosis of type II mutants. The relevance of these modifications in A. alternata AaSdhB sequence in conferring boscalid resistance is discussed.

  16. Development and validation of UV-spectrophotometric methods for the determination of sumatriptan succinate in bulk and pharmaceutical dosage form and its degradation behavior under varied stress conditions

    Directory of Open Access Journals (Sweden)

    Kudige Nagaraj Prashanth

    2014-04-01

    Full Text Available The aim of the present work is to develop sensitive, simple, accurate, precise and cost effective UV-spectrophotometric methods for the determination of sumatriptan succinate (STS, an anti-migraine drug, in bulk and pharmaceutical dosage form; and also to monitor the degradation behavior of the drug under different ICH prescribed stress conditions. Two methods were developed using different solvents, 0.1 M HCl (method A and acetonitrile (method B. The calibration graphs are linear over the range of 0.2–6.0 μg ml−1 in both the methods with a correlation coefficient (r of 0.9999. The apparent molar absorptivity values are 7.59 × 104 and 7.81 × 104 l mol−1 cm−1, for method A and method B, respectively. The other optical characteristics such as Sand