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Sample records for 5a1 succinate semialdehyde

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

    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.

  2. Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) Deficiency

    Di Rosa, G.; Malaspina, P; P. Blasi(INAF Arcetri); Dionisi-Vici, C.; Rizzo, C; Tortorella, G; Crutchfield, S. R.; Gibson, K. M.

    2009-01-01

    In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficie...

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

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

    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. PMID:2864395

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

    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.

  6. Efficacy of Vigabatrin Intervention in a Mild Phenotypic Expression of Succinic Semialdehyde Dehydrogenase Deficiency

    Casarano, M.; Alessandrì, M G.; Salomons, G.S.; E. Moretti; Jakobs, C.; Gibson, K. M.; G. Cioni; Battini, R.

    2011-01-01

    We report a patient with succinic semialdehyde dehydrogenase deficiency who presented a mild phenotype including developmental language delay, in association with the typical elevations of 4-hydroxybutyric acid (GHB) in biological fluids and MRI alterations. Two pathogenic mutations were identified one transversion (c.278 G>T) in exon 1 and another (c.1557 T>G) in exon 10. Both parents are carriers of one of the mutations, confirming compound-heterozygosity in their affected child. To reduce ...

  7. Modeling conformational redox-switch modulation of human succinic semialdehyde dehydrogenase.

    Tamazian, Gaik; Ho Chang, Jeong; Knyazev, Sergey; Stepanov, Eugene; Kim, Kyung-Jin; Porozov, Yuri

    2015-12-01

    Succinic semialdehyde dehydrogenase (SSADH) converts succinic semialdehyde (SSA) to succinic acid in the mitochondrial matrix and is involved in the metabolism of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). The molecular structure of human SSADH revealed the intrinsic regulatory mechanism--redox-switch modulation--by which large conformational changes are brought about in the catalytic loop through disulfide bonding. The crystal structures revealed two SSADH conformations, and computational modeling of transformation between them can provide substantial insights into detailed dynamic redox modulation. On the basis of these two clear crystal structures, we modeled the conformational motion between these structures in silico. For that purpose, we proposed and used a geometry-based coarse-grained mathematical model of long-range protein motion and the related modeling algorithm. The algorithm is based on solving the special optimization problem, which is similar to the classical Monge-Kantorovich mass transportation problem. The modeled transformation was supported by another morphing method based on a completely different framework. The result of the modeling facilitates better interpretation and understanding of the SSADH biological role. PMID:26422261

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

    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.

  9. Saturation transfer difference NMR studies on substrates and inhibitors of succinic semialdehyde dehydrogenases

    Saturation transfer difference (STD) NMR experiments on Escherichia coli and Drosophila melanogaster succinic semialdehyde dehydrogenase (SSADH, EC1.2.1.24) suggest that only the aldehyde forms and not the gem-diol forms of the specific substrate succinic semialdehyde (SSA), of selected aldehyde substrates, and of the inhibitor 3-tolualdehyde bind to these enzymes. Site-directed mutagenesis of the active site cysteine311 to alanine in D. melanogaster SSADH leads to an inactive product binding both SSA aldehyde and gem-diol. Thus, the residue cysteine311 is crucial for their discrimination. STD experiments on SSADH and NAD+/NADP+ indicate differential affinity in agreement with the respective cosubstrate properties. Epitope mapping by STD points to a strong interaction of the NAD+/NADP+ adenine H2 proton with SSADH. Adenine H8, nicotinamide H2, H4, and H6 also show STD signals. Saturation transfer to the ribose moieties is limited to the anomeric protons of E. coli SSADH suggesting that the NAD+/NADP+ adenine and nicotinamide, but not the ribose moieties are important for the binding of the coenzymes

  10. Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency.

    Horvath, Gabriella-Ana; Hukin, Juliette; Stockler-Ipsiroglu, Sylvia G; Aroichane, Maryam

    2016-08-01

    We describe for the first time two patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, who were found to have abnormal electroretinogram (ERG) examinations at baseline, or 6 months after vigabatrin treatment was started. This was somewhat reversible with L-taurine treatment, or minimally progressive. The mechanism of injury to the retina may be induced by elevations of γ-aminobutyric acid causing peripheral photoreceptor and ganglion cell damage, and this can be exacerbated by the use of vigabatrin. The use of taurine supplementation in tandem with vigabatrin may allow reversal of retinopathy and mitigate or slow down further deterioration. Further prospective clinical trials are required to evaluate this further. We recommend starting L-taurine therapy together with vigabatrin if a trial of vigabatrin is commenced in a patient with SSADH deficiency. Close monitoring of visual fields or ERG is also recommended at baseline and during vigabatrin therapy. PMID:27104484

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

    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.

  12. Human brain aldehyde reductases: relationship to succinic semialdehyde reductase and aldose reductase.

    Hoffman, P L; Wermuth, B; von Wartburg, J P

    1980-08-01

    Human brain contains multiple forms of aldehyde-reducing enzymes. One major form (AR3), as previously shown, has properties that indicate its identity with NADPH-dependent aldehyde reductase isolated from brain and other organs of various species; i.e., low molecular weight, use of NADPH as the preferred cofactor, and sensitivity to inhibition by barbiturates. A second form of aldehyde reductase ("SSA reductase") specifically reduces succinic semialdehyde (SSA) to produce gamma-hydroxybutyrate. This enzyme form has a higher molecular weight than AR3, and uses NADH as well as NADPH as cofactor. SSA reductase was not inhibited by pyrazole, oxalate, or barbiturates, and the only effective inhibitor found was the flavonoid quercetine. Although AR3 can also reduce SSA, the relative specificity of SSA reductase may enhance its in vivo role. A third form of human brain aldehyde reductase, AR2, appears to be comparable to aldose reductases characterized in several species, on the basis of its activity pattern with various sugar aldehydes and its response to characteristic inhibitors and activators, as well as kinetic parameters. This enzyme is also the most active in reducing the aldehyde derivatives of biogenic amines. These studies suggest that the various forms of human brain aldehyde reductases may have specific physiological functions. PMID:6778961

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

    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.

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

    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.

  15. The effects of a ketogenic diet on ATP concentrations and the number of hippocampal mitochondria in Aldh5a1−/− mice

    Nylen, Kirk; Velazquez, Jose Luis Perez; Sayed, Venus; Gibson, K. Michael; Burnham, W.M.; Snead, O. Carter

    2009-01-01

    Summary BACKGROUND Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inborn error of GABA metabolism characterized clinically by ataxia, psychomotor retardation and seizures. A mouse model of SSADH deficiency, the Aldh5a1−/− mouse, has been used to study the pathophysiology and treatment of this disorder. Recent work from our group has shown that the ketogenic diet (KD) is effective in normalizing the Aldh5a1−/− phenotype, although the mechanism of the effect remains unclear. METHODS Here, we examine the effects of a KD on the number of hippocampal mitochondria as well as on ATP levels in hippocampus. Electron microscopy was performed to determine the number of mitochondria in the hippocampus of Aldh5a1−/− mice. Adenosine triphosphate (ATP) levels were measured in hippocampal extracts. RESULTS Our results show that the KD increases the number of mitochondria in Aldh5a1−/− mice. We also show that Aldh5a1−/− mice have significant reductions in hippocampal ATP levels as compared to controls, and that the KD restores ATP in mutant mice to normal levels. CONCLUSIONS & GENERAL SIGNIFICANCE Taken together, our data suggest that the KD’s actions on brain mitochondria may play a role in the diet’s ability to treat murine SSADH deficiency. PMID:19168117

  16. Structure Determination and Characterization of the Vitamin B6 Degradative Enzyme 2-(Acetamidomethylene)succinate Hydrolase†‡

    McCulloch, Kathryn M.; Mukherjee, Tathagata; Begley, Tadhg P.; Ealick, Steven E.

    2010-01-01

    The gene identification and kinetic characterization of E-2-(acetamidomethylene)succinate (E-2AMS) hydrolase has recently been described. This enzyme catalyzes the final reaction in the degradation of vitamin B6 and produces succinic semialdehyde, acetate, ammonia, and carbon dioxide from E-2AMS. The structure of E-2AMS hydrolase was determined to 2.3 Å using SAD phasing. E-2AMS hydrolase is a member of the α/β hydrolase superfamily and utilizes a serine/histidine/aspartic acid catalytic tria...

  17. The Succinated Proteome

    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.

  18. Succinic anhydrides from epoxides

    Coates, Geoffrey W.; Rowley, John M.

    2013-07-09

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  19. Succinic anhydrides from epoxides

    Coates, Geoffrey W; Rowley, John M

    2014-12-30

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  20. Structure Determination and Characterization of the Vitamin B[superscript 6] Degradative Enzyme (E)-2-(Acetamidomethylene)succinate Hydrolase

    McCulloch, Kathryn M.; Mukherjee, Tathagata; Begley, Tadhg P.; Ealick, Steven E. (Cornell); (TAM)

    2010-06-22

    The gene identification and kinetic characterization of (E)-2-(acetamidomethylene)succinate (E-2AMS) hydrolase has recently been described. This enzyme catalyzes the final reaction in the degradation of vitamin B{sub 6} and produces succinic semialdehyde, acetate, ammonia, and carbon dioxide from E-2AMS. The structure of E-2AMS hydrolase was determined to 2.3 {angstrom} using SAD phasing. E-2AMS hydrolase is a member of the {alpha}/{beta} hydrolase superfamily and utilizes a serine/histidine/aspartic acid catalytic triad. Mutation of either the nucleophilic serine or the aspartate resulted in inactive enzyme. Mutation of an additional serine residue in the active site causes the enzyme to be unstable and is likely structurally important. The structure also provides insight into the mechanism of hydrolysis of E-2AMS and identifies several potential catalytically important residues.

  1. Synthesis of carbon-14 labeled doxylamine succinate

    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. (author)

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

    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.

  3. Molecular docking and enzymatic evaluation to identify selective inhibitors of aspartate semialdehyde dehydrogenase

    Luniwal, Amarjit; Wang, Lin; Pavlovsky, Alexander; Erhardt, Paul W.; Ronald E. Viola

    2012-01-01

    Microbes that have gained resistance against antibiotics pose a major emerging threat to human health. New targets must be identified that will guide the development of new classes of antibiotics. The selective inhibition of key microbial enzymes that are responsible for the biosynthesis of essential metabolites can be an effective way to counter this growing threat. Aspartate semialdehyde dehydrogenases (ASADHs) produce an early branch point metabolite in a microbial biosynthetic pathway for...

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

    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 of the...... cofactor dissociated from the protein and gave a molecular weight of 46,401-46,418. Acetylenic GABA and NaBH4 were used for protein modification, and they reacted with the native and yellow enzymes but had no effect on the colorless enzyme. Pyridoxal 5'-phosphate bound covalently to the protein after NaBH4...

  5. Production of Succinic Acid for Lignocellulosic Hydrolysates

    Davison, B.H.; Nghiem, J.

    2002-06-01

    The purpose of this Cooperative Research and Development Agreement (CRADA) is to add and test new metabolic activities to existing microbial catalysts for the production of succinic acid from renewables. In particular, they seek to add to the existing organism the ability to utilize xylose efficiently and simultaneously with glucose in mixtures of sugars or to add succinic acid production to another strain and to test the value of this new capability for production of succinic acid from industrial lignocellulosic hydrolyasates. The Contractors and Participant are hereinafter jointly referred to as the 'Parties'. Research to date in succinic acid fermentation, separation and genetic engineering has resulted in a potentially economical process based on the use of an Escherichia coli strain AFP111 with suitable characteristics for the production of succinic acid from glucose. Economic analysis has shown that higher value commodity chemicals can be economically produced from succinic acid based on repliminary laboratory findings and predicted catalytic parameters. The initial target markets include succinic acid itself, succinate salts, esters and other derivatives for use as deicers, solvents and acidulants. The other commodity products from the succinic acid platform include 1,4-butanediol, {gamma}-butyrolactone, 2-pyrrolidinone and N-methyl pyrrolidinone. Current economic analyses indicate that this platform is competitive with existing petrochemical routes, especially for the succinic acid and derivatives. The report presents the planned CRADA objectives followed by the results. The results section has a combined biocatalysis and fermentation section and a commercialization section. This is a nonproprietary report; additional proprietary information may be made available subject to acceptance of the appropriate proprietary information agreements.

  6. Aminoadipate semialdehyde synthase mRNA knockdown reduces the lysine requirement of a mouse hepatic cell line

    a-Aminoadipate d-semialdehyde synthase (AASS) is the bifunctional enzyme containing the lysine a-ketoglutarate reductase (LKR) and saccharopine dehydrogenase activities responsible for the first two steps in the irreversible catabolism of lysine. A rare disease in humans, familial hyperlysinemia, c...

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

    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.

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

    Arachea, Buenafe T; Liu, Xuying; Pavlovsky, Alexander G; Viola, Ronald E

    2010-02-01

    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. PMID:20124701

  9. Role of succinic acid in chemical evolution

    Negron-Mendoza, A.; Ponnamperuma, C.

    1982-01-01

    Succinic acid is converted into other carboxylic acids by ionizing radiation. The results obtained have been correlated with the ready formation of this compound in prebiotic experiments. Its role in biological systems may be related to its prebiotic occurrence.

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

    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.

  11. Cloning and characterization of a gene (msdA) encoding methylmalonic acid semialdehyde dehydrogenase from Streptomyces coelicolor.

    Zhang, Y. X.; Tang, L.; Hutchinson, C R

    1996-01-01

    A homolog of the mmsA gene of Pseudomonas aeruginosa, which encodes methylmalonic acid semialdehyde dehydrogenase (MSDH) and is involved in valine catabolism in pseudomonads and mammals, was cloned and sequenced from Streptomyces coelicolor. Of the two open reading frames (ORFs) found, which are convergently transcribed and separated by a 62-nucleotide noncoding region, the deduced amino acid sequence of the msdA ORF (homologous to mmsA) is similar to a variety of prokaryotic and eukaryotic a...

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

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine; Duchampt, Adeline; Bäckhed, Fredrik; Mithieux, Gilles

    2016-07-12

    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. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN. PMID:27411015

  13. 2-Amino-5-bromopyridinium hydrogen succinate

    Hoong-Kun Fun

    2010-03-01

    Full Text Available In the title compound, C5H6BrN2+·C4H5O4−, the pyridine N atom of the 2-amino-5-bromopyridine molecule is protonated. The protonated N atom and the amino group are linked via N—H...O hydrogen bonds to the carboxylate O atoms of the singly deprotonated succinate anion. The hydrogen succinate anions are linked via O—H...O hydrogen bonds. A weak intermolecular C—H...O hydrogen bond is also observed.

  14. Molecular docking and enzymatic evaluation to identify selective inhibitors of aspartate semialdehyde dehydrogenase.

    Luniwal, Amarjit; Wang, Lin; Pavlovsky, Alexander; Erhardt, Paul W; Viola, Ronald E

    2012-05-01

    Microbes that have gained resistance against antibiotics pose a major emerging threat to human health. New targets must be identified that will guide the development of new classes of antibiotics. The selective inhibition of key microbial enzymes that are responsible for the biosynthesis of essential metabolites can be an effective way to counter this growing threat. Aspartate semialdehyde dehydrogenases (ASADHs) produce an early branch point metabolite in a microbial biosynthetic pathway for essential amino acids and for quorum sensing molecules. In this study, molecular modeling and docking studies were performed to achieve two key objectives that are important for the identification of new selective inhibitors of ASADH. First, virtual screening of a small library of compounds was used to identify new core structures that could serve as potential inhibitors of the ASADHs. Compounds have been identified from diverse chemical classes that are predicted to bind to ASADH with high affinity. Next, molecular docking studies were used to prioritize analogs within each class for synthesis and testing against representative bacterial forms of ASADH from Streptococcus pneumoniae and Vibrio cholerae. These studies have led to new micromolar inhibitors of ASADH, demonstrating the utility of this molecular modeling and docking approach for the identification of new classes of potential enzyme inhibitors. PMID:22464683

  15. 21 CFR 520.784 - Doxylamine succinate tablets.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  16. The effect of alpha-tocopheryl succinate on succinate respiration in rat liver mitochondria

    Sobotka, O.; Drahota, Zdeněk; Kučera, O.; Endlicher, R.; Rauchová, Hana; Červinková, Z.

    2015-01-01

    Roč. 64, Suppl.5 (2015), S609-S615. ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : tocopheryl succinate * Complex II * liver * mitochondria * homogenate * hepatocytes Subject RIV: ED - Physiology Impact factor: 1.293, year: 2014

  17. Is the COL5A1 rs12722 Gene Polymorphism Associated with Running Economy?

    Bertuzzi, Rômulo; Pasqua, Leonardo A.; Bueno, Salomão; Lima-Silva, Adriano Eduardo; Matsuda, Monique; Marquezini, Monica; Saldiva, Paulo H.

    2014-01-01

    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 ...

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

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

    Bertuzzi, Rômulo; Pasqua, Leonardo A; Bueno, Salomão; Lima-Silva, Adriano Eduardo; Matsuda, Monique; Marquezini, Monica; Saldiva, Paulo H

    2014-01-01

    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. PMID:25188268

  20. Is the COL5A1 rs12722 Gene Polymorphism Associated with Running Economy?

    Bertuzzi, Rômulo; Pasqua, Leonardo A.; Bueno, Salomão; Lima-Silva, Adriano Eduardo; Matsuda, Monique; Marquezini, Monica; Saldiva, Paulo H.

    2014-01-01

    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. PMID:25188268

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

    2015-01-01

    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.

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

    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.

  3. Materials and methods for efficient succinate and malate production

    Jantama, Kaemwich; Haupt, Mark John; Zhang, Xueli; Moore, Jonathan C; Shanmugam, Keelnatham T; Ingram, Lonnie O'Neal

    2014-04-08

    Genetically engineered microorganisms have been constructed to produce succinate and malate in mineral salt media in pH-controlled batch fermentations without the addition of plasmids or foreign genes. The subject invention also provides methods of producing succinate and malate comprising the culture of genetically modified microorganisms.

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

    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.

  5. Biodegradable polyesters based on succinic acid

    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

  6. Efficient, Antibiotic Marker-Free Transformation of a Dicot and a Monocot Crop with Glutamate 1-Semialdehyde Aminotransferase Selectable Marker Genes.

    Ferradini, Nicoletta; Giancaspro, Angelica; Nicolia, Alessandro; Gadaleta, Agata; Veronesi, Fabio; Rosellini, Daniele

    2016-01-01

    Antibiotic-free, efficient in vitro selection in plant genetic engineering can improve risk perception and speed up pre-market scrutiny of genetically modified crops. We provide a protocol for genetic transformation of two important crops, durum wheat and alfalfa, using a bacterial and a plant-derived selectable marker gene encoding mutated, gabaculine-insensitive glutamate 1-semialdehyde aminotransferase (GSA) enzymes. These methods can potentially be applied, with minor adaptations, to many other monocot and dicot crop plants. PMID:26614283

  7. FORMULATION AND EVALUATION OF METAPROLOL SUCCINATE EXTENDED RELEASE PELLETS

    Ahishek Perumalla; Manivannan, R.; Nelluri Rama Rao; M. Radhakrishna; Devareddy Sandeep

    2012-01-01

    The aim and of the present study is to develop a pharmaceutically stable and quality improved formulation of Metoprolol succinate extended release pellets. To achieve this goal various prototype formulation trials were formulated and the evaluated with respect to the various quality controls such as dissolution, assay and stability studies will be under taken. Metoprolol succinate is used in the treatment of hyper tension, angina pectoris (chest pain) and myocardial infarction. The study was...

  8. Hydroxypropyl Methylcellulose Acetate Succinate: Potential Drug–Excipient Incompatibility

    Dong, Zedong; Choi, Duk Soon

    2008-01-01

    The stability of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and its potential incompatibility with active pharmaceutical ingredients (API) carrying hydroxyl group(s) were investigated in this research. HPMC-AS may undergo hydrolysis under harsh processing conditions with the generation of succinic acid and acetic acid, which can form ester bond(s) with the hydroxyl group(s) in API. In this case, the hot-melt extrusion (HME) product prepared from HPMC-AS and our model compound (...

  9. Economical succinic acid production from cane molasses by Actinobacillus succinogenes.

    Liu, Yu-Peng; Zheng, Pu; Sun, Zhi-Hao; Ni, Ye; Dong, Jin-Jun; Zhu, Lei-Lei

    2008-04-01

    In this work, production of succinic acid by Actinobacillus succinogenes CGMCC1593 using cane molasses as a low cost carbon source was developed. In anaerobic bottles fermentation, succinic acid concentration of 50.6+/-0.9 g l(-1) was attained at 60 h using an optimum medium containing molasses pretreated with sulfuric acid, resulting in a succinic acid yield of 79.5+/-1.1% and sugar utilization of 97.1+/-0.6%. When batch fermentation was carried out in a 5-l stirred bioreactor with pretreated molasses, 46.4 g l(-1) of succinic acid was attained at 48 h and faster cells growth was also observed. Fed batch fermentation was performed to minimize the substrate (sugar) inhibition effect, giving 55.2 g l(-1) of succinic acid and 1.15 g l(-1)h(-1) of productivity at 48 h. The present study suggests that the inexpensive cane molasses could be utilized for the economical and efficient production of succinic acid by A. succinogenes. PMID:17532626

  10. Bitterness of glucose/galactose: novel mutations in the SLC5A1 gene.

    Pode-Shakked, Ben; Reish, Orit; Aktuglu-Zeybek, Cigdem; Kesselman, Dafna; Dekel, Benjamin; Bujanover, Yoram; Anikster, Yair

    2014-01-01

    Glucose galactose malabsorption (GGM) is a rare autosomal recessive disorder characterized by life-threatening osmotic diarrhea at infancy. When the intake of the offending sugars (namely, glucose, galactose and lactose) is ceased, the diarrhea promptly stops. Mutations in the SLC5A1 gene, encoding the sodium-glucose co-transporter located in the brush border of enterocytes, have been shown to cause the disease. More than 300 subjects of diverse origin have been reported worldwide, most of whom are a result of a consanguineous union. We examined 6 patients from 4 families presenting with complaints consistent with GGM and responsive to the appropriate fructose-based diet. Genomic DNA of the patients was polymerase chain reaction amplified for each of the 15 exons of the SLC5A1 gene and analyzed by nucleotide sequencing. The analysis lead to the identification of 2 novel mutations: a 1915 del C mutation, a frameshift mutation leading to a premature stop at codon 645; and a substitution missense mutation of T to C on nucleotide 947 (exon 9) causing a L316P substitution. In addition, G426R and C255W mutations previously described were identified; in both cases, the patients were shown to be homozygous and their parents heterozygous for the mutation. Of note, additional patients who underwent a similar evaluation at our center for suspected GGM did not show mutations in the SLC5A1 gene. Because the latter did not previously undergo a diagnostic algorithm in full, for instance, one that may consist of a glucose breath hydrogen test and an empiric attempt of a dietary switch to galactomin, we suggest that molecular genotyping of such patients should only follow such appropriate clinical evaluation. PMID:24048166

  11. Recent advances in production of succinic acid from lignocellulosic biomass.

    Akhtar, Junaid; Idris, Ani; Abd Aziz, Ramlan

    2014-02-01

    Production of succinic acid via separate enzymatic hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) are alternatives and are environmentally friendly processes. These processes have attained considerable positions in the industry with their own share of challenges and problems. The high-value succinic acid is extensively used in chemical, food, pharmaceutical, leather and textile industries and can be efficiently produced via several methods. Previously, succinic acid production via chemical synthesis from petrochemical or refined sugar has been the focus of interest of most reviewers. However, these expensive substrates have been recently replaced by alternative sustainable raw materials such as lignocellulosic biomass, which is cheap and abundantly available. Thus, this review focuses on succinic acid production utilizing lignocellulosic material as a potential substrate for SSF and SHF. SSF is an economical single-step process which can be a substitute for SHF - a two-step process where biomass is hydrolyzed in the first step and fermented in the second step. SSF of lignocellulosic biomass under optimum temperature and pH conditions results in the controlled release of sugar and simultaneous conversion into succinic acid by specific microorganisms, reducing reaction time and costs and increasing productivity. In addition, main process parameters which influence SHF and SSF processes such as batch and fed-batch fermentation conditions using different microbial strains are discussed in detail. PMID:24292125

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

    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.

  13. Genetic and Biochemical Characterization of 4-Carboxy-2-Hydroxymuconate-6-Semialdehyde Dehydrogenase and Its Role in the Protocatechuate 4,5-Cleavage Pathway in Sphingomonas paucimobilis SYK-6

    Masai, Eiji; Momose, Kiyotaka; Hara, Hirofumi; Nishikawa, Seiji; Katayama, Yoshihiro; Fukuda, Masao

    2000-01-01

    Protocatechuate (PCA) is the key intermediate metabolite in the lignin degradation pathway of Sphingomonas paucimobilis SYK-6 and is metabolized to pyruvate and oxaloacetate via the PCA 4,5-cleavage pathway. We characterized the 4-carboxy-2-hydroxymuconate-6-semialdehyde (CHMS) dehydrogenase gene (ligC). CHMS is the 4,5-cleavage product of PCA and is converted into 2-pyrone-4,6-dicarboxylate (PDC) by LigC. We found that ligC was located 295 bp downstream of ligB, which encodes the large subun...

  14. Mutant E. coli strain with increased succinic acid production

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2001-09-25

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  15. Disease: H00835 [KEGG MEDICUS

    Full Text Available ient in affected individuals impairing the formation of succinic acid from succinic s...ettiford JM, Jakobs C, Theodore WH Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. J Inherit Metab Dis 32:343-52 (2009) ... ...H00835 Succinic semialdehyde dehydrogenase (SSADH) deficiency; 4-Hydroxybutyric aciduria (4-HBA) Succinic... semialdehyde dehydrogenase (SSADH) deficiency, also known as 4-hydroxybutyric aciduri...a (4-HBA), is an autosomal recessive inborn error of metabolism. Clinical features include intellectual disa

  16. Biophysical properties of phenyl succinic acid derivatised hyaluronic acid

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

    2010-01-01

    Modification of hyaluronic acid (HA) with aryl succinic anhydrides results in new biomedical properties of HA as compared to non-modified HA, such as more efficient skin penetration, stronger binding to the skin, and the ability to blend with hydrophobic materials. In the present study, hyaluronic...

  17. FORMULATION AND EVALUATION OF METAPROLOL SUCCINATE EXTENDED RELEASE PELLETS

    Ahishek Perumalla

    2012-11-01

    Full Text Available The aim and of the present study is to develop a pharmaceutically stable and quality improved formulation of Metoprolol succinate extended release pellets. To achieve this goal various prototype formulation trials were formulated and the evaluated with respect to the various quality controls such as dissolution, assay and stability studies will be under taken. Metoprolol succinate is used in the treatment of hyper tension, angina pectoris (chest pain and myocardial infarction. The study was undertaken with an aim to formulate Metoprolol succinate extended release pellets. The optimized batch MSER CF7 is made up of 7% wetting agent and 4.5% binder. The evaluation tests that were conducted for the pellets also showed satisfactory results.The best trial was optimized by comparing the drug release profile with the innovator and the MSER F7 showed better results compared to the other formulations and the evaluation studies were conducted for the MSER F7. It showed good results in formulation of stable dose.The pellets were evaluated for the flow properties, sieve analysis and accelerated stability studies for 3months. The pellets showed good flow properties and also showed uniform size which indicates uniform coating.Finally we concluded that the Metoprolol succinate pellets MSER F7 are prepared and these showed good physico-chemical properties and the dissolution results showed satisfactory results when compared with the innovator drug.

  18. Evidence for a Dual Role of an Active Site Histidine in [alpha]-Amino-[beta]-carboxymuconate-[epsilon]-semialdehyde Decarboxylase

    Huo, Lu; Fielding, Andrew J.; Chen, Yan; Li, Tingfeng; Iwaki, Hiroaki; Hosler, Jonathan P.; Chen, Lirong; Hasegawa, Yoshie; Que, Jr., Lawrence; Liu, Aimin (GSU); (Kansai); (UMMC); (UMM)

    2012-10-09

    The previously reported crystal structures of {alpha}-amino-{beta}-carboxymuconate-{epsilon}-semialdehyde decarboxylase (ACMSD) show a five-coordinate Zn(II)(His){sub 3}(Asp)(OH{sub 2}) active site. The water ligand is H-bonded to a conserved His228 residue adjacent to the metal center in ACMSD from Pseudomonas fluorescens (PfACMSD). Site-directed mutagenesis of His228 to tyrosine and glycine in this study results in a complete or significant loss of activity. Metal analysis shows that H228Y and H228G contain iron rather than zinc, indicating that this residue plays a role in the metal selectivity of the protein. As-isolated H228Y displays a blue color, which is not seen in wild-type ACMSD. Quinone staining and resonance Raman analyses indicate that the blue color originates from Fe(III)-tyrosinate ligand-to-metal charge transfer. Co(II)-substituted H228Y ACMSD is brown in color and exhibits an electron paramagnetic resonance spectrum showing a high-spin Co(II) center with a well-resolved {sup 59}Co (I = 7/2) eight-line hyperfine splitting pattern. The X-ray crystal structures of as-isolated Fe-H228Y (2.8 {angstrom}) and Co-substituted (2.4 {angstrom}) and Zn-substituted H228Y (2.0 {angstrom} resolution) support the spectroscopic assignment of metal ligation of the Tyr228 residue. The crystal structure of Zn-H228G (2.6 {angstrom}) was also determined. These four structures show that the water ligand present in WT Zn-ACMSD is either missing (Fe-H228Y, Co-H228Y, and Zn-H228G) or disrupted (Zn-H228Y) in response to the His228 mutation. Together, these results highlight the importance of His228 for PfACMSD's metal specificity as well as maintaining a water molecule as a ligand of the metal center. His228 is thus proposed to play a role in activating the metal-bound water ligand for subsequent nucleophilic attack on the substrate.

  19. Succinate dehydrogenase subunit D and succinate dehydrogenase subunit B mutation analysis in canine phaeochromocytoma and paraganglioma.

    Holt, D E; Henthorn, P; Howell, V M; Robinson, B G; Benn, D E

    2014-07-01

    Phaeochromocytomas (PCs) are tumours of the adrenal medulla chromaffin cells. Paragangliomas (PGLs) arise in sympathetic ganglia (previously called extra-adrenal PCs) or in non-chromaffin parasympathetic ganglia cells that are usually non-secretory. Parenchymal cells from these tumours have a common embryological origin from neural crest ectoderm. Several case series of canine PCs and PGLs have been published and a link between the increased incidence of chemoreceptor neoplasia in brachycephalic dog breeds and chronic hypoxia has been postulated. A similar link to hypoxia in man led to the identification of germline heterozygous mutations in the gene encoding succinate dehydrogenase subunit D (SDHD) and subsequently SDHA, SDHB and SDHC in similar tumours. We investigated canine PCs (n = 6) and PGLs (n = 2) for SDHD and SDHB mutations and in one PGL found a somatic SDHD mutation c.365A>G (p.Lys122Arg) in exon 4, which was not present in normal tissue from this brachycephalic dog. Two PCs were heterozygous for both c.365A>G (p.Lys122Arg) mutation and an exon 3 silent variant c.291G>A. We also identified the heterozygous SDHB exon 2 mutation c.113G>A (p.Arg38Gln) in a PC. These results illustrate that genetic mutations may underlie tumourigenesis in canine PCs and PGLs. The spontaneous nature of these canine diseases and possible association of PGLs with hypoxia in brachycephalic breeds may make them an attractive model for studying the corresponding human tumours. PMID:24813157

  20. A novel organic nonlinear optical crystal: Creatininium succinate

    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

  1. Internal electron transfer within mitochondrial succinate-cytochrome C reductase

    Internal electron transfer within succinate-cytochrome C reductase from pigeon breast muscle mitochondria was followed by the pulse radiolytic technique. The electron equivalent is transferred from an unknown donor to b type cytochrome(s), in a first order process with a rate constant of: 660 +- 150s-1. This process might be the rate determining step of electron transfer in mitochondria, since it is similar in rate to the turnover number of the mitochondrial respiratory chain

  2. Molecular properties of succinate dehydrogenase isolated from Micrococcus luteus (lysodeikticus).

    Crowe, B A; Owen, P.(Imperial College London, London, United Kingdom)

    1983-01-01

    Succinate dehydrogenase (EC 1.3.99.1) of Micrococcus luteus was selectively precipitated from Triton X-100-solubilized membranes by using specific antiserum. The precipitated enzyme contained equimolar amounts of four polypeptides with apparent molecular weights of 72,000, 30,000, 17,000, and 15,000. The 72,000 polypeptide possessed a covalently bound flavin prosthetic group and appeared to be strongly antigenic as judged by immunoprinting experiments. Low-temperature absorption spectroscopy ...

  3. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency.

    Ehinger, Johannes K; Piel, Sarah; Ford, Rhonan; Karlsson, Michael; Sjövall, Fredrik; Frostner, Eleonor Åsander; Morota, Saori; Taylor, Robert W; Turnbull, Doug M; Cornell, Clive; Moss, Steven J; Metzsch, Carsten; Hansson, Magnus J; Fliri, Hans; Elmér, Eskil

    2016-01-01

    Mitochondrial complex I (CI) deficiency is the most prevalent defect in the respiratory chain in paediatric mitochondrial disease. This heterogeneous group of diseases includes serious or fatal neurological presentations such as Leigh syndrome and there are very limited evidence-based treatment options available. Here we describe that cell membrane-permeable prodrugs of the complex II substrate succinate increase ATP-linked mitochondrial respiration in CI-deficient human blood cells, fibroblasts and heart fibres. Lactate accumulation in platelets due to rotenone-induced CI inhibition is reversed and rotenone-induced increase in lactate:pyruvate ratio in white blood cells is alleviated. Metabolomic analyses demonstrate delivery and metabolism of [(13)C]succinate. In Leigh syndrome patient fibroblasts, with a recessive NDUFS2 mutation, respiration and spare respiratory capacity are increased by prodrug administration. We conclude that prodrug-delivered succinate bypasses CI and supports electron transport, membrane potential and ATP production. This strategy offers a potential future therapy for metabolic decompensation due to mitochondrial CI dysfunction. PMID:27502960

  4. Study of exon 12 polymorphism of the human thromboxane synthase (CYP5A1) gene in Egyptian stroke patients

    Thromboxane synthase (CYP5A1) catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent mediator of platelet aggregation, vasoconstriction and bronchoconstriction. It has been implicated in the patho-physiological process of a variety of diseases, such as atherosclerosis, myocardial infarction, stroke and asthma. On the basis of the hypothesis that variations of the CYP5A1 gene may play an important role in human diseases, we performed screening for the prevalence of exon12 polymorphism of the human Thromboxane synthase (CYP5A1) gene among Egyptian normal and stroke patients. Using sequence-specific PCR, we examined the allelic prevalence in 70 Egyptian patients with ischemic strokes and in 70 controls. In addition, we compared the CYP5A1 allelic prevalence in 30 patients with stroke recurrence despite Aspirin use, in comparison with patients who have not experienced recurrent stroke while taking Aspirin. The frequencies of the CYP5A1*9 mutant (substitution of guanine by adenine near the heme-binding catalytic domain) and of the wild-type allele were 0.197(19.7%) and 0.803 (80.3%) respectively; they did not differ significantly between stroke patients and controls. The CYP5A1*9 mutant was significantly more prevalent among stroke patients with history of previous cerebrovascular attacks; even after adjusting for the common risk factors for cardiovascular disease (odds ratio (OR)1.73, 95%, confidence interval ( CI) 1.10-2.73; p=0.017). Among stroke patients, the presence of the CYP5A1 wild type allele was more frequent among the hypertensives (OR 1.68, 95% CI, 1.01-2.79; p=0.045), and less frequent among the diabetics (OR 0.55, 95%, CI 0.36-0.84; p=0.006). Also among stroke patients, the CYP5A1*9 mutant was significantly more prevalent among those, who failed secondary Aspirin prophylaxis compared to those with successful secondary Aspirin prophylaxis (OR 1.49, 95%, CI 1.06-2.11). This study provides evidence for high prevalence of the CYP5A1*9 mutant

  5. Tryptophan depletion and formation of alpha-aminoadipic and gamma-glutamic semialdehydes in porcine burger patties with added phenolic-rich fruit extracts.

    Ganhão, Rui; Morcuende, David; Estévez, Mario

    2010-03-24

    The effect of added fruit extracts on the oxidation of muscle proteins in porcine burger patties subjected to cooking and chill storage was studied. Extracts from arbutus berries (Arbutus unedo L., AU), common hawthorns (Crataegus monogyna L., CM), dog roses (Rosa canina L., RC), and elm-leaf blackberries (Rubus ulmifolius Schott, RU) were prepared, characterized, added to burger patties (3% of total weight), and evaluated as inhibitors of protein oxidation. Negative (no added extract, C) and positive control (added quercetin, 230 mg/kg, Q) groups were also included in the design. Protein oxidation was assessed by means of tryptophan loss using fluorescence spectroscopy (FS) and formation of the specific protein carbonyls alpha-aminoadipic (AAS) and gamma-glutamic semialdehyde (GGS) using liquid chromatography and mass spectroscopy (LC-MS). Both advanced methodologies (FS and LC-MS) were found to be reliable and specific protein oxidation measurements that allow us to gain chemical insight into protein oxidation. The mechanisms likely involved in the oxidative reactions affecting proteins during cooking and storage of burger patties are profusely discussed. Phenolic-rich fruit extracts protected tryptophan residues against oxidation and inhibited the formation of both semialdehydes in burger patties during cooking and subsequent chill storage. In general, RC, RU, and AU were the most effective inhibitors of protein oxidation, with this effect being more intense than that of pure polyphenols like quercetin. These fruit extracts could be considered functional ingredients as their antioxidant actions contribute to the enhancement of the nutritional value of the meat products. PMID:20170109

  6. Succinic acid production with metabolically engineered E. coli recovered from two-stage fermentation.

    Ma, Jiang-Feng; Jiang, Min; Chen, Ke-Quan; Xu, Bing; Liu, Shu-Wen; Wei, Ping; Ying, Han-Jie

    2010-10-01

    Escherichia coli AFP111 cells recovered from spent two-stage fermentation broth were investigated for additional production of succinic acid under anaerobic conditions. Recovered cells produced succinic acid in an aqueous environment with no nutrient supplementation except for glucose and MgCO(3). In addition, initial glucose concentration and cell density had a significant influence on succinic acid mass yield and productivity. Although the final concentration of succinic acid from recovered cells was lower than from two-stage fermentation, an average succinic acid mass yield of 0.85 g/g was achieved with an average productivity of 1.81 g/l h after three rounds of recycling, which was comparable to two-stage fermentation. These results suggested that recovered cells might be reused for the efficient production of succinic acid. PMID:20495946

  7. Synthesis and characterization of novel poly(butylene succinate-co-2-methyl-1,3-propylene succinates

    2011-04-01

    Full Text Available Poly(butylene succinate (PBSu, poly(2-methyl-1,3-propylene succinate (PMPSu, and PBSu-rich copolyesters were synthesized using an effective catalyst, titanium tetraisopropoxide. Measurements of intrinsic viscosity (1.20–1.28 dl/g and gel permeation chromatography demonstrated the success of the preparation of polyesters with high molecular weights. The compositions of the copolyesters were determined in three approaches from 1H and 13C NMR (nuclear magnetic resonance analyses, and good agreement between the results was obtained. The distributions of the comonomers were found to be random from the spectra of carbonyl carbon. Their thermal properties were elucidated using a differential scanning calorimeter and a thermogravimetric analyzer. No marked difference exists among the thermal stabilities of these polyesters. However, the window between the glass transition and the melting temperatures becomes narrower with the increase in the concentration of 2-methyl-1,3-propylene succinate in the copolymers. Additionally, the cold crystallization ability decreases considerably. Finally, PMPSu is an amorphous homopolymer. Wide-angle X-ray diffractograms of isothermally crystallized copolyesters also follow the same trend.

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

    Hardik Patel* and M. M. Patel

    2012-01-01

    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 ad...

  9. Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation in COL5A1.

    Monroe, Glen R; Harakalova, Magdalena; van der Crabben, Saskia N; Majoor-Krakauer, Danielle; Bertoli-Avella, Aida M; Moll, Frans L; Oranen, Björn I; Dooijes, Dennis; Vink, Aryan; Knoers, Nine V; Maugeri, Alessandra; Pals, Gerard; Nijman, Isaac J; van Haaften, Gijs; Baas, Annette F

    2015-06-01

    Different forms of Ehlers-Danlos syndrome (EDS) exist, with specific phenotypes and associated genes. Vascular EDS, caused by heterozygous mutations in the COL3A1 gene, is characterized by fragile vasculature with a high risk of catastrophic vascular events at a young age. Classic EDS, caused by heterozygous mutations in the COL5A1 or COL5A2 genes, is characterized by fragile, hyperextensible skin and joint laxity. To date, vessel rupture in four unrelated classic EDS patients with a confirmed COL5A1 mutation has been reported. We describe familial occurrence of a phenotype resembling vascular EDS in a mother and her two sons, who all died at an early age from arterial ruptures. Diagnostic Sanger sequencing in the proband failed to detect aberrations in COL3A1, COL1A1, COL1A2, TGFBR1, TGFBR2, SMAD3, and ACTA2. Next, the proband's DNA was analyzed using a next-generation sequencing approach targeting 554 genes linked to vascular disease (VASCULOME project). A novel heterozygous mutation in COL5A1 was detected, resulting in an essential glycine substitution at the C-terminal end of the triple helix domain (NM_000093.4:c.4610G>T; p.Gly1537Val). This mutation was also present in DNA isolated from autopsy material of the index's brother. No material was available from the mother, but the mutation was excluded in her parents, siblings and in the father of her sons, suggesting that the COL5A1 mutation occurred in the mother's genome de novo. In conclusion, we report familial occurrence of lethal arterial events caused by a COL5A1 mutation. PMID:25845371

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

    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. PMID:25491999

  11. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    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... propylene glycol hydrogen succinate). The food additive succistearin (stearoyl propylene glycol...

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

    Carrozzo, Rosalba; Verrigni, Daniela; Rasmussen, Magnhild; de Coo, Rene; Amartino, Hernan; Bianchi, Marzia; Buhas, Daniela; Mesli, Samir; Naess, Karin; Born, Alfred Peter; Woldseth, Berit; Prontera, Paolo; Batbayli, Mustafa; Ravn, Kirstine; Joensen, Fróði; Cordelli, Duccio M; Santorelli, Filippo Maria; Tulinius, Mar; Darin, Niklas; Duno, Morten; Jouvencel, Philippe; Burlina, Alberto; Stangoni, Gabriela; Bertini, Enrico; Redonnet-Vernhet, Isabelle; Wibrand, Flemming; Dionisi-Vici, Carlo; Uusimaa, Johanna; Vieira, Paivi; Osorio, Andrés Nascimento; McFarland, Robert; Taylor, Robert W; Holme, Elisabeth; Ostergaard, Elsebet

    2016-01-01

    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 findin...

  13. Metabolic evolution of energy-conserving pathways for succinate production in Escherichia coli

    Zhang, Xueli; Jantama, Kaemwich; Moore, Jonathan C.; Jarboe, Laura R.; Shanmugam, Keelnatham T.; Lonnie O. Ingram

    2009-01-01

    During metabolic evolution to improve succinate production in Escherichia coli strains, significant changes in cellular metabolism were acquired that increased energy efficiency in two respects. The energy-conserving phosphoenolpyruvate (PEP) carboxykinase (pck), which normally functions in the reverse direction (gluconeogenesis; glucose repressed) during the oxidative metabolism of organic acids, evolved to become the major carboxylation pathway for succinate production. Both PCK enzyme acti...

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

    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. PMID:27487822

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

    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...

  16. Simultaneous saccharification and fermentation of cassava to succinic acid by Escherichia coli NZN111.

    Chen, Cuixia; Ding, Shaopeng; Wang, Dezheng; Li, Zhimin; Ye, Qin

    2014-07-01

    In this study, the production of succinic acid from cassava starch and raw cassava instead of glucose by Escherichia coli NZN111 was investigated. During the two-stage fermentation, simultaneous saccharification and fermentation (SSF) was applied in the anaerobic stage. The results showed that both the productivity and specific productivity in the process conducted at 40°C were higher than those in the cultivation conducted at 37°C. The yield of succinic acid based on the amount of added starch reached the highest level 0.86 g/g and cassava starch was almost totally hydrolyzed in the SSF process. With the improved cell density, 127.13 g/L of succinic acid was obtained. When the liquefied crude cassava powder was used directly in SSF, 106.17 g/L of succinic acid was formed. The result showed that crude cassava powder could be another cheap raw material for succinic acid formation. PMID:24787322

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

    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. PMID:25682224

  18. Succinic Acid Production from Lignocellulosic Hydrolysate by Basfia succiniciproducens

    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.

  19. Enhanced performance of alkylated graphene reinforced polybutylene succinate nanocomposite

    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.

  20. Succinic acid production from lignocellulosic hydrolysate by Basfia succiniciproducens.

    Salvachúa, Davinia; Smith, Holly; St 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 60g/L reached up to 30g/L, with metabolic yields of 0.69g/g, and an overall productivity of 0.43g/L/h. These results demonstrate that B. succiniciproducens may be an attractive platform organism for bio-SA production from biomass hydrolysates. PMID:27179951

  1. Cardiac-specific succinate dehydrogenase deficiency in Barth syndrome.

    Dudek, Jan; Cheng, I-Fen; Chowdhury, Arpita; Wozny, Katharina; Balleininger, Martina; Reinhold, Robert; Grunau, Silke; Callegari, Sylvie; Toischer, Karl; Wanders, Ronald Ja; Hasenfuß, Gerd; Brügger, Britta; Guan, Kaomei; Rehling, Peter

    2015-01-01

    Barth syndrome (BTHS) is a cardiomyopathy caused by the loss of tafazzin, a mitochondrial acyltransferase involved in the maturation of the glycerophospholipid cardiolipin. It has remained enigmatic as to why a systemic loss of cardiolipin leads to cardiomyopathy. Using a genetic ablation of tafazzin function in the BTHS mouse model, we identified severe structural changes in respiratory chain supercomplexes at a pre-onset stage of the disease. This reorganization of supercomplexes was specific to cardiac tissue and could be recapitulated in cardiomyocytes derived from BTHS patients. Moreover, our analyses demonstrate a cardiac-specific loss of succinate dehydrogenase (SDH), an enzyme linking the respiratory chain with the tricarboxylic acid cycle. As a similar defect of SDH is apparent in patient cell-derived cardiomyocytes, we conclude that these defects represent a molecular basis for the cardiac pathology in Barth syndrome. PMID:26697888

  2. Formulation and evaluation of nasal mucoadhesive microspheres of sumatriptan succinate.

    Jain, Snehal A; Chauk, Dheeraj S; Mahajan, Hitendra S; Tekade, Avinash R; Gattani, Surendra G

    2009-12-01

    The purpose of present research work was to develop mucoadhesive microspheres for nasal delivery with the aim to avoid hepatic first-pass metabolism, improve therapeutic efficacy and enhance residence time. For the treatment of migraine, hydroxypropyl methylcellulose (HPMC) K4M and K15M based microspheres containing sumatriptan succinate (SS) were prepared by spray-drying technique. The microspheres were evaluated with respect to the yield, particle size, incorporation efficiency, swelling property, in vitro mucoadhesion, in vitro drug release, histological study and stability. Microspheres were characterized by differential scanning calorimetry, scanning electron microscopy and X-ray diffraction study. It was found that the particle size, swelling ability and incorporation efficiency of microspheres increases with increasing drug-to-polymer ratio. HPMC-based microspheres show adequate mucoadhesion and do not have any destructive effect on nasal mucosa. On the basis of these results, SS microspheres based on HPMC may be considered as a promising nasal delivery system. PMID:19888880

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

    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.

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

    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.

  5. Effects of dissolved CO2 levels on the growth of Mannheimia succiniciproducens and succinic acid production.

    Song, Hyohak; Lee, Jeong Wook; Choi, Sol; You, Jong Kyun; Hong, Won Hi; Lee, Sang Yup

    2007-12-15

    A capnophilic rumen bacterium Mannheimia succiniciproducens produces succinic acid as a major fermentation end product under CO(2)-rich anaerobic condition. Since succinic acid is produced by carboxylation of C3 compounds during the fermentation, intracellular CO(2) availability is important for efficient succinic acid formation. Here, we investigated the metabolic responses of M. succiniciproducens to the different dissolved CO(2) concentrations (0-260 mM). Cell growth was severely suppressed when the dissolved CO(2) concentration was below 8.74 mM. On the other hand, cell growth and succinic acid production increased proportionally as the dissolved CO(2) concentration increased from 8.74 to 141 mM. The yields of biomass and succinic acid on glucose obtained at the dissolved CO(2) concentration of 141 mM were 1.49 and 1.52 times higher, respectively, than those obtained at the dissolved CO(2) concentration of 8.74 mM. It was also found that the additional CO(2) source provided in the form of NaHCO(3), MgCO(3), or CaCO(3) had positive effects on cell growth and succinic acid production. However, growth inhibition was observed when excessive bicarbonate salts were added. By the comparison of the activities of key enzymes, it was found that PEP carboxylation by PEP carboxykinase (PckA) is the most important for succinic acid production as well as the growth of M. succiniciproducens by providing additional ATP. PMID:17570706

  6. ATP-Based Ratio Regulation of Glucose and Xylose Improved Succinate Production

    Zhang, Fengyu; Li, Jiaojiao; Liu, Huaiwei; Liang, Quanfeng; Qi, Qingsheng

    2016-01-01

    We previously engineered E. coli YL104H to efficiently produce succinate from glucose. Furthermore, the present study proved that YL104H could also co-utilize xylose and glucose for succinate production. However, anaerobic succinate accumulation using xylose as the sole carbon source failed, probably because of an insufficient supply of energy. By analyzing the ATP generation under anaerobic conditions in the presence of glucose or xylose, we indicated that succinate production was affected by the intracellular ATP level, which can be simply regulated by the substrate ratio of xylose to glucose. This finding was confirmed by succinate production using an artificial mixture containing different xylose to glucose ratios. Using xylose mother liquor, a waste containing both glucose and xylose derived from xylitol production, a final succinate titer of 61.66 g/L with an overall productivity of 0.95 g/L/h was achieved, indicating that the regulation of the intracellular ATP level may be a useful and efficient strategy for succinate production and can be extended to other anaerobic processes. PMID:27315279

  7. ATP-Based Ratio Regulation of Glucose and Xylose Improved Succinate Production.

    Zhang, Fengyu; Li, Jiaojiao; Liu, Huaiwei; Liang, Quanfeng; Qi, Qingsheng

    2016-01-01

    We previously engineered E. coli YL104H to efficiently produce succinate from glucose. Furthermore, the present study proved that YL104H could also co-utilize xylose and glucose for succinate production. However, anaerobic succinate accumulation using xylose as the sole carbon source failed, probably because of an insufficient supply of energy. By analyzing the ATP generation under anaerobic conditions in the presence of glucose or xylose, we indicated that succinate production was affected by the intracellular ATP level, which can be simply regulated by the substrate ratio of xylose to glucose. This finding was confirmed by succinate production using an artificial mixture containing different xylose to glucose ratios. Using xylose mother liquor, a waste containing both glucose and xylose derived from xylitol production, a final succinate titer of 61.66 g/L with an overall productivity of 0.95 g/L/h was achieved, indicating that the regulation of the intracellular ATP level may be a useful and efficient strategy for succinate production and can be extended to other anaerobic processes. PMID:27315279

  8. STUDYING PSYCHOIMMUNOMODULATING EFFECT OF SUCCINATE PHENOTROPIL IN EXPERIMENTAL MODEL

    M. A. Samotrueva

    2014-07-01

    Full Text Available Аbstract.  Psychoimmunomodulating  properties  of  phenotropil  succinate,  a  new  phenotropil  derivative,  were  studied in  a model of cyclophosphamide-induced    immunodepression and  lypopolysaccharideinduced  immune  stress,  following  intraperitoneal  injections  of  the  drug  at  different  schedules  (from  a  single  injection  up  to  a  7-day  course,  and  at  varying  doses  (25  mg/kg,  50  mg/kg,  and  100  mg/kg.  It  was  found  that the  studied  substance  shows  a  clear  ability  to  eliminate  disorders  of  various  immune  compartments.  Moreover,  phenotropil  succinate  was  able  to  restore  behavioral  reactions  in  “Suоk-test”.  These  results  provide  evidence for  development  of  this  substance  aimed  for  correction  of  neuroimmune  disturbances.  (Med.  Immunol.,  2011,  vol.  13,  N  1,  pp  55-60

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

    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.

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

    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.

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

    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

  12. Succinic acid production from xylose mother liquor by recombinant Escherichia coli strain

    Wang, Honghui; Pan, Jiachuan; Wang, Jing; Wang, Nan; Jie ZHANG; Li, Qiang; Wang, Dan; Zhou, Xiaohua

    2014-01-01

    Succinic acid (1,4-butanedioic acid) is identified as one of important building-block chemicals. Xylose mother liquor is an abundant industrial residue in xylitol biorefining industry. In this study, xylose mother liquor was utilized to produce succinic acid by recombinant Escherichia coli strain SD121, and the response surface methodology was used to optimize the fermentation media. The optimal conditions of succinic acid fermentation were as follows: 82.62 g L−1 total initial sugars, 42.27 ...

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

    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.

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

    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...... 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...... genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we demonstrate how systems biology tools coupled with directed evolution and selection allows non-intuitive, rapid and substantial re...

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

    Gunnarsson, Ingólfur Bragi

    utilization of this feedstock could potentially lower the costs for succinic acid production. The biochemical methane potential of L. digitata, post hydrolysis solid residue (PHSR) and fermentation broth after succinic acid fermentation was also determined. In a biorefinery, biogas production is important for...... amounted up to 10.0 g L-1. However, the production of succinic acid from this type of hydrolysate resulted in much higher product titer and substrate utilization compared to ethanol fermentation, partially because A. succinogenes is able to ferment both glucose and xylose into succinic acid. Jerusalem...... energy recovery as well as for minimizing waste and generating an additional product in the form of fertilizer. Energy recovery of PHSR and fermentation broth through anaerobic digestion corresponded to 298 and 285 NmL CH4 g-1 VSadded, respectively. To further increase the integration of the different...

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

    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

  17. Differential labeling of the subunits of respiratory complex III with [3H]succinic anhydride, [14C]succinic anhydride, and p-diazobenzene-[35S]sulfonate

    Exposure of antimycin-treated Complex III (ubiquinol-cytochrome c reductase) purified from bovine heart mitochondria to [3H]succinic anhydride plus [35S]p-diazobenzenesulfonate (DABS) resulted in somewhat uniform relative labeling of the eight measured subunits of the complex by [3H]succinic anhydride. In contrast, relative labeling by [35S]DABS was similar to [3H]succinic anhydride for the subunits of high molecular mass, i.e., core proteins, cytochromes, and the iron-sulfur protein, but greatly reduced for the polypeptides of molecular mass below 15 kDa. With Complex II depleted in the iron-sulfur protein the relative labeling of core protein I by exposure of the complex to [3H]succinic anhydride was significantly enhanced, whereas labeling of the polypeptides represented by SDS-PAGE bands 7 and 8 was significantly inhibited. Dual labeling of the subunits of Complex III by 14C- and 3H-labeled succinic anhydride before and after dissociation of the complex by sodium dodecyl sulfate, respectively, was measured with the complex in its oxidized, reduced, and antimycin-inhibited states. Subunits observed to be most accessible or reactive to succinic anhydride were core protein II, the iron-sulfur protein, and polypeptides of SDS-PAGE bands 7,8, and 9. Two additional polypeptides of molecular masses 23 and 12kDa, not normally resolved by gel-electrophoresis, were detected. Reduction of the complex resulted in a significant change of 14C/3H labeling ratio of core protein only, whereas treatment of the complex with antimycin resulted in decreases in 14C/3H labeling ratios of core proteins I and II, cytochrome c1, and a polypeptide of molecular mass 13kDa identified as an antimycin-binding protein

  18. Effect of Growth Phase Feeding Strategies on Succinate Production by Metabolically Engineered Escherichia coli▿

    Jiang, Min; Liu, Shu-wen; Ma, Jiang-feng; Chen, Ke-quan; Yu, Li; Yue, Fang-fang; Xu, Bing; WEI, PING

    2009-01-01

    Aerobic growth conditions significantly influenced anaerobic succinate production in two-stage fermentation by Escherichia coli AFP111 with knockouts in rpoS, pflAB, ldhA, and ptsG genes. At a low cell growth rate limited by glucose, enzymes involved in the reductive arm of the tricarboxylic acid cycle and the glyoxylate shunt showed elevated activities, providing AFP111 with intracellular redox balance and increased succinic acid yield and productivity.

  19. Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms

    Patel, Komal; Patel, Amit; Dave, Jayant; Patel, Chaganbhai

    2012-01-01

    Aim and Background: The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of telmisartan and metoprolol succinate in combined tablet dosage form. Materials and Methods: The method is based on the absorbance correction equations for analysis of both the drugs using methanol as solvent. Telmisartan has absorbance maxima at 296 nm and metoprolol succinate has absorbance maxima at 223 nm in methanol...

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

    A. Sathyaraj

    2012-01-01

    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 ...

  1. Succinic acid in aqueous solution : connecting microscopic surface composition and macroscopic surface tension

    Werner, Josephina; Julin, Jan; Dalirian, Maryam; Prisle, Nønne; Öhrwall, Gunnar; Persson, Ingmar; Björneholm, Olle; Riipinen, Ilona

    2014-01-01

    The water vapor interface of aqueous solutions of succinic acid, where pH values and bulk concentrations were varied, has been studied using surface sensitive X-ray photoelectron spectroscopy (XPS) and molecular dynamics (MD) simulations. It was found that succinic acid has a considerably higher propensity to reside in the aqueous surface region than its deprotonated form, which is effectively depleted from the surface due to the two strongly hydrated carboxylate groups. From both XPS experim...

  2. Carbon dioxide metabolism by Actinomyces viscosus: pathways for succinate and aspartate production.

    Brown, A T; Breeding, L C

    1980-01-01

    14C-labeled bicarbonate was incorporated into trichloroacetic acid-insoluble material by cell suspensions of A. viscosus strain M100 and also into the four-carbon fermentation product, succinate, but not into the three-carbon fermentation product, lactate. The initial step in the conversion of 14C-labeled bicarbonate into both trichloroacetic acid-insoluble material and succinate was catalyzed by the enzyme phosphoenolypyruvate carboxylase, which served to convert the glycolytic intermediate,...

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

    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.

  4. Metoprolol succinate extended release/hydrochlorothiazide combination tablets

    James W Hainer

    2007-07-01

    Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

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

    J. Vanhanen; Hyvärinen, A.-P.; Anttila, T.; T. Raatikainen; Viisanen, Y; H. Lihavainen

    2008-01-01

    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 concentrati...

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

    H. Lihavainen; Viisanen, Y; Anttila, T.; A.-P. Hyvärinen; J. Vanhanen

    2008-01-01

    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 concentrati...

  7. Preparation of biodegradable porous poly(butylene succinate microspheres

    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.

  8. Urinary Bladder Paragangliomas: Analysis of Succinate Dehydrogenase and Outcome.

    Gupta, Sounak; Zhang, Jun; Rivera, Michael; Erickson, Lori A

    2016-09-01

    Paragangliomas of the urinary bladder can arise sporadically or as a part of hereditary syndromes including those with underlying mutations in the succinate dehydrogenase (SDH) genes, which serve as tumor suppressors. SDH deficiency can be screened for by absence of immunohistochemical detection of SDHB. In this study of 11 cases, clinical follow-up was available for 9/11 cases. The cases were reviewed and graded based on the grading system for adrenal pheochromocytomas and paragangliomas (GAPP) criteria. Immunohistochemistry was performed for Ki67 and SDHB. Proliferative index was calculated by quantification of Ki67-positive cells at hot spots. The medical record was accessed for documentation of germline SDH mutations. Urinary bladder paragangliomas had a female predilection (8/11 cases), and 5/11 cases exhibited metastatic behavior. Patients with metastatic disease tended to be younger (mean age 43 vs 49 years), have larger lesions (5.8 vs 1.5 cm), and presented with catecholamine excess (4/4 vs 2/6 patients with non-metastatic lesions). Patients with metastatic disease had a higher mean Ki67 proliferation rate (4.9 vs 1.3 %) and GAPP score (mean of 5.8 vs 3.8) (p = 0.01). IHC for SDHB expression revealed loss of expression in 2/6 cases of non-metastatic paragangliomas compared to 4/5 patients with metastatic paragangliomas. Interestingly, of these four patients, two had a documented mutation of SDHB, one patient had a SDHC mutation, and another patient had a history of familial disease without mutation analysis being performed. Our study, suggests that SDH loss was suggestive of metastatic behavior in addition to younger age at diagnosis, larger tumor size, and higher Ki67 proliferation rate and catecholamine type. PMID:27262318

  9. Differentiation-specific action of orphan nuclear receptor NR5A1 (SF-1): transcriptional regulation in luteinizing bovine theca cells

    Walther, Norbert; Jansen, Martina; Akbary, Wasima; Ivell, Richard

    2006-01-01

    Background The orphan nuclear receptor NR5A1 (steroidogenic factor-1, SF-1) is a master regulator of tissue-specific gene expression in reproductive and steroidogenic tissues. Two activating functions, AF-1 and AF-2, have been described to function in a cooperative manner to recruit transcriptional coactivators to the promoter regions of NR5A1-controlled genes. Methods The role of the NR5A1 activating functions AF-1 and AF-2 was studied in primary bovine theca cells. Bovine theca cells were i...

  10. Significance of CO2 donor on the production of succinic acid by Actinobacillus succinogenes ATCC 55618

    Zou Wei

    2011-10-01

    Full Text Available Abstract Background Succinic acid is a building-block chemical which could be used as the precursor of many industrial products. The dissolved CO2 concentration in the fermentation broth could strongly regulate the metabolic flux of carbon and the activity of phosphoenolpyruvate (PEP carboxykinase, which are the important committed steps for the biosynthesis of succinic acid by Actinobacillus succinogenes. Previous reports showed that succinic acid production could be promoted by regulating the supply of CO2 donor in the fermentation broth. Therefore, the effects of dissolved CO2 concentration and MgCO3 on the fermentation process should be investigated. In this article, we studied the impacts of gaseous CO2 partial pressure, dissolved CO2 concentration, and the addition amount of MgCO3 on succinic acid production by Actinobacillus succinogenes ATCC 55618. We also demonstrated that gaseous CO2 could be removed when MgCO3 was fully supplied. Results An effective CO2 quantitative mathematical model was developed to calculate the dissolved CO2 concentration in the fermentation broth. The highest succinic acid production of 61.92 g/L was obtained at 159.22 mM dissolved CO2 concentration, which was supplied by 40 g/L MgCO3 at the CO2 partial pressure of 101.33 kPa. When MgCO3 was used as the only CO2 donor, a maximal succinic acid production of 56.1 g/L was obtained, which was just decreased by 7.03% compared with that obtained under the supply of gaseous CO2 and MgCO3. Conclusions Besides the high dissolved CO2 concentration, the excessive addition of MgCO3 was beneficial to promote the succinic acid synthesis. This was the first report investigating the replaceable of gaseous CO2 in the fermentation of succinic acid. The results obtained in this study may be useful for reducing the cost of succinic acid fermentation process.

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

    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.

  12. Doxofylline and methylprednisolone sodium succinate are stable and compatible under normal injection conditions.

    Xu, Fan; Feng, Enfu; Su, Li; Xu, Guili

    2013-03-01

    To assess the physical compatibility and chemical stability of doxofylline with methylprednisolone sodium succinate in 0.9% sodium chloride or 5% dextrose injection for intravenous infusion. Twenty mL doxofylline solution (0.74 mg/mL) and 1 mL methylprednisolone sodium succinate solution (0.15 mg/mL) were added into 250 mL polyolefin bags containing 5% dextrose injection or 0.9% sodium chloride injection, and stored for 24 h at 20-25(°)C. Chemical compatibility was measured with high-performance liquid chromatography (HPLC), and physical compatibility was determined visually. The results showed that samples were clear and colorless when viewed in normal fluorescent room light. The pH value exhibited little change. The particulate content of > 25 μm was low and within the specification limit. The particulate content of > 10 μm decreased over time and was similar to the control solution. Analysis of chemical stability revealed that doxofylline is stable with methylprednisolone sodium succinate for up to 24 h, and the degradation of methylprednisolone sodium succinate is unrelated to doxofylline, but is closely related to the pH value of the solution. Doxofylline and methylprednisolone sodium succinate did not affect the stability of each other. PMID:23455194

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

    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.

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

    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.

  15. Pretreatment of spent sulphite liquor via ultrafiltration and nanofiltration for bio-based succinic acid production.

    Pateraki, Chrysanthi; Ladakis, Dimitrios; Stragier, Lutgart; Verstraete, Willy; Kookos, Ioannis; Papanikolaou, Seraphim; Koutinas, Apostolis

    2016-09-10

    Ultrafiltration and nanofiltration of spent sulphite liquor (SSL) has been employed to evaluate the simultaneous production of lignosulphonates and bio-based succinic acid using the bacterial strains Actinobacillus succinogenes and Basfia succiniciproducens. Ultrafiltration with membranes of 10, 5 and 3kDa molecular weight cut-off results in significant losses of lignosulphonates (26-50%) in the permeate stream, while nanofiltration using membrane with 500Da molecular weight cut-off results in high retention yields of lignosulphonates (95.6%) in the retentate stream. Fed-batch bioreactor cultures using permeates from ultrafiltrated SSL resulted in similar succinic acid concentration (27.5g/L) and productivity (0.4g/L/h) by both strains. When permeates from nanofiltrated SSL were used, the strain B. succiniciproducens showed the highest succinic acid concentration (33.8g/L), yield (0.58g per g of consumed sugars) and productivity (0.48g/L/h). The nanofiltration of 1t of thick spent sulphite liquor could lead to the production of 306.3kg of lignosulphonates and 52.7kg of succinic acid, whereas the ultrafiltration of 1t of thick spent sulphite liquor using a 3kDa membrane could result in the production of 237kg of lignosulphonates and 71.8kg of succinic acid when B. succiniproducens is used in both cases. PMID:27374402

  16. Succinate-dependent energy generation and pyruvate dehydrogenase complex activity in isolated Ascaris suum mitochondria

    Body wall muscle from the parasitic nematode, Ascaris suum, contain unique anaerobic mitochondria that preferentially utilize fumarate and branched-chain enoyl CoA's as terminal electron acceptors instead of oxygen. While electron transport in these organelles is well characterized, the role of oxygen in succinate-dependent phosphorylation is still not clearly defined. Therefore, the present study was designed to more fully characterize succinate metabolism in these organelles as well as the in vitro regulation of a key mitochondrial enzyme, the pyruvate dehydrogenase complex (PDC). In the absence of added adenine nucleotides, incubations in succinate resulted in substantial elevations in intramitochrondrial ATP levels, but ATP/ADP ratios were considerably higher in incubations with malate. The stimulation of phosphorylation in aerobic incubations with succinate was rotenone sensitive and appears to be Site I dependent. Increase substrate level phosphorylation, coupled to propionate formation, or additional sites of electron-transport associated ATP synthesis were not significant. Under aerobic conditions, 14CO2 evolution from 1,4-[14C]succinate was stimulated and NADH/NAD+ ratios were elevated, but the formation of 14C propionate was unchanged

  17. Succinate-dependent energy generation and pyruvate dehydrogenase complex activity in isolated Ascaris suum mitochondria

    Campbell, T.A.

    1988-01-01

    Body wall muscle from the parasitic nematode, Ascaris suum, contain unique anaerobic mitochondria that preferentially utilize fumarate and branched-chain enoyl CoA's as terminal electron acceptors instead of oxygen. While electron transport in these organelles is well characterized, the role of oxygen in succinate-dependent phosphorylation is still not clearly defined. Therefore, the present study was designed to more fully characterize succinate metabolism in these organelles as well as the in vitro regulation of a key mitochondrial enzyme, the pyruvate dehydrogenase complex (PDC). In the absence of added adenine nucleotides, incubations in succinate resulted in substantial elevations in intramitochrondrial ATP levels, but ATP/ADP ratios were considerably higher in incubations with malate. The stimulation of phosphorylation in aerobic incubations with succinate was rotenone sensitive and appears to be Site I dependent. Increase substrate level phosphorylation, coupled to propionate formation, or additional sites of electron-transport associated ATP synthesis were not significant. Under aerobic conditions, {sup 14}CO{sub 2} evolution from 1,4-({sup 14}C)succinate was stimulated and NADH/NAD{sup +} ratios were elevated, but the formation of {sup 14}C propionate was unchanged.

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

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

    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 CdCl2-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

  20. Two novel mutations in the NR5A1 gene as a cause of disorders of sex development in a Pakistani cohort of 46,XY patients.

    Hussain, S; Amar, A; Najeeb, M N; Khaliq, S

    2016-06-01

    NR5A1 plays a central role in gonadal development and regulation by transcriptional regulation of key modulators involved in steroidogenesis. Mutations in human NR5A1 are frequently associated with 46,XY disorders of sex development (DSD). We analysed a Pakistani cohort of patients with 46,XY DSD, presenting with variable degrees of gonadal dysgenesis, for NR5A1 mutations. The study identified three mutations (p.Tyr03X, p.Glu07X and p.Gln299HisfsX386), of which two are novel, in these patients with 46,XY DSD. The mutations, p.Tyr03X and novel p.Glu07X, are located in the coding region of the gene, corresponding to DNA-binding domain of the predicted protein. In silico analysis for the novel homozygous p.Gln299HisfsX386 mutation in ligand-binding domain of NR5A1 revealed subtle changes in overall tertiary conformation which is predicted to affect the normal physiology of this mutant protein. This study reveals two novel mutations with altered NR5A1 protein in twenty patients with 46,XY DSD, highlighting the critical role of NR5A1 protein in gonadal development and differentiation. In conclusion, the current and previous studies suggest that the NR5A1 mutations are present in around 8-15% of patients with 46,XY DSD presenting with gonadal dysgenesis. For the clinical utility of NR5A1 gene mutations, more comprehensive studies with large 46,XY DSD patient series in different populations are suggested. PMID:26260161

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

    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.

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

    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.

  3. Secondary isotope effects in intramolecular catalysis. Mono-p-bromophenyl succinate hydrolysis

    Gandour, R.D.; Stella, V.J.; Coyne, M.; Schowen, R.L.; Icaza, E.A.

    1978-04-28

    Kinetic isotope effects have been measured for the intramolecular nucleophilic carboxylate-catalyzed hydrolysis, k/sub s/, of mono-p-bromophenyl succinate and mono-p-bromophenyl succinate-d/sub 4/. The resulting isotope effect, k/sub s//sup h/sub 4///k/sub s//sup d/sub 4//, equals 1.035, a normal effect. This is contrary to what is expected for acyl transfer reactions where the transition-state structure resembles a tetrahedral intermediate. However, the direction of the isotope effect is in agreement with a transition-state structure resembling succinic anhydride. Combining this result with previous kinetic and structural studies, a detailed transition-state structure for the hydrolysis reaction is proposed. 31 references, 2 tables.

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

    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.

  5. Synthesis of tocopheryl succinate phospholipid conjugates and monitoring of phospholipase A2 activity

    Pedersen, Palle Jacob; Viart, Helene Marie-France; Melander, Fredrik;

    2012-01-01

    Tocopheryl succinates (TOSs) are, in contrast to tocopherols, highly cytotoxic against many cancer cells. In this study the enzyme activity of secretory phospholipase A2 towards various succinate-phospholipid conjugates has been investigated. The synthesis of six novel phospholipids is described,...

  6. Regulation of fructose uptake and catabolism by succinate in Azospirillum brasilense.

    Mukherjee, A; S. Ghosh

    1987-01-01

    Fructose uptake and catabolism in Azospirillum brasilense is dependent on three fructose-inducible enzymes (fru-enzymes): (i) enzyme I and (ii) enzyme II of the phosphoenolpyruvate:fructose phosphotransferase system and (iii) 1-phosphofructokinase. In minimal medium containing 3.7 mM succinate and 22 mM fructose as sources of carbon, growth of A. brasilense was diauxic, succinate being utilized in the first phase of growth and fructose in the second phase with a lag period between the two gro...

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

    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...

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

    Hadi Sarir; Ghodsieh Emdadifard; Homayoun Farhangfar; Hossein TaheriChadorneshin

    2015-01-01

    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-α) and interleukin-6 (IL-6) production induced by high-intensity interval training (HIIT). Materials and Methods: In the ...

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

    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. PMID:21058317

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

    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.

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

    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. PMID:27382725

  12. Nano-encapsulation of coenzyme Q10 using octenyl succinic anhydride modified starch

    Octenyl succinic anhydride modified starch (OSA-ST) was used to encapsulate Coenzyme Q10 (CoQ10). CoQ10 was dissolved in rice bran oil (RBO), and incorporated into an aqueous OSA-ST solution. High pressure homogenization (HPH) of the mixture was conducted at 170 MPa for 5-6 cycles. The resulting ...

  13. H2-dependent anaerobic growth of Escherichia coli on L-malate: succinate formation.

    Macy, J; Kulla, H; Gottschalk, G

    1976-02-01

    Escherichia coli grew anaerobically on L-malate only in the presence of H2; 91% of the L-malate utilized was converted to succinate. Anaerobically isolated membrane vesicles catalyzed the reduction of fumarate with H2 and contained a b-type cytochrome. Cytochrome c552 was present in the "periplasmic space." PMID:1107323

  14. Immunolocalization of succinate dehydrogenase in the esophagus epithelium of domesticated mammals

    Meyer, W.; Kacza, J.; I. N. Hornickel; Schoennagel, B.

    2013-01-01

    Using immunohistochemistry and transmission electron microscopy (TEM), the esophagus epithelia of seven domesticated mammals (horse, cattle, goat, pig, dog, laboratory rat, cat) of three nutrition groups (herbivorous, omnivorous, carnivorous) were studied to get first information about energy generation, as demonstrated by succinate dehydrogenase (SDH) activities. Distinct reaction intensities could be observed in all esophageal cell layers of the different species studied reflecting moderate...

  15. A complete industrial system for economical succinic acid production by Actinobacillus succinogenes.

    Li, Jian; Zheng, Xiao-Yu; Fang, Xiao-Jiang; Liu, Shu-Wen; Chen, Ke-Quan; Jiang, Min; Wei, Ping; Ouyang, Ping-Kai

    2011-05-01

    An industrial fermentation system using lignocellulosic hydrolysate, waste yeast hydrolysate, and mixed alkali to achieve high-yield, economical succinic acid production by Actinobacillus succinogenes was developed. Lignocellulosic hydrolysate and waste yeast hydrolysate were used efficiently as carbon sources and nitrogen source instead of the expensive glucose and yeast extract. Moreover, as a novel method for regulating pH mixed alkalis (Mg(OH)(2) and NaOH) were first used to replace the expensive MgCO(3) for succinic acid production. Using the three aforementioned substitutions, the total fermentation cost decreased by 55.9%, and 56.4 g/L succinic acid with yield of 0.73 g/g was obtained, which are almost the same production level as fermentation with glucose, yeast extract and MgCO(3). Therefore, the cheap carbon and nitrogen sources, as well as the mixed alkaline neutralize could be efficiently used instead of expensive composition for industrial succinic acid production. PMID:21470857

  16. Coordination compounds of succinate some 3d-metals with thiosemicarbazone furfurol

    In article the results of synthesis and investigations of the Ni (II), Co (II), Cu (II) and Zn succinates with thiosemicarbazone furfurol complexes were shown. The consistence, individuality, the pattern of coordination of apical ligand and the thermal behavior of obtained complexes were established. (author)

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

    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....

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

    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 enz...

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

    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...

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

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

    2007-01-01

    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...

  1. Integration of Succinic Acid Production in a Dry Mill Ethanol Facility

    None

    2006-08-01

    This project seeks to address both issues for a dry mill ethanol biorefinery by lowering the cost of sugars with the development of an advanced pretreatment process, improving the economics of succinic acid (SA), and developing a model of an ethanol dry mill to evaluate the impact of adding different products and processes to a dry mill.

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

    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.

  3. Inhibition of mitochondrial glycerol-3-phosphate dehydrogenase by alpha-tocopheryl succinate

    Rauchová, Hana; Vokurková, Martina; Drahota, Zdeněk

    2014-01-01

    Roč. 53, AUG (2014), s. 409-413. ISSN 1357-2725 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : brown adipose tissue mitochondria * oxygen consumption * glycerol-3-phosphate * succinate * reactive oxygen species Subject RIV: ED - Physiology Impact factor: 4.046, year: 2014

  4. Inhibition of Salmonella Typhimurium by Anaerobic Cecal Bacteria in Media Supplemented with Lactate and Succinate

    The ability of anaerobic cecal microflora of broilers to inhibit growth of Salmonella Typhimurium in media supplemented with lactate and succinate was examined. Cecal cultures were prepared by collecting ceca of processed broilers from a commercial processing facility, inoculating broth media with 1...

  5. ATP5A1 and ATP5B are highly expressed in glioblastoma tumor cells and endothelial cells of microvascular proliferation.

    Xu, Guiyan; Li, Jian Yi

    2016-02-01

    Glioblastoma (GBM) is the most common primary malignant brain tumor. Microvascular proliferation is one of the characteristic pathologic features of GBM. Mitochondrial dysfunction plays an important role in the pathogenesis of GBM. In this study, microvascular proliferation from GBM and normal brain blood vessels were laser microdissected and total RNA was isolated from these microvasculatures. The difference of mRNA expression profiles among GBM microvasculature, normal brain blood vessels and GBM tumor cells was evaluated by mitochondria and metabolism PCR gene arrays. It was found that the mRNA levels of ATP5A1 and ATP5B in GBM tumor cells as well as microvascular proliferation were significantly higher compared with normal brain blood vessels. Immunohistochemical stains with anti-ATP5A1 antibody or anti-ATP5B antibody were performed on tissue microarray, which demonstrated strongly positive expression of ATP5A1 and ATP5B in GBM tumor cells and GBM microvascular proliferation while normal blood vessels were negative. By analyzing The Cancer Genome Atlas data sets for GBM and other cancers, genomic DNA alterations (mutation, amplification or deletion) were less likely the reason for the high expression of ATP5A1 and ATP5B in GBM. Our miRNA microarray data showed that miRNAs that target ATP5A1 or ATP5B were down-regulated, which might be the most likely reason for the high expression of ATP5A1 and ATP5B in GBM tumor cells and microvascular proliferation. These findings help us better understand the pathogenesis of GBM, and agents against ATP5A1 and/or ATP5B might effectively kill both tumor cells and microvascular proliferation in GBM. MiRNAs, such as Let-7f, miR-16, miR-23, miR-100 and miR-101, that target ATP5A1 or ATP5B, might be potential therapeutic agents for GBM. PMID:26526033

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

    M. V. Soura

    2016-01-01

    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.

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

    Hybertson, Brooks M.

    2007-01-01

    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 supercriti...

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

    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

  9. A novel splice variant in the N-propeptide of COL5A1 causes an EDS phenotype with severe kyphoscoliosis and eye involvement.

    Sofie Symoens

    Full Text Available BACKGROUND: The Ehlers-Danlos Syndrome (EDS is a heritable connective tissue disorder characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. The classic subtype of EDS is caused by mutations in one of the type V collagen genes (COL5A1 and COL5A2. Most mutations affect the type V collagen helical domain and lead to a diminished or structurally abnormal type V collagen protein. Remarkably, only two mutations were reported to affect the extended, highly conserved N-propeptide domain, which plays an important role in the regulation of the heterotypic collagen fibril diameter. We identified a novel COL5A1 N-propeptide mutation, resulting in an unusual but severe classic EDS phenotype and a remarkable splicing outcome. METHODOLOGY/PRINCIPAL FINDINGS: We identified a novel COL5A1 N-propeptide acceptor-splice site mutation (IVS6-2A>G, NM_000093.3_c.925-2A>G in a patient with cutaneous features of EDS, severe progressive scoliosis and eye involvement. Two mutant transcripts were identified, one with an exon 7 skip and one in which exon 7 and the upstream exon 6 are deleted. Both transcripts are expressed and secreted into the extracellular matrix, where they can participate in and perturb collagen fibrillogenesis, as illustrated by the presence of dermal collagen cauliflowers. Determination of the order of intron removal and computational analysis showed that simultaneous skipping of exons 6 and 7 is due to the combined effect of delayed splicing of intron 7, altered pre-mRNA secondary structure, low splice site strength and possibly disturbed binding of splicing factors. CONCLUSIONS/SIGNIFICANCE: We report a novel COL5A1 N-propeptide acceptor-splice site mutation in intron 6, which not only affects splicing of the adjacent exon 7, but also causes a splicing error of the upstream exon 6. Our findings add further insights into the COL5A1 splicing order and show for the first time that a single COL5A1 acceptor-splice site

  10. Comments on recently published "L-threonine phthalate" and pure and doped "L-lysinium succinate" crystals

    Petrosyan, A. M.

    2016-04-01

    It is shown that the recently published papers on "L-threonine phthalate" (Theras et al. (2015) [2]) and pure and doped "L-lysinium succinate" (Kalaivani et al. (2015) [11,16]) misidentified the targeted compounds.

  11. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    Wu, Kun; ZHAO Yan; Liu, Bai-He; Li, Yao; Liu, Fang; Guo, Jian; Yu, Wei-Ping

    2002-01-01

    AIM: To investigate the effects of growth inhibition of human gastric cancer SGC-7901 cell with RRR-α-tocopheryl succinate (VES), a derivative of natural Vitamin E, via inducing apoptosis and DNA synthesis arrest.

  12. DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR SIMULTANEOUS ESTIMATION OF METOPROLOL SUCCINATE AND TELMISARTAN IN COMBINED PHARMACEUTICAL FORMULATION

    Mayur Modi*, Rikin Shah and R.C. Mashru

    2012-01-01

    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 eq...

  13. Liquid–liquid extraction of gallium(III with n-octylaniline from succinate media

    T. N. SHILMKAR

    2005-06-01

    Full Text Available The distribution equilibrium of gallium(III between n-octylaniline dissolved in toluene and acidic aqueous succinate media has been investigated as a function of the concentration of extractant in the organic phase and concentration of hydrogen ions and gallium(III ions in the aqueous phase. The stoichiometry of the extracted species was determined on the basis of slope analysis.Gallium(III is extracted by the anion exchange mechanism as [RNH3+Ga(succinate2]org. The temperature dependence of the extraction equilibria was examined by the temperature variationmethod. The extraction process is favoured with increasing temperature. It was found that a large number of cations and anions have a high tolerance limit. The selectivity of the extraction is increased by the use of suitable masking agents. The method affords the binary separation of gallium(III from associated elements and was further extended to the analysis of a synthetic mixture.

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

    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.

  15. Reactive processing of maleic anhydride-grafted poly(butylene succinate and the compatibilizing effect on poly(butylene succinate nanocomposites

    Z. A. Mohd Ishak

    2013-04-01

    Full Text Available In this study, maleic anhydride-grafted poly(butylene succinate (PBS-g-MA was synthesized via reactive meltgrafting process using different initiator contents. The grafting efficiency was increased with the initiator content, manifested by the higher degree of grafting in PBS-g-MA. The grafting reaction was confirmed through Fourier transform infrared (FTIR spectroscopy and nuclear magnetic resonance (NMR spectroscopy. Then, PBS-g-MA was incorporated into organo-montmorillonite (OMMT filled poly(butylene succinate (PBS nanocomposites as compatibilizer. Mechanical properties of PBS nanocomposites were enhanced after compatibilized with PBS-g-MA, due to the better dispersion of OMMT in PBS matrix and the improved filler-matrix interfacial interactions. This was verifiable through X-ray diffraction (XRD, transmission electron microscopy (TEM and scanning electron microscopy (SEM. Differential scanning calorimetry (DSC showed that the degree of crystallinity and melting temperature increased after addition of PBS-g-MA. However, the presence of PBS-g-MA did not favor the thermal stability of the nanocomposites, as reported in the thermogravimetry (TGA.

  16. Actinobacillus succinogenes ATCC 55618 fermentation medium optimization for the production of succinic acid by response surface methodology.

    Zhu, Li-Wen; Wang, Cheng-Cheng; Liu, Rui-Sang; Li, Hong-Mei; Wan, Duan-Ji; Tang, Ya-Jie

    2012-01-01

    As a potential intermediary feedstock, succinic acid takes an important place in bulk chemical productions. For the first time, a method combining Plackett-Burman design (PBD), steepest ascent method (SA), and Box-Behnken design (BBD) was developed to optimize Actinobacillus succinogenes ATCC 55618 fermentation medium. First, glucose, yeast extract, and MgCO(3) were identified to be key medium components by PBD. Second, preliminary optimization was run by SA method to access the optimal region of the key medium components. Finally, the responses, that is, the production of succinic acid, were optimized simultaneously by using BBD, and the optimal concentration was located to be 84.6 g L(-1) of glucose, 14.5 g L(-1) of yeast extract, and 64.7 g L(-1) of MgCO(3). Verification experiment indicated that the maximal succinic acid production of 52.7 ± 0.8 g L(-1) was obtained under the identified optimal conditions. The result agreed with the predicted value well. Compared with that of the basic medium, the production of succinic acid and yield of succinic acid against glucose were enhanced by 67.3% and 111.1%, respectively. The results obtained in this study may be useful for the industrial commercial production of succinic acid. PMID:23093852

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

    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.

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

    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.

  19. Alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels

    Procházka, L.; Dong, L.F.; Vališ, Karel; Freeman, R.; Ralph, S.J.; Turánek, J.; Neužil, Jiří

    2010-01-01

    Roč. 15, č. 7 (2010), s. 782-794. ISSN 1360-8185 R&D Projects: GA AV ČR(CZ) KAN200520703; GA AV ČR(CZ) IAA500520702; GA AV ČR(CZ) IAA500520602 Institutional research plan: CEZ:AV0Z50520701 Keywords : Vitamin E succinate * apoptosis * Noxa-Bak Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.397, year: 2010

  20. The H+/O ratio of proton translocation linked to the oxidation of succinate by mitochondria.

    Krab, K; Soos, J; Wikström, M

    1984-12-10

    In a recent communication Lehninger and co-workers (Costa, L.E., Reynaferje, B., and Lehninger, A.L. (1984) J. Biol. Chem. 259, 4802-4811) reported values approaching 8 for the H+/O ratio of vectorial proton ejection from rat liver mitochondria respiring with succinate. Here we present a rigorous analysis of these measurements which reveals that they may significantly overestimate the true H+/O stoicheiometry. PMID:6096164

  1. Preparation and Characterization of Octenyl Succinic Anhydride Modified Taro Starch Nanoparticles

    Jiang, Suisui; Dai, Lei; Qin, Yang; Xiong, Liu; Sun, Qingjie

    2016-01-01

    The polar surface and hydrophilicity of starch nanoparticles (SNPs) result in their poor dispersibility in nonpolar solvent and poor compatibility with hydrophobic polymers, which limited the application in hydrophobic system. To improve their hydrophobicity, SNPs prepared through self-assembly of short chain amylose debranched from cooked taro starch, were modified by octenyl succinic anhydride (OSA). Size via dynamic light scattering of OSA-SNPs increased compared with SNPs. Fourier transfo...

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

    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.

  3. Health expenditure comparison of extended-release metoprolol succinate and immediate-release metoprolol tartarate

    Vaidya V; Patel P

    2012-01-01

    Varun Vaidya, Pranav PatelCollege of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USABackground: Metoprolol, a selective beta-1 blocker, is available in two different salt forms in the market – metoprolol succinate (MS) and metoprolol tartarate (MT). Both the formulations are Food and Drug Administration approved for the treatment of hypertension. Several studies have shown similar efficacies between the two salts; however, they differ in their pharmacokin...

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

    M. V. Soura

    2016-01-01

    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, prolo...

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

    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.

  6. FORMULATION AND RELEASE CHARACTERISTICS OF HPMC MATRIX TABLETS OF METOPROLOL SUCCINATE

    Sobhita Rani P et al.

    2012-01-01

    The objective of this study was to design and evaluate oral sustained drug delivery system for Metoprolol succinate using pH sensitive polymer HPMC and sodium alginate and to evaluate its efficacy in reducing the hypertension. The drug filler blend was mixed with various concentrations of hydrophilic polymers such as HPMC, sodium alginate and combination of both the matrixing agents. The tablets were prepared by wet granulation method. Matrix tablets were evaluated for weight variation, conte...

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

    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...

  8. Synthesis and physicochemical characterization of chemically modified chitosan by succinic anhydride

    Karine Gargioni Pereira Correa de Mello; Leandra de Cássia Bernusso; Ronaldo Nogueira de Moraes Pitombo; Bronislaw Polakiewicz

    2006-01-01

    The N-succinil-chitosan is a chemically modified derivative of the biopolymer chitosan. The succinic anhydride attached to the free amino groups presented along the chitosan's polymer chain imparts to the molecule different physicochemical properties not exhibited before the modification. These chemical modifications enhance chitosan's solubility in slightly acid, neutral and alkaline media. These properties are related to the long alkyl chains attached to hydrophilic parts. In this case the ...

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

    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.

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

    2011-01-01

    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 vari...

  11. Mutations in sdh (succinate dehydrogenase genes) alter the thiamine requirement of Salmonella typhimurium.

    Enos-Berlage, J L; Downs, D. M.

    1997-01-01

    Mutants lacking the first enzyme in de novo purine synthesis (PurF) can synthesize thiamine if increased levels of pantothenate are present in the culture medium (J. L. Enos-Berlage and D. M. Downs, J. Bacteriol. 178:1476-1479, 1996). Derivatives of purF mutants that no longer required pantothenate for thiamine-independent growth were isolated. Analysis of these mutants demonstrated that they were defective in succinate dehydrogenase (Sdh), an enzyme of the tricarboxylic acid cycle. Results o...

  12. Study and modification of poly(butylene succinate) properties, a biobased and biodegradable polyester

    Freyermouth, Floriane

    2014-01-01

    Within the frame of sustainable development, biobased and biodegradable polymers are going to play an important role according to economic and environmental perspectives. The polyolefins currently used in packaging and automotive industries will be replaced by biomaterials. The poly(butylene succinate), an “old” aliphatic polyester, has recently regained interest thanks to its biobased and biodegradable potential and mechanical properties similar to polyolefins. However, this polyester is ver...

  13. Efficient and repeated production of succinic acid by turning sugarcane bagasse into sugar and support.

    Chen, Pengcheng; Tao, Shengtao; Zheng, Pu

    2016-07-01

    Here we reported an endeavor in making full use of sugarcane bagasse for biological production of succinic acid. Through NaOH pre-treatment and multi-enzyme hydrolysis, a reducing sugar solution mainly composed of glucose and xylose was obtained from the sugarcane bagasse. By optimizing portions of cellulase, xylanase, β-glucanase and pectinase in the multi-enzyme "cocktail", the hydrolysis percentage of the total cellulose in pre-treated sugarcane bagasse can be as high as 88.5%. A. succinogenes CCTCC M2012036 was used for converting reducing sugars into succinic acid in a 3-L bioreactor with a sugar-fed strategy to prevent cell growth limitation. Importantly, cells were found to be adaptive on the sugarcane bagasse residue, offering possibilities of repeated batch fermentation and replacement for MgCO3 with soluble NaHCO3 in pH modulation. Three cycles of fermentation without activity loss were realized with the average succinic acid yield and productivity to be 80.5% and 1.65g·L(-1)·h(-1). PMID:27035471

  14. Aqueous Phase Photo-Oxidation of Succinic Acid: Changes in Hygroscopic Properties and Reaction Products

    Hudson, P. K.; Ninokawa, A.; Hofstra, J.; de Lijser, P.

    2013-12-01

    Atmospheric aerosol particles have been identified as important factors in understanding climate change. The extent to which aerosols affect climate is determined, in part, by hygroscopic properties which can change as a result of atmospheric processing. Dicarboxylic acids, components of atmospheric aerosol, have a wide range of hygroscopic properties and can undergo oxidation and photolysis reactions in the atmosphere. In this study, the hygroscopic properties of succinic acid aerosol, a non-hygroscopic four carbon dicarboxylic acid, were measured with a humidified tandem differential mobility analyzer (HTDMA) and compared to reaction products resulting from the aqueous phase photo-oxidation reaction of hydrogen peroxide and succinic acid. Reaction products were determined and quantified using gas chromatography-flame ionization detection (GC-FID) and GC-mass spectrometry (GC-MS) as a function of hydrogen peroxide:succinic acid concentration ratio and photolysis time. Although reaction products include larger non-hygroscopic dicarboxylic acids (e.g. adipic acid) and smaller hygroscopic dicarboxylic acids (e.g. malonic and oxalic acids), comparison of hygroscopic growth curves to Zdanovskii-Stokes-Robinson (ZSR) predictions suggests that the hygroscopic properties of many of the product mixtures are largely independent of the hygroscopicity of the individual components. This study provides a framework for future investigations to fully understand and predict the role of chemical reactions in altering atmospheric conditions that affect climate.

  15. Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment

    Pornchai Rojsitthisak

    2011-02-01

    Full Text Available A novel series of succinyl derivatives of three curcuminoids were synthesized as potential prodrugs. Symmetrical (curcumin and bisdesmethoxycurcumin and unsymmetrical (desmethoxycurcumin curcuminoids were prepared through aldol condensation of 2,4-pentanedione with different benzaldehydes. Esterification of these compounds with a methyl or ethyl ester of succinyl chloride gave the corresponding succinate prodrugs in excellent yields. Anticolon cancer activity of the compounds was evaluated using Caco-2 cells. The succinate prodrugs had IC50 values in the 1.8–9.6 ��M range, compared to IC50 values of 3.3–4.9 μM for the parent compounds. Curcumin diethyl disuccinate exhibited the highest potency and was chosen for stability studies. Hydrolysis of this compound in phosphate buffer at pH 7.4 and in human plasma followed pseudo first-order kinetics. In phosphate buffer, the kobs and t1/2 for hydrolysis indicated that the compound was much more stable than curcumin. In human plasma, this compound was able to release curcumin, therefore our results suggest that succinate prodrugs of curcuminoids are stable in phosphate buffer, release the parent curcumin derivatives readily in human plasma, and show anti-colon cancer activity.

  16. Out of plane distortions of the heme b of Escherichia coli succinate dehydrogenase.

    Quang M Tran

    Full Text Available The role of the heme b in Escherichia coli succinate dehydrogenase is highly ambiguous and its role in catalysis is questionable. To examine whether heme reduction is an essential step of the catalytic mechanism, we generated a series of site-directed mutations around the heme binding pocket, creating a library of variants with a stepwise decrease in the midpoint potential of the heme from the wild-type value of +20 mV down to -80 mV. This difference in midpoint potential is enough to alter the reactivity of the heme towards succinate and thus its redox state under turnover conditions. Our results show both the steady state succinate oxidase and fumarate reductase catalytic activity of the enzyme are not a function of the redox potential of the heme. As well, lower heme potential did not cause an increase in the rate of superoxide production both in vitro and in vivo. The electron paramagnetic resonance (EPR spectrum of the heme in the wild-type enzyme is a combination of two distinct signals. We link EPR spectra to structure, showing that one of the signals likely arises from an out-of-plane distortion of the heme, a saddled conformation, while the second signal originates from a more planar orientation of the porphyrin ring.

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

    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. PMID:26551652

  18. Significance of CO2 donor on the production of succinic acid by Actinobacillus succinogenes ATCC 55618

    Zou Wei; Zhu Li-Wen; Li Hong-Mei; Tang Ya-Jie

    2011-01-01

    Abstract Background Succinic acid is a building-block chemical which could be used as the precursor of many industrial products. The dissolved CO2 concentration in the fermentation broth could strongly regulate the metabolic flux of carbon and the activity of phosphoenolpyruvate (PEP) carboxykinase, which are the important committed steps for the biosynthesis of succinic acid by Actinobacillus succinogenes. Previous reports showed that succinic acid production could be promoted by regulating ...

  19. Genetic associations of body composition, flexibility and injury risk with ACE, ACTN3 and COL5A1 polymorphisms in Korean ballerinas

    Kim, Jun Ho; Jung, Eun Sun; Kim, Chul-Hyun; Youn, Hyeon; Kim, Hwa Rye

    2014-01-01

    [Purpose] The purpose of this study was to exam the association of body composition, flexibility, and injury risk to genetic polymorphisms including ACE ID, ACTN3 RX, and COL5A1 polymorphisms in ballet dancers in Korea. [Methods] For the purpose of this study, elite ballerinas (n = 97) and normal female adults (n = 203) aged 18 to 39 were recruited and these participants were tested for body weight, height, body fat, fat free mass, flexibility, injury risks on the joints and gene polymorphism...

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

    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

  1. Model-driven in Silico glpC Gene Knockout Predicts Increased Succinate Production from Glycerol in Escherichia Coli

    Bashir Sajo Mienda

    2015-04-01

    Full Text Available Metabolic engineered targeting for increased succinate production in Escherichia coli using glycerol as a low cost carbon source has attracted global attention in recent years. Succinate production in engineered E. coli has progressed significantly using an experimental trial and error approach. The use of a model-guided, targeted metabolic gene knockout prediction for increased succinate production from glycerol under anaerobic conditions in E. coli still remains largely underexplored. In this study, we applied a model-driven, targeted glpC/b2243 in silico metabolic gene knockout using E. coli genome scale model iJO1366 under the OptFlux software platform with the aim of predicting high succinate flux. The results indicated that the mutant model lacking the glpC/b2243 gene will demonstrate increased succinate flux that is 30% higher than its wild-type control model. We can hypothesize that an additional NADH molecule was generated following the deletion of the gene and/or the alternatively preferred GldA-DhaKLM fermentative route for glycerol metabolism in E. coli may have been activated. Although the exact metabolic mechanism involved in increasing the succinate flux still remains obscure; the current study informs other studies that a model-driven, metabolic glpC/b2243 gene knockout could be applicable in filling our knowledge gap using a comprehensive experimental inquiry in the future; leading to a better understanding of the underlying metabolic function of this gene in relation to succinate production in E. coli from glycerol.

  2. Preparation and performance of hydroxypropyl methylcellulose esters of substituted succinates for in vitro supersaturation of a crystalline hydrophobic drug.

    Yin, Ligeng; Hillmyer, Marc A

    2014-01-01

    We prepared hydroxypropyl methylcellulose (HPMC) esters of substituted succinates and examined their performance for improving the aqueous solubility of crystalline hydrophobic drugs in spray-dried dispersions (SDDs). From one HPMC, we synthesized five HPMC esters using various monosubstituted succinic anhydrides. These HPMC esters along with a commercial HPMC acetate succinate (HPMCAS) were spray-dried from solutions with phenytoin. The SDDs with different matrices at 10 wt % loading had very similar bulk properties with a minimal amount of detectable crystalline phenytoin as revealed by scanning electron microscopy (SEM), powder X-ray diffraction (powder XRD), and differential scanning calorimetry (DSC). In solution, while the SDD with HPMCAS was very effective at achieving high levels of phenytoin supersaturation initially, it was not competent at maintaining such supersaturation due to the rapid crystallization of the dissolved phenytoin. Alternatively, SDDs with several synthesized HPMC esters of substituted succinates not only achieved rather high initial supersaturation but also maintained high concentrations for extended time (i.e., 1.5 h and longer). Such maintenance was largely ascribed to the inhibition of phenytoin nucleation. Structure-property relationships were established, and the most successful systems contained a high degree of substitution and a combination of a thioether with neighboring weak electron-withdrawing groups in the substituted succinic anhydrides. The effective maintenance of supersaturated solutions was only found in SDDs with rather low drug loadings, which indicates the significance of sufficiently high concentrations of polymer additives in the dissolution media. PMID:24320108

  3. Performance analyses of a neutralizing agent combination strategy for the production of succinic acid by Actinobacillus succinogenes ATCC 55618.

    Wang, Cheng-Cheng; Zhu, Li-Wen; Li, Hong-Mei; Tang, Ya-Jie

    2012-05-01

    A neutralizing agent combination strategy was developed to enhance the succinic acid production by Actinobacillus succinogenes ATCC 55618. First, a maximal succinic acid production of 48.2 g/L was obtained at a culture pH of 7.5. Second, NaOH and KOH were screened to identify the optimal neutralizing agent for pH control. However, the production of succinic acid did not increase, and severe cell flocculation was observed due to a high concentration of metal ions when only one neutralizing agent was used to control pH. Finally, a neutralizing agent combination strategy was developed with a supply of neutralizing agents with OH(-) and carbonate. The cell flocculation was eliminated, and a maximum succinic acid production of 59.2 g/L was obtained with 5 M NaOH and 40 g/L of MgCO(3); this production was 27.9% higher than that obtained with NaOH alone. The results obtained in this study may be useful for the large-scale industrial production of succinic acid. PMID:22002101

  4. Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers

    Tseng, B. S.; Kasper, C. E.; Edgerton, V. R.

    1994-01-01

    The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.

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

    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.

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

    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.

  7. Mitochondrially Targeted Vitamin E Succinate Modulates Expression of Mitochondrial DNA Transcripts and Mitochondrial Biogenesis

    Truksa, Jaroslav; Dong, L.F.; Rohlena, Jakub; Stursa, J.; Vondrusová, Magdaléna; Goodwin, J.; Nguyen, M.; Klučková, Katarína; Rychtarčíková, Zuzana; Lettlová, Sandra; Spáčilová, Jana; Stapelberg, M.; Zoratti, M.; Neužil, Jiří

    2015-01-01

    Roč. 22, č. 11 (2015), s. 883-900. ISSN 1523-0864 R&D Projects: GA ČR GAP301/10/1937; GA AV ČR KAN200520703; GA ČR GAP305/12/1708; GA ČR GAP301/12/1851; GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:86652036 Keywords : ALPHA-TOCOPHERYL SUCCINATE * ELECTRON-TRANSPORT CHAIN * RESPIRATORY COMPLEX-II Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.407, year: 2014

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

    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 °C, pH of reaction system 8.4, concentration of starch slurry 36.8% (in proportion to water, w/w), amount of OSA 3% (...

  9. Polarographic study of dioxo-uranium(VI)-8-hydroxyquinoline-succinate system and thermodynamic parameters

    The dioxo-uranium(VI)-8-hydroxyquinoline-succinate system has been studied polarographically at constant ionic strength (μ = 0.6 M KCl) in aqueous alcohol (7:3) at different temperatures. The reduction of the simple and mixed complexes is reversible and diffusion controlled. The DeFord-Hume and Schaap-McMaster methods have been applied in the determination of composition and stability constants of the simple and mixed complexes respectively. The thermodynamic parameters ΔG, ΔH and ΔS have also been calculated. (author)

  10. Ercella succinigenes gen. nov., sp. nov., ananaerobic succinate-producing bacterium

    Van Gelder, A.H.; Sousa, D.Z.; Rijpstra, W.I.C.; J. S. Sinninghe Damsté; Stams, A. J. M.; Sánchez-Andrea, I.

    2014-01-01

    A novel anaerobic succinate-producing bacterium, strain ZWBT, was isolated from sludge collected from a biogas desulfurization bioreactor (Eerbeek, The Netherlands). Cells were non-spore forming, motile, slightly curved rods (0.4 to 0.5 µm in diameter and 2 to 3 µm in length), and stained Gram-negative. The temperature range for growth was 25 to 40°C, with an optimum at 37°C. The pH range for growth was 7.0 to 9.0, with an optimum at pH 7.5. Strain ZWBT ferments glycerol and several carbohydr...

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

    Amita Bhatia; Rahul K Gupta; Bhattacharya, Sati N.; Hyoung Jin Choi

    2012-01-01

    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 consider...

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

    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.

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

    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.

  14. EFFECT OF PROCESSING AND POLYMER VARIABLES ON INVITRO RELEASE OF METOPROLOL SUCCINATE EXTENDED RELEASE TABLETS

    N. N. Rajendran et al.

    2011-01-01

    The present study was aimed to develop an extended release tablet of Metoprolol Succinate for the treatment of hypertension. Four extended release formulations F1-F4 were developed using varying proportions of Hydroxyl propyl methyl cellulose K100M, Sodium carboxy methyl cellulose and Eudragit L30 D55 by wet granulation. Five extended release formulations F5-F9 containing HPMC K100M and HPMC 5cps in varying concentration were developed by direct compression. The physico-chemical and in-vitro...

  15. POLYSACCHARIDE GUM (KONDAGOGU GUM) MATRIX TABLETS FOR ORAL SUSTAINED DELIVERY OF METOPROLOL SUCCINATE

    N. Aswani; Vinay, S.; T. M. Pramod Kumar; Valluru Ravi; N Srujana

    2011-01-01

    The present study has been undertaken to develop a sustained-release tablet dosage form for metoprolol succinate using kondagugu gum as the rate-controlling polymer. The prepared tablets were coated will shellac as an enteric coat polymer and evaluated for tablet properties. In vitro release studies of prepared tablets were carried out for 2 hrs in pH 1.2 HCl buffer and 22 hrs in pH 6.8phosphate buffer. In addition, swelling, kinetics of drug release from the matrices and stability of the tab...

  16. Radiation-induced alterations in succinate dehydrogenase activity in the muscle of pigeon

    The histochemical changes in succinate dehydrogenase were investigated in pectoralis major muscle of pigeon exposed to sub-lethal dose (400 rad) of γ-irradiation. Biochemical study was also carried out after 200, 300 and 400 rad of irradiation. In the present study the overall decrease in enzyme activity could be due to the structural and/or functional damage to mitochondria after treatment of pigeon to different sub-lethal doses of γ-irradiation. The significance of these results has been discussed with special reference to oxidative metabolism. (author)

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

    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...

  18. Adsorption of alkenyl succinic anhydride from solutions in carbon tetrachloride on a fine magnetite surface

    Balmasova, O. V.; Ramazanova, A. G.; Korolev, V. V.

    2016-06-01

    The adsorption of alkenyl succinic anhydride from a solution in carbon tetrachloride on a fine magnetite surface at a temperature of 298.15 K is studied using fine magnetite, which forms the basis of magnetic fluids, as the adsorbent. An adsorption isotherm is recorded and interpreted in terms of the theory of the volume filling of micropores (TVFM). Adsorption process parameters are calculated on the basis of the isotherm. It is shown that at low equilibrium concentrations, the experimental adsorption isotherm is linear in the TVFM equation coordinates.

  19. Fabrication of Modified Release Tablet Formulation of Metoprolol Succinate using Hydroxypropyl Methylcellulose and Xanthan Gum

    Gohel, Mukesh C.; Parikh, Rajesh K.; Nagori, Stavan A.; Jena, Dillip G.

    2009-01-01

    The present investigation was undertaken to fabricate modified release tablet of metoprolol succinate using hydroxypropyl methylcellulose (HPMC) and xanthan gum as a matrixing agent. A 32 full factorial design was employed for the optimization of formulation. The percentage drug released at a given time (Y60, Y240 and Y720) and the time required for a given percentage of drug to be released (t50%) were selected as dependent variables. The in vitro drug dissolution study was carried out in pH ...

  20. [Age-related Peculiarities of Succinate Effect on Induced Lipid Peroxidation in Rat Liver Mitochondria].

    Grishina, E V; Khaustova, Ya V; Vasilieva, A A; Mayevsky, E I

    2015-01-01

    The antioxidant effect of succinate and 3-hydroxybutyrate oxidation on the kinetics of lipid peroxidation induced by ATP-Fe2+ complex in isolated rat liver mitochondria of old (1.0-1.5 years) and young (3 months) male rats was investigated. The rate of induced lipid peroxidation V(LPO) in rat liver mitochondria and the half-time of oxygen consumption Δt50, which included the lag period and the initiation. phase, was recorded polarographically. Without exogenous oxidative-substrates V(LPO) was slightly higher in mitochondria of old animals, but the onset of lipid peroxidation cascade was significantly earlier than in young animals. Incubation of mitochondria with 5mM succinate for 1 min inhibited V(LPO) by 15% in young animals and by 35% in old animals. However, only in mitochondria of old animals Δt50 increased by 19% as compared to lipid peroxidation without substrates. V(LPO) in mitochondria of young animals did not significantly change during 3-hydroxybutyrate oxidation, while in mitochondria of old animals it was reduced by 19% with a slight increase in Δt50. To simulate age-dependent dysfunction we damaged isolated mitochondria by a series of freeze-thaw cycles, which caused a significant increase of V(LPO) of.both age groups. Succinate oxidation inhibited V(LPO) in damaged mitochondria in all cases by 56%, as compared to V(LPO) without oxidative substrates and extended At50 twofold in mitochondria of young animals. Oxidation of 3-hydroxybutyrate had no effect on V(LPO) in damaged mitochondria regardless of animal, age and extended Δt50 by 48% in mitochondria of young animals. Thus, the antioxidant effect of succinate oxidation can prevent lipid peroxidation damage and may exhibit geroprotective action at the level of aging mitochondria. Therefore, the antioxidant effect is due to the process of substrate oxidation in the respiratory chain but not because of an interaction of their structures with membrane lipids per se. PMID:26394470

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

    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.

  2. NEW ANALYTICAL METHODS AND THEIR VALIDATION FOR THE ESTIMATION OF METOPROLOL SUCCINATE IN BULK AND MARKETED FORMULATION

    Viral Bechara

    2015-02-01

    Full Text Available Metoprolol succinate is cardiovascular agent. Mainly used for the treatment of hypertension, heart failure, and cardiovascular diseases. Purpose: Analytical methods are required to characterize drug substances and drug products composition during all phases of pharmaceutical development. Development of methods to achieve the final goal of ensuring the quality of drug substances and drug products must be implemented in conjunction with an understanding of the chemical behavior and physicochemical properties of the drug substance. This determination requires highly sophisticated instruments and methods like HPLC, HPTLC and Spectrophotometer. Hence there was a need for the development of newer, simple, sensitive, rapid, accurate and reproducible analytical methods for the routine estimation of metoprolol succinate in bulk and pharmaceutical dosage form. Methods: The present work describes two new spectrophotometric methods for the determination of metoprolol succinate in bulk and marketed formulations. Method A is based on oxidation reaction. Metoprolol succinate in presence of acidic medium reacts with excess amount of chloramine-T and remaining chloramine-T react with malachite green to produce orange colour chromogen which showed λmax at 516 nm. In Method B, the drug was diazotised with sodium nitrite in presence of hydrochloric acid and then it was coupled with β-naphthol in alkaline medium. Which produce red colour chromogen which showed λmax at 688 nm. Results: The linearity was found in concentration range of 5-30μg/ml for both method A and method B. The correlation coefficient was found to be 0.9983 and 0.9993 for method A and method B respectively. The methods were validated as per ICH guidelines. The LOD and LOQ for estimation of Metoprolol succinate were found as 0.0773, 0.2343 for method A and 0.0667, 0.2021 for method B respectively. Conclusion: Proposed methods were successfully applied for the quantitative estimation of

  3. Activation of glyoxylate pathway without the activation of its related gene in succinate-producing engineered Escherichia coli.

    Zhu, Li-Wen; Li, Xiao-Hong; Zhang, Lei; Li, Hong-Mei; Liu, Jian-Hua; Yuan, Zhan-Peng; Chen, Tao; Tang, Ya-Jie

    2013-11-01

    For the first time, glyoxylate pathway in the biosynthesis of succinate was activated without the genetic manipulations of any gene related with glyoxylate pathway. Furthermore, the inactivation of succinate biosynthesis by-products genes encoding acetate kinase (ackA) and phosphotransacetylase (pta) was proven to be the key factor to activate glyoxylate pathway in the metabolically engineered Escherichia coli under anaerobic conditions. In order to enhance the succinate biosynthesis specifically, the genes (i.e., ldhA, ptsG, ackA-pta, focA-pflB, adhE) that disrupt by-products biosynthesis pathways were combinatorially deleted, while the E. coli malate dehydrogenase (MDH) was overexpression. The highest succinate production of 150.78 mM was obtained with YJ003 (ΔldhA, ptsG, ackA-pta), which were 5-folds higher than that obtained with wild type control strain DY329 (25.13 mM). For further understand the metabolic response as a result of several genetic manipulations, an anaerobic stoichiometric model that takes into account the glyoxylate pathway have successfully been implemented to estimate the intracellular fluxes in various recombinant E. coli. The fraction to the glyoxylate pathway from OAA in DY329 was 0 and 31% in YJ003, which indicated that even without the absence of the iclR mutation; the glyoxylate pathway was also activated by deleting the by-products biosynthetic genes, and to be responsible for the higher succinate yields. For further strengthen glyoxylate pathway, a two-stage fed-batch fermentation process was developed by using a 600 g l(-1) glucose feed to achieve a cell growth rate of 0.07 h(-1) in aerobic fermentation, and using a 750 g l(-1) glucose feed to maintain the residual glucose concentration around 40 g l(-1) when its residual level decreased to 10gl(-1) in anaerobic fermentation. The best mutant strain YJ003/pTrc99A-mdh produces final succinate concentration of 274 mM by fed-batch culture, which was 10-folds higher than that obtained

  4. Freeze drying: exploring potential in development of orodispersible tablets of sumatriptan succinate.

    Gugulothu, Dalapathi; Desai, Preshita; Pandharipande, Pranav; Patravale, Vandana

    2015-03-01

    The present investigation is aimed at development and characterization of sumatriptan succinate orodispersible tablets (ODTs) prepared by freeze drying technology. The tablet excipients were screened and the composition was optimized based on parameters which involved general appearance, tablet size and shape, uniformity of weight, mechanical properties, surface pH, moisture analysis, drug content, wetting time, in vitro and in vivo disintegration time. Furthermore, fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron micrograph of cross-section of the tablet and in vitro dissolution studies were performed. Studies revealed that formulation containing gelatin-mannitol (3.75% w/v and 3.5% w/v, respectively) with camphor as a volatile pore forming agent exhibited superior properties with disintegration time of less than 10 s. Furthermore, in vitro release studies revealed 90% release of drug from developed dosage form within 10 min, thus suggesting rapid drug dissolution followed by faster onset of action, which forms a strong rationale for development of ODTs of sumatriptan succinate. The developed technology is simple, which involves few steps and can be easily scaled up. Thus, it holds enormous potential for commercial exploitation. PMID:24384027

  5. Study on fluorescence properties of carbogenic nanoparticles and their application for the determination of ferrous succinate

    Sun Wen [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Du Yingxiang, E-mail: du_yingxiang@126.co [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China) and Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China) and Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China); Wang Yunqing [Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China)

    2010-08-15

    A new type of fluorescent nanomaterial named carbogenic nanoparticles (NPs) has drawn considerable attention recently. In this study, we adopted a direct and simple synthetic method to produce the carbogenic NPs and investigated the fluorescence properties of the as-prepared carbogenic NPs in detail. It was found that the fluorescence of carbogenic NPs was stable with the variance of environmental conditions such as pH, temperature and UV irradiation. More interestingly, we found carbogenic NPs exhibited high selectivity and sensitivity towards ferric ions. Under optimum conditions, a good linear relationship could be obtained between the fluorescence intensity and concentration of ferric ions in the range of 5.0x10{sup -5}-5.0x10{sup -4} mol L{sup -1}, and the limit of detection is 11.2 {mu}mol L{sup -1}. Based on the fluorescence quenching of carbogenic NPs, a rapid and specific quantitative method was proposed for the determination of ferrous succinate. The content of ferrous succinate in commercial tablets determined by the present method was agreed with the spectrophotometric method results and the reproducibility and the recovery of the proposed method were satisfactory.

  6. Study on fluorescence properties of carbogenic nanoparticles and their application for the determination of ferrous succinate

    A new type of fluorescent nanomaterial named carbogenic nanoparticles (NPs) has drawn considerable attention recently. In this study, we adopted a direct and simple synthetic method to produce the carbogenic NPs and investigated the fluorescence properties of the as-prepared carbogenic NPs in detail. It was found that the fluorescence of carbogenic NPs was stable with the variance of environmental conditions such as pH, temperature and UV irradiation. More interestingly, we found carbogenic NPs exhibited high selectivity and sensitivity towards ferric ions. Under optimum conditions, a good linear relationship could be obtained between the fluorescence intensity and concentration of ferric ions in the range of 5.0x10-5-5.0x10-4 mol L-1, and the limit of detection is 11.2 μmol L-1. Based on the fluorescence quenching of carbogenic NPs, a rapid and specific quantitative method was proposed for the determination of ferrous succinate. The content of ferrous succinate in commercial tablets determined by the present method was agreed with the spectrophotometric method results and the reproducibility and the recovery of the proposed method were satisfactory.

  7. Crystallization and degradation behaviors of poly(butylene succinate)/poly(Z-L-lysine) composites

    Tan, Licheng; Hu, Jun; Ye, Suwen; Wei, Junchao, E-mail: weijunchao@ncu.edu.cn; Chen, Yiwang

    2014-01-10

    Highlights: • A new biodegradable poly(butylene succinate) (PBS)/poly(Z-L-lysine) (PZlys) composites were successfully prepared through physical blend. • PZlys may greatly affected the crystallization behaviors of PBS without changing its crystalline structure. • The degradation speed of PBS may be greatly accelerated by introduction of PZlys in PBS matrix. - Abstract: A new type of biodegradable poly(butylene succinate) (PBS)/poly(Z-L-lysine) (PZlys) composites were prepared. The crystallization behaviors were investigated by differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and polarizing optical microscopy (POM) and the results showed that PZlys can restrict the crystallization of PBS, the crystallization speed of PBS/PZlys were slower than that of PBS, and the crystallization degree of the composites were smaller than that of PBS. However, the WAXD results showed that the incorporation of PZlys did not change the crystalline structure of PBS. The in vitro degradation experiments demonstrated that the degradation speed of the composites were faster than that of PBS. Moreover, the mechanical properties of the composites showed that the composites with a proper composition (for example, 80/20) can keep the mechanical properties of PBS without evident difference, which implied that the composites might be potentially useful as biodegradable materials.

  8. Crystallization and degradation behaviors of poly(butylene succinate)/poly(Z-L-lysine) composites

    Highlights: • A new biodegradable poly(butylene succinate) (PBS)/poly(Z-L-lysine) (PZlys) composites were successfully prepared through physical blend. • PZlys may greatly affected the crystallization behaviors of PBS without changing its crystalline structure. • The degradation speed of PBS may be greatly accelerated by introduction of PZlys in PBS matrix. - Abstract: A new type of biodegradable poly(butylene succinate) (PBS)/poly(Z-L-lysine) (PZlys) composites were prepared. The crystallization behaviors were investigated by differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and polarizing optical microscopy (POM) and the results showed that PZlys can restrict the crystallization of PBS, the crystallization speed of PBS/PZlys were slower than that of PBS, and the crystallization degree of the composites were smaller than that of PBS. However, the WAXD results showed that the incorporation of PZlys did not change the crystalline structure of PBS. The in vitro degradation experiments demonstrated that the degradation speed of the composites were faster than that of PBS. Moreover, the mechanical properties of the composites showed that the composites with a proper composition (for example, 80/20) can keep the mechanical properties of PBS without evident difference, which implied that the composites might be potentially useful as biodegradable materials

  9. Ercella succinigenes gen. nov., sp. nov., an anaerobic succinate-producing bacterium.

    van Gelder, Antonie H; Sousa, Diana Z; Rijpstra, W Irene C; Damsté, Jaap S Sinninghe; Stams, Alfons J M; Sánchez-Andrea, Irene

    2014-07-01

    A novel anaerobic succinate-producing bacterium, strain ZWB(T), was isolated from sludge collected from a biogas desulfurization bioreactor (Eerbeek, the Netherlands). Cells were non-spore-forming, motile, slightly curved rods (0.4-0.5 µm in diameter and 2-3 µm in length), and stained Gram-negative. The temperature range for growth was 25-40 °C, with an optimum at 37 °C. The pH range for growth was 7.0-9.0, with an optimum at pH 7.5. Strain ZWB(T) was able to ferment glycerol and several carbohydrates mainly to H2, succinate and acetate. Sulfur and fumarate could be used as electron acceptors by strain ZWB(T). The G+C content of the genomic DNA was 37.6 mol%. The most abundant fatty acids were iso-C14 : 0 and iso-C16 : 0 DMA. On the basis of 16S rRNA gene sequence similarity, strain ZWB(T) belongs to the family Ruminococcaceae and it is distantly related to Saccharofermentans acetigenes JCM 14006(T) (92.1%). Based on the physiological features and phylogenetic analysis, strain ZWB(T) represents a novel species of a new genus, for which the name Ercella succinigenes gen. nov., sp. nov. is proposed. The type strain of Ercella succinigenes is ZWB(T) ( = DSM 27333(T) = JCM 19283(T)). PMID:24776531

  10. Precursors for sergeant-and-soldiers experiments: dimethyl succinic acid on Cu(110)

    Karageorgaki, Chrysanthi; Roth, Christian; Parschau, Manfred; Ernst, Karl-Heinz [EMPA, Swiss Federal Laboratories for Materials Science and Technology, Duebendorf (Switzerland)

    2011-07-01

    In order to better understand chiral recognition at the molecular level, we are currently studying interactions between different chiral butanedioc acids, like tartaric acid (TA), malic acid (MA) and 2,3-dimethyl succinic acid (DMSU) as well as achiral analogues like succinic acid (SU), meso-TA and meso-DMSU on metal surfaces. This led to first a observation of chiral amplification 2D crystals via the so-called ''sergeant-and soldiers effect''. In order to discriminate if through-substrate or lateral hydrogen bonding dominates the chiral recognition at surfaces, we currently synthesize chiral DMSU, i.e., replacing the hydroxyl groups of TA by methyl. Here we present LEED, XPS, TPD and RAIRS results of achiral meso-DMSU (HOOC-CH(CH{sub 3})-CH(CH{sub 3})-COOH) on Cu(110). Besides coverage-dependent ''surface-explosion'' decomposition chemistry and ordered C{sub 2}-symmetric structures, DMSU spontaneously undergoes symmetry breaking, observed as superposition of mirror domains in LEED, which makes this system indeed interesting for doping experiments with chiral DMSU.

  11. EFFECT OF PROCESSING AND POLYMER VARIABLES ON INVITRO RELEASE OF METOPROLOL SUCCINATE EXTENDED RELEASE TABLETS

    N. N. Rajendran et al.

    2011-12-01

    Full Text Available The present study was aimed to develop an extended release tablet of Metoprolol Succinate for the treatment of hypertension. Four extended release formulations F1-F4 were developed using varying proportions of Hydroxyl propyl methyl cellulose K100M, Sodium carboxy methyl cellulose and Eudragit L30 D55 by wet granulation. Five extended release formulations F5-F9 containing HPMC K100M and HPMC 5cps in varying concentration were developed by direct compression. The physico-chemical and in-vitro release characteristics of all the formulations were investigated and compared. Two formulations, F7 and F8 have shown not more 25% drug release in 1st h, 20-40% drug release at 4th h, 40-60% drug release at 8th h and not less than 80% at 20th h and the release pattern conform with USP specification for 24 h extended release formulation. It can be conclusively stated that optimum concentration of HPMC K100M (58-65% by direct compression method can yield an extended release of Metoprolol succinate for 24 hours.

  12. FORMULATION AND EVALUATION OF METOPROLOL SUCCINATE PULSATILE DRUG DELIVERY SYSTEM FOR CHRONO BIOLOGICAL DISORDER: ANTI HYPERTENSION

    A. Anil Kumar et al

    2012-10-01

    Full Text Available The objective of the present study was to develop and evaluate an oral pulsatile drug delivery system to mimic the circadian rhythm of the disease by releasing the drug with a distinct predetermined log time of 5 hrs (+ 0.25 hrs. The basic design of the pulse in cap formulation of metoprolol provides time controlled release to treat the nocturnal symptoms of hypertension and angina pectoris. The pulsincap formulation of Metoprolol provides time controlled release to treat the nocturnal symptoms of hypertension and angina pectoris. If the formulation is administered in the night at 10.00 pm symptoms that are experienced in early morning hours could be avoided. In the present study, polymer such as Guargum selected for colon targeting of Metoprolol succinate. Metoprolol succinate granules were prepared using these polymers to prolong and target to the colon. Granules were prepared by wet granulation technique using different polymers in different ratios. These granules filled into the formaldehyde treated capsules and plugged with optimized HPMC plug, to maintain the 5hr lag time. Finally capsules are enteric coated with enteric coating polymers and conducted dissolution studies with different pH mediums.

  13. Conformation of succinic acid: its pH dependence by Licry-NMR analysis

    Chidichimo, G.; Formoso, P.; Golemme, A.; Imbardelli, D.

    The conformations of fully protonated (H2SA), fully deprotonated (SA=) and monoprotonated (HSA-) succinic acid have been investigated by means of nuclear magnetic resonance spectroscopy in liquid crystal mesophases (Licry-NMR). H-H and 13C-H direct dipolar couplings have been determined by measuring 1H-NMR and 13C-NMR spectra from quaternary nematic-lyotropic solutions of myristyltrimethylammonium bromide (MTAB), decanol, deuterated water and succinic acid (in each of its three different protonated forms). Direct dipolar couplings have been used to investigate the conformational equilibrium of the molecule in its three different protonation forms. Data could be interpreted in terms of a single conformation for each of the investigated forms. The dihedral angle between the H3-C5'-C5 and the C5'-C5-H1 planes gradually increases when going from the fully protonated H2SA species to the SA= ions. Our findings are different from those obtained by other authors by analysis of Jij couplings. In that case an equilibrium conformation between the gauche and trans conformers had been obtained.

  14. Crystallization and melting behavior of poly (ethylene succinate) in presence of graphene nanoplatelets

    Highlights: • Poly (ethylene succinate)/graphene nanocomposites were characterized in this work. • Dynamic and isothermal crystallization rates were enhanced upon graphene addition. • Overall crystallinity and melting remained almost unchanged in presence of graphene. • Graphene changed crystal perfection and its effect was found concentration-dependent. - Abstract: In this study, poly (ethylene succinate)/graphene nanoplatelets composites were prepared via solution casting method in different compositions and analyzed via differential scanning calorimetry. Crystallization and melting characteristics in both dynamic (non-isothermal) and isothermal modes were investigated at various cooling rates and isothermal temperatures. It was confirmed that graphene, while being incompatible with the matrix polymer, could act as nucleating agent so that hot (melt) crystallization rates, intensities, and positions were increased in the dynamic mode. However, the overall crystallinity remained almost unchanged. Cold crystallization was also decreased to lower temperatures on graphene addition; however its enthalpy was also reduced. Similar findings were observed for the isothermal mode, but to a lesser extent. The presence of graphene changed the perfection of crystals as their thermodynamic stability against heating and recrystallization behavior varied

  15. COL5A1: Fine genetic mapping, intron/exon organization, and exclusion as candidate gene in families with tuberous sclerosis complex 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II

    Greenspan, D.S. [Univ. of Wisconsin, Madison, WI (United States); Papenberg, K.A.; Marchuk, D.A. [Duke Univ., Durham, NC (United States)] [and others

    1994-09-01

    Type V collagen is the only fibrillar collagen which has yet to be implicated in the pathogenesis of genetic diseases in humans or mice. To begin examining the possible role of type V collagen in genetic disease, we have previously mapped COL5A1, the gene for the {alpha}1 chain of type V collagen, to 9q23.2{r_arrow}q34.3 and described two restriction site polymorphisms which allowed us to exclude COL5A1 as candidate gene for nail-patella syndrome. We have now used these polymorphisms to exclude COL5A1 as candidate gene for tuberous sclerosis complex 1 and Ehlers-Danlos syndrome type II. In addition, we describe a CA repeat, with observed heterozygosity of about 0.5, in a COL5A1 intron, which has allowed us to exclude COL5A1 as a candidate gene in hereditary hemorrhagic telangiectasia and to place COL5A1 on the CEPH family genetic map between markers D9S66 and D9S67. We have also determined the entire intron/exon organization of COL5A1, which will facilitate characterization of mutations in genetic diseases with which COL5A1 may be linked in future studies.

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

    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 and...

  17. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

    2015-01-01

    Roč. 15, č. 401 (2015). ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.362, year: 2014

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

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

    2014-01-01

    Biogas is an attractive renewable energy carrier. However, it contains CO2 which limits certain applications of biogas. Here we report a novel approach for removing CO2 from biogas and capturing it as a biochemical through a biological process. This approach entails converting CO2 into bio-succin...

  19. Linkage and radiation hybrid mapping of the porcine gene for subunit C of succinate dehydrogenase complex (SDHC)

    Stratil, Antonín; Reiner, G.; Peelman, L. J.; Poucke, M.; Geldermann, H.

    2001-01-01

    Roč. 32, č. 2 (2001), s. 110-112. ISSN 0268-9146 R&D Projects: GA AV ČR KSK5052113; GA ČR GA523/00/0669 Keywords : succinate dehydrogenase complex Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.020, year: 2001

  20. Bid integrates intrinsic and extrinsic signaling in apoptosis induced by alpha-tocopheryl succinate in human gastric carcinoma cells

    Zhao, Y.; Li, R.; Xia, W.; Neužil, Jiří; Lu, Y.; Zhang, H.; Zhao, X.; Zhang, X.; Sun, C.; Wu, K.

    2010-01-01

    Roč. 288, č. 1 (2010), s. 42-49. ISSN 0304-3835 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Alpha-tocopheryl succinate * signaling * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.864, year: 2010

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

    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.

  2. Enhanced cycling performance of lithium metal secondary batteries with succinic anhydride as an electrolyte additive

    The effect of succinic anhydride (SA) as an electrolyte additive on the cycling performance of Li electrode is discussed. As the SA content in the electrolyte increased from 2 to 5 to 10 wt%, the capacity retention of LiCoO2/Li cell is greatly improved owing to the modification of the solid electrolyte interphase (SEI) layer and the suppression of dendrite growth on the Li electrode. In particular, when 10 wt% SA is introduced into the electrolyte, the Li electrode thickness increases only about 45 μm (from 100 to 145 μm) after 40 cycles, whereas an increase of about 210 μm occurs without SA. This amazing enhancement in cycling performance is also augmented by a much smaller increase in the bulk resistance of the LiCoO2/Li cell after cycling with 10 wt% SA

  3. Succinic acid production from duckweed (Landoltia punctata) hydrolysate by batch fermentation of Actinobacillus succinogenes GXAS137.

    Shen, Naikun; Wang, Qingyan; Zhu, Jing; Qin, Yan; Liao, Siming; Li, Yi; Zhu, Qixia; Jin, Yanling; Du, Liqin; Huang, Ribo

    2016-07-01

    Duckweed is potentially an ideal succinic acid (SA) feedstock due to its high proportion of starch and low lignin content. Pretreatment methods, substrate content and nitrogen source were investigated to enhance the bioconversion of duckweed to SA and to reduce the costs of production. Results showed that acid hydrolysis was an effective pretreatment method because of its high SA yield. The optimum substrate concentration was 140g/L. The optimum substrate concentration was 140g/L. Corn steep liquor powder could be considered a feasible and inexpensive alternative to yeast extract as a nitrogen source. Approximately 57.85g/L of SA was produced when batch fermentation was conducted in a 1.3L stirred bioreactor. Therefore, inexpensive duckweed can be a promising feedstock for the economical and efficient production of SA through fermentation by Actinobacillus succinogenes GXAS137. PMID:27023386

  4. Immunolocalization of succinate dehydrogenase in the esophagus epithelium of domesticated mammals

    W. Meyer

    2013-05-01

    Full Text Available Using immunohistochemistry and transmission electron microscopy (TEM, the esophagus epithelia of seven domesticated mammals (horse, cattle, goat, pig, dog, laboratory rat, cat of three nutrition groups (herbivorous, omnivorous, carnivorous were studied to get first information about energy generation, as demonstrated by succinate dehydrogenase (SDH activities. Distinct reaction intensities could be observed in all esophageal cell layers of the different species studied reflecting moderate to strong metabolic activities. The generally strong staining in the stratum basale indicated that new cells are continuously produced. The latter feature was confirmed by a thick, and in the horse generally highly active stratum spinosum. Only in the pig, reaction intensity variations occurred, obviously related to differences in physical feed quality or restricted feed allocation. The immunohistochemical results were corroborated by the presence of intact mitochondria in the esophageal cells of all species and nutrition types studied, except for the horse. Possible relationships between SDH reaction intensities and feed structure, mass or consistency are discussed.

  5. Preparation and Characterization of Octenyl Succinic Anhydride Modified Taro Starch Nanoparticles.

    Jiang, Suisui; Dai, Lei; Qin, Yang; Xiong, Liu; Sun, Qingjie

    2016-01-01

    The polar surface and hydrophilicity of starch nanoparticles (SNPs) result in their poor dispersibility in nonpolar solvent and poor compatibility with hydrophobic polymers, which limited the application in hydrophobic system. To improve their hydrophobicity, SNPs prepared through self-assembly of short chain amylose debranched from cooked taro starch, were modified by octenyl succinic anhydride (OSA). Size via dynamic light scattering of OSA-SNPs increased compared with SNPs. Fourier transform infrared spectroscopy data indicated the OSA-SNPs had a new absorption peak at 1727 cm-1, which was the characteristic peak of carbonyl, indicating the formation of the ester bond. The dispersibility of the modified SNPs in the mixture of water with nonpolar solvent increased with increasing of degree of substitution (DS). OSA-SNPs appear to be a potential agent to stabilize the oil-water systems. PMID:26918568

  6. Preparation and Characterization of Octenyl Succinic Anhydride Modified Taro Starch Nanoparticles.

    Suisui Jiang

    Full Text Available The polar surface and hydrophilicity of starch nanoparticles (SNPs result in their poor dispersibility in nonpolar solvent and poor compatibility with hydrophobic polymers, which limited the application in hydrophobic system. To improve their hydrophobicity, SNPs prepared through self-assembly of short chain amylose debranched from cooked taro starch, were modified by octenyl succinic anhydride (OSA. Size via dynamic light scattering of OSA-SNPs increased compared with SNPs. Fourier transform infrared spectroscopy data indicated the OSA-SNPs had a new absorption peak at 1727 cm-1, which was the characteristic peak of carbonyl, indicating the formation of the ester bond. The dispersibility of the modified SNPs in the mixture of water with nonpolar solvent increased with increasing of degree of substitution (DS. OSA-SNPs appear to be a potential agent to stabilize the oil-water systems.

  7. Discovery of Potent Succinate-Ubiquinone Oxidoreductase Inhibitors via Pharmacophore-linked Fragment Virtual Screening Approach.

    Xiong, Li; Zhu, Xiao-Lei; Gao, Hua-Wei; Fu, Yu; Hu, Sheng-Quan; Jiang, Li-Na; Yang, Wen-Chao; Yang, Guang-Fu

    2016-06-22

    Succinate-ubiquinone oxidoreductase (SQR) is an attractive target for fungicide discovery. Herein, we report the discovery of novel SQR inhibitors using a pharmacophore-linked fragment virtual screening approach, a new drug design method developed in our laboratory. Among newly designed compounds, compound 9s was identified as the most potent inhibitor with a Ki value of 34 nM against porcine SQR, displaying approximately 10-fold higher potency than that of the commercial control penthiopyrad. Further inhibitory kinetics studies revealed that compound 9s is a noncompetitive inhibitor with respect to the substrate cytochrome c and DCIP. Interestingly, compounds 8a, 9h, 9j, and 9k exhibited good in vivo preventive effects against Rhizoctonia solani. The results obtained from molecular modeling showed that the orientation of the R(2) group had a significant effect on binding with the protein. PMID:27225833

  8. Synthesis, characterization and thermal behavior of solid state compounds of heavy trivalent lanthanide succinates

    Highlights: ► Thermal stability of compounds was investigated. ► Determination of the gaseous products released. ► The results also provided information concerning the denticity of the ligand. - Abstract: Solid-state Ln–L compounds, where Ln stands for heavy trivalent lanthanides or yttrium(III) (Tb–Lu, Y) and L is succinate, have been synthesized. Simultaneous thermogravimetry and differential thermal analysis (TG-DTA), differential scanning calorimetry (DSC), infrared spectroscopy, TG-DTA coupled to FTIR, elemental analysis, X-ray powder diffractometry and complexometry were used to characterize and study the thermal behavior of these compounds. For the terbium to thulium and yttrium compounds, the dehydration, as well the thermal decomposition of the anhydrous compound occurs in two consecutive steps, while ytterbium and lutetium the dehydration occurs in a single step. The results also led to information about the ligand's denticity, thermal stability and thermal decomposition of these compounds

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

    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. PMID:26797225

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

    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. Hydrocortisone sodium succinate suppressed production of interleukin-10 by human peripheral blood mononuclear cells: clinical significance.

    Kohka H

    1999-02-01

    Full Text Available Corticoids are well known for their immunosuppressive properties. Interleukin-10 (IL-10 is an intrinsic antiinflammatory peptide in immune diseases, originally identified as cytokine synthesis inhibitory factor. We examined the effect of hydrocortisone sodium succinate (HSS on the production of IL-10 by human peripheral blood mononuclear cells (PBMCs. PBMCs from healthy volunteers and cancer-burden patients were preincubated separately with or without HSS for 1 h, then stimulated with 5 microg/ml lipopolysaccharide (LPS. Production of IL-10 by human PBMCs was detected with LPS stimulation and its production was higher in cancer-burden patients than in normal volunteers, although this was not statistically significant. HSS suppressed production of IL-10 by LPS-stimulated PBMCs in a dose-dependent manner both in normal volunteers and in cancer-burden patients. These results indicate that, in addition to their antiinflammatory properties, corticoids act to restore the immunosuppressive states even in cancer-burden states.

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

    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.

  13. Preparation of nanocomposites based on poly(Butylene Succinate) and montmorillonite organoclay via in situ polymerization

    Nanocomposites based on poly(butylene succinate) (PBS) and organophilic montmorillonite were synthesized via in situ polymerization using three different clay compositions (4, 6 and 8 wt%). The products were characterized by several different techniques. X-ray diffraction was useful to confirm the increase of the interlayer spacing of the clay due to the presence of the polymer chains among layers. Thermal analysis indicated that the polymerization method chosen led to materials with lower thermal stability compared to the pure PBS, due to the difficulty of chain growth in the presence of the clay. Low-field NMR technique was used to assess clay dispersion in the polymer, with exfoliated structures predominating in the nanocomposites. (author)

  14. FORMULATION AND RELEASE CHARACTERISTICS OF HPMC MATRIX TABLETS OF METOPROLOL SUCCINATE

    Sobhita Rani P et al.

    2012-04-01

    Full Text Available The objective of this study was to design and evaluate oral sustained drug delivery system for Metoprolol succinate using pH sensitive polymer HPMC and sodium alginate and to evaluate its efficacy in reducing the hypertension. The drug filler blend was mixed with various concentrations of hydrophilic polymers such as HPMC, sodium alginate and combination of both the matrixing agents. The tablets were prepared by wet granulation method. Matrix tablets were evaluated for weight variation, content uniformity, friability, hardness, thickness, swelling index, and in vitro dissolution. The assays of different formulations were determined and the drug content was found between 85-115%. The weight variation was observed to be within the prescribed limits for each formulation. In-Vitro drug release studies carried out with different formulation tablets in 0.1N Hcl for 2hrs, pH 6.8 phosphate buffer for 12hrs. Up to 2 hr study the formulation shows low release in gastric medium (0.1N Hcl. From the 2 hr up to 12 hr study percentage of drug release was increased in intestinal fluid (pH 6.8 buffer. In these studies, the F1, F3 and F5 formulations showed the better drug release in compared to others. By swelling index it was concluded that the tablet shows matrix type of release in the intestine. These formulations follow zero order release kinetics known by Higuchi plot. The matrix formulation F1, F3 and F5 showed sustained release of Metoprolol succinate by the diffusion mechanism. Studies reveal that HPMC, sodium alginate sustained release matrix tablets can drive and make available the intact drug for local action for hypertension treatment.

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

    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.

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

    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.

  17. Mechanical and thermal properties of basalt fiber reinforced poly(butylene succinate) composites

    Highlights: ► Novel basalt fiber-reinforced biodegradable poly(butylene succinate) composites have been successfully fabricated with various fiber loadings. ► The tensile and flexural properties of the PBS matrix resin are improved significantly by increasing the fiber loading in the composites. ► The impact strength of the BF/PBS composite decreases with the addition fibers primarily and increases with increasing fiber loading due to energy dissipation when the fibers are pulled out. ► Heat deflection temperature tests clearly show that the HDT of the basalt fiber reinforced PBS composites is significantly higher than the HDT of the PBS resin. - Abstract: Basalt fiber (BF) reinforced poly(butylene succinate) (PBS) composites have been fabricated with different fiber contents by a injection molding method and their tensile, flexural and impact properties, as well as thermal stability have been investigated. The tensile and flexural properties of the PBS matrix resin are improved markedly by increasing the fiber contents in the composites. The values are relatively higher than the natural fiber/PP systems reported earlier by other research groups. The heat deflection temperature (HDT) and Vicat softening temperature (VST) of the composites are significantly higher than those of the neat PBS resin. Scanning electron microscopy (SEM) conducted on the fracture surfaces of the composites reveals superior interfacial linkage between the basalt fibers and PBS matrix. The results suggest that the BF/PBS composites may be a potential candidate of PP or PP composites to manufacturing some daily commodities to solve the “white pollution” in environmental management.

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

    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.

  19. Targeting succinate:ubiquinone reductase potentiates the efficacy of anticancer therapy.

    Kruspig, Björn; Valter, Kadri; Skender, Belma; Zhivotovsky, Boris; Gogvadze, Vladimir

    2016-08-01

    Mitochondria play a pivotal role in apoptosis: permeabilization of the outer mitochondrial membrane and the release of pro-apoptotic proteins from the intermembrane space of mitochondria are regarded as the key event in apoptosis induction. Here we demonstrate how non-toxic doses of the mitochondrial Complex II inhibitor thenoyltrifluoroacetone (TTFA), which specifically inhibits the ubiquinone-binding site of succinate dehydrogenase (SDH), synergistically stimulated cell death, induced by harmless doses of cisplatin in a panel of chemoresistant neuroblastoma cell lines. Apoptotic cell death was confirmed by cytochrome c release from the mitochondria, cleavage of poly ADP-ribose polymerase, processing of caspase-3, which is an important executive enzyme in apoptosis, and caspase-3-like activity. Methyl malonate, an inhibitor of the SDHA subunit partially reversed apoptosis stimulated by TTFA in SK-N-BE(2) neuroblastoma cells (NB), indicating that sensitization requires oxidation of succinate. In contrast, in IMR-32 NB cells, the same concentrations of TTFA markedly suppressed cisplatin-induced apoptosis. Comparison of oxygen consumption in cisplatin-resistant SK-N-BE(2) and cisplatin-sensitive IMR-32 cells clearly demonstrated impaired Complex II activity in IMR-32 cells. We also found that in SK-N-BE(2) cells co-treatment with cisplatin and TTFA markedly stimulated formation of reactive oxygen species (ROS), whereas in IMR cells, cisplatin-mediated ROS production was attenuated by TTFA, which explains apoptosis suppression in these cells. Thus, functionally active SDH is a prerequisite for the ROS-mediated sensitization to treatment by TTFA. PMID:27140478

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

    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

  1. Mechanical and thermal properties of basalt fiber reinforced poly(butylene succinate) composites

    Zhang Yihe, E-mail: zyh@cugb.edu.cn [State Key Laboratory of Geological Processes and Mineral Resources, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences (Beijing), Beijing 100083 (China); Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon (Hong Kong); Yu Chunxiao [State Key Laboratory of Geological Processes and Mineral Resources, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences (Beijing), Beijing 100083 (China); Chu, Paul K. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon (Hong Kong); Lv Fengzhu [State Key Laboratory of Geological Processes and Mineral Resources, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences (Beijing), Beijing 100083 (China); Zhang Changan; Ji Junhui [Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100101 (China); Zhang Rui [State Key Laboratory of Geological Processes and Mineral Resources, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences (Beijing), Beijing 100083 (China); Wang Heli [School of Materials Science and Technology, China University of Geosciences (Beijing), Beijing 100083 (China)

    2012-04-16

    Highlights: Black-Right-Pointing-Pointer Novel basalt fiber-reinforced biodegradable poly(butylene succinate) composites have been successfully fabricated with various fiber loadings. Black-Right-Pointing-Pointer The tensile and flexural properties of the PBS matrix resin are improved significantly by increasing the fiber loading in the composites. Black-Right-Pointing-Pointer The impact strength of the BF/PBS composite decreases with the addition fibers primarily and increases with increasing fiber loading due to energy dissipation when the fibers are pulled out. Black-Right-Pointing-Pointer Heat deflection temperature tests clearly show that the HDT of the basalt fiber reinforced PBS composites is significantly higher than the HDT of the PBS resin. - Abstract: Basalt fiber (BF) reinforced poly(butylene succinate) (PBS) composites have been fabricated with different fiber contents by a injection molding method and their tensile, flexural and impact properties, as well as thermal stability have been investigated. The tensile and flexural properties of the PBS matrix resin are improved markedly by increasing the fiber contents in the composites. The values are relatively higher than the natural fiber/PP systems reported earlier by other research groups. The heat deflection temperature (HDT) and Vicat softening temperature (VST) of the composites are significantly higher than those of the neat PBS resin. Scanning electron microscopy (SEM) conducted on the fracture surfaces of the composites reveals superior interfacial linkage between the basalt fibers and PBS matrix. The results suggest that the BF/PBS composites may be a potential candidate of PP or PP composites to manufacturing some daily commodities to solve the 'white pollution' in environmental management.

  2. COL5A1: Genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberous sclerosis 1, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II

    Greenspan, D.S. [Univ. of Wisconsin Medical School, Madison, WI (United States); Northrup, H.; Au, K.S. [Univ. of Texas Medical School, Houston, TX (United States)] [and others

    1995-02-10

    COL5A1, the gene for the {alpha}1 chain of type V collagen, has been considered a candidate gene for certain diseases based on chromosomal location and/or disease phenotype. We have employed 3{prime}-untranslated region RFLPs to exclude COL5A1 as a candidate gene in families with tuberous sclerosis 1, Ehlers-Danlos syndrome type H, and nail-patella syndrome. In addition, we describe a polymorphic simple sequence repeat (SSR) within a COL5A1 intron. This SSR is used to exclude COL5A1 as a candidate gene in hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease) and to add COL5A1 to the existing map of {open_quotes}index{close_quotes} markers of chromosome 9 by evaluation of the COL5A1 locus on the CEPH 40-family reference pedigree set. This genetic mapping places COL5A1 between markers D9S66 and D9S67. 14 refs., 1 fig., 2 tabs.

  3. 78 FR 56921 - South Bay Salt Pond Restoration Project, Phase 2 (Ponds R3, R4, R5, S5, A1, A2W, A8, A8S, A19...

    2013-09-16

    ... Fish and Wildlife Service South Bay Salt Pond Restoration Project, Phase 2 (Ponds R3, R4, R5, S5, A1... restoration of ponds R3, R4, R5, S5, A1, A2W, A8, A8S, A19, A20, and A21 at the Don Edwards National Wildlife... 2 of the South Bay Salt Pond Restoration Project and consists of restoring and enhancing over...

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

    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.

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

    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. PMID:4065321

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

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

    2015-01-01

    corresponded to 298 and 285 NmL CH4 g− 1 VSadded, respectively. PHSR could potentially be used for: dietary food additive, fish feed, bioenergy production and added value products. This study opens possibility to conceive different biorefinery scenarios in which the efficient use of the macroalgal biomass......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...

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

    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.

  8. Polymer blends of polylactic acid (PLA) and polybutylene succinate-adipate

    Ma, Wenguang

    A series of blends consisting of polylactic acid (PLA) and aliphatic succinate polyester (BionolleRTM #3000) had been prepared and investigated. The results of mechanical property investigations showed that using 20 wt% Bionolle#3000 can significantly increase the toughness of PLA. BionolleRTM #3000 also reduces the physical aging rate of PLA so blends remain tough longer. Conversely, the stiffness of BionolleRTM #3000 can be significantly increased by blending in PLA. DMA and DSC results show that PLA/BionolleRTM 3000 blends are not thermodynamically miscible, but are compatible blends. Studies have also been performed to determine the amount and rate of aerobic biodegradation of PLA/aliphatic succinate polyester blends in biologically active composting, enzymatic, and soil environments. The changes in molecular weight, molecular structure and thermal properties in the composting environment were also studied by GPC, NMR and DSC analyses. The research results showed BionolleRTM #3000 had a high degradation rate, while PLA had a low degradation rate. PLA/BionolleRTM #3000 blends had moderate degradation rates that increased with BionolleRTM #3000 content. The melt flow behavior of PLA/BionolleRTM #3000 blends has been studied by capillary rheometry. The relationship of the blends' viscosity with their composition, shear stress, shear rate, and temperature has been investigated. Power law index and activation energy of PLA, BionolleRTM #3000 and their blends have been calculated. The experimental and theoretical data can let us understand the processability of PLA/BionolleRTM #3000 blends. A scanning electron microscope (SEM) was used to investigate the morphological structure of the PLA/BionolleRTM #3000 blends. Micrographs of the samples made from different methods (blown film, extrudate and compression molding sheet) were taken; their differences in morphology were compared. For comparison, the micrographs of blend PLA/BionolleRTM #6000 was also studied. The

  9. A hybrid of ant colony optimization and minimization of metabolic adjustment to improve the production of succinic acid in Escherichia coli.

    Chong, Shiue Kee; Mohamad, Mohd Saberi; Mohamed Salleh, Abdul Hakim; Choon, Yee Wen; Chong, Chuii Khim; Deris, Safaai

    2014-06-01

    This paper presents a study on gene knockout strategies to identify candidate genes to be knocked out for improving the production of succinic acid in Escherichia coli. Succinic acid is widely used as a precursor for many chemicals, for example production of antibiotics, therapeutic proteins and food. However, the chemical syntheses of succinic acid using the traditional methods usually result in the production that is far below their theoretical maximums. In silico gene knockout strategies are commonly implemented to delete the gene in E. coli to overcome this problem. In this paper, a hybrid of Ant Colony Optimization (ACO) and Minimization of Metabolic Adjustment (MoMA) is proposed to identify gene knockout strategies to improve the production of succinic acid in E. coli. As a result, the hybrid algorithm generated a list of knockout genes, succinic acid production rate and growth rate for E. coli after gene knockout. The results of the hybrid algorithm were compared with the previous methods, OptKnock and MOMAKnock. It was found that the hybrid algorithm performed better than OptKnock and MOMAKnock in terms of the production rate. The information from the results produced from the hybrid algorithm can be used in wet laboratory experiments to increase the production of succinic acid in E. coli. PMID:24763079

  10. Evaluation of the efficacyof aminolevulinic acid-dependent photodynamic therapy on melanoma cancer cells treated with tocopherol succinate (in-vitro

    Homa Kouchesfahani

    2012-01-01

    Full Text Available Background: Photodynamic therapy (PDT using 5-aminolevulinic acid (ALA to produce an intracellular photo-sensitizer, a protoporphyrin molecule IX (PPIX which absorbs light and targets cells, is a promising cancer treatment. Unfortunately, treatment failures are still a common occurrence when ALA is used. In this study, in order to enhance the efficacy of ALA-dependent photodynamic therapy, the effects of photodynamic therapy on melanoma cancer cells were studied after treating them with tocopherol succinate.Materials and Methods: In this experimental study melanoma cells were cultured in RPMI 1640 medium for 24 h. then, cells were treated with tocopherol succinate (6μm/ml. After 48 and 72 hours, the mediums were replaced by serum-free medium in the darkness, with ALA, 0.1mg/ml and then cells incubated for 4h. After that, cells were irradiated by using Nd: YAG laser (532 nm. After 24h, cell survival was measured by the MTT assay.Results: Twenty-four hours after PDT, among compared groups, pretreated cells with tocopherol succinate showed significant lower cell viability than control group. Conclusion: Induction of differentiation by using tocopherol succinate augmented intracellular PPIX accumulation in cells treated with ALA. Therefore phototoxic cell death after exposure to 532nm light enhances significantly in tocopherol succinate-pretreated cells. This study suggests that tocopherol succinate may act as a biological enhancer of ALA based photodynamic therapy

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

    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...

  12. Solution viscosity – molar mass relationships for poly(butylene succinate) and discussion on molar mass analysis

    Q. Charlier; Girard, E; F. Freyermouth; M. Vandesteene; N. Jacquel; C. Ladaviere; Rousseau, A.; F. Fenouillot

    2015-01-01

    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 ...

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

    Sojitra Rajanit; Virani Paras; HashumatiRaj

    2015-01-01

    The present manuscript describe simple, sensitive, rapid, accurate, precise and economical first derivative spectrophotometric method for the simultaneous determination of Nifedipine (NIF)and Metoprolol Succinate (MET)in 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 nifedi...

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

    Ginoya Charmi G.; Dinesh V. Thakkar

    2013-01-01

    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. ...

  15. FORMULATION AND IN VITRO EVALUATION OF METOPROLOL SUCCINATE FLOATING TABLETS BY USING TWO VISCOSITY GRADE OF HPMC

    Shubhrajit Mantry et al

    2012-01-01

    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 formi...

  16. Preparation and optimization of sustained release matrix tablets of metoprolol succinate and taro gum using response surface methodology

    Soumya, M.; Y. A. Chowdary; V. Naga Swapna; N. D. Prathyusha; R. Geethika; B. Jyostna; K. Sai Krishna Mohan

    2014-01-01

    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 variou...

  17. Activation of Astroglial Calcium Signaling by Endogenous Metabolites Succinate and Gamma-Hydroxybutyrate in the Nucleus Accumbens

    Molnár, Tünde; Héja, László; Emri, Zsuzsa; Simon, Ágnes; Nyitrai, Gabriella; Pál, Ildikó; Kardos, Julianna

    2011-01-01

    Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. 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 neur...

  18. Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens

    Zsuzsa Emri; Julianna Kardos

    2011-01-01

    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 neu...

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

    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. S-nitrosylation of the Mitochondrial Chaperone TRAP1 Sensitizes Hepatocellular Carcinoma Cells to Inhibitors of Succinate Dehydrogenase

    Rizza, Salvatore; Montagna, Costanza; Cardaci, Simone;

    2016-01-01

    . We find that hepatocyte GSNOR deficiency is characterized by mitochondrial alteration and by marked increases in succinate dehydrogenase (SDH) levels and activity. We find that this depends on the selective S-nitrosylation of Cys(501) in the mitochondrial chaperone TRAP1, which mediates its......-nitrosylation in HCC, a novel molecular target in SDH, and a first-in-class therapy to treat the disease. Cancer Res; 76(14); 1-13. ©2016 AACR....

  1. Synthesis and characterization of poly(3-thiophene methyl acetate)/poly(tetramethylene succinate) nanomembranes. Biocompatibility and biodegradability assays

    Pérez Madrigal, Maria del Mar

    2011-01-01

    The present study reports the fabrication of free-standing nanomembranes with semiconducting and biodegradable properties. Nanomembranes have been prepared by spin-coating mixtures of a semiconducting polythiophene derivative, poly(3-thiophene methyl acetate), and a biodegradable polyester, poly(tetramethylene succinate). Both the roughness and thickness of the nanomembranes, which ranged from 3 to 20 nm and from 20 to 80 nm, respectively, were precisely controlled through the spin-coater ...

  2. 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

    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.

  3. Phytoglycogen octenyl succinate, an amphiphilic carbohydrate nanoparticle, and epsilon-polylysine to improve lipid oxidative stability of emulsions.

    Scheffler, Siqi L; Wang, Xue; Huang, Lei; San-Martin Gonzalez, Fernanda; Yao, Yuan

    2010-01-13

    Phytoglycogen octenyl succinate (PG-OS) and epsilon-polylysine (EPL) were used to form oil-in-water emulsions with enhanced lipid oxidative stability. PG-OS is an amphiphilic carbohydrate nanoparticle prepared using octenyl succinate (OS) substitution of phytoglycogen (PG). PG-OS had a dispersed molecular density nearly 20 times that of waxy corn starch octenyl succinate (WCS-OS). Fish oil-in-water emulsions were prepared using PG-OS, WCS-OS, and Tween 20, stored at 55 degrees C for 6 days, and monitored for the accumulation of hydroperoxide and thiobarbituric acid reactive substances (TBARS). The result indicated that PG-OS may lead to high lipid oxidative stability, and that the addition of EPL may further improve the oxidative stability of emulsions. To address the interaction between PG-OS and EPL, zeta-potential was determined for various systems. The results indicated a possible formation of an interfacial complex layer comprising both PG-OS and EPL. This complex layer may provide both physical and electrostatic barriers against pro-oxidative compounds. PMID:19928899

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

    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. PMID:26802183

  5. Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies

    Parviz, Mahsa; Vogel, Kara; Gibson, K Michael; Pearl, Phillip L.

    2014-01-01

    Clinical disorders known to affect inherited gamma-amino butyric acid (GABA) metabolism are autosomal recessively inherited succinic semialdehyde dehydrogenase and GABA-transaminase deficiency. The clinical presentation of succinic semialdehyde dehydrogenase deficiency includes intellectual disability, ataxia, obsessive-compulsive disorder and epilepsy with a nonprogressive course in typical cases, although a progressive form in early childhood as well as deterioration in adulthood with worse...

  6. The degradation and adsorption behaviors of enzyme on poly(butylene succinate) single crystals.

    Jiang, Xi; Yang, Ju-Ping; Wang, Xiao-Hong; Zhou, Jian-Jun; Li, Lin

    2009-12-01

    The enzymatic degradation behavior of poly(butylene succinate) (PBS) single crystals with a lipase from Pseudomonas cepacia (lipase PS) is monitored using atomic force microscopy (AFM) in phosphate buffer at pH 6.8 and 40 degrees C. In-situ AFM results show that enzymatic degradation of the single crystal starts from the crystal edges rather than the chain-folded surfaces and the lamellar thickness remains constant during the whole degradation process. Total internal reflection fluorescence microscopy (TIRFM) is used for the first time to study the adsorption behavior of lipase onto the PBS crystal surface. The results clearly show that the enzyme molecules preferentially adsorb on the lateral surfaces of the single crystal but not on the chain-folded surfaces. AFM force-distance curve measurements and force-volume imaging obtained using a lipase-immobilized AFM tip show that small and large adhesive forces exist in the flat-on and edge-on areas of a PBS banded spherulite, respectively, which correspond to the chain-folded surface and lateral edges of a single crystal. PMID:19953521

  7. A study on reactive blending of (poly lactic acid) and poly (butylene succinate co adipate)

    Bureepukdee, C.; Suttiruengwong, S.; Seadan, M.

    2015-07-01

    This research aims to study the blending of Polylactic acid (PLA) and Polybutylene succinate co adipate (PBSA) in order to understand the role of peroxide in free radical reaction on the compatibilization between these two biodegradable polyesters. Various ratios of PLA/PBSA blends with and without reactive agents were prepared in the twin screw extruder. Two types of peroxides, Di (tert-butylperoxyisopropyl) benzene (DTBP) and 2, 5-Dimethyl-2, 5-(t-butylperoxy) hexane (DTBH), were used with various concentrations to compare. From the torques measurement, DTBP was more reactive with PLA and PBSA than DTBH. PLA and PBSA 80:20, 60:40, 50:50, 40:60, and 20:80% by weight were melt-blended in a twin screw extruder. The reactive polymer blends were also prepared for the same ratios of the blends with addition of 0.08 and 0.1 phr of DTBP. The mechanical, thermal, rheological, and morphological properties were investigated. The impact strengths of the non-reactive blend increased with the increasing in PBSA content. The optimal impact strength was obtained at 40%wt of PBSA with 0.1 phr of DTBP. Adding 0.08 and 0.1 phr of DTBP led to the co continuous phase morphology of PLA/PBSA blends. The per cent crystallinity of PLA increased when blended with PBSA. PBSA might induce the crystallization of PLA.

  8. Tabletability assessment of conventional formulations containing Vitamin E tocopheryl polyethylene glycol succinate.

    Jin, Feiyan; Tatavarti, Aditya

    2010-04-15

    Vitamin E tocopheryl polyethylene glycol succinate (TPGS) is known to enhance the bioavailability of poorly water-soluble drugs via solubility and permeability enhancement. Few studies have evaluated feasibility of formulating TPGS in conventional solid dosage forms such as tablets due to processing challenges resulting from its waxy nature and low melting point (approximately 37 degrees C). The objective of this study is to systematically investigate the tabletability of conventional high shear wet granulation (WG) formulations incorporated with Vitamin E TPGS. Impact of critical formulation variables such as levels of TPGS, hydroxypropyl cellulose (binder) and Prosolv (extragranular filler) on product quality attributes was studied using a full factorial experimental design. The potential influence of temperature elevation during processing was assessed through a heated die fitted onto a compaction simulator. Bilayer tabletability of the TPGS formulation was also assessed in combination with a secondary non-TPGS formulation. TPGS levels significantly impacted tensile strength (TS), disintegration time and dissolution. Heat sensitivity studies indicated that TS reduction upon exposure to heat was minimized by higher levels of extragranular fillers. Acceptable interfacial strength of bilayer tablets was achieved and tablets could be coated without the need for hydroalcoholic solutions. The study demonstrates preliminary feasibility to develop monolithic and bilayer coated tablet formulations containing up to 10% (w/w) TPGS for the given compound and drug load. Further studies are required to validate these findings at larger scales. PMID:20083178

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

    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

  10. Non-isothermal melt crystallization of poly(tetramethylene succinate) under high pressure: Characterization and kinetics

    Rohindra, David [Graduate School of Engineering, Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1-S8-33, O-okayama, Meguro-ku, Tokyo 152-8552 (Japan); School of Biological and Chemical Sciences, Faculty of Science, Technology and Environment, The University of the South Pacific, Suva (Fiji); Kuboyama, Keiichi [Graduate School of Engineering, Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1-S8-33, O-okayama, Meguro-ku, Tokyo 152-8552 (Japan); Ougizawa, Toshiaki, E-mail: tougizawa@op.titech.ac.jp [Graduate School of Engineering, Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1-S8-33, O-okayama, Meguro-ku, Tokyo 152-8552 (Japan)

    2012-10-10

    Highlights: Black-Right-Pointing-Pointer Non-isothermal crystallization of PTMS under high pressure is reported. Black-Right-Pointing-Pointer Nucleation pattern analyzed using Ozawa model. Black-Right-Pointing-Pointer Crystallization and nucleation behavior changed above 300 MPa. - Abstract: The non-isothermal melt crystallization behavior (characterization and kinetics) of poly(tetramethylene succinate) (PTMS) under high pressure was investigated using high pressure differential thermal analysis (HP-DTA). Wide angle X-ray diffraction (WAXD), small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), polarized optical microscopy (POM), and density measurement were used to study the crystal structure, the melting temperature and the morphology of the samples crystallized under various pressures. No new crystal structure or formation of extended chain crystals were found in the pressure crystallized samples. Optical micrographs revealed nucleation density decreased and spherulite morphology changed (presence of banding pattern) above 300 MPa. DTA crystallization curves showed a single exothermic peak at all pressures which shifted to higher temperatures with increasing pressure and became broad above 300 MPa. The kinetics was studied using the Ozawa model. A change in the nucleation pattern was predicted from the Ozawa exponent, instantaneous at low pressures and sporadic above 300 MPa. From kinetic and morphological results it was found that a critical pressure region existed around 300 MPa.

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

    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.

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

    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. PMID:6232269

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

    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.

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

    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.

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

    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. Bone Formation from Porcine Dental Germ Stem Cells on Surface Modified Polybutylene Succinate Scaffolds

    Nergis Abay

    2016-01-01

    Full Text Available Designing and providing a scaffold are very important for the cells in tissue engineering. Polybutylene succinate (PBS has high potential as a scaffold for bone regeneration due to its capacity in cell proliferation and differentiation. Also, stem cells from 3rd molar tooth germs were favoured in this study due to their developmentally and replicatively immature nature. In this study, porcine dental germ stem cells (pDGSCs seeded PBS scaffolds were used to investigate the effects of surface modification with fibronectin or laminin on these scaffolds to improve cell attachment, proliferation, and osteogenic differentiation for tissue engineering applications. The osteogenic potentials of pDGSCs on these modified and unmodified foams were examined to heal bone defects and the effects of fibronectin or laminin modified PBS scaffolds on pDGSC differentiation into bone were compared for the first time. For this study, MTS assay was used to assess the cytotoxic effects of modified and unmodified surfaces. For the characterization of pDGSCs, flow cytometry analysis was carried out. Besides, alkaline phosphatase (ALP assay, von Kossa staining, real-time PCR, CM-Dil, and immunostaining were applied to analyze osteogenic potentials of pDGSCs. The results of these studies demonstrated that pDGSCs were differentiated into osteogenic cells on fibronectin modified PBS foams better than those on unmodified and laminin modified PBS foams.

  17. Influence of spaceflight on succinate dehydrogenase activity and soma size of rat ventral horn neurons

    Ishihara, A.; Ohira, Y.; Roy, R. R.; Nagaoka, S.; Sekiguchi, C.; Hinds, W. E.; Edgerton, V. R.

    1996-01-01

    Succinate dehydrogenase (SDH) activities and soma cross-sectional areas (CSA) of neurons in the dorsolateral region of the ventral horn at the L5 segmental level of the spinal cord in the rat were determined after 14 days of spaceflight and after 9 days of recovery on earth. The results were compared to those in age-matched ground-based control rats. Spinal cords were quick-frozen, and the SDH activity and CSA of a sample of neurons with a visible nucleus were determined using a digitizer and a computer-assisted image analysis system. An inverse relationship between CSA and SDH activity of neurons was observed in all groups of rats. No change in mean CSA or mean SDH activity or in the size distribution of neurons was observed following spaceflight or recovery. However, there was a selective decrease in the SDH activity of neurons with soma CSA between 500 and 800 microns2 in the flight rats, and this effect persisted for at least 9 days following return to 1 g. It remains to be determined whether the selected population of motoneurons or the specific motor pools affected by spaceflight may be restricted to specific muscles.

  18. Investigation on growth, structure and characterization of succinate salt of 8-hydroxyquinoline: An organic NLO crystal

    Thirumurugan, R.; Babu, B.; Anitha, K.; Chandrasekaran, J.

    2015-04-01

    8-Hydroxyquinolinium succinate (8-HQSU) has been synthesized and single crystals were grown from ethanol solvent by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated by single crystal X-ray diffraction analysis. It reveals that 8-HQSU crystallizes in monoclinic system with non-centro symmetric space group P21. FTIR, 1H and 13C NMR spectral investigations have been carried out to identify the vibrational modes of various functional groups and placement of proton and carbon in the 8-HQSU compound, respectively. UV-vis-NIR transmission spectrum shows the cutoff wavelength around 357 nm. In addition, a photoluminescence spectral analysis was carried out for 8-HQSU crystals. The thermal properties of crystals were evaluated from TGA and DTA techniques and the crystal was found to be stable up to 145 °C. The dielectric studies show that the dielectric constant and dielectric loss decrease exponentially with frequency at different temperatures. Photoconductivity studies were carried out on the grown crystals it reveals the positive photo conducting nature. Powder second harmonic generation property of the crystal was confirmed by Kurtz and Perry powder SHG technique and it is found to be 1.3 times greater than that of KDP.

  19. Tocopherol Succinate: Modulation of Antioxidant Enzymes and Oncogene Expression, and Hematopoietic Recovery

    Purpose: A class of naturally occurring isoforms of tocopherol (tocols) was shown to have varying degrees of protection when administered before radiation exposure. We recently demonstrated that α-tocopherol succinate (TS) is a potential radiation prophylactic agent. Our objective in this study was to further investigate the mechanism of action of TS in mice exposed to 60Co γ-radiation. Methods and Materials: We evaluated the effects of TS on expression of antioxidant enzymes and oncogenes by quantitative RT-PCR in bone marrow cells of 60Co γ-irradiated mice. Further, we tested the ability of TS to rescue and repopulate hematopoietic stem cells by analyzing bone marrow cellularity and spleen colony forming unit in spleen of TS-injected and irradiated mice. Results: Our results demonstrate that TS modulated the expression of antioxidant enzymes and inhibited expression of oncogenes in irradiated mice at different time points. TS also increased colony forming unit-spleen numbers and bone marrow cellularity in irradiated mice. Conclusions: Results provide additional support for the observed radioprotective efficacy of TS and insight into mechanisms.

  20. Dispersion of multi-walled carbon nanotubes in biodegradable poly(butylene succinate) matrix.

    Ray, Suprakas Sinha; Vaudreuil, Sébastien; Maazouz, Abderrahim; Bousmina, Mosto

    2006-07-01

    This communication describes the preparation, characterization and properties of biodegradable poly(butylene succinate) (PBS)/multi-walled carbon nanotubes (MWCNTs) nanocomposite. Nanocomposite was prepared by melt-blending in a batch mixer and the amount of MWCNTs loading was 3 wt%. State of dispersion-distribution of the MWCNTs in the PBS matrix was examined by scanning and transmission electron microscopic observations that revealed homogeneous distribution of stacked MWCNTs in PBS matrix. The investigation of the thermomechanical behavior was performed by dynamic mechanical thermal analysis. Results demonstrated substantial enhancement in the mechanical properties of PBS, for example, at room temperature, storage flexural modulus increased from 0.64 GPa for pure PBS to 1.2 GPa for the nanocomposite, an increase of about 88% in the value of the elastic modulus. The tensile modulus and thermal stability of PBS were moderately improved after nanocomposite preparation with 3 wt% of MWCNTs, while electrical conductivity of neat PBS dramatically increased after nanocomposite formation. For example, the in plane conductivity increased from 5.8 x 10(-9) S/cm for neat PBS to 4.4 x 10(-3) for nanocomposite, an increase of 10(6) fold in value of the electrical conductivity. PMID:17025148

  1. Development and optimization of press coated floating pulsatile drug delivery of sumatriptan succinate.

    Jagdale, Swati C; Pawar, Chandrakala R

    2014-01-01

    Floating pulsatile is combined approach designed according to circadian rhythm to deliver the drug at right time, in right quantity and at right site as per pathophysiological need of disease with prolong gastric residence and lag phase followed by burst release. As the migraine follows circadian rhythm in which headache is more painful at the awakening time, the dosage form should be given during night time to release drug when pain get worsen. Present work deals with formulation and optimization of floating pulsatile tablet of sumatriptan succinate. Core tablet containing crospovidone as superdisintegrant (10%) showed burst release. Lag time was maintained using swellable polymer as polyoxN12K and xanthum gum. 3(2) experimental design was carried out. Developed formulations were evaluated for physical characteristics, in vitro and in vivo study. Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum (26.56%) of total polymer weight showed floating lag time 15±2 sec, drug content 99.58±0.2 %, hardness 6±0.2 Kg/cm(2) and drug release 99.54±2% with pulsatile manner followed lag period of 7±0.1h. In vivo x-ray study confirms prolong gastric residence of system. Programmable pulsatile release has been achieved by formulation F2 which meet demand of chronotherapeutic objective of migraine. PMID:24893996

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

    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.

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

    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.

  4. Effects of Radiation on Mechanical Properties of Poly (butylene succinate) and Cassava Starch Blends

    This research compared the effects of gamma and electron beam irradiation at different doses on the mechanical properties of polymer blends between poly(butylene succinate) (PBS) and cassava starch. Two types of starch were used to prepare thermoplastic starch (TPS), native cassava starch and hydrophobic starch. PBS/TPS blends were compounded at five different weight ratios using a twin-screw extruder. Mechanical properties and degradation were evaluated in comparison to unirradiated samples. Results indicated that the incorpora- tion of TPS prepared from native cassava starch decreased the mechanical properties of PBS/TPS blends, whereas the addition of TPS prepared from hydrophobic starch improved the mechanical properties of the blends. In addition, the maximum mechanical properties of PBS/TPS blends were achieved when samples were exposed to irradiation at 120 kGy. Using soil burial evaluation, the degradation rate of blends was found to increase with the addition of TPS. Therefore we have demonstrated in this study that the type of TPS and irradiation treatment can significantly alter the mechanical properties and degradation of PBS/TPS blends.

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

    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.

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

    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.

  7. POLYSACCHARIDE GUM (KONDAGOGU GUM MATRIX TABLETS FOR ORAL SUSTAINED DELIVERY OF METOPROLOL SUCCINATE

    N. Aswani

    2011-04-01

    Full Text Available The present study has been undertaken to develop a sustained-release tablet dosage form for metoprolol succinate using kondagugu gum as the rate-controlling polymer. The prepared tablets were coated will shellac as an enteric coat polymer and evaluated for tablet properties. In vitro release studies of prepared tablets were carried out for 2 hrs in pH 1.2 HCl buffer and 22 hrs in pH 6.8phosphate buffer. In addition, swelling, kinetics of drug release from the matrices and stability of the tablet formulations were also investigated. Mathematical analysis of the release kinetics showed that the nature of drug release from the matrix tablets has followed super case II transport. FTIR and DSC studies have shown that no chemical interaction occurred between the drug and polymers used. The optimized formulation (F4 showed negligible difference in release mechanism as well as release kinetics when stability study was done for three months at 40±20 C and 75±5% RH.

  8. Effect of vitamin E succinate on the proliferation of human breast cancer cells

    ZHANG Wei; ZHANG Jun-chu; ZHU Da-qiao; YE Lai-ying; ZHANG Ling-zhen; WANG Qiang

    2005-01-01

    Objective:To investigate the growth inhibition and apoptosis induced by vitamin E succinate (VES) on human breast cancer cells and to analyze the possible mechanism in this process. Methods: Human breast cancer cell line Bcap-37 was treated with VES for 12, 24 and 48 h at the concentrations of 5,10 and 20 μg/ml. Then MTT assay was employed to detect the inhibitory effect of VES on the growth of breast cancer cells. Flow cytometry was used to analyze the cell cycle and apoptosis. To find out whether the Fas/FasL pathway was involved in this process, RT-PCR and flow cytometry assay were used to detect the Fas expression at the mRNA and protein level. Results: VES exhibited a significant inhibitory effect on the growth of human breast cancer cells, presenting in a dose- and time-dependant manner. The apoptotic rate of Bcap-37 cells was 0.6%, rose to 21.0% and 37.5% after treated with VES for 24 and 48h at the concentration of 20μg/ml. Fas mRNA transcription was upregulated after VES treatment and cell surface Fas expression increased according to the flow cytometry assay. Conclusion:Significant growth inhibition and apoptosis are induced in human breast cancer cells after treated with VES. The modulation of Fas/FasL pathway may related to the upregulation of Fas molecule on the cancer cell surface.

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

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

    2015-01-01

    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 (εr = 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. PMID:26238975

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

    Smiga-Matuszowicz, Monika; Janicki, Bartosz; Jaszcz, Katarzyna; Łukaszczyk, Jan; Kaczmarek, Marcin; Lesiak, Marta; Sieroń, Aleksander L; Simka, Wojciech; Mierzwiński, Maciej; Kusz, Damian

    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 3h 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. PMID:25491802

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

    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

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

    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

  13. Mutations in Succinate Dehydrogenase Subunit C Increase Radiosensitivity and Bystander Responses

    Zhou, Hongning; Hei, Tom K.

    Although radiation-induced bystander effect is well studied in the past decade, the precise mech-anisms are still unclear. It is likely that a combination of pathways involving both primary and secondary signaling processes is involved in producing a bystander effect. There is recent evidence that mitochondria play a critical role in bystander responses. Recently studies found that a mutation in succinate dehydrogenese subunit C (SDHC), an integral membrane protein in complex II of the electron transport chain, resulted in increased superoxide, oxidative stress, apoptosis, tumorigenesis, and genomic instability, indicating that SDHC play a critical role in maintaining mitochondrial function. In the present study, using Chinese hamster fibroblasts (B1 cells) and the mutants (B9 cells) containing a single base substitution that produced a premature stop codon resulting in a 33-amino acid COOH-terminal truncation of the SDHC protein, we found that B9 cells had an increase in intracellular superoxide content, nitric oxide species, and mitochondrial membrane potential when compared with wild type cells. After irradiated with a grade of doses of gamma rays, B9 cells show an increased radiosensitivity, especially at high doses. The HPRT- mutant yield after gamma-ray irradiation in B9 cells was significantly higher than that of B1 cells. A single, 3Gy dose of gamma-rays increased the background mutant level by more than 4 fold. In contrast, the mutant induction was less than 2 fold in B1 cells. In addition, B9 cells produced a higher bystander mutagenesis after alpha particle irradiation than the B1 cells. Furthermore, pretreated with carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), a nitric oxide scavenger, significantly decreased the bystander effect. Our findings demonstrate that a mutation in SDHC increases radiosensitivity in both directly irradiated cells and in neighboring bystander cells, and mito-chondrial function play an essential role in

  14. Stimulatory effect of butoctamide hydrogen succinate on REM sleep in normal humans.

    Mizuki, Y; Suetsugi, M; Hotta, H; Ushijima, I; Yamada, M

    1995-05-01

    1. The efficacy of butoctamide hydrogen succinate (BAHS) was compared with that of nitrazepam on the basis of the polysomnograms and the subjective assessments. 2. Twelve healthy male students were divided into three groups consisting of 4 subjects each with were administered BAHS 600 mg, nitrazepam 5 mg, and BAHS 600 mg + nitrazepam 5 mg, respectively. 3. Polygraphic recordings were made for 8 consecutive nights for each subject, and the polysomnograms were evaluated by computerized automatic analysis using the interval histogram method. 4. An inert placebo was administered on the first 3 nights and on the seventh and eighth nights, and the test article regimen was administered on the fourth, fifth and sixth nights. 5. The test articles and the placebo were administered orally at 22:30 hr, and the recording of polysomnograms was started at 23:00 hr and ended at 8:00 hr the next morning. 6. The subjects were requested to fill out the subjective assessment of sleep before falling asleep and after arising the next morning. 7. BAHS increased REM sleep and decreased stage 2 sleep significantly; however, it failed to affect stage 1, 3 or 4 sleep. 8. Nitrazepam increased significantly the total sleep time and stage 2 sleep but decreased significantly the stage 3 sleep and decreased slightly the stages 1, 4 and REM sleep. 9. The combined treatment with BAHS and nitrazepam did not alter the sleep parameters except for increasing the total sleep time. 10. No obvious changes were observed in the subjective assessments after administration of the drugs. 11. These findings suggest that BAHS results in a unique sleep pattern different from benzodiazepines, and that BAHS may be suitable for treating insomnia in elderly patients and those with drug abuse, manic-depressive illness or schizophrenia. PMID:7624490

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

    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. PMID:19618298

  16. Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

    Liu, Yuling; Xu, Yingqi; Wu, Minghui; Fan, Lijiao; He, Chengwei; Wan, Jian-Bo; Li, Peng; Chen, Meiwan; Li, Hui

    2016-01-01

    Mitoxantrone (MIT) is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES) amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT) micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC50) value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines). In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy. PMID:27471384

  17. The inhibition of low carbon steel corrosion in hydrochloric acid solutions by succinic acid

    The effect of succinic acid (SA) on the corrosion inhibition of a low carbon steel (LCS) electrode has been investigated in aerated non-stirred 1.0 M HCl solutions in the pH range (2-8) at 25 oC. Weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques were applied to study the metal corrosion behaviour in the absence and presence of different concentrations of SA under the influence of various experimental conditions. Measurements of open circuit potential (OCP) as a function of time till steady-state potentials (E st) were also established. Surface analysis using energy dispersive X-ray (EDX) and scanning electron microscope (SEM) allowed us to clarify the mechanistic aspects and evaluate the relative inhibition efficiency. Results obtained showed that SA is a good 'green' inhibitor for LCS in HCl solutions. The polarization curves showed that SA behaves mainly as an anodic-type inhibitor. EDX and SEM observations of the electrode surface confirmed existence of a protective adsorbed film of the inhibitor on the electrode surface. The inhibition efficiency increases with increase in SA concentration, pH of solution and time of immersion. Maximum inhibition efficiency (∼97.5%) is obtained at SA concentrations >0.01 M at pH 8. The effect of SA concentration and pH on the potential of zero charge (PZC) of the LCS electrode in 1.0 M HCl solutions has been studied and the mechanism of adsorption is discussed. Results obtained from weight loss, polarization and impedance measurements are in good agreements

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

    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.

  19. Health expenditure comparison of extended-release metoprolol succinate and immediate-release metoprolol tartarate

    Vaidya V

    2012-02-01

    Full Text Available Varun Vaidya, Pranav PatelCollege of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USABackground: Metoprolol, a selective beta-1 blocker, is available in two different salt forms in the market – metoprolol succinate (MS and metoprolol tartarate (MT. Both the formulations are Food and Drug Administration approved for the treatment of hypertension. Several studies have shown similar efficacies between the two salts; however, they differ in their pharmacokinetic properties and are therefore priced differently. The primary objective of this study was to compare the overall health care expenditures of hypertensive patients on MT and MS to see if the price difference in the two preparations is offset by savings in overall expenditure.Methods: Two cohorts of patients using MT and MS were selected from the 2008 Medical Expenditure Panel Survey. Propensity score matching technique was used to balance the cohorts on various parameters such as demographic information, insurance status, and comorbidity score. Patients using MT were matched to patients using MS on the logit of propensity score using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score. Multiple regression analysis was carried out to examine the association between health expenditure and type of metoprolol salt, adjusting for other covariates.Results: A total of 742 patients were found to use metoprolol (MT-388, MS-354. After propensity score matching, a total of 582 patients were left in the sample for final analysis (291 patients in each cohort. The average annual health care expenditure was slightly higher in the MT cohort; however, after adjusting for covariates in a multivariate analysis, the difference was found to be statistically insignificant (P = 0.23.Conclusion: Both the products of metoprolol were found to have similar average annual total health care expenditure; however, MS once a day has higher out

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

    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

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

    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.

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

    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.

  3. Polarographic study of simple and mixed ligand complexes of Eu(III) with imidazole and succinate

    The formation of simple and mixed ligand complexes of Eu(III) with imidazole (Im) and succinate (Succ2-) has been studied polarographically at 25deg C+-0.1deg C, μ=1.0 (NaClO4) and pH=6. The reduction of the complexes at d.m.e. is quasi-reversible and diffusion-controlled. Eu(III) forms six successive complexes with Im, viz. [Eu(Im)]3+, [Eu(Im)2]3+, [Eu(Im)2]3+, [Eu(Im)3]3+, [Eu(Im)4]3+, [Eu(Im)5]3+, and[Eu(Im)6]3+. Their stability constant values are: logβ10=3.6, logβ20=4.6, logβ30=6.5, logβ40=7.8, logβ50=8.4 and logβ60=9.6 respectively. With succ2-, Eu(III) forms four successive complexes; [Eu(Succ)]+, [Eu(Succ)2]-, [Eu(Succ)3]3- and [Eu(Succ)4]5- with the stability constants, logβ01=3.8, logβ02=4.6, logβ03=5.3 and logβ04=6.9 respectively. Eu(III) forms five mixed ligand complexes; [Eu(Im)(Succ)2]-, Eu(Im)2(Succ)2]-, [Eu(Im)3(Succ)2], [Eu(Im)4(Succ)2] and [Eu(Im)5(Succ)]+ with stability constants, logβ12=6.1, logβ22=8.0, logβ32=9.5, logβ42=10.9 and logβ51=10.2 respectively. (author)

  4. Synthesis and computational investigation of molecularly imprinted nanospheres for selective recognition of alpha-tocopherol succinate

    Piacham, Theeraphon; Nantasenamat, Chanin; Isarankura-Na-Ayudhya, Chartchalerm; Prachayasittikul, Virapong

    2013-01-01

    Molecularly imprinted polymers (MIPs) are macromolecular matrices that can mimic the functional properties of antibodies, receptors and enzymes while possessing higher durability. As such, these polymers are interesting materials for applications in biomimetic sensor, drug synthesis, drug delivery and separation. In this study, we prepared MIPs and molecularly imprinted nanospheres (MINs) as receptors with specific recognition properties toward tocopherol succinate (TPS) in comparison to tocopherol (TP) and tocopherol nicotinate (TPN). MIPs were synthesized using methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as crosslinking agent and dichloromethane or acetronitrile as porogenic solvent under thermal-induced polymerization condition. Results indicated that imprinted polymers of TPS-MIP, TP-MIP and TPN-MIP all bound specifically to their template molecules at 2 folds greater than the non-imprinted polymers. The calculated binding capacity of all MIP was approximately 2 mg per gram of polymer when using the optimal rebinding solvent EtOH:H2O (3:2, v/v). Furthermore, the MINs toward TPS and TP were prepared by precipitation polymerization that yielded particles that are 200-400 nm in size. The binding capacities of MINs to their templates were greater than that of the non-imprinted nanospheres when using the optimal rebinding solvent EtOH:H2O (4:1, v/v). Computer simulation was performed to provide mechanistic insights on the binding modalities of template-monomer complexes. In conclusion, we had successful prepared MIPs and MINs for binding specifically to TP and TPS. Such MIPs and MINs have great potential for industrial and medical applications, particularly for the selective separation of TP and TPS. PMID:26622214

  5. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

    Singh, Vijay K.; Wise, Stephen Y.; Fatanmi, Oluseyi O.; Beattie, Lindsay A.; Ducey, Elizabeth J.; Seed, Thomas M.

    2014-01-01

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. PMID:23814114

  6. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. (author)

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

    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.

  8. Pharmacokinetic, residue and irritation aspects of chloramphenicol sodium succinate and a chloramphenicol base formulation following intramuscular administration to ruminants.

    Nouws, J F; Vree, T B; Holtkamp, J; Baakman, M; Driessens, F; Guelen, P J

    1986-07-01

    The disposition of chloramphenicol (CAP) and of its glucuronide metabolite in plasma and milk was studied following a single intramuscular injection of a chloramphenicol base formulation (Amicol Forte; product A) and of chloramphenicol sodium succinate (product B) to dairy cows. The dose applied of both formulations was equivalent to 50 mg CAP base/kg body weight. The HPLC determined CAP concentrations were microbiologically active. Product A revealed 30% higher plasma CAP peak concentrations (13.0 vs 9.0 micrograms/ml) and 36% larger areas under the plasma concentration-time curves than product B, whereas their absorption and elimination half-lives were of the same order of magnitude. In the onset phase (during 4 h p.i.) unhydrolysed CAP sodium succinate could be detected in plasma and the glucuronide fraction was 26% of the parent drug. After 25 h p.i. the glucuronide fraction equalled that of the parent drug. The maximum CAP concentration in milk was for product B equal to, and for product A 80% of, the CAP plasma concentration. In milk no chloramphenicol glucuronide metabolites could be detected. HPLC methods for detecting ultra-trace CAP concentrations in edible tissues were developed by the employment of extraction with or without a clean-up procedure. Seven days after i.m. administration of product A and B to calves, the CAP residue concentrations in the kidney, liver, and muscle were less than 2 nanogram/g tissue. Traces of CAP residues could be still found at the injection site and in the urine. Chloramphenicol sodium succinate (product B) caused extensive tissue irritation at the injection site, while in the case of product A the irritation was limited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3750804

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

    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.

  10. Therapeutic effect of recombinant lentiviral vector containing succinate dehydrogenase iron-sulfur protein on the treatment of experimental autoimmunity myocarditis.

    Han, Lina; Wang, Chunxi; Guo, Shuli; Liu, Siyu; Yang, Liming

    2016-08-01

    Cardiac autoimmune reaction takes part in myocarditis, dilated cardiomyopathy and heart failure. Existing literature has confirmed that the occurrence of cardiomyopathy belongs to mitochondrial diseases and is related to the oxidative respiratory chain subunit. The special structure of iron-sulfur protein (ISP) is responsible for the oxidative stress in oxidative phosphorylation, which is also a target that is easily attacked by various damage factors. Using gene therapy technology to restore succinate dehydrogenase iron-sulfur protein (SDISP) function- and thus resume myocardial mitochondria function and myocardial function is hypothesized to alleviate the experimental autoimmunity myocarditis (EAM). PMID:27372865

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

    P. S. Jain; Patel, M.K. (Martin); S B Bari; S. J. Surana

    2012-01-01

    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 amlodipi...

  12. Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil in Pharmaceutical Formulation by Thin-Layer Chromatographic-Densitometric Method

    Sunil L. Baldania; Ankit B. Parmar; Bhatt, Kashyap K.; Shah, Dimal A.; Chhalotiya, Usmangani K.

    2012-01-01

    A new, simple, accurate, and precise high-performance thin-layer chromatographic (HPTLC) method is described for simultaneous analysis of metoprolol succinate and olmesartan medoxomil in pharmaceutical formulations. The separations were achieved on prepared TLC plates precoated with silica gel G 60 F254 and the plates were developed with methanol-ethyl acetate-toluene-glacial acetic acid 2.5 : 3 : 4.5 : 0.3%v/v/vas mobile phase. Detection and evaluation of chromatograms were performed densito...

  13. Normal and Reversed-Phase HPTLC Methods for Simultaneous Estimation of Telmisartan and Metoprolol Succinate in Pharmaceutical Formulation

    Nawale, Prajakta S.; Shirkhedkar, Atul A.; Surana, Sanjay J.; Patil, Amod S.

    2012-01-01

    Two simple precise normal-phase (Method I) and reversed-phase (Method II) HPTLC/densitometry method have been developed for simultaneous determination of telmisartan and metoprolol succinate in bulk and in combined tablet formulation. Method I was developed with aluminium plates precoated with silica gel 60F254S, and toluene : propanol : methanol : triethylamine (8 : 1 : 1 : 0.5 v/v) was used as as mobile phase. Method II was carried out using aluminium coated with RP-18 silica gel 60 F254S H...

  14. DEVELOPMENT AND VALIDATION OF TLC-DENSITOMETRIC AND HPLC METHODS FOR DETERMINATION OF OLMESARTAN MEDOXOMIL AND METOPROLOL SUCCINATE IN COMBINATION

    Chitlange Sohan S.; Talole Reshma A.; Bhusal Ramesh D.; Nikumbh Monesh B.

    2012-01-01

    Rapid, accurate and sensitive methods for the identification and quantification of Olmesartan Medoxomil (OLME) and Metoprolol Succinate (METO) were developed by TLC-densitometry and HPLC at 222 nm. The first developed method was TLC-densitometry, where mixture of OLME and METO were separated on silica gel TLC 60 F254 plates using Toluene:Methanol:Glacial acetic acid (7.0:2.5:0.5 v/v/v) as mobile phase and scanning of the separated bands at 222 nm. Linearity was observed in the concentration ...

  15. Design, Synthesis and Characterisation of Novel Biodegradable Aliphatic Copolyesters- Poly(ethylene sebacate-co-butylene succinate and Poly(ethylene sebacate-co-butylene adipate

    L. SOWBAGYALAKSHMI PRABHA

    2012-12-01

    Full Text Available Synthesis of novel aliphatic biodegradable copolyesters namely Poly (ethylene sebacate-co-butylene succinate and Poly (ethylene sebacate-co-butylene adipate were carried out using Poly (butylene Succinate, Poly (Butylene Adipate and Poly (Ethylene Sebacate in presence of Poly Phosphoric acid. Synthesis of Poly (Butylene Succinate, Poly (Butylene Adipate and Poly (Ethylene Sebacate were carried out using respective diols and diacids in presence of titanium tetrabutoxide as catalyst. Newly synthesized copolyesters were characterized by solubility studies, viscosity measurements, thermal analysis, IR Spectroscopy and Nuclear Magnetic Resonance Spectroscopy (1H-NMR and 13C-NMR. The characteristic peaks present in the homopolyesters were recorded in the copolymers as well. DSC analysis of the copolyesters showed multiple melting peaks, while increase of methylene units in the di-acid decreased the Tg.

  16. Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate

    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

  17. Synthesis and physicochemical characterization of chemically modified chitosan by succinic anhydride

    Karine Gargioni Pereira Correa de Mello

    2006-07-01

    Full Text Available The N-succinil-chitosan is a chemically modified derivative of the biopolymer chitosan. The succinic anhydride attached to the free amino groups presented along the chitosan's polymer chain imparts to the molecule different physicochemical properties not exhibited before the modification. These chemical modifications enhance chitosan's solubility in slightly acid, neutral and alkaline media. These properties are related to the long alkyl chains attached to hydrophilic parts. In this case the hydrophilic part of D-glucosamine promotes stronger interactions with the water molecules, and consequently, enhances the solubility of the chitosan polymer. Non-modified free chitosan is soluble only in acidic medium (pH A N-succinil-quitosana é um derivado quimicamente modificado do biopolímero quitosana. A inserção de substituintes de anidrido succínico nas aminas protonadas presentes ao longo da cadeia do polímero quitosana, conferem diferentes características físico-químicas a molécula de quitosana. Esta modificação química, possibilitou à quitosana, solubilidade em pHs que variam do ácido (2.0 a 3.0 até alcalino (13.0 a 14.0. Estas propriedades são atribuídas ao alongamento da cadeia alquílica, que afasta a parte hidrofílica da cadeia fechada da D-glicosamina, facilitando o acesso da água, a qual irá estabelecer uma interação mais forte com a molécula de quitosana. Esta propriedade não está presente em amostras de quitosana pura, a qual sabe-se que solubiliza-se apenas em pH abaixo de 5.5. Estas modificações na quitosana possibilitam novas aplicações na área de biotecnologia, uma vez que a solubilidade em meio neutro e levemente alcalino é importante na área biológica.

  18. 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

    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.

  19. Carbon Flux Analysis by 13C Nuclear Magnetic Resonance To Determine the Effect of CO2 on Anaerobic Succinate Production by Corynebacterium glutamicum

    Radoš, Dušica; David L Turner; Fonseca, Luís L.; Carvalho, Ana Lúcia; Blombach, Bastian; Eikmanns, Bernhard J.; Neves, Ana Rute; Santos, Helena

    2014-01-01

    Wild-type Corynebacterium glutamicum produces a mixture of lactic, succinic, and acetic acids from glucose under oxygen deprivation. We investigated the effect of CO2 on the production of organic acids in a two-stage process: cells were grown aerobically in glucose, and subsequently, organic acid production by nongrowing cells was studied under anaerobic conditions. The presence of CO2 caused up to a 3-fold increase in the succinate yield (1 mol per mol of glucose) and about 2-fold increase i...

  20. Effect of stretching on the mechanical properties in melt-spun poly(butylene succinate)/microfibrillated cellulose (MFC) nanocomposites.

    Zhou, Mi; Fan, Mao; Zhao, Yongsheng; Jin, Tianxiang; Fu, Qiang

    2016-04-20

    In order to prepare poly(butylene succinate)/microfibrillated cellulose composites with high performance, in this work, microfibrillated cellulose (MFC) was first treated by acetylchloride with ball-milling to improve its interfacial compatibility with poly(butylene succinate) (PBS). Then melt stretching processing was adopted to further improve the dispersion and orientation of MFC in as-spun PBS fiber. And the effect of MFC on the crystalline structure and mechanical properties were systematically investigated for the melt-spun fibers prepared with two different draw ratios. The dispersion, alignment of the MFC and interfacial crystalline structure in the composite fibers are significantly influenced by the stretching force during the melt spinning. The possible formation of nanohybrid shish kebab (NHSK) superstructure where aligned MFC as shish and PBS lamellae as kebab has been suggested via SEM and SAXS in the composite fibers prepared at the high draw ratio. Large improvement in tensile strength has been realized at the high draw ratio due to the enhanced orientation and dispersion of MFC as well as the formation of NHSK. PMID:26876865

  1. No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

    Dobrovic Alexander

    2009-09-01

    Full Text Available Abstract Background Succinate dehydrogenase (SDH and fumarate hydratase (FH are tricarboxylic acid (TCA cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1α (HIF-1α prolyl hydroxylases leading to sustained HIF-1α expression in tumours. Since HIF-1α is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas.

  2. Application of design of experiment for polyox and xanthan gum coated floating pulsatile delivery of sumatriptan succinate in migraine treatment.

    Jagdale, Swati C; Pawar, Chandrakala R

    2014-01-01

    Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 3(2) experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm(2), and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study. PMID:25530963

  3. Cross-linking of succinate-grafted chitosan and its effect on the capability to adsorb Pb(II) ion

    Masykur, Abu; Juari Santosa, Sri; Jumina, Dwi Siswanta dan

    2016-02-01

    The aim of this research was to improve the adsorption capacity of chitosan by modification of the chitosan using various cross-linking agents and followed by grafting using succinate anhydride. Succinate anhydride was grafted into chitosan that had been cross-linked using ethylene glycol di-glycidyl ether (EGDE), diethylene glycol diglycidyl ether (DEGDE) andbisphenolAdiglycidyl ether (BADGE) on the hydroxyl group of chitosan to yield Chit- EGDE-Suc, Chit-DEGDE-Suc, and Chit-BADGE-Suc, respectively. Modified chitosans were analyzed using FTIR and TG-DTA and then applied as adsorbents for Pb(II) ion. Adsorption was carried out in batch condition with a variation of solution pH, contact time, and concentration of Pb(II) in the solution. Adsorption ofPb(II) ion reached optimum condition at pH 5 and contact time of 120 minutes. Adsorption of Pb(II) ion on all of the adsorbents fit well the pseudo-second order kinetic equation. Adsorption capacities of Pb(II) on Chit-EGDE-Suc, Chit-DEGDE-SucdanChit-BADGE-Suc were 0.333, 0.388 and 0.898 mmolg-1, respectively, which mean that the adsorption of Chit-BADGE-Suc was the highest and followed by Chit- DEGDE-Suc and Chit-EGDE-Suc.

  4. Nanoparticles of Poly(Lactide-Co-Glycolide)-d-a-Tocopheryl Polyethylene Glycol 1000 Succinate Random Copolymer for Cancer Treatment

    Ma, Yuandong; Zheng, Yi; Liu, Kexin; Tian, Ge; Tian, Yan; Xu, Lei; Yan, Fei; Huang, Laiqiang; Mei, Lin

    2010-07-01

    Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization using stannous octoate as catalyst. The obtained random copolymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded nanoparticles made of PLGA-TPGS copolymer were prepared by a modified solvent extraction/evaporation method. The nanoparticles were then characterized by various state-of-the-art techniques. The results revealed that the size of PLGA-TPGS nanoparticles was around 250 nm. The docetaxel-loaded PLGA-TPGS nanoparticles could achieve much faster drug release in comparison with PLGA nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa). The results also indicated that PLGA-TPGS-based nanoparticles were biocompatible, and the docetaxel-loaded PLGA-TPGS nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for PLGA-TPGS nanoparticles was in time- and concentration-dependent manner. In conclusion, PLGA-TPGS random copolymer could be acted as a novel and promising biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.

  5. The effect of metoprolol succinate on the cardiac function of patients with thalassaemia cardiomyopathy: a double-blind randomised study

    Kojury, Javad; Zolghadrasli, Abdolali; Karimi, Mehran; Babaee Beighi, Mohammad Ali; Namazi, Soha

    2014-01-01

    Background Heart failure is the most common cause of mortality in β-thalassaemia major. However, the management of this disease, apart from chelation therapy, is largely empirical. Therefore, we decided to evaluate the effect of metoprolol succinate on patients with thalassaemia cardiomyopathy (TCM). Materials and methods In this clinical trial, 45 patients with TCM were randomised to receive either metoprolol (n=26) or placebo (n=19). Echocardiography and a 6 min walk test were performed at baseline and repeated after 6 months and the values compared. Results In the metoprolol group, left ventricular ejection fraction (LVEF) rose from 38.65% to 42.84% (pmetoprolol group decreased from 154.31 to 144.26 g (p=0.02), while in the placebo group it increased from 174.32 to 200.15 g (p=0.68); the difference between the two groups was significant (pmetoprolol group from 42.19 to 36.73 cm3 (pMetoprolol succinate as a β-blocker may have the potential to significantly improve systolic function in patients with TCM and reverse LV remodelling to the same extent as in other types of cardiomyopathy. Trial registration number NCT01863173.

  6. Systems-wide analysis and engineering of metabolic pathway fluxes in bio-succinate producing Basfia succiniciproducens.

    Becker, Judith; Reinefeld, Jasper; Stellmacher, René; Schäfer, Rudolf; Lange, Anna; Meyer, Hanna; Lalk, Michael; Zelder, Oskar; von Abendroth, Gregory; Schröder, Hartwig; Haefner, Stefan; Wittmann, Christoph

    2013-11-01

    Basfia succiniciproducens has been recently isolated as novel producer for succinate, an important platform chemical. In batch culture, the wild type exhibited a high natural yield of 0.75 mol succinate (mol glucose)⁻¹. Systems-wide ¹³C metabolic flux analysis identified undesired fluxes through pyruvate-formate lyase (PflD) and lactate dehydrogenase (LdhA). The double deletion strain B. succiniciproducens ΔldhA ΔpflD revealed a 45% improved product yield of 1.08 mol mol⁻¹. In addition, metabolic flux analysis unraveled the parallel in vivo activity of the oxidative and reductive branch of the TCA cycle in B. succiniciproducens, whereby the oxidative part mainly served for anabolism. The wild type re-directed surplus NADH via a cycle involving malic enzyme or via transhydrogenase, respectively, to supply NADPH for anabolism, because the fluxes through the oxidative PPP and isocitrate dehydrogenase, that also provide this cofactor, were not sufficient. This was not observed for the deletion mutants, B. succiniciproducens ΔpflD and ΔldhA ΔpflD, where PPP and isocitrate dehydrogenase flux alone matched with the reduced anabolic NADPH demand. The integration of the production performance into the theoretical flux space, computed by elementary flux mode analysis, revealed that B. succiniciproducens ΔldhA ΔpflD reached 62% of the theoretical maximum yield. PMID:23832568

  7. Roles of Fas signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells

    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.

  8. 99mtechnetium-dimercapto-succinic acid renal scanning and excretory urography in diagnosis of renal scars in children

    McLorie, G.A.; Aliabadi, H.; Churchill, B.M.; Ash, J.M.; Gilday, D.L. (Hospital for Sick Children, Toronto, Ontario (Canada))

    1989-09-01

    We compared the ability of excretory urography (without tomography) and 99mtechnetium-dimercapto-succinic acid renal scanning to detect renal scars in 32 children with primary vesicoureteral reflux. These children did not have hydronephrosis, renal failure or urinary tract obstruction. In all cases both studies were conducted within a 10-month period. The findings from both modalities were in agreement for 51 of the 64 renal units evaluated (80%). Evaluation of the excretory urogram indicated 6 cases of diffuse and 2 of focal scarring that were not detected by evaluation of the renal scan. The sensitivity of excretory urography to detect renal scars was 84% and the specificity was 83%. The 99mtechnetium-dimercapto-succinic acid renal scan showed 5 cases of focal renal scarring not detected by excretory urography. The sensitivity of the renal scan to detect renal scars was 77% and the specificity was 75%. We conclude that neither study alone could effectively replace the other for the detection of renal scars, and recommend that both be included in the initial evaluation and followup of patients with renal scars.

  9. The Effect of Methyl, Hydroxyl, and Ketone Functional Groups on the Heterogeneous Oxidation of Succinic Acid Aerosol by OH Radicals

    Chan, M.; Zhang, H.; Wilson, K. R.

    2013-12-01

    The heterogeneous oxidation of atmospheric organic aerosols can influence their effects on climate, human health, and visibility. During oxidation, functionalization occurs when an oxygenated functional group is added to a molecule, leaving the carbon skeleton intact. Fragmentation involves carbon-carbon bond cleavage and produces two products with smaller carbon numbers than the parent compound. To gain better insights into how the molecular structure of more oxygenated organic compounds affects heterogeneous reactivity, succinic acid aerosols are photo-oxidized in an aerosol flow tube reactor, and the reaction products are analyzed using Direct Analysis in Real Time Mass Spectrometry for online chemical analysis. The effect of various functional groups (CH3, OH, C=O) along the carbon backbone on the heterogeneous reaction mechanisms are also investigated using model compounds. For this series of compounds, the formation of more oxygenated products through functionalization can be explained by well-known condensation-phase reactions such as Russell and Bennett and Summers. The number of fragmentation products is found to increase with the presence of OH and CH3 groups. This can be attributed to the increased number of tertiary carbons, enhancing the fragmentation after multiple oxidation steps. Smaller dicaids (oxalic acid and malonic acid) can be formed through the fragmentation processes in the heterogeneous oxidation of succinic acid. The effect of molecular structure on reaction kinetics, volatilization, and the relative importance of functionalization and fragmentation pathways will be discussed.

  10. Effect of peroxide and chain extender on mechanical properties and morphology of poly (butylene succinate)/poly (lactic acid) blends

    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.

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

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

    1997-01-01

    Reactive oxygen species are formed in the body by several natural processes and by induced oxidative stress. The reactive oxygen species may react with the various biomolecules of the body, including proteins. In order to assess the impact of oxidative damage to proteins, we have tried to identify...... oxidized amino acids in blood proteins which might serve as biomarkers of oxidative damage. When oxidative damage is induced into bovine serum albumin by metal-catalysed oxidation systems, the aldehyde groups formed can be derivatized by fluoresceinamine (FINH2). Following acid hydrolysis of FINH2...... 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...

  12. Effects of 14 days of spaceflight and nine days of recovery on cell body size and succinate dehydrogenase activity of rat dorsal root ganglion neurons

    Ishihara, A.; Ohira, Y.; Roy, R. R.; Nagaoka, S.; Sekiguchi, C.; Hinds, W. E.; Edgerton, V. R.

    1997-01-01

    The cross-sectional areas and succinate dehydrogenase activities of L5 dorsal root ganglion neurons in rats were determined after 14 days of spaceflight and after nine days of recovery. The mean and distribution of the cross-sectional areas were similar to age-matched, ground-based controls for both the spaceflight and for the spaceflight plus recovery groups. The mean succinate dehydrogenase activity was significantly lower in spaceflight compared to aged-matched control rats, whereas the mean succinate dehydrogenase activity was similar in age-matched control and spaceflight plus recovery rats. The mean succinate dehydrogenase activity of neurons with cross-sectional areas between 1000 and 2000 microns2 was lower (between 7 and 10%) in both the spaceflight and the spaceflight plus recovery groups compared to the appropriate control groups. The reduction in the oxidative capacity of a subpopulation of sensory neurons having relatively large cross-sectional areas immediately following spaceflight and the sustained depression for nine days after returning to 1 g suggest that the 0 g environment induced significant alterations in proprioceptive function.

  13. Screening of detergents for solubilization, purification and crystallization of membrane proteins: a case study on succinate:ubiquinone oxidoreductase from Escherichia coli

    Shimizu, Hironari; Nihei, Coh-ichi; Inaoka, Daniel Ken; Mogi, Tatushi; Kita, Kiyoshi; Harada, Shigeharu

    2008-01-01

    Succinate:ubiquinone oxidoreductase was solubilized and purified from E. coli inner membranes using several different detergents and the phospholipid content of each preparation was analyzed. The preparation with the lowest phospholipid content crystallized in two different crystal forms using detergent mixtures composed of n-alkyl-oligoethylene glycol monoether and n-alkyl-maltoside.

  14. Synthesis of 5,6-dihydroquinolines and succinates via the reaction of α,α-dicyanoolefins and acetylenic esters in a ratio of 2:1

    Alizadeh, A.; Hosseini, S.Y.; Sedighian, H.; Bayat, F.; Zhu, Z.; Dušek, Michal

    2015-01-01

    Roč. 71, č. 41 (2015), s. 7885-7891. ISSN 0040-4020 Institutional support: RVO:68378271 Keywords : alpha,alpha-dicyanoolefin * dialkyl acetylenedicarboxylate * 5,6-dihydroquinoline * 2-(3,4-dihydronaphthalen-1(2H)-ylidene) * malononitriles * succin Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.641, year: 2014

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

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

    2016-01-01

    hydrolysis (PHSR), makes 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 added value-lower volume products (antioxidants)....

  16. Production of fermentable sugars from corn fiber using soaking in aqueous ammonia (saa) pretreatment and fermentation to succinic acid by Escherichia coli afp184

    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 ...

  17. Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to provitamin-to-vitamin conversion

    Neužil, Jiří; Massa, H.

    2005-01-01

    Roč. 327, č. 4 (2005), s. 1024-1027. ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : vitamin E * alpha-tocopheryl succinate * hepatic processing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  18. Artificial primary marine aerosol production: a laboratory study with varying water temperature, salinity and succinic acid concentration

    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.

  19. Silica gel modified with ethylenediamine and succinic acid-adsorption and calorimetry of cations in aqueous solution

    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 Cu2+ > Co2+ > Ni2+. ► 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 MCl2 (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−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−1 for Cu2+, Co2+ and Ni2+, respectively. Based on these values, the metals are preferentially adsorbed in the order Cu2+ > Co2+ > Ni2+. The other thermodynamic data for these systems are favorable at the solid/liquid interface, suggesting the efficacy of this modified silica for cation removal from solution

  20. Carbon flux analysis by 13C nuclear magnetic resonance to determine the effect of CO2 on anaerobic succinate production by Corynebacterium glutamicum.

    Radoš, Dušica; Turner, David L; Fonseca, Luís L; Carvalho, Ana Lúcia; Blombach, Bastian; Eikmanns, Bernhard J; Neves, Ana Rute; Santos, Helena

    2014-05-01

    Wild-type Corynebacterium glutamicum produces a mixture of lactic, succinic, and acetic acids from glucose under oxygen deprivation. We investigated the effect of CO2 on the production of organic acids in a two-stage process: cells were grown aerobically in glucose, and subsequently, organic acid production by nongrowing cells was studied under anaerobic conditions. The presence of CO2 caused up to a 3-fold increase in the succinate yield (1 mol per mol of glucose) and about 2-fold increase in acetate, both at the expense of l-lactate production; moreover, dihydroxyacetone formation was abolished. The redistribution of carbon fluxes in response to CO2 was estimated by using (13)C-labeled glucose and (13)C nuclear magnetic resonance (NMR) analysis of the labeling patterns in end products. The flux analysis showed that 97% of succinate was produced via the reductive part of the tricarboxylic acid cycle, with the low activity of the oxidative branch being sufficient to provide the reducing equivalents needed for the redox balance. The flux via the pentose phosphate pathway was low (~5%) regardless of the presence or absence of CO2. Moreover, there was significant channeling of carbon to storage compounds (glycogen and trehalose) and concomitant catabolism of these reserves. The intracellular and extracellular pools of lactate and succinate were measured by in vivo NMR, and the stoichiometry (H(+):organic acid) of the respective exporters was calculated. This study shows that it is feasible to take advantage of natural cellular regulation mechanisms to obtain high yields of succinate with C. glutamicum without genetic manipulation. PMID:24610842

  1. Effect of Anorganic Substance on Physical Properties of Poly (Butylene Succinate -co- Adipate) Irradiated by Electron Beam

    Poly(butylene succinate-co-adipate), PBSA were electron beam irradiated in the presence of inorganic materials. The samples gave high gel fraction by irradiation in the presence of 2% silicon dioxide and 2% carbon black. It was found that addition of carbon black (CB) was effective for improving the heat stability of the sample. This is because of three-dimensional carbon black- polymer networks. Irradiated PBSA sheets broke immediately at 110 oC with load 6.67 kgf/cm2, while irradiated the same sample mixed with 2% carbon black did not break at the same condition. Biodegradability of crosslinked PBSA by soil burial tests was accelerated by addition of carbon black. (author)

  2. Structural Elucidation of α-Cyclodextrin-Succinic Acid Pseudo Dodecahydrate: Expanding the Packing Types of α-Cyclodextrin Inclusion Complexes

    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.

  3. Mitochondrially Targeted alpha-Tocopheryl Succinate Is Antiangiogenic: Potential Benefit Against Tumor Angiogenesis but Caution Against Wound Healing

    Rohlena, Jakub; Dong, L.-F.; Klučková, Katarína; Zobalová, Renata; Goodwin, J.; Tilly, D.; Štursa, Jan; Pecinová, Alena; Philimonenko, Anatoly; Hozák, Pavel; Banerjee, J.; Ledvina, Miroslav; Sen, Ch.K.; Houštěk, Josef; Coster, M.J.; Neužil, Jiří

    2011-01-01

    Roč. 15, č. 12 (2011), s. 2923-2935. ISSN 1523-0864 R&D Projects: GA MŠk(CZ) 1M0520; GA AV ČR(CZ) KAN200520703; GA ČR(CZ) GA305/07/1008; GA ČR(CZ) GAP301/10/1937; GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z50110509; CEZ:AV0Z4055905; CEZ:AV0Z5052915 Keywords : Analogs of alpha-tocopheryl succinate * MitoVES * inhibition of angiogenesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.456, year: 2011

  4. Characterization of poly(butylene succinate)/glycerol co-plasticized thermoplastic gelatin prepared by melt blending

    Oliviero, Maria; Sorrentino, Andrea; Iannace, Salvatore

    2015-12-01

    Biodegradable thermoplastic poly(butylene succinate)/gelatin (PBS/TPG) blends with various blending ratios were prepared by melt mixing technique. The main goal of these blends is to improve the water sensitivity of thermoplastic gelatin by blending it with a hydrophobic biodegradable polymer obtained also from renewable resources. The incorporation of PBS yielded a decrease in absorbed moisture. Under the relative humidity 50 and 100%, the absorbed moisture obtained values were 19 and 229% for pure TPG, 12.3 and 127% for TPG/PBS(80/20), and 1.7 and 37% for TPG/PBS(20/80), respectively. The water resistance increased only for the samples containing a high value of PBS (>40%wt). Furthermore, mechanical properties and morphological analyses revealed that PBS/TPG blends were immiscible.

  5. Expression of Ascaris suum malic enzyme in a mutant Escherichia coli allows production of succinic acid from glucose

    Stols, L.; Donnelly, M.I. [Argonne National Lab., IL (United States); Kulkarni, G.; Harris, B.G. [Univ. of North Texas, Fort Worth, TX (United States)

    1997-12-31

    The malic enzyme gene of Ascaris suum was cloned into the vector pTRC99a in two forms encoding alternative amino-termini. The resulting plasmids, pMEA1 and pMEA2, were introduced into Escherichia coli NZN111, a strain that is unable to grow fermentatively because of inactivation of the genes encoding pyruvate dissimilation. Induction of pMEA1, which encodes the native animoterminus, gave better overexpression of malic enzyme, approx 12-fold compared to uninduced cells. Under the appropriate culture conditions, expression of malic enzyme allowed the fermentative dissimilation of glucose by NZN111. The major fermentation product formed in induced cultures was succinic acid.

  6. Effects of synthetic detergents on in vivo activity of tissue phosphatases and succinic dehydrogenase from Mystus vittatus

    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.

  7. Sirtuin 3 (SIRT3) Regulates α-Smooth Muscle Actin (α-SMA) Production through the Succinate Dehydrogenase-G Protein-coupled Receptor 91 (GPR91) Pathway in Hepatic Stellate Cells.

    Li, Ying Hui; Choi, Dae Hee; Lee, Eun Hye; Seo, Su Ryeon; Lee, Seungkoo; Cho, Eun-Hee

    2016-05-01

    Sirtuin 3 (SIRT3) is an NAD(+)-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 expression were increased. Moreover, we found that GPR91 knockdown or resveratrol treatment improved the steatosis in MCD diet-fed mice. This investigation revealed a novel mechanism of the SIRT3-SDH-GPR91 cascade in MCD diet-induced HSC activation in NAFLD. These findings highlight the biological significance of novel strategies aimed at targeting SIRT3 and GPR91 in HSCs with the goal of improving NAFLD treatment. PMID:26912655

  8. DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR SIMULTANEOUS ESTIMATION OF METOPROLOL SUCCINATE AND TELMISARTAN IN COMBINED PHARMACEUTICAL FORMULATION

    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.

  9. Improved Succinic Acid Production in the Anaerobic Culture of an Escherichia coli pflB ldhA Double Mutant as a Result of Enhanced Anaplerotic Activities in the Preceding Aerobic Culture▿

    Wu, Hui; Li, Zhi-Min; Zhou, Li; Ye, Qin

    2007-01-01

    Escherichia coli NZN111 is a pflB ldhA double mutant which loses its ability to ferment glucose anaerobically due to redox imbalance. In this study, two-stage culture of NZN111 was carried out for succinic acid production. It was found that when NZN111 was aerobically cultured on acetate, it regained the ability to ferment glucose with succinic acid as the major product in subsequent anaerobic culture. In two-stage culture carried out in flasks, succinic acid was produced at a level of 11.26 ...

  10. Intensive swimming exercise-induced oxidative stress and reproductive dysfunction in male wistar rats: protective role of alpha-tocopherol succinate.

    Manna, Indranil; Jana, Kuladip; Samanta, Prabhat Kumar

    2004-04-01

    In the present study, 30 male rats (age 3 mos, Wt 128.6 +/- 3.7 g) were randomly divided into Control group (CG), Experimental group (EG), and Supplemented group (SG), 10 per group. An exercise protocol (3 hrs swimming per day, 5 days a week for 4 weeks) was followed in EG and SG, with no exercise in CG. In SG, alpha-tocopherol succinate was injected sub-cutaneously at a dose of 50 mg x kg(- 1) per body weight per day. After 4 weeks of exercise, significant diminutions (p Intensive swimming exercise-induced oxidative stress causes dysfunction in the male reproductive system, which can be protected by alpha-tocopherol succinate. PMID:15064426

  11. Preparation of poly(glycidylmethacrylate-divinylbenzene) weak acid cation exchange stationary phases with succinic anhydride, phthalic anhydride, and maleic anhydride for ion chromatography.

    Liu, Junwei; Wang, Yong; Wu, Shuchao; Zhang, Peimin; Zhu, Yan

    2016-08-01

    In this work, poly(glycidylmethacrylate-divinylbenzene) microspheres were prepared and applied for the preparation of weak acid cation exchange stationary phases. Succinic anhydride, phthalic anhydride, and maleic anhydride were selected as carboxylation reagents to prepare three weak acid cation exchangers by direct chemical derivatization reaction without solvent or catalyst. The diameters and dispersity of the microspheres were characterized by scanning electron microscopy; the amount of accessible epoxy groups and mechanical stability were also measured. The weak acid cation exchangers were characterized by Fourier transform infrared spectroscopy; the content of carboxyl groups was measured by traditional acid base titration method. The chromatographic properties were characterized and compared by separating alkali, alkaline earth metal ions and ammonium and polar amines. The separation properties enhanced in the order of succinic anhydride, phthalic anhydride, and maleic anhydride modified poly(glycidylmethacrylate-divinylbenzene) cation exchangers. PMID:27288092

  12. Artificial primary marine aerosol production: a laboratory study with varying water temperature, salinity, and succinic acid concentration

    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.

  13. Degradation studies of 1, 6-diisocyanatohexane-extended poly (1, 4-butylene succinate) - bioactive glass scaffolds for bone tissue repair applications

    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.

  14. c-Jun N-terminal kinase is required for vitamin E succinate-induced apoptosis in human gastric cancer cells

    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.

  15. Mixed Micelles made of Poly(ethylene glycol)-Phosphatidylethanolamine Conjugate and D-α-tocopheryl Polyethylene Glycol 1000 Succinate as Pharmaceutical Nanocarriers for Camptothecin

    Mu, L; Elbayoumi, T.A.; Torchilin, V.P.

    2005-01-01

    Micelles from the mixture of poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) and D-α-tocopheryl polyetheyene glycol 1000 succinate (TPGS) were prepared loaded with the poorly soluble anticancer drug camptothecin (CPT). The solubilization of CPT by the mixed micelles was more efficient than with earlier described micelles made of PEG-PE alone. CPT-loaded mixed micelles were stable upon storage and dilution and firmly retained the incorporated drug. The cytotoxicity of the CP...

  16. 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

    Samira Siyamak; Nor Azowa Ibrahim; Sanaz Abdolmohammadi; Wan Md Zin Bin Wan Yunus; Mohamad Zaki AB Rahman

    2012-01-01

    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 ...

  17. INFLUENCE OF METOPROLOL SUCCINATE ON REGULATORY AND ADAPTIVE STATUS OF PATIENTS WITH CHRONIC HEART FAILURE FUNCTIONAL CLASS I. RESULTS OF NOT COMPARATIVE STUDY

    V. G. Tregubov

    2016-01-01

    Full Text Available Aim. To estimate metoprolol succinate effect on regulatory and adaptive status (RAS of patients with сhronic heart failure (CHF functional class (FC I and arterial hypertension (HT I-II stages. Material and methods. 51 patients with CHF FC I and HT I-II stage, (30 men and 21 women aged 52.6±1.4 yeas. Cardio-respiratory synchronism (CRS test, 6-minute walking test, tread-mill burden test with registration of maximal oxygen consumption, 24-hour blood pressure monitoring, echocardiography and determination of N-terminal pro-brain natriuretic peptide (NT-proBNP blood level were performed initially and after 6 months of therapy with metoprolol succinate (dose 78.1±5.7 mg/day in sustained-release presentation. Results. Metoprolol succinate therapy had no significant effect on RAS (there was no unidirectional dynamics of the basic CRS test parameters: a range of synchronization decreased significantly from 8.8±0.4 to 7.2±0.6 сardio-respiratory cycles per minute (in 18%; р<0.05, and duration of CRS development on the minimal boundary from 18.8±2.2 to 14.3±1.2 сardiocycles (in 24%; р<0,05; RAS index considerably did not change, myocardium structure, exercise tolerance and neuro-humoral activity. Metoprolol therapy only moderately improved left ventricle diastolic function. Conclusion. Metoprolol succinate therapy has no significant effect on RAS of patients with CHF FC I and HT I-II stages.

  18. α-Tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells

    Lim, Soo-Jeong; Choi, Moon Kyung; Kim, Min Jung; Kim, Joo Kyoung

    2009-01-01

    Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of α-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavag...

  19. Interpolyelectrolyte Complexes of Eudragit® EPO with Hypromellose Acetate Succinate and Eudragit® EPO with Hypromellose Phthalate as Potential Carriers for Oral Controlled Drug Delivery

    Jeganathan, Balamurugan; Prakya, Vijayalakshmi

    2015-01-01

    The objective of this study was to compare a novel controlled release tablet formulation based on interpolyelectrolyte complex (PEC). Interpolymer interactions between the countercharged polymers like Eudragit® EPO (polycation) and hypromellose acetate succinate (polyanion) and Eudragit® EPO and hypromellose phthalate (polyanion) were investigated with a view to their use in per oral controlled release drug delivery systems. The formation of inter-macromolecular ionic bonds between cationic p...

  20. Synthesis of high molecular weight polylactic acid from aqueous lactic acid co-catalyzed by tin(II)chloride dihydrate and succinic anhydride

    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.

  1. Dicty_cDB: Contig-U14191-1 [Dicty_cDB

    Full Text Available A8FDV4) RecName: Full=Methylmalonate semialdehyde dehydrogenase... 252 e-102 AM711867_792( AM711867 |pid:none) Clavibacter michi...ecName: Full=Probable methylmalonate-semialdehyde dehydrogenase [acylating], mitochondria...4 e-108 (A0RDW1) RecName: Full=Methylmalonate semialdehyde dehydrogenase... 269 e-108 AM920437_281( AM920437 |pid:none) Pen... MC0-3 ch... 270 e-103 (A5YBJ3) RecName: Full=Methylmalonate semialdehyde dehydrogenase......263198_897( AM263198 |pid:none) Listeria welshimeri serovar 6b s... 141 2e-57 AI1188( AI1188 ) succinate semialdehyde dehydrogena

  2. Development and Validation of a Specific Stability Indicating High Performance Liquid Chromatographic Methods for Related Compounds and Assay of Solifenacin Succinate

    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.

  3. 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

    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.

  4. SuccinSite: a computational tool for the prediction of protein succinylation sites by exploiting the amino acid patterns and properties.

    Hasan, Md Mehedi; Yang, Shiping; Zhou, Yuan; Mollah, Md Nurul Haque

    2016-03-23

    Lysine succinylation is an emerging protein post-translational modification, which plays an important role in regulating the cellular processes in both eukaryotic and prokaryotic cells. However, the succinylation modification site is particularly difficult to detect because the experimental technologies used are often time-consuming and costly. Thus, an accurate computational method for predicting succinylation sites may help researchers towards designing their experiments and to understand the molecular mechanism of succinylation. In this study, a novel computational tool termed SuccinSite has been developed to predict protein succinylation sites by incorporating three sequence encodings, i.e., k-spaced amino acid pairs, binary and amino acid index properties. Then, the random forest classifier was trained with these encodings to build the predictor. The SuccinSite predictor achieves an AUC score of 0.802 in the 5-fold cross-validation set and performs significantly better than existing predictors on a comprehensive independent test set. Furthermore, informative features and predominant rules (i.e. feature combinations) were extracted from the trained random forest model for an improved interpretation of the predictor. Finally, we also compiled a database covering 4411 experimentally verified succinylation proteins with 12 456 lysine succinylation sites. Taken together, these results suggest that SuccinSite would be a helpful computational resource for succinylation sites prediction. The web-server, datasets, source code and database are freely available at . PMID:26739209

  5. The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2

    Cline Brandon H

    2012-09-01

    Full Text Available Abstract Background A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling. Results Administration of DS (25 mg/kg/day, intraperitoneal in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2. Conclusions Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.

  6. Evaluation of an integrated biorefinery based on fractionation of spent sulphite liquor for the production of an antioxidant-rich extract, lignosulphonates and succinic acid.

    Alexandri, Maria; Papapostolou, Harris; Komaitis, Michael; Stragier, Lutgart; Verstraete, Willy; Danezis, Georgios P; Georgiou, Constantinos A; Papanikolaou, Seraphim; Koutinas, Apostolis A

    2016-08-01

    Spent sulphite liquor (SSL) has been used for the production of lignosulphonates (LS), antioxidants and bio-based succinic acid. Solvent extraction of SSL with isopropanol led to the separation of approximately 80% of the total LS content, whereas the fermentations carried out using the pretreated SSL with isopropanol led to the production of around 19g/L of succinic acid by both Actinobacillus succinogenes and Basfia succiniciproducens. Fractionation of SSL via nanofiltration to separate the LS and solvent extraction using ethyl acetate to separate the phenolic compounds produced a detoxified sugar-rich stream that led to the production of 39g/L of succinic acid by B. succiniciproducens. This fractionation scheme resulted also in the production of 32.4g LS and 1.15g phenolic-rich extract per 100g of SSL. Both pretreatment schemes removed significant quantities of metals and heavy metals. This novel biorefinery concept could be integrated in acidic sulphite pulping mills. PMID:27176670

  7. Efficient carbon dioxide utilization and simultaneous hydrogen enrichment from off-gas of acetone-butanol-ethanol fermentation by succinic acid producing Escherichia coli.

    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. PMID:27142628

  8. Selective separation and characterisation of stress degradation products and process impurities of prucalopride succinate by LC-QTOF-MS/MS.

    Mahamuni, Baira Shandilya; Jajula, Anupama; Awasthi, Atul; Kalariya, Pradipbhai D; Talluri, M V N Kumar

    2016-06-01

    The present study reports the degradation behaviour of a new prokinetic agent, Prucalopride succinate, under various stress conditions as per International Conference on Harmonization guidelines (ICH, Q1A (R2)). The investigation involved monitoring decomposition of the drug under hydrolytic (acidic, basic and neutral), oxidative, photolytic and thermal stress conditions followed by characterization of the degradation products (DPs) and process related impurities (IMPs). A rapid, precise, accurate and robust reverse phase high performance liquid chromatography (RP-HPLC) method has been developed involving mobile phase of 20mM ammonium bicarbonate buffer and acetonitrile: methanol (80:20v/v) on a Waters Xbridge-C8 (150mm×4.6mm i.d., 3.5μm) column using gradient elution. The drug was found to be degraded in hydrolytic (acidic) and oxidative conditions, whereas it was stable under basic and neutral hydrolytic, photolytic and thermal stress conditions. The method was extended to LC-ESI-QTOF-MS/MS for the structural characterization of DPs and process related IMPs. Structural characterization was carried out based on the generated molecular formula of DPs and its fragment ions. It has been observed that two major DPs were formed under each acid hydrolysis and oxidative stress conditions. The most probable mechanisms involved in the formation of DPs were also proposed. Finally, the method was validated in the term of specificity, linearity, accuracy, precision, and robustness as per ICH guidelines, Q2 (R1). PMID:27037978

  9. Efficacy and biodistribution of tocopheryl polyethylene glycol succinate noncovalent functionalized single walled nanotubes loading doxorubicin in sarcoma bearing mouse model.

    Wang, Yongjun; Xu, Hui; Liu, Hongzhuo; Wang, Yan; Sun, Jin; He, Zhonggui

    2012-06-01

    The aim of this study is to develop the noncovalent functionalized single walled nanotubes loading doxorubicin. A tocopheryl polyethylene glycol succinate (TPGS) noncovalent modification of single walled carbon nanotubes (SWNTs) loading antitumor agent doxorubicin (Dox) via the physical absorption was developed. Dox was successfully loaded onto the surface of carbon nanotubes (loading amount was 168.7 microg/ml), which was confirmed by UV-vis-NIR absorbance spectra and dynamic light scattering assay. ICR mice bearing mouse sarcoma tumor were subjected to intratumoral injection of TPGS-SWNTs-Dox. Based on the in vivo antitumor activities of the locally injected the formulation into the tumor bearing mice, it was shown that there was modest (up to 50.2%) delay of tumor growth compared with the groups receiving no treatment, which was better than free dox (up to 40.2%). The biodistribution studies demonstrated that there were the longest retention time in tumor, the highest tumor accumulation, as well as less accumulation in other solid tissues, especially in heart, when tumor bearing mice were administered with TPGS-SWNTs-Dox. It may be attributed to the enhanced permeability and retention (EPR) effect of TPGS-SWNTs-Dox. The histopathological findings revealed that the new carbon nanomaterials were a safe vehicle for topical drug delivery systems. These results suggested that the noncovalent modification of carbon nanotubes by TPGS for anticancer agents may be a promising strategy for cancer treatment. PMID:22764414

  10. Determination of succinate-dehydrogenase-inhibitor fungicide residues in fruits and vegetables by liquid chromatography-tandem mass spectrometry.

    Abad-Fuentes, Antonio; Ceballos-Alcantarilla, Eric; Mercader, Josep V; Agulló, Consuelo; Abad-Somovilla, Antonio; Esteve-Turrillas, Francesc A

    2015-05-01

    In recent years, a second generation of succinate-dehydrogenase-inhibitor (SDHI) fungicides has been introduced into the market for effective treatment of fruit and vegetable crops, with fluxapyroxad, boscalid, fluopyram, penflufen, bixafen, penthiopyrad, and isopyrazam being some of the members of this new class of agrochemical. We herein report the development of an analytical procedure for the determination of residues of these SDHI fungicides in food samples, based on a modification of the QuEChERS extraction method followed by ultra-performance liquid chromatography coupled to tandem-mass-spectrometry determination. The proposed method reached limits of detection from 0.8 to 2.0 μg L(-1). Apple, strawberry, tomato, and spinach samples were used as model samples. Spiked samples, from 10 to 1000 μg kg(-1), were analysed by the proposed method and quantitative recoveries were obtained (from 81 to 115 % for apples, from 84 to 136 % for strawberries, from 84 to 135 % for tomatoes, and from 80 to 136 % for spinach), with precision better than 20 % in all cases. Thus, the proposed method can be used for the analysis of SDHI fungicide residues to efficiently ensure that marketed fruits and vegetables comply with the maximum residue levels established by competent authorities. PMID:25796526

  11. Ocular melanoma imaging with 99m Tc (V)Dimercapto succinic acid in Thyrotoxic (Grave's) patients pretreated with radioiodine

    Ocular melanoma in Thyrotoxic patients is a very rare type of cancer, where its exact cause or link between the radiation exposure due to radioiodine therapy or other external radiation exposure on its development is still an unsolved puzzle. In the recent years the ectopic production of melanin and presence of somatostatin receptors in medullary thyroid carcinoma demonstrated its neuroendocrine origin. Thereafter the accumulation of 99mTc (V) Dimercapto succinic acid in medullary thyroid carcinoma cells were also reported. In 1991, Feggi et al demonstrated the scintigraphic uptake of radiolabelled monoclonal antibodies directed against melanoma in follicular thyroid adenoma. On this basis we conducted studies with 99m Tc (V) DMSA, in two thyrotoxic patients, received radioiodine therapy in 1985 and 1986 respectively and developed choroidal melanoma (in one case lacrimal gland was also involved), however the exact etiology was not established. The DMSA cold kits were prepared locally and labeled at five-valent state of 99m Technetium. Proper quality control methods were applied and the dose of 10 mCi was injected in each patient. The whole body images as well as brain SPECT images were taken after two hrs. and analyzed for further evaluation. The 99mTc(V) DMSA accumulation in melanoma site was seen in SPECT images .Our findings were further confirmed by CT and histochemistry. It further corroborates the neuroendocrine origin of melanoma having originated from the neural crest during development as mentioned in literature

  12. Stabilizing effect of 2-(triphenylphosphoranylidene) succinic anhydride as electrolyte additive on the lithium metal of lithium metal secondary batteries

    Highlights: • TPSA was introduced as a Li metal anode surface-stabilizing electrolyte additive. • TPSA forms resistive SEI upon Li metal, which hinders Li dendrite formation. • TPSA improves capacity retention ability of Li metal compared to bare electrolyte. -- Abstract: We introduce 2-(triphenylphosphoranylidene) succinic anhydride (TPSA) as a lithium (Li) metal anode surface-stabilizing electrolyte additive for improving the cycle performance of Li metal secondary batteries. We verified that TPSA is readily decomposed on Li metal anodes before the decomposition of liquid electrolytes, and forms stable surface layers, i.e., a solid electrolyte interface (SEI). Consequently, TPSA was found to improve the cycle performance of unit cells consisting of LiCoO2/Li metal. The unit cells containing 3 wt.% of TPSA retain 85% of the initial discharge capacity after 100 cycles, whereas the unit cells that do not contain TPSA showed catastrophic failure after only 50 cycles. Each unit cell was operated at C/2 rate (0.8 mA cm−2) in the voltage range 3.0–4.2 V vs. Li/Li+. The TPSA-derived SEI suppresses continuous electrolyte decomposition, and thereby Li dendrite formation as well. The effect of TPSA was characterized by scanning electron microscopy, electrochemical impedance spectroscopy, and X-ray photoelectron spectroscopy

  13. A split and rearranged nuclear gene encoding the iron-sulfur subunit of mitochondrial succinate dehydrogenase in Euglenozoa

    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.

  14. Effect of organo-modified montmorillonite on poly(butylene succinate/poly(butylene adipate-co-terephthalate nanocomposites

    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.

  15. Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate.

    Wu, Dan; Katsumi, Hidemasa; Quan, Ying-Shu; Kamiyama, Fumio; Kusamori, Kosuke; Sakane, Toshiyasu; Yamamoto, Akira

    2016-09-01

    Available formulations of sumatriptan succinate (SS) have low bioavailability or are associated with site reactions. We developed various types of self-dissolving microneedle arrays (MNs) fabricated from sodium hyaluronate as a new delivery system for SS and evaluated their skin permeation and irritation in terms of clinical application. In vitro permeation studies with human skin, physicochemical properties (needle length, thickness and density), and penetration enhancers (glycerin, sodium dodecyl sulfate and lauric acid diethanolamide) were investigated. SS-loaded high-density MNs of 800 µm in length were the optimal formulation and met clinical therapeutic requirements. Penetration enhancers did not significantly affect permeation of SS from MNs. Optical coherence tomography images demonstrated that SS-loaded high-density MNs (800 µm) uniformly created drug permeation pathways for the delivery of SS into the skin. SS-loaded high-density MNs induced moderate primary skin irritations in rats, but the skin recovered within 72 h of removal of the MNs. These findings suggest that high-density MNs of 800 µm in length are an effective and promising formulation for transdermal delivery of SS. To our knowledge, this is the first report of SS permeation across human skin using self-dissolving MNs. PMID:26878569

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

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

    1986-09-01

    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 responding O2 and pH electrodes were used to collect data every 10 ms. The response time for each electrode was experimentally measured in each experiment and suitable corrections for electrode relaxations were made. With uncorrected data obtained after 0.8 s, the extrapolation back to zero time on the basis of single-exponential curve fitting confirmed values close to 8.0 as previously reported (Costa et al., 1984). The data directly obtained, however, indicate an initial burst in H+/O ratio that peaked to values of approximately 20 to 30 prior to 50 ms and which was no longer evident after 0.3 s. Newer information and considerations that place all extrapolation methods in question are discussed. PMID:3019443

  17. DEVELOPMENT AND VALIDATION OF TLC-DENSITOMETRIC AND HPLC METHODS FOR DETERMINATION OF OLMESARTAN MEDOXOMIL AND METOPROLOL SUCCINATE IN COMBINATION

    Chitlange Sohan S.

    2012-06-01

    Full Text Available Rapid, accurate and sensitive methods for the identification and quantification of Olmesartan Medoxomil (OLME and Metoprolol Succinate (METO were developed by TLC-densitometry and HPLC at 222 nm. The first developed method was TLC-densitometry, where mixture of OLME and METO were separated on silica gel TLC 60 F254 plates using Toluene:Methanol:Glacial acetic acid (7.0:2.5:0.5 v/v/v as mobile phase and scanning of the separated bands at 222 nm. Linearity was observed in the concentration range of 500-2500 ng/band for OLME and 500-3000 ng/band for METO. The second method was HPLC, where the mixture of OLME and METO separated on thermo scientific BDS Hypersil, C18 column (5µm p.s, 250 mm  4.6 mm, flow rate 1 mL/min. The mobile phase selected was Phosphate buffer 0.05M (pH adjusted to 3.0±0.5 with Orthophosphoric acid: Acetonitrile (60:40 v/v with detection at 222 nm. Linearity was observed in the concentration range of 25-200 µg/mL for OLME and 25-225 µg/mL for METO. Both methods were validated according to ICH guideline and value of linearity, precision, robustness, LOD, LOQ, selectivity, recovery were found to be good in accordance with the prescribed value.

  18. Simultaneous ammonia and nitrate removal in an airlift reactor using poly(butylene succinate) as carbon source and biofilm carrier.

    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. PMID:27343453

  19. Solution viscosity – molar mass relationships for poly(butylene succinate and discussion on molar mass analysis

    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.

  20. Dynamics of three organic acids (malic, acetic and succinic acid) in sunflower exposed to cadmium and lead.

    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. PMID:23819268

  1. Succinic acid in levels produced by yeast (Saccharomyces cerevisiae) during fermentation strongly impacts wheat bread dough properties.

    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. PMID:24423552

  2. A new point mutation in the iron-sulfur subunit of succinate dehydrogenase confers resistance to boscalid in Sclerotinia sclerotiorum.

    Wang, Yong; Duan, Yabing; Wang, Jianxin; Zhou, Mingguo

    2015-09-01

    Research has established that mutations in highly conserved amino acids of the succinate dehydrogenase (SDH) complex in various fungi confer SDH inhibitor (SDHI) resistance. For Sclerotinia sclerotiorum (Lib.) de Bary, a necrotrophic fungus with a broad host range and a worldwide distribution, boscalid resistance has been attributed to the mutation H132R in the highly conserved SdhD subunit protein of the SDH complex. In our previous study, however, only one point mutation, A11V in SdhB (GCA to GTA change in SdhB), was detected in S. sclerotiorum boscalid-resistant (BR) mutants. In the current study, replacement of the SdhB gene in a boscalid-sensitive (BS) S. sclerotiorum strain with the mutant SdhB gene conferred resistance. Compared with wild-type strains, BR and GSM (SdhB gene in the wild-type strain replaced by the mutant SdhB gene) mutants were more sensitive to osmotic stress, lacked the ability to produce sclerotia and exhibited lower expression of the pac1 gene. Importantly, the point mutation was not located in the highly conserved sequence of the iron-sulfur subunit of SDH. These results suggest that resistance based on non-conserved vs. conserved protein domains differs in mechanism. In addition to increasing our understanding of boscalid resistance in S. sclerotiorum, the new information will be useful for the development of alternative antifungal drugs. PMID:25441450

  3. Research of vitamin E succinate combined with paclitaxel on the apoptosis of Her-2 over-expressing breast cancer cells

    Li Li; Tingting Yan; Yan Zhao; Qiuying Jiang

    2011-01-01

    Objective: The aim of this study was to detect apoptosis rates of Her-2 overexpression breast cancer cells, which were administrated with vitamin E succinate (VES) combined with paclitaxel at different dosages, or administrated alone; to discuss the mechanism of their actions. Methods: Using immunohistochemical method to detect Her-2 expression of MDA-MB-453 cells. Using TUNEL assay to detect apoptosis rates of MDA-MB-453 cells, with the concentrations at 10, 20 mg/L of VES and 50, 100 nmol/L of paclitaxel, and also combined together for 24 or 48 h. Then compared apoptosis action of various combinations. Results: The expression rate of 95% Her-2 was interval (63.32%, 69.60%); VES and paclitaxel both induced apoptosis of MDA-MB-453 cells, and it is dose to time dependence. It was strongest in apoptosis at 10 mg/L VES and 100 nmol/L paclitaxel in MDA-MB-453 cells 48 h later. Conclusion: VES and paclitaxel both induced apoptosis of MDA-MB-453 cells. It is stronger when the two drugs are administrated together. The mechanism is probably related to reduction of bcl-2 expression, so as to be more sensitive to paclitaxel. Synergistic effect is also possible for the two drugs influence tumor cells in different growing phases.

  4. Enhanced osteogenic activity of a poly(butylene succinate)/calcium phosphate composite by simple alkaline hydrolysis

    Bone engineering offers the prospect of alternative therapies for clinically relevant skeletal defects. Poly(butylene succinate) (PBSu) is a biodegradable and biocompatible polyester which may possess some limitations in clinical use due to its hydrophobicity. In order to overcome these limitations and increase the bioactivity, a simple and convenient surface hydrolysis of PBSu, PBSu/hydroxyapatite and PBSu/β-tricalcium phosphate (TCP) films was performed. The resulting surfaces (i.e., HPBSu, HPBSu/HA and HPBSu/TCP) were tested for their physicochemical property, biocompatibility and osteogenic potency. The results showed that surface hydrolysis significantly increased surface roughness and hydrophilicity of the composites, with the HPBSu/TCP possessing the most pronounced results. All the materials appeared to be biocompatible and supported in vitro growth and osteoblast differentiation of hMSCs, and the alkaline hydrolysis significantly enhanced the hMSC cell proliferation and the osteogenic potency of PBSu/TCP compared with the non-hydrolyzed sample. In conclusion, the HPBSu/TCP possessed better hydrophilicity, biocompatibility and osteogenic potency in vitro, suggesting that this simple and convenient alkaline hydrolysis could be used to augment the biological property of PBSu-based composites for bone engineering in vivo. (paper)

  5. Preparation and optimization of sustained release matrix tablets of metoprolol succinate and taro gum using response surface methodology

    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.

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

    Xi Yang

    2016-04-01

    Full Text Available 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 decrease of Tg to around room temperature and an increase in the elongation at break of PLA from 14% to 165% and 460%, respectively, were determined. The crystallinity was increased from 2.1% to 8.4% for PLA/PBSA and even more, to 10.6%, for PLA-CA-PBSA. Due to the inherent poor miscibility between the PBSA and PLA, phase separation occurred in the blend, while PLA-CA-PBSA showed no phase separation which, together with the higher crystallinity, led to better oxygen barrier properties compared to neat PLA and PLA/PBSA. A higher resistance to migration during hydrolytic degradation for the PLA-CA-PBSA compared to the PLA/PBSA indicated that the plasticization effect of PBSA in the coupled material would be retained for a longer time period.

  7. FORMULATION AND IN VITRO EVALUATION OF METOPROLOL SUCCINATE FLOATING TABLETS BY USING TWO VISCOSITY GRADE OF HPMC

    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.

  8. Biological denitrification using poly(butylene succinate) as carbon source and biofilm carrier for recirculating aquaculture system effluent treatment.

    Zhu, Song-Ming; Deng, Ya-Le; Ruan, Yun-Jie; Guo, Xi-Shan; Shi, Ming-Ming; Shen, Jia-Zheng

    2015-09-01

    Nitrate removal is essential for the sustainable operation of recirculating aquaculture system (RAS). This study evaluated the heterotrophic denitrification using poly(butylene succinate) as carbon source and biofilm carrier for RAS wastewater treatment. The effect of varied operational conditions (influent type, salinity and nitrate loading) on reactor performance and microbial community was investigated. The high denitrification rates of 0.53 ± 0.19 kg NO3(-)-N m(-3) d(-1) (salinity, 0‰) and 0.66 ± 0.12 kg NO3(-)-Nm(-3) d(-1) (salinity, 25‰) were achieved, and nitrite concentration was maintained below 1mg/L. In addition, the existence of salinity exhibited more stable nitrate removal efficiency, but caused adverse effects such as excessive effluent dissolved organic carbon (DOC) and dissimilation nitrate reduce to ammonia (DNRA) activity. The degradation of PBS was further confirmed by SEM and FTIR analysis. Illumina sequencing revealed the abundance and species changes of functional denitrification and degradation microflora which might be the primary cause of varied reactor performance. PMID:26093254

  9. Controlled-release fertilizer prepared using a biodegradable aliphatic copolyester of poly(butylene succinate) and dimerized fatty acid.

    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. PMID:25715823

  10. The Effect of Crystallizing and Non-crystallizing Cosolutes on Succinate Buffer Crystallization and the Consequent pH Shift in Frozen Solutions

    Sundaramurthi, Prakash; Suryanarayanan, Raj (UMM)

    2011-09-06

    To effectively inhibit succinate buffer crystallization and the consequent pH changes in frozen solutions. Using differential scanning calorimetry (DSC) and X-ray diffractometry (XRD), the crystallization behavior of succinate buffer in the presence of either (i) a crystallizing (glycine, mannitol, trehalose) or (ii) a non-crystallizing cosolute (sucrose) was evaluated. Aqueous succinate buffer solutions, 50 or 200 mM, at pH values 4.0 or 6.0 were cooled from room temperature to -25 C at 0.5 C/min. The pH of the solution was measured as a function of temperature using a probe designed to function at low temperatures. The final lyophiles prepared from these solutions were characterized using synchrotron radiation. When the succinic acid solution buffered to pH 4.0, in the absence of a cosolute, was cooled, there was a pronounced shift in the freeze-concentrate pH. Glycine and mannitol, which have a tendency to crystallize in frozen solutions, remained amorphous when the initial pH was 6.0. Under this condition, they also inhibited buffer crystallization and prevented pH change. At pH 4.0 (50 mM initial concentration), glycine and mannitol crystallized and did not prevent pH change in frozen solutions. While sucrose, a non-crystallizing cosolute, did not completely prevent buffer crystallization, the extent of crystallization was reduced. Sucrose decomposition, based on XRD peaks attributable to {beta}-D-glucose, was observed in frozen buffer solutions with an initial pH of 4.0. Trehalose completely inhibited crystallization of the buffer components when the initial pH was 6.0 but not at pH 4.0. At the lower pH, the crystallization of both trehalose dihydrate and buffer components was evident. When retained amorphous, sucrose and trehalose effectively inhibited succinate buffer component crystallization and the consequent pH shift. However, when trehalose crystallized or sucrose degraded to yield a crystalline decomposition product, crystallization of buffer was

  11. Discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as novel, highly potent and selective, orally bioavailable inhibitors of Tyrosine Threonine Kinase, TTK.

    Laufer, Radoslaw; Li, Sze-Wan; Liu, Yong; Ng, Grace; Lang, Yunhui; Feher, Miklos; Brokx, Richard; Beletskaya, Irina; Hodgson, Richard; Mao, Guodong; Plotnikova, Olga; Awrey, Donald E; Mason, Jacqueline M; Wei, Xin; Lin, Dan Chi-Chia; Che, Yi; Kiarash, Reza; Madeira, Brian; Fletcher, Graham C; Mak, Tak W; Bray, Mark R; Pauls, Henry W

    2016-08-01

    TTK/Mps1 is a key kinase controlling progression of cell division via participation in the mitotic spindle assembly checkpoint and is overexpressed in a number of human cancers. Herein we report the discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as a potent, novel class of TTK inhibitors. The series was identified by means of bioisosteric replacement of the related imidazopyrazine and imidazopyridazine scaffolds. Optimization led to the identification of compounds with excellent potency (Ki=0.8nM) and exceptional kinase selectivity. The SAR indicates a strong dependence of activity on the presence of the N-cyclopropyl-2-methylbenzamide moiety delineating the geometry for 1½ type kinase inhibitor. Molecular modeling indicates the extensive and optimal contacts, mediated through H-bonds and hydrophobic interactions, are responsible for the selectivity and potency of the inhibitors. The compounds demonstrate a strong anti-proliferative activity in a panel of human cancer cell lines (HCT116 GI50<15nM) and good rodent pharmacokinetics (oral %F 97%). PMID:27335255

  12. Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma

    Recent evidence suggests that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that tumorous tissues have higher 5α-reductase (5αR) and lower 3α-hydroxysteroid oxidoreductase (3α-HSO) and 20α-HSO activities. The resulting higher levels of 5α-reduced progesterone metabolites such as 5α-pregnane-3,20-dione (5αP) in tumorous tissue promote cell proliferation and detachment, whereas the 4-pregnene metabolites, 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αDHP), more prominent in normal tissue, have the opposite (anti-cancer-like) effects. The aim of this study was to determine if the differences in enzyme activities between tumorous and nontumorous breast tissues are associated with differences in progesterone metabolizing enzyme gene expression. Semi-quantitative RT-PCR was used to compare relative expression (as a ratio of 18S rRNA) of 5αR type 1 (SRD5A1), 5αR type 2 (SRD5A2), 3α-HSO type 2 (AKR1C3), 3α-HSO type 3 (AKR1C2) and 20α-HSO (AKR1C1) mRNAs in paired (tumorous and nontumorous) breast tissues from 11 patients, and unpaired tumor tissues from 17 patients and normal tissues from 10 reduction mammoplasty samples. Expression of 5αR1 and 5αR2 in 11/11 patients was higher (mean of 4.9- and 3.5-fold, respectively; p < 0.001) in the tumor as compared to the paired normal tissues. Conversely, expression of 3α-HSO2, 3α-HSO3 and 20α-HSO was higher (2.8-, 3.9- and 4.4-fold, respectively; p < 0.001) in normal than in tumor sample. The mean tumor:normal expression ratios for 5αR1 and 5αR2 were about 35–85-fold higher than the tumor:normal expression ratios for the HSOs. Similarly, in the unmatched samples, the tumor:normal ratios for 5αR were significantly higher than the ratios for the HSOs. The study shows changes in progesterone metabolizing enzyme gene expression in human breast carcinoma. Expression of SRD5A1 (5αR1) and SRD5A2 (5αR2) is elevated, and expression of AKR1C1

  13. Molecular characterization and detection of mutations associated with resistance to succinate dehydrogenase-inhibiting fungicides in Alternaria solani.

    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] 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 H133R exchanges in AsSdhC and AsSdhD, respectively. The H134R exchange in AsSdhC was observed in A. solani isolates with

  14. Mobilized progenitor cells as a bridging therapy for radiation casualties: a brief review of tocopherol succinate-based approaches.

    Singh, Vijay K; Singh, Pankaj K; Wise, Stephen Y; Seed, Thomas M

    2011-07-01

    Nuclear detonation through either military or terrorist action would most likely lead to a mass-casualty scenario involving victims with varying degrees of exposure to ionizing radiation. As a result of radiation injury to the hematopoietic system, victims would suffer from a lack of red blood cells that deliver oxygen, immune cells that detect and eliminate infectious agents, and blood platelets that promote blood clot formation. In part, these symptoms are generally referred to as acute radiation syndrome (ARS). While some victims of moderate to high levels of radiation will be beyond saving, most will have received enough radiation to injure but not kill their bone marrow cells completely. Such people will recover from their injuries but face a 30-60day period during which they cannot fully fight infections and are prone to uncontrolled bleeding and anemia. To keep them alive until their hematopoietic system recovers, they must receive supportive care. Recently, using experimental animal models of ARS, transfusion of myeloid progenitor cells have been tried as a bridging therapy for radiation-exposed animals. Such cells have been shown to be effective in protecting animals exposed to lethal doses of radiation. These myeloid progenitors (along with of other hematopoietic progenitor cell types) can be mobilized out of the bone marrow into the blood for the reconstitution of hematopoiesis. This review discusses various approaches to the mobilization of progenitors using different mobilizing agents, and their utility as a bridging therapy for radiation casualties. We suggest that α-tocopherol succinate (TS) is an optimal mobilizing agent for progenitors. The extent of progenitor mobilization TS elicits in experimental mice is comparable to clinically used drugs such as recombinant granulocyte-colony stimulating factor rhG-CSF/Neupogen® and the bicyclam AMD3100 (plerixafor/Mozobil); therefore, we propose that TS be considered for further translational development

  15. Targeted drug delivery nanosystems based on copolymer poly(lactide)-tocopheryl polyethylene glycol succinate for cancer treatment

    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.

  16. Biocompatibility and drug release behavior of scaffolds prepared by coaxial electrospinning of poly(butylene succinate) and polyethylene glycol

    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

  17. Slowly digestible waxy maize starch prepared by octenyl succinic anhydride esterification and heat-moisture treatment: glycemic response and mechanism.

    He, Jinhua; Liu, Jie; Zhang, Genyi

    2008-01-01

    The mechanism and molecular structure of the slowly digestible waxy maize starch prepared by octenyl succinic anhydride (OSA) esterification and heat-moisture treatment were investigated. The in vitro Englyst test showed a proportion of 28.3% slowly digestible starch (SDS) when waxy maize starch was esterified with 3% OSA (starch weight based, and it is named OSA-starch), and a highest SDS content of 42.8% was obtained after OSA-starch (10% moisture) was further heated at 120 degrees C for 4 h (named HOSA-starch). The in vivo glycemic response of HOSA-starch, which showed a delayed appearance of blood glucose peak and a significant reduction (32.2%) of the peak glucose concentration, further confirmed its slow digestion property. Amylopectin debranching analysis revealed HOSA-starch had the highest resistance to debranching enzymes of isoamylase and pullulanase, and a simultaneous decrease of K m and V m (enzyme kinetics) was also shown when HOSA-starch was digested by either alpha-amylase or amyloglucosidase, indicating that the slow digestion of HOSA-starch resulted from an uncompetitive inhibition of enzyme activity during digestion. Size exclusion chromatography analysis of HOSA-starch showed fragmented amylopectin molecules with more nonreducing ends that are favorable for RS conversion to SDS by the action of amyloglucosidase in the Englyst test. Further solubility analysis indicates that the water-insolubility of HOSA-starch is caused by OSA-mediated cross-linking of amylopectin and the hydrophobic interaction between OSA-modified starch molecules. The water-insolubility of HOSA-starch would decrease its enzyme accessibility, and the digestion products with attached OSA molecules might also directly act as the uncompetitive inhibitor to reduce the enzyme activity leading to a slow digestion of HOSA-starch. PMID:18067261

  18. Biocompatibility and drug release behavior of scaffolds prepared by coaxial electrospinning of poly(butylene succinate) and polyethylene glycol

    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

  19. Succinate-bonded cellulose: A regenerable and powerful sorbent for cadmium-removal from spiked high-hardness groundwater

    The primary objective of this work was to evaluate a chemically modified cellulose for the sorption efficiency and selectivity to remove cadmium from spiked high-hardness groundwater. Heterogeneous esterification of cellulose with succinic anhydride in toluene under basic conditions has proceeded very efficiently to yield the succinylated cellulose (SC) with fairly high DS value, as confirmed by FTIR and solid-state MAS 13C NMR spectroscopies. Deprotonation of the free carboxylic acid group was achieved by alkaline treatment of SC with saturated NaHCO3 aqueous solution. Batch experiments were carried out on the resulting sodic material (NaSC) to examine its cadmium-removing capability in both distilled water (DW) and spiked groundwater (GW). The results obtained from the sorption characteristics (kinetics, isotherms and pH effect) have revealed that NaSC material is particularly effective in removing cadmium from both DW and GW solutions, with a maximum uptake of 185.2 and 178.6 mg g-1, respectively. These comparable sorption capacities strongly suggest that NaSC sorbent is highly selective to heavy metal over alkaline earth cations (Ca2+ and Mg2+) and therefore less susceptible to interference from background ions, naturally present in groundwater. On the other hand, cadmium sorption is shown to decrease with a decrease in pH which is indubitably inherent to the competing proton during the ion-exchange process. Furthermore, the material has proven to be efficiently regenerable by using a NaCl brine solution. Thus, the use of the sorbent sequentially to the first regeneration led to nearly no attenuation in the material's capacity for cadmium-removal. Finally, the sorption effectiveness of NaSC is compared to those of other low-cost sorbents so far reported in the literature.

  20. EFFICACY AND SAFETY OF METOPROLOL SUCCINATE IN HIGH DOSES IN PATIENTS WITH STABLE COURSE OF ISCHEMIC HEART DISEASE

    S. N. Tolpygina

    2016-01-01

    Full Text Available Aim. To compare two initial doses (50 or 100mg/day ofmetoprolol succinate in control released presentation (Betaloc ZOK, AstraZeneca for achievement of target level of heart rate (HR in patients with stable course of ischemic heart disease (IHD.Material and methods. 50 patients (34 men and 16 women, aged 61,3 y.o., in average with IHD were involved into the open randomized comparative study. IHD duration was from 1 to 22 years (8,3 years in average. 47 patients completed study, 3 patients drop out because of side effects. Previous therapy with β-blockers or other HR reducing drugs was replaced on metoprolol. Patients were randomized in 2 groups (G1 and G2. The initial metoprolol dose was 50 mg in G1 patients and 100 mg - in G2 patients. The dose was enlarged twice if necessary. Study duration was 6 weeks. The change of HR, blood pressure, electrocardiogram parameters was evaluated. Patients filled in Seattle angina questionnaire initially and after 6 weeks treatment. Therapy tolerability was also estimated.Results. In 6 weeks of therapy 61% of G1 patients and 87,5% of G2 patients (p<0,01 reached HR target. Dependence of achievement of target HR and dose of metoprolol was observed (r=0,3; p=0,056. Improvement of the HR control was accompanied by reduction of frequency of angina attacks and increase of life quality.Conclusion. Metoprolol (Betaloc ZOK 200 mg/day provides more effective HR control in patients with IHD vs metoprolol 50-100 mg/day and has good tolerability.

  1. Determination of Content of Potassium Sodium Pehydroandrographolide Succinate for Injection by HPLC%HPLC法测定注射用炎琥宁的含量

    王爱红

    2015-01-01

    OBJECTIVE To estsblish an HPLC method for the determination of Potassium Sodium Pehydroan-drographolide Succinate for Injection.METHODS The HPLC was using Agilent Zorbox C18 column(5μm,250mm ×4.6mm)at room temperature,using 0.05%Potassium Dihydrogen Phospate-Methanol(350∶650) as mobile phase, Calculate the contents according to the peak area with external standard.RESULTS The average recovery of sam-ple was 98.4%.It showed this method was feasible to determine Potassium Sodium Pehydroandrographolide Succi-nate for Injection.CONCLUSION The method is simple,convenient and accurate,It can be used for the inspection of Potassium Sodium Pehydroandrographolide Succinate for Injection.%目的:建立一种注射用炎琥宁含量测定方法,用于生产和市场监督。方法以 Agilent Zorbox C18(5μm,250mm ×4.6mm)为色谱柱;以0.05%磷酸二氢钾溶液(用磷酸调pH值至2.5)-甲醇(350∶650)为流动相;以外标法计算峰面积。结果该法回收率为98.4%,表明该法用于注射用炎琥宁含量测定是可行的。结论该法简便易行,结果准确,可用于注射用炎琥宁含量测定。

  2. Effect of temperature on formation of two new lanthanide metal-organic frameworks: Synthesis, characterization and theoretical studies of Tm(III)-succinate

    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 [Tm2(L)3(H2O)2]·H2O, (H2L=succinic acid), has triclinic cell parameters of a=7.61780(10), b=10.58050(10), c=12.71030(10), α=95.3130(10), β=107.4370(10), γ=111.0960(10) and a cell volume of 888.446(16) Å3. 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), β=101.303(10) and a cell volume of 1776.72(3) Å3. 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 [Tm2(C4H4O4)3(H2O)2]H2O in two different crystalline phases under the influence of reaction temperature. Highlights: ► Was synthesized new MOFs based on Tm3+ ions and succinic acid in different temperature. ► The change in the temperature leads to two compounds with different crystalline systems. ► The Sparkle AM1, PM3 and PM6 models were used to comparison of the theoretical and experimental cell.

  3. Miscibility, Crystallization, and Rheological Behavior of Solution Casting Poly(3-hydroxybutyrate)/poly(ethylene succinate) Blends Probed by Differential Scanning Calorimetry, Rheology, and Optical Microscope Techniques

    Sun, Wei-hua; Qiao, Xiao-ping; Cao, Qi-kun; Liu, Jie-ping

    2010-02-01

    The miscibility and crystallization of solution casting biodegradable poly(3-hydroxybutyrate)/poly(ethylene succinate) (PHB/PES) blends was investigated by differential scanning calorimetry, rheology, and optical microscopy. The blends showed two glass transition temperatures and a depression of melting temperature of PHB with compositions in phase diagram, which indicated that the blend was partially miscible. The morphology observation supported this result. It was found that the PHB and PES can crystallize simultaneously or upon stepwise depending on the crystallization temperatures and compositions. The spherulite growth rate of PHB increased with increasing of PES content. The influence of compositions on the spherulitic growth rate for the partially miscible polymer blends was discussed.

  4. Synthesis and Antimicrobial Activities of Amides of Chiral Benzyl Ethers of N-Boc Protected Aminols of L-amino acids with Succinic Acid

    The research work presented in this article describes a synthesis of chiral amides. Chiral benzyl ethers of N-Boc protected aminols reacted with succinic acid using 2,4,6-trichloro-1,3,5-triazine (TCT) as a coupling agent producing chiral amides in high yields. The synthetic amides were investigated for their antifungal and antibacterial activities against different bacterial and fungal strains. All the compounds showed excellent zone of inhibition against the three tested bacterial strains and good to moderate activity against one fungal strain. (author)

  5. The effect of epoxidized soybean oil on mechanical and rheological properties of poly(butylene succinate)/lignin via vane extruder

    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.

  6. Development and Validation of a Specific Stability Indicating High Performance Liquid Chromatographic Methods for Related Compounds and Assay of Solifenacin Succinate

    Reddy, B. V. Rami; Reddy, B. Srinivasa; N. V. V. S. S. Raman; Reddy, K. Subhash; Rambabu, C.

    2013-01-01

    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, ...

  7. Cybernetic Model Application in Succinate Fermentation%控制论模型在丁二酸发酵过程中的应用

    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.

  8. THERMAL PROPERTY, MISCIBILITY AND CRYSTALLIZATION BEHAVIOR OF POLY(3-HYDROXYBUTYRATE-co 3-YDROXYHEXANOATE) AND POLY(BUTYLENE SUCCINATE-ADIPATE) (PHBHHX/PBSA) BLENDS

    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.

  9. D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery

    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

  10. Preparation and characterization of new succinic anhydride grafted Posidonia for the removal of organic and inorganic pollutants

    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.

  11. Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D-α-tocopheryl polyethylene glycol 1000 succinate nanoemulsions

    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

  12. Synthesis and characterization of polyester copolymers based on poly(butylene succinate) and poly(ethylene glycol)

    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

  13. Synthesis and characterization of polyester copolymers based on poly(butylene succinate) and poly(ethylene glycol)

    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, 1HNMR, DSC and PLM. The copolymer composition was in good agreement with that expected from the feed composition of the reactants. The melting temperature (Tm), crystallization temperature (Tc), and crystallinity (Xc) 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 1H NMR spectra using the relative intensities of the proton peaks. As a sample, the 1H NMR spectrum of polyester copolymer with 10 mol% of PEG is shown in Fig. 2: CO-(CH2)2-CO; O-CH2- and C-(CH2)2-C from the SA and BD unit at δ2.59; δ 4.08 and δ1.67; O-(CH2CH2)n-O from the PEG unit at δ 3.61. The molar composition of polyester copolymer was measured as the area ratio of δ3.61/(δ4.08 + δ1.67) 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: ► The introduction of PEG unit changed the flexibility of PBS main chain. ► PEG unit did not alter the crystal form of PBS in copolymers. ► PEG unit hindered the formation of ring-banded spherulite morphology in copolymers. ► The copolyesters had good in vitro degradation performance. ► The composition ratio of PEG unit can adjust the in vitro degradation performance.

  14. Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens.

    Molnár, Tünde; Héja, László; Emri, Zsuzsa; Simon, Agnes; Nyitrai, Gabriella; Pál, Ildikó; Kardos, Julianna

    2011-01-01

    Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca(2+) 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 Ca(2+) transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca(2+) transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca(2+) dynamics evoked by GHB suggested that Ca(2+) 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 Ca(2+) signal remained in mice lacking GABA(B) 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 GABA(B) 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 Ca(2+) signaling in astrocytic networks. PMID:22180742

  15. Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens

    Zsuzsa Emri

    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.

  16. 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

    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.

  17. Enhancement of malate-production and increase in sensitivity to dimethyl succinate by mutation of the VID24 gene in Saccharomyces cerevisiae.

    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. PMID:26983942

  18. Crystallization and crystallographic analysis of the ligand-binding domain of the Pseudomonas putida chemoreceptor McpS in complex with malate and succinate

    The crystallization of the ligand-binding domain of the methyl-accepting chemotaxis protein chemoreceptor McpS (McpS-LBD) is reported. Methyl-accepting chemotaxis proteins (MCPs) are transmembrane proteins that sense changes in environmental signals, generating a chemotactic response and regulating other cellular processes. MCPs are composed of two main domains: a ligand-binding domain (LBD) and a cytosolic signalling domain (CSD). Here, the crystallization of the LBD of the chemoreceptor McpS (McpS-LBD) is reported. McpS-LBD is responsible for sensing most of the TCA-cycle intermediates in the soil bacterium Pseudomonas putida KT2440. McpS-LBD was expressed, purified and crystallized in complex with two of its natural ligands (malate and succinate). Crystals were obtained by both the counter-diffusion and the hanging-drop vapour-diffusion techniques after pre-incubation of McpS-LBD with the ligands. The crystals were isomorphous and belonged to space group C2, with two molecules per asymmetric unit. Diffraction data were collected at the ESRF synchrotron X-ray source to resolutions of 1.8 and 1.9 Å for the malate and succinate complexes, respectively

  19. Trace analysis of doxylamine succinate in animal feed, human urine, and wastewater by GC using a rubidium-sensitized nitrogen detector

    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.

  20. The influence of antioxidant and post-synthetic treatment on the properties of biodegradable poly(butylene succinates modified with poly(propylene oxide

    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.

  1. Supramolecular micellar nanoaggregates based on a novel chitosan/vitamin E succinate copolymer for paclitaxel selective delivery

    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

  2. 聚(丁二酸丁二醇酯丁二酸环己烷二甲醇酯)的合成与表征%Synthesis and Characterization of Copolyesters of Succinic Acid-1,4-Butanediol/Succinic Acid-1,4-Cyclohexanedimethanol

    余瑾; 程小苗; 周艺峰; 聂王焰

    2009-01-01

    用熔融缩聚法合成了一系列聚(丁二酸丁二醇酯丁二酸环己烷二甲醇酯)的无规共聚物.用FT-IR,~1H-NMR,DSC,TGA,XRD及水降解测试等方法表征了材料的结构与性能.通过DSC和TGA分析得到产物的熔点虽然较聚丁二酸丁二醇酯(PBS)有所降低,但是热分解温度却得到了提高;XRd测试结果表明,共聚物的晶体结构并没有发生改变;水降解测试结果表明,共聚物较PBS的降解速率有所提高.%A series of copolyesters of succinic acid-1,4-butanediol/succinic acid-1,4-cycl- ohexanedimethanol were synthesized and characterized by means of Fourier transform infrared spectroscopic(FT-IR), hydrogen nuclear magnetic resonance spectrum (~1H-NMR), differential scanning calorimetry ( DSC), thermogravimetry analysis (TGA), X-ray diffraction (XRD) and hydrolytic degradation. Though the melting temperature decreased, the copolymers showed the higher thermal decomposition temperature which was justified by TGA. X-ray diffraction shows that the crystal structure of copolymers is the same as poly (butylene succinate) (PBS). The results of hydrolytic degradation show that the rate of biodegradation of copolymers are higher than that of PBS.

  3. 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.

    Siyamak, Samira; Ibrahim, Nor Azowa; Abdolmohammadi, Sanaz; Yunus, Wan Md Zin Bin Wan; Rahman, Mohamad Zaki Ab

    2012-01-01

    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. PMID:22343368

  4. 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

    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.

  5. Utilization of α-olefins obtained by pyrolysis of waste high density polyethylene to synthesize α-olefin-succinic-anhydride based cold flow improvers

    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.

  6. Development and evaluation of vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate-mixed polymeric phospholipid micelles of berberine as an anticancer nanopharmaceutical

    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. PMID:27217747

  7. Suppression of γ-Aminobutyric Acid (GABA) Transaminases Induces Prominent GABA Accumulation, Dwarfism and Infertility in the Tomato (Solanum lycopersicum L.)

    Koike, Satoshi; Matsukura, Chiaki; Takayama, Mariko; Asamizu, Erika; Ezura, Hiroshi

    2013-01-01

    Tomatoes accumulate γ-aminobutyric acid (GABA) at high levels in the immature fruits. GABA is rapidly converted to succinate during fruit ripening through the activities of GABA transaminase (GABA-T) and succinate semialdehyde dehydrogenase (SSADH). Although three genes encoding GABA-T and both pyruvate- and α-ketoglutarate-dependent GABA-T activities have been detected in tomato fruits, the mechanism underlying the GABA-T-mediated conversion of GABA has not been fully understood. In this wor...

  8. How and why does tomato accumulate a large amount of GABA in the fruit?

    Mariko eTakayama; Hiroshi eEzura

    2015-01-01

    γ-Aminobutyric acid (GABA) has received much attention as a health-promoting functional compound, and several GABA-enriched foods have been commercialized. In higher plants, GABA is primarily metabolized via a short pathway called the GABA shunt. The GABA shunt bypasses two steps (the oxidation of α-ketoglutarate to succinate) of the tricarboxylic acid (TCA) cycle via reactions catalysed by three enzymes: glutamate decarboxylase (GAD), GABA transaminase (GABA-T) and succinic semialdehyde dehy...

  9. How and why does tomato accumulate a large amount of GABA in the fruit?

    Takayama, Mariko; Ezura, Hiroshi

    2015-01-01

    Gamma-aminobutyric acid (GABA) has received much attention as a health-promoting functional compound, and several GABA-enriched foods have been commercialized. In higher plants, GABA is primarily metabolized via a short pathway called the GABA shunt. The GABA shunt bypasses two steps (the oxidation of α-ketoglutarate to succinate) of the tricarboxylic acid (TCA) cycle via reactions catalyzed by three enzymes: glutamate decarboxylase, GABA transaminase, and succinic semialdehyde dehydrogenase....

  10. HPLC测定穿琥宁中的聚合物%Research of polymer in potassium dehydroandrogapholide succinate

    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、

  11. Sedation with 4-hydroxybutyric acid: a potential pitfall in the diagnosis of SSADH deficiency.

    Wolf, N.I.; Haas, D.; Hoffmann, G.F.; Jakobs, C.; Salomons, G.S.; Wevers, R.A.; Engelke, U.F.H.; Rating, D.

    2004-01-01

    Deficiency of succinic semialdehyde dehydrogenase (SSADH) is a rare neurometabolic disorder with accumulation of 4-hydroxybutyric acid (4-HBA) as a biochemical hallmark. We present a boy with an unresolved severe neurological disorder and intermittent elevation of 4-HBA in serum and CSF which was la

  12. Sequence Classification: 389262 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31793773|ref|NP_856266.1| 4-AMINOBUTYRATE AMINOTRA...NSAMINASE) (GABA AMINOTRANSFERASE) (GABA-AT) || http://www.ncbi.nlm.nih.gov/protein/31793773 ... ...NSFERASE GABT (GAMMA-AMINO-N-BUTYRATE TRANSAMINASE) (GABA TRANSAMINASE) (GLUTAMATE:SUCCINIC SEMIALDEHYDE TRA

  13. Sequence Classification: 399013 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|15609726|ref|NP_217105.1| 4-AMINOBUTYRATE AMINOTRA...NSAMINASE) (GABA AMINOTRANSFERASE) (GABA-AT) || http://www.ncbi.nlm.nih.gov/protein/15609726 ... ...NSFERASE GABT (GAMMA-AMINO-N-BUTYRATE TRANSAMINASE) (GABA TRANSAMINASE) (GLUTAMATE:SUCCINIC SEMIALDEHYDE TRA

  14. A preliminary study on the dynamic-mechanical behaviour of compression moulded polypropylene/carbon fiber composites interfacially modified by a succinic anhydride grafted atactic polypropylene from polymer wastes

    García-Martínez, Jesús María; Areso, Susana; Collar, Emilia P.

    2016-05-01

    Present communication is devoted to the study of the effect of a novel interfacial agent in polypropylene/carbon fibre composites. The interfacial agent used is a succinic anhydride grafted atactic polypropylene containing both succinic bridges and side grafts (aPP-SASA) and with 5.6% (5.6.10-4g/mol) of grafting content obtained at the GIP labs. The study considers the study dynamic-mechanical behaviour with temperature at a frequency of 1 hz to ascertain the differences in the interfacial activity. The samples were compression molded in order to isolate as far as possible the effect of the solely aPP-SASA in absence of those synergetic effects due to the preferential orientation of the fibres.

  15. Development and evaluation of vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate-mixed polymeric phospholipid micelles of berberine as an anticancer nanopharmaceutical

    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

  16. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    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

  17. Biodegradation of poly(lactic acid), poly(hydroxybutyrate-co-hydroxyvalerate), poly(butylene succinate) and poly(butylene adipate-co-terephthalate) under anaerobic and oxygen limited thermophilic conditions

    Jutakan Boonmee; Charnwit Kositanont; Thanawadee Leejarkpai

    2016-01-01

    In order to study the biodegradation behavior of biodegradable plastics in landfill conditions, four types of biodegradable plastics including poly(lactic acid) (PLA), poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), poly(butylene succinate) (PBS), and poly(butylene adipate-co-terephthalate) (PBAT) were tested by burying in sludge mixed soil medium under anaerobic and oxygen limited conditions. The experiments were operated at 52 ± 2ºC in dark conditions according to ISO15985. The degree of b...

  18. 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

    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.

  19. 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

    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.

  20. Enhanced oral delivery of paclitaxel using acetylcysteine functionalized chitosan-vitamin E succinate nanomicelles based on a mucus bioadhesion and penetration mechanism.

    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

    2013-09-01

    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. PMID:23909663

  1. Online solid phase extraction LC-MS/MS method for the analysis of succinate dehydrogenase inhibitor fungicides and its applicability to surface water samples.

    Gulkowska, Anna; Buerge, Ignaz J; Poiger, Thomas

    2014-10-01

    A sensitive and selective analytical method, based on online solid phase extraction coupled to LC-MS/MS, was developed and validated to determine traces of several recently introduced fungicides in surface water and wastewater. The list of target analytes included eight succinate dehydrogenase inhibitors (bixafen, boscalid, fluopyram, flutolanil, fluxapyroxad, isopyrazam, penflufen, and penthiopyrad), and two other fungicides with different modes of action, fenpyrazamine and fluopicolide. Detection and quantification limits in various matrices were in the range of 0.1 to 2 and 0.5 to 10 ng/L, respectively. Moderate signal suppression was observed in surface water (≤15%) and wastewater (≤25%) and was well compensated by the selected internal standard. The intra- and inter-day precisions were generally <10 and <20%, respectively. The applicability of the method was demonstrated in a study on the occurrence of fungicides in the river Glatt, Switzerland, that drains a catchment area of 419 km(2) with a substantial proportion of agricultural land. Of the studied compounds, only boscalid and fluopicolide were detected in flow-proportional weekly composite samples, generally at low concentrations up to 15 and 5 ng/L, respectively. While fluopicolide was detected in only 30% of the samples above the LOD of 0.5 ng/L, boscalid was detected in all samples analyzed between March and October 2012. PMID:25146353

  2. (+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo.

    dos Santos, G A S; Abreu e Lima, R S; Pestana, C R; Lima, A S G; Scheucher, P S; Thomé, C H; Gimenes-Teixeira, H L; Santana-Lemos, B A A; Lucena-Araujo, A R; Rodrigues, F P; Nasr, R; Uyemura, S A; Falcão, R P; de Thé, H; Pandolfi, P P; Curti, C; Rego, E M

    2012-03-01

    The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy. PMID:21869839

  3. Characterization and expression of a cDNA, AmphiSDHD,encoding the amphioxus cytochrome b small subunit in mitochondrial succinate-ubiquinone oxidoreductase

    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. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate

    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.

  5. Preparation and Evaluation of Diclofenac Sodium Tablet Coated with Polyelectrolyte Multilayer Film Using Hypromellose Acetate Succinate and Polymethacrylates for pH-Dependent, Modified Release Drug Delivery.

    Jeganathan, Balamurugan; Prakya, Vijayalakshmi; Deshmukh, Abhijit

    2016-06-01

    Polyelectrolyte multilayer (PEM) film formed due to the electrostatic interaction between oppositely charged polyelectrolytes is of considerable interest because of their potential applications as both drug carriers and surface-modifying agents. In this study, in vitro studies were carried out on polyelectrolyte complexes formulated with Eudragit E (EE) and hypromellose acetate succinate (HPMCAS). The complexes of EE and HPMCAS were formulated by non-stoichiometric method. The prepared IPCs were investigated using Fourier transform infrared spectroscopy. Diclofenac sodium (DS) tablets were prepared and were coated with polymer solution of HPMCAS and EE to achieve pH-dependent and sustained-release tablets. Tablets were evaluated for their physical characteristics and in vitro drug release. The results of pharmacokinetic studies in rabbits showed that the selected formulation (F6) exhibited a delayed peak plasma concentration and marked sustained-release effect of drug in the in vivo drug release in comparison with marketed tablet. The suitable combination of PEM film based on EE and HPMCAS demonstrated potential candidate for targeted release of DS in the lower part of the gastrointestinal (GI) tract. PMID:26283195

  6. Solubilized delivery of paliperidone palmitate by D-alpha-tocopheryl polyethylene glycol 1000 succinate micelles for improved short-term psychotic management.

    Muthu, Madaswamy S; Sahu, Ashish K; Sonali; Abdulla, Allabakshi; Kaklotar, Dhansukh; Rajesh, Chellappa V; Singh, Sanjay; Pandey, Bajarangprasad L

    2016-01-01

    The objective of this work was to formulate paliperidone palmitate-loaded d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for improved antipsychotic effect during short-term management of psychotic disorders. Vitamin E TPGS micelles containing paliperidone palmitate were prepared by the solvent casting method and control paliperidone palmitate formulations were prepared by simple sonication method. The prepared micelles and control paliperidone palmitate formulations were evaluated for different parameters. Particle sizes of prepared micelles, control paliperidone palmitate formulations were determined at 25 °C by dynamic light scattering technique and external surface morphology was determined by transmission electron microscopy analysis. The encapsulation efficiency was determined by spectrophotometery. In-vitro release studies of micelles and control formulations were carried out by dialysis bag diffusion method. The particle sizes of the paliperidone palmitate-loaded TPGS micelles were 26.5 nm. About 92% of drug encapsulation efficiency was achieved with micelles. The drug release from paliperidone palmitate-loaded TPGS micelles was sustained for more than 24 h with 40% of drug release. The TPGS product, i.e. paliperidone palmitate-loaded micelles, resulted in nano-sized delivery, solubility enhancement and permeability of the micelles which provided an improved and prolonged anti-psychotic effect in comparison to control paliperidone palmitate formulation. PMID:24853962

  7. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate.

    Costa-Nunes, João P; Cline, Brandon H; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W M; Strekalova, Tatyana

    2015-01-01

    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. PMID:26064929

  8. Preparation and characterization of single and dual propylene oxide and octenyl succinic anhydride modified starch carriers for the microencapsulation of essential oils.

    Baranauskienė, Renata; Rutkaitė, Ramunė; Pečiulytė, Laura; Kazernavičiūtė, Rita; Venskutonis, Petras Rimantas

    2016-08-10

    Hydroxypropylation with propylene oxide followed by esterification with octenyl succinic anhydride (OSA) was used to produce modified potato starch derivatives suitable for the encapsulation of essential oils. Caraway essential oil (EO) was encapsulated by spray-drying into enzymatically hydrolyzed dual/single modified and native starches. The EO microencapsulation efficiency in different modified starches, the retention of volatile aroma compounds, the emulsion particle size and the microstructure of the spray-dried encapsulated powdered products, as well as the compositional aroma changes taking place during the processing and storage for up to 8 months have been estimated. The increase of OSA content from 0.97 to 2.52% in the P-native structure and from 0.91% to 2.66% in P-HP resulted in the significant increase in the encapsulating capacity, evaluated as a percentage of the total EO retained, from 61.6 to 88.0% and 73.8% to 84.0%, respectively. However, the compositional changes of the microencapsulated caraway EO constituents were not remarkable. Additionally, the effect of pure and encapsulated caraway EO products on the oxidative stability of commercial rapeseed oil and mayonnaise was evaluated using the instrumental Oxipres method and it was shown that they were more effective in emulsion type products by the up to 1.8-fold increase in the oxidative stability of mayonnaise. PMID:27465989

  9. Uptake of intact TPGS (d-alpha-tocopheryl polyethylene glycol 1000 succinate) a water-miscible form of vitamin E by human cells in vitro

    Traber, M.G.; Thellman, C.A.; Rindler, M.J.; Kayden, H.J.

    1988-09-01

    The mechanism by which TPGS (alpha-tocopheryl succinate esterified to polyethylene glycol 1000 (PEG 1000)) delivers tocopherol (vitamin E) was studied in human fibroblasts and erythrocytes and a human intestinal cell line, Caco-2. The total cellular tocopherol content of saponified samples of fibroblasts or Caco-2 incubated for 4 h with TPGS (4 mumol/L) increased 10-fold without an increase in the free tocopherol content of nonsaponified samples. A 24-h incubation resulted in a free tocopherol content of approximately 20%, suggesting that intracellular hydrolysis of ester bonds had occurred. The increase in total tocopherol content after a 4-h incubation with TPGS was temperature dependent; no change was measurable at 4 degrees C. Addition of metabolic inhibitors during incubation with TPGS at 37 degrees C did not prevent the increase. (/sup 14/C)TPGS (synthesized from (/sup 14/C)PEG 1000) was taken up by Caco-2 cells but (/sup 14/C)PEG 1000 was not. The intracellular total tocopherol (pmol) equaled the (/sup 14/C)TPGS (pmol), unequivocally demonstrating uptake of the intact TPGS molecule.

  10. Uptake of intact TPGS (d-alpha-tocopheryl polyethylene glycol 1000 succinate) a water-miscible form of vitamin E by human cells in vitro

    The mechanism by which TPGS (alpha-tocopheryl succinate esterified to polyethylene glycol 1000 [PEG 1000]) delivers tocopherol (vitamin E) was studied in human fibroblasts and erythrocytes and a human intestinal cell line, Caco-2. The total cellular tocopherol content of saponified samples of fibroblasts or Caco-2 incubated for 4 h with TPGS (4 mumol/L) increased 10-fold without an increase in the free tocopherol content of nonsaponified samples. A 24-h incubation resulted in a free tocopherol content of approximately 20%, suggesting that intracellular hydrolysis of ester bonds had occurred. The increase in total tocopherol content after a 4-h incubation with TPGS was temperature dependent; no change was measurable at 4 degrees C. Addition of metabolic inhibitors during incubation with TPGS at 37 degrees C did not prevent the increase. [14C]TPGS (synthesized from [14C]PEG 1000) was taken up by Caco-2 cells but [14C]PEG 1000 was not. The intracellular total tocopherol (pmol) equaled the [14C]TPGS (pmol), unequivocally demonstrating uptake of the intact TPGS molecule

  11. SUBSTITUTION OF HIGH-YIELD-PULP FOR HARDWOOD BLEACHED KRAFT PULP IN PAPER PRODUCTION AND ITS EFFECT ON ALKENYL SUCCINIC ANHYDRIDE SIZING

    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.

  12. 高取代度丁二酸酯玉米淀粉的半干法制备及性能研究%Study on Preparation and Properties of High DS Succinate Cornstarch by Semi-dry Process

    吴修利; 吴修顺; 刘冰许

    2013-01-01

    Preparation of succinate starch with high degree of substitution (DS) by semi-dry process was studied using cornstarch as raw material,succinic anhydride as esterifying agent,and sodium bicarbonate as catalyst. The effects of different parameters on the DS were discussed with the aim to provide a theoretical basis for the industrial production. The results showed that the suitable parameters for the preparation of succinate starch were as follows: amount of succinic anhydride 9% (in proportion to starch, m/m), water content 25% (m/m), amount of NaHCO3 4%(in proportion to starch,m/m),reaction temperature 135 ℃ ,reaction period 2 h. The DS was 0. 163 3 under the suitable parameters. Some changes in the structure of succinate starch with high DS were discovered,a new characteristic absorption peak emerged,the gelatinization temperature was decreased and the peak viscosity was increased.%为给丁二酸酯淀粉的工业化生产提供理论依据,以玉米淀粉为原料、NaHCO3为催化剂、丁二酸酐为酯化剂,利用半干法工艺合成高取代度丁二酸酯淀粉,探讨了不同反应参数对丁二酸酯淀粉取代度的影响,结果表明:在丁二酸酐用量为淀粉质量的9%、反应体系含水量为25%、NaHCO3用量为淀粉质量的4%、135℃反应2h的条件下可获得取代度为0.163 3的高取代度丁二酸酯淀粉;与原淀粉相比,丁二酸酯淀粉结构发生了一定程度的变化,出现了新的特征吸收峰,证实了丁二酸酯淀粉中丁二酸酯基的存在,并且其糊化温度降低、峰值黏度增加.

  13. 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

    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 Sandell’s sensitivity, limit of detection (LOD and limit of quantification (LOQ values are also reported. The accuracy and precision of the methods were evaluated based on intra-day and inter-day variations. The accuracy of the methods was further confirmed by standard addition procedure. The degradation behavior of the drug was studied by subjecting STS to an acid and alkaline hydrolysis, oxidative, thermal and UV degradation. This study indicated that STS was degraded in alkaline medium and in oxidative condition. The proposed methods were successfully applied to the determination of STS in tablets and the results obtained are comparable with the official method.

  14. Paclitaxel-loaded poly(glycolide-co-ε-caprolactone-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

    Zhao TJ

    2013-05-01

    Full Text Available Tiejun Zhao,1 Hezhong Chen,1 Yuchao Dong,2 Jiajun Zhang,1 Haidong Huang,2 Ji Zhu,1 Wei Zhang21Institute of Cardiothoracic Surgery, 2Respiratory Department, Changhai Hospital, Shanghai, People's Republic of ChinaAbstract: In order to improve the therapeutic efficacy and minimize the side effects of lung cancer chemotherapy, the formulation of paclitaxel-loaded poly(glycolide-co-ε-caprolactone-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles (PTX-loaded [PGA-co-PCL]-b-TPGS2k NPs was prepared. The novel amphiphilic copolymer (PGA-co-PCL-b-TPGS2k was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded (PGA-co-PCL-b -TPGS2k NPs were characterized in terms of size, size distribution, zeta potential, drug encapsulation, surface morphology, and drug release. In vitro cellular uptakes of NPs were investigated with confocal laser scanning microscopy, indicating the coumarin 6-loaded (PGA-co-PCL-b -TPGS2k NPs could be internalized by human lung cancer A-549 cells. The antitumor effect of PTX-loaded NPs was evaluated, both in vitro and in vivo, on an A-549 cell tumor-bearing mouse model via intratumoral injection. The commercial PTX formulation Taxol was chosen as the reference. Experimental results showed that the PTX-loaded NPs possessed higher cytotoxicity and could effectively inhibit the growth of tumor. All the results suggested that amphiphilic copolymer (PGA-co-PCL-b -TPGS2k could act as a potential biological material for nanoformulation in the treatment of lung cancer.Keywords: (PGA-co-PCL-b TPGS2k, paclitaxel, nanoparticles, drug delivery, lung cancer

  15. YgfX (CptA) is a multimeric membrane protein that interacts with the succinate dehydrogenase assembly factor SdhE (YgfY).

    McNeil, Matthew B; Iglesias-Cans, Marina C; Clulow, James S; Fineran, Peter C

    2013-07-01

    Serratia sp. strain ATCC 39006 produces the red-pigmented antibiotic prodigiosin. Prodigiosin biosynthesis is regulated by a complex hierarchy that includes the uncharacterized protein YgfX (DUF1434). The ygfX gene is co-transcribed with sdhE, an FAD assembly factor essential for the flavinylation and activation of the SdhA subunit of succinate dehydrogenase (SDH), a central enzyme in the tricarboxylic acid cycle and electron transport chain. The sdhEygfX operon is highly conserved within the Enterobacteriaceae, suggesting that SdhE and YgfX function together. We performed an extensive mutagenesis to gain molecular insights into the uncharacterized protein YgfX, and have investigated the relationship between YgfX and SdhE. YgfX localized to the membrane, interacted with itself, forming dimers or larger multimers, and interacted with SdhE. The transmembrane helices of YgfX were critical for protein function and the formation of YgfX multimers. Site-directed mutagenesis of residues conserved in DUF1434 proteins revealed a periplasmic tryptophan and a cytoplasmic aspartate that were crucial for YgfX activity. Both of these amino acids were required for the formation of YgfX multimers and interactions with SdhE but not membrane localization. Multiple cell division proteins were identified as putative interaction partners of YgfX and overexpression of YgfX had effects on cell morphology. These findings represent an important step in understanding the function of DUF1434 proteins. In contrast to a recent report, we found no evidence that YgfX and SdhE form a toxin-antitoxin system. In summary, YgfX functions as a multimeric membrane-bound protein that interacts with SdhE, an important FAD assembly factor that controls SDH activity. PMID:23657679

  16. Effect of a novel insulinotropic agent, succinic acid monoethyl ester, on lipids and lipoproteins levels in rats with streptozotocin-nicotinamideinduced type 2 diabetes

    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.

  17. Cloning, expression and protective immunity evaluation of the full-length cDNA encoding succinate dehydrogenase iron-sulfur protein of Schistosoma japonicum

    YU JunLong; WANG ShiPing; LI WenKai; DAI Gan; XU ShaoRui; HE Zhuo; PENG XianChu; ZHOU SongHua; LIU XueQin

    2007-01-01

    1071-bp fragment was obtained from the Schistosoma japonicum (Chinese strain) adult cDNA library after the 3' and 5' ends of the incomplete expression sequence tag (EST) of succinate dehydrogenase iron-sulfur protein of Schistosoma japonicum (SjSDISP) were amplified by the anchored PCR with 2pairs of primers designed according to the EST of SjSDISP and the sequence of multiclone sites of the library vector. Sequence analysis indicated that the fragment was a full-length cDNA with a complete open reading frame (ORF), encoding 278 amino acid residues. The fragment was cloned into prokaryotic expression vector pQE30, and subsequently sequenced and expressed in Escherichia coll.SDS-PAGE and Western-blot analyses showed that the recombinant protein was about 32 kD and could be recognized by the polyclonal antisera from rabbits immunized with Schistosoma japonicum adult worm antigen. Compared with the FCA controls, mice vaccinated with rSjSDISP (test) or rSjGST (positive control) all revealed high levels of specific antibody and significant reduction in worm burden, liver eggs per gram (LEPG), fecal eggs per gram (FEPG) and intrauterine eggs. These results suggest that SjSDISP may be a novel and partially protective vaccine candidate against schistosomiasis. In contrast to the worm burden reduction rate, the higher degree of egg reduction rate in the test group also suggested that SjSDISP vaccine may primarily play a role in anti-embryonation or anti-fecundity immunity.

  18. Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST.

    Pantaleo, Maria A; Astolfi, Annalisa; Urbini, Milena; Nannini, Margherita; Paterini, Paola; Indio, Valentina; Saponara, Maristella; Formica, Serena; Ceccarelli, Claudio; Casadio, Rita; Rossi, Giulio; Bertolini, Federica; Santini, Donatella; Pirini, Maria G; Fiorentino, Michelangelo; Basso, Umberto; Biasco, Guido

    2014-01-01

    Mutations of genes encoding the subunits of the succinate dehydrogenase (SDH) complex were described in KIT/PDGFRA wild-type GIST separately in different reports. In this study, we simultaneously sequenced the genome of all subunits, SDHA, SDHB, SDHC, and SDHD in a larger series of KIT/PDGFRA wild-type GIST in order to evaluate the frequency of the mutations and explore their biological role. SDHA, SDHB, SDHC, and SDHD were sequenced on the available samples obtained from 34 KIT/PDGFRA wild-type GISTs. Of these, in 10 cases, both tumor and peripheral blood (PB) were available, in 19 cases only tumor, and in 5 cases only PB. Overall, 9 of the 34 patients with KIT/PDGFRA wild-type GIST carried mutations in one of the four subunits of the SDH complex (six patients in SDHA, two in SDHB, one in SDHC). WB and immunohistochemistry analysis showed that patients with KIT/PDGFRA wild-type GIST who harbored SDHA mutations exhibited a significant downregulation of both SDHA and SDHB protein expression, with respect to the other GIST lacking SDH mutations and to KIT/PDGFRA-mutated GIST. Clinically, four out of six patients with SDHA mutations presented with metastatic disease at diagnosis with a very slow, indolent course. Patients with KIT/PDGFRA wild-type GIST may harbor germline and/or de novo mutations of SDH complex with prevalence for mutations within SDHA, which is associated with a downregulation of SDHA and SDHB protein expression. The presence of germline mutations may suggest that these patients should be followed up for the risk of development of other cancers. PMID:23612575

  19. Polymeric micelles of amphiphilic graft copolymer of α-tocopherol succinate-g-carboxymethyl chitosan for tamoxifen delivery: Synthesis, characterization and in vivo pharmacokinetic study.

    Jena, Sunil K; Sangamwar, Abhay T

    2016-10-20

    Novel amphiphilic graft copolymers were prepared from low molecular weight carboxymethyl chitosan (LMW Cmc) and α-tocopherol succinate (TS) via an amidation reaction and confirmed by (1)H NMR and IR spectroscopy. These graft copolymers are self-assembled to nanosized core-shell-structural micelles in an aqueous milieu. The critical micelle concentration (CMC) decreased with an increasing substitution of TS on LMW Cmc, which ranged from 7.94×10(-8) to 1.58×10(-6)g/mL. Cmc-TS4.5 (Cmc-TS with a charged molar ratio of TS to glucosamine units of Cmc∼4.5) was shown maximum TMX loading up to 8.08±0.98%. Both blank and TMX-loaded PM's of Cmc-TS4.5 exhibit spherical shape with particle size below 200nm. An in vitro release study in simulated gastric and intestinal fluid demonstrated that TMX release from TMX-PM4.5 (TMX-PMs prepared with amphiphilic polymer Cmc-TS4.5, and the weight ratio of Cmc-TS4.5 to TMX was 8:1) was slow and pH dependent. In vivo oral absorption study revealed Cmc-TS4.5 based PM's permeated the epithelial barrier via the paracellular route without causing any intestinal damage. In vivo toxicity study demonstrated the safety of PM's after oral administration. Compared to tamoxifen control, TMX-PM4.5 dosed to fasted female Sprague Dawley rats showed a 1.9 fold increase in AUC0-72h. Thus, the results suggested that Cmc-TS micelles are a promising carrier for TMX delivery. PMID:27474667

  20. Effect of nanofiller’s size and shape on the solid state microstructure and thermal properties of poly(butylene succinate) nanocomposites

    Papageorgiou, Dimitrios G.; Chrissafis, Konstantinos; Pavlidou, Eleni [Solid State Physics Section, Physics Department, Aristotle University of Thessaloniki, 541 24 Thessaloniki (Greece); Deliyanni, Eleni A.; Papageorgiou, George Z.; Terzopoulou, Zoi [Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki (Greece); Bikiaris, Dimitrios N., E-mail: dbic@chem.auth.gr [Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki (Greece)

    2014-08-20

    Highlights: • The microstructure and thermal properties of PBSu-based nanocomposites were studied. • Ag and SiO{sub 2} were dispersed more uniformly, compared to GO and MWCNTs. • PBSu/Ag nanocomposites exhibited higher nucleation activity and faster rates. • The order of nucleation efficiency of the fillers was GO < MWCNTs < SiO{sub 2} < Ag. • The activation energy of nanocomposite samples was lower than that of PBSu. - Abstract: We report a study of the solid state microstructure and crystallization kinetics of poly(butylene succinate) (PBSu) reinforced with nanofillers of different shapes, sizes and geometries such as silver, silica (SiO{sub 2}), multi-walled carbon nanotubes (MWCNTs) and graphene oxide (GO). The solid state structure of neat polymer and nanocomposites were investigated by X-ray diffraction (XRD), polarized optical microscopy (POM) and transmission electron microscopy (TEM). The results indicated that the nanocomposite samples exhibited enhanced crystallinity and nucleation density, along with smaller spherulite size. Additionally, the spherical nanofillers were dispersed more uniformly in the polymeric matrix, than the other two filler types. The crystallization kinetics under both isothermal and dynamic conditions were also studied and as was expected, the nanocomposite samples, crystallize at higher rates due to the increased number of nucleation sites, as was calculated with Avrami, Dobreva and Friedman’s methods. From the crystallization study it was found that the nanocomposite filled with Ag nanoparticles exhibited the highest rates from all other fillers followed from SiO{sub 2} and MWCNTs while GO showed the lowest rates.

  1. Succinate Dehydrogenase Subunit B (SDHB Is Expressed in Neurofibromatosis 1-Associated Gastrointestinal Stromal Tumors (Gists: Implications for the SDHB Expression Based Classification of Gists

    Jeanny H. Wang, Jerzy Lasota, Markku Miettinen

    2011-01-01

    Full Text Available Gastrointestinal Stromal Tumor (GIST is the most common mesenchymal tumor of the digestive tract. GISTs develop with relatively high incidence in patients with Neurofibromatosis-1 syndrome (NF1. Mutational activation of KIT or PDGFRA is believed to be a driving force in the pathogenesis of familial and sporadic GISTs. Unlike those tumors, NF1-associated GISTs do not have KIT or PGDFRA mutations. Similarly, no mutational activation of KIT or PDGFRA has been identified in pediatric GISTs and in GISTs associated with Carney Triad and Carney-Stratakis Syndrome. KIT and PDGFRA-wild type tumors are expected to have lesser response to imatinib treatment. Recently, Carney Triad and Carney-Stratakis Syndrome -associated GISTs and pediatric GISTs have been shown to have a loss of expression of succinate dehydrogenase subunit B (SDHB, a Krebs cycle/electron transport chain interface protein. It was proposed that GISTs can be divided into SDHB- positive (type 1, and SDHB-negative (type 2 tumors because of similarities in clinical features and response to imatinib treatment. In this study, SDHB expression was examined immunohistochemically in 22 well-characterized NF1-associated GISTs. All analyzed tumors expressed SDHB. Based on SDHB-expression status, NF1-associated GISTs belong to type 1 category; however, similarly to SDHB type 2 tumors, they do not respond well to imatinib treatment. Therefore, a simple categorization of GISTs into SDHB-positive and-negative seems to be incomplete. A classification based on both SDHB expression status and KIT and PDGFRA mutation status characterize GISTs more accurately and allow subdivision of SDHB-positive tumors into different clinico-genetic categories.

  2. High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects.

    Greta Jakobsdottir

    Full Text Available INTRODUCTION: Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs, particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation. OBJECTIVE: To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks. MATERIAL AND METHODS: Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin - acetic acid; guar gum - propionic acid; or a mixture - butyric acid. At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks. RESULTS AND DISCUSSION: Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet.

  3. Superparamagnetic iron oxide--loaded poly(lactic acid)-D-alpha-tocopherol polyethylene glycol 1000 succinate copolymer nanoparticles as MRI contrast agent.

    Prashant, Chandrasekharan; Dipak, Maity; Yang, Chang-Tong; Chuang, Kai-Hsiang; Jun, Ding; Feng, Si-Shen

    2010-07-01

    We developed a strategy to formulate supraparamagnetic iron oxides (SPIOs) in nanoparticles (NPs) of biodegradable copolymer made up of poly(lactic acid) (PLA) and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) for medical imaging by magnetic resonance imaging (MRI) of high contrast and low side effects. The IOs-loaded PLA-TPGS NPs (IOs-PNPs) were prepared by the single emulsion method and the nanoprecipitation method. Effects of the process parameters such as the emulsifier concentration, IOs loading in the nanoparticles, and the solvent to non-solvent ratio on the IOs distribution within the polymeric matrix were investigated and the formulation was then optimized. The transmission electron microscopy (TEM) showed direct visual evidence for the well dispersed distribution of the IOs within the NPs. We further investigated the biocompatibility and cellular uptake of the IOs-PNPs in vitro with MCF-7 breast cancer cells and NIH-3T3 mouse fibroblast in close comparison with the commercial IOs imaging agent Resovist. MRI imaging was further carried out to investigate the biodistribution of the IOs formulated in the IOs-PNPs, especially in the liver to understand the liver clearance process, which was also made in close comparison with Resovist. We found that the PLA-TPGS NPs formulation at the clinically approved dose of 0.8 mg Fe/kg could be cleared within 24 h in comparison with several weeks for Resovist. Xenograft tumor model MRI confirmed the advantages of the IOs-PNPs formulation versus Resovist through the enhanced permeation and retention (EPR) effect of the tumor vasculature. PMID:20434210

  4. Poly(trimethylene terephthalate)/Poly(butylenes succinate) blend: Phase behavior and mechanical property control using its transesterification system as the compatibilizer

    Chen, Jianxiang [School of Chemistry and Chemical Engineering, Yangzhou University, Jiangsu 225002 (China); Provincial Key Laboratory of Environmental Material and Engineering, Jiangsu 225002 (China); Wu, Defeng, E-mail: dfwu@yzu.edu.cn [School of Chemistry and Chemical Engineering, Yangzhou University, Jiangsu 225002 (China); Provincial Key Laboratory of Environmental Material and Engineering, Jiangsu 225002 (China)

    2014-12-15

    Poly(trimethylene terephthalate)/poly(butylenes succinate) (PTT/PBS) blends and their ester-exchanged system were prepared by melt mixing for the phase behavior and the viscoelasticity studies. A typical two-phase structure can be seen on the blends because two polymers are immiscible thermodynamically. The phase inversion behavior of the blends can be well determined by the blending ratio dependence of their dynamic rheological responses, which can also be predicted by the viscous Utracki model based on the viscosity ratio. However, the dynamic viscoelastic responses of the blends cannot be well described by the emulsion model because two polymers are highly asymmetric in their viscoelasticity. Besides, transesterification is an effective approach of reducing interfacial tension and improving final phase morphology of the blends, which can be evaluated qualitatively from viscoelastic response alterations after ester exchange reaction. The mechanical properties of PTT/PBS blends were also studied. The results reveal that the ester-exchanged blends show mechanical strengths even lower than the pristine ones because of bulk degradation accompanied with transesterification, despite their improved phase structure. However, they can be used as the good compatibilizer to improve phase adhesion of the pristine blends, enhancing strengths of the PTT based blends or toughness of the PBS based blends evidently. - Highlights: • Phase inversion of the blends can be determined by their rheological responses. • Improved phase morphology can be evaluated from viscoelasticity alterations. • The ester-exchanged system is suitable to be used as the compatibilizer. • Mechanical properties can be controlled by introducing ester-exchanged system.

  5. Alpha-tocopheryl succinate inhibits autophagic survival of prostate cancer cells induced by vitamin K3 and ascorbate to trigger cell death.

    Marco Tomasetti

    Full Text Available BACKGROUND: The redox-silent vitamin E analog α-tocopheryl succinate (α-TOS was found to synergistically cooperate with vitamin K3 (VK3 plus ascorbic acid (AA in the induction of cancer cell-selective apoptosis via a caspase-independent pathway. Here we investigated the molecular mechanism(s underlying cell death induced in prostate cancer cells by α-TOS, VK3 and AA, and the potential use of targeted drug combination in the treatment of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: The generation of ROS, cellular response to oxidative stress, and autophagy were investigated in PC3 prostate cancer cells by using drugs at sub-toxic doses. We evaluated whether PARP1-mediated apoptosis-inducing factor (AIF release plays a role in apoptosis induced by the combination of the agents. Next, the effect of the combination of α-TOS, VK3 and AA on tumor growth was examined in nude mice. VK3 plus AA induced early ROS formation associated with induction of autophagy in response to oxidative stress, which was reduced by α-TOS, preventing the formation of autophagosomes. α-TOS induced mitochondrial destabilization leading to the release of AIF. Translocation of AIF from mitochondria to the nucleus, a result of the combinatorial treatment, was mediated by PARP1 activation. The inhibition of AIF as well as of PARP1 efficiently attenuated apoptosis triggered by the drug combination. Using a mouse model of prostate cancer, the combination of α-TOS, VK3 and AA was more efficient in tumor suppression than when the drugs were given separately, without deleterious side effects. CONCLUSIONS/SIGNIFICANCE: α-TOS, a mitochondria-targeting apoptotic agent, switches at sub-apoptotic doses from autophagy-dependent survival of cancer cells to their demise by promoting the induction of apoptosis. Given the grim prognosis for cancer patients, this finding is of potential clinical relevance.

  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.

    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. Determination of Methylprednisolone Sodium Succinate and Free Methylprednisolone in Methylprednisolone Sodium Succinate for Injection by HPLC%HPLC法测定注射用甲泼尼龙琥珀酸钠主药及游离甲泼尼龙含量

    杨家爱

    2013-01-01

    目的:建立反相HPLC法测定注射用甲泼尼龙琥珀酸钠主药及游离甲泼尼龙的含量.方法:采用Kromasil(250 mm×4.6 mm,5μm)色谱柱,以甲醇-10 mmol·L-1醋酸铵缓冲液(以冰醋酸调pH至5.3)(55∶ 45)为流动相,流速:1.0 ml·min-1,检测波长:245 nm,柱温:35℃,进样体积:20μl.结果:琥珀酸甲泼尼龙在0.01176 ~0.7056 mg·ml-11浓度范围内呈良好线性关系(r =0.9999);平均回收率为98.2%,RSD为0.3%(n=9);游离甲泼尼龙在0.00262~0.0262 mg·ml-1 1浓度范围内呈良好线性关系(r =0.9999);平均回收率为96.5%,RSD为0.8%(n=9).结论:本法简便、准确、重复性好,可用于注射用甲泼尼龙琥珀酸钠的质量控制.%Objective:To develop an HPLC method for the determination of methylprednisolone sodium succinate and free methylprednisolone in methylprednisolone sodium succinate for injection.Method:A Kromasil column(250 mm × 4.6 mm,5 μm) was adopted with the mobile phase of methanol-10 mmol·L-1 ammonium acetate buffer(adjusting pH to 5.3 with acetic acid) (55∶45)at the flow rate of 1.0 ml · min-1.The detection wave length was 245 nm,the column temperature was 35℃ and the injection volume was 20 μl.Result:A good linear correlation of methylprednisolone hemisuccinate and free methylprednisolone were observed within the range of 0.01176-0.7056 mg · ml-1 (r =0.9999) and 0.00262-0.0262 mg · ml-1 (r =0.9999) with the average recovery of 98.2% (RSD =0.3%,n =9) and 96.5% (RSD =0.8%,n =9),respectively.Conclusion:The method is simple,accurate and repeatable,and can be used in the quality control of methylprednisolone sodium succinate for injection.

  8. 琥珀酸美托洛尔缓释片体外释药特性评价%Evaluation of In Vitro Release of Metoprolol Succinate Sustained-release Tablets

    董萱; 陆步实; 周立新; 孙磊

    2012-01-01

    以进口的琥珀酸美托洛尔缓释片为参比制剂,采用f2相似因子法评价自研制剂和参比制剂在不同pH值的释放介质中体外释放行为的相似性,结果显示f2值均大于50,两种制剂体外释放行为相似.运用药物释放动力学模型拟合琥珀酸美托洛尔的释放过程,释放动力学特征以Higuchi模型拟合较好,根据Peppas方程,其释放机制是药物扩散和骨架溶蚀的共同作用.%Metoprolol succinate sustained-release tablets were used as reference preparation, which have been imported from overseas. The release behavior similarity was investigated between the reference and self-prepared tablets in release mediums at different pH. Similar factors (f2) were used to evaluate the similarity of release curves. The values of f2 were all more than 50. The release behaviors were similar. Appling the release kinetic models to the tablets at different release mediums, the release of metoprolol succinate was basically in conformity with the Higuchi model. According to the Peppas equation, the release of metoprolol succinate was affected by drug diffusion and matrix erosion.

  9. 琥珀酸美托洛尔缓释片的制备及释放度研究%Study on the preparation and release of Metoprolol Succinate Sustained-release Tablets

    王曦林; 余海清; 舒红利

    2016-01-01

    目的:研究琥珀酸美托洛尔缓释片的制备方法与释放度。方法通过直接压片法制备琥珀酸美托洛尔缓释片,采用正交试验对其处方工艺加以优化,高效液相色谱法测定体外释放度,对处方工艺的重复性进行考察,比较其F2相似因子与市售片的差异。结果各批次取样点释放度的SD值都在2%以下,F2值分别是87.2、91.5、92.6。结论制备的琥珀酸美托洛尔缓释片和市售片具有相似的释放行为,且处方工艺稳定。%Objective To study the preparation method of Metoprolol Succinate Sustained-release Tablets and release.Methods By direct compression method by metoprolol succinate sustained-release tablets, and by orthogonal test on the prescription process to be optimized, the in vitro release degree was measured by high performance liquid chromatography(HPLC) method, the formulation and process repeatability were investigated, the F2 similar factor and a commercially available tablet differences.Results:The SD values of the release degree of each batch sample were below 2%, the F2 value was 87.2, 91.5, 92.6. Conclusion The preparation of Metoprolol Succinate Sustained-release Tablets and tablet with the release of similar behavior, and the formulation of stability.

  10. X-ray Ray Studies on Crystalline Complexes Involving Amino Acids and Peptides. XXIV. Different Ionization States and Novel Aggregation Patterns in the Complexes of Succinic Acid with DL- and L-Histidine

    Prasad, Sridhar G; Vijayan, M.

    1993-01-01

    Diffusion of acetonitrile into an aqueous solution of DL-histidine and succinic acid in 1:3 molar proportions results in the crystals of DL-histidine hemisuccinate dihydrate [triclinic, P, a = 7.654(1), b = 8.723(1), c = 9.260(1)A , \\alpha = 77.23(1), \\beta = 72.37(1) and \\gamma = 82.32 (1)]. The replacement of DL-histidine by L-histidine in the crystallization experiment under identical conditions leads to crystals of L-histidine semisuccinate trihydrate [orthorhombic, P212121, a = 7.030 (1)...

  11. 琥珀酸美托洛尔缓释片的制备与含量测定%Preparation of Metoprolol Succinate Sustained-Release Tablet and Its Content Determination

    张华; 徐荣

    2016-01-01

    目的:研究琥珀酸美托洛尔缓释片的制备及含量测定方法。方法采用正交实验设计法,以药物体外释放度为指标优选出制备最佳条件。利用高效液相色谱法测定不同批号琥珀酸美托洛尔缓释片的含量。结果琥珀酸美托洛尔缓释片以设计的速度平稳缓慢释药,与上市品比较,两者具有相似的体外释放特征;琥珀酸美托洛尔含量测定浓度在10~70μg•mL-1的范围内线性关系良好,r为0.9998。结论用优选处方制备的琥珀酸美托洛尔缓释片释放度符合要求,制备工艺简单且含量测定方法快速、灵敏、重复性好。%Objective To establish a method of preparing metoprolol succinate sustained-release tablet and its content determination. Methods The formulation was optimized through the orthogonal design test by using release rate of the drug as an indicator.The different batches of metoprolol succinate sustained-release tablets were determined by HPLC. Results The tablets could release drug steadily and slowly as designed,which was similar to imported tablets. The linear range of metoprolol succinate was 10-70 μg�mL-1( r=0.999 8) . Conclusion The releasing rate of metoprolol succinate sustained-release tablet prepared in optimum condition can meet the requirement. This preparation technology is simple, the assay method is rapid, sensitive and reproducible.

  12. The Influence of Green Surface Modification of Oil Palm Mesocarp Fiber by Superheated Steam on the Mechanical Properties and Dimensional Stability of Oil Palm Mesocarp Fiber/Poly(butylene succinate) Biocomposite

    Yoon Yee Then; Nor Azowa Ibrahim; Norhazlin Zainuddin; Hidayah Ariffin; Wan Md Zin Wan Yunus; Buong Woei Chieng

    2014-01-01

    In this paper, superheated steam (SHS) was used as cost effective and green processing technique to modify oil palm mesocarp fiber (OPMF) for biocomposite applications. The purpose of this modification was to promote the adhesion between fiber and thermoplastic. The modification was carried out in a SHS oven at various temperature (200–230 °C) and time (30–120 min) under normal atmospheric pressure. The biocomposites from SHS-treated OPMFs and poly(butylene succinate) (PBS) at a weight ratio ...

  13. RP-HPLC法测定注射用甲泼尼龙琥珀酸钠的含量%RP-HPLC determination of methylprednisolone sodium succinate for injection

    李洁; 刘毅; 李杨

    2012-01-01

    Objective:To develop an RP - HPLC method for the determination of methylprednisolone sodium succi nate for injection. Methods;An Agilent TC C18(2)column(4.6 mm×250 mm,5 μn)was adopted with a mobile phase of water - tetrahydrofuran - formic acid(650:350:1) at the flow rate of 1.0 mL·min-1'. The detection wavelength was 245 nm,the column temperature was 30℃ ,and the volume of injection was 20ΜL. Results:A good linear correlation of methylprednisolone hemisuccinate was observed within the range of 0.01 - 0. 69 mg o mL-1 ( r = 0.9999). The average recovery was 98.3 % wih RSD 0. 3% (n=9). Conclusion:The method is simple, accurate and repeatable, it can be used for the quality control of methylprednisolone sodium succinate for injection.%目的:建立反相HPLC法测定注射用甲泼尼龙琥珀酸钠的含量.方法:采用Agilent TC C18(2)(4.6 mm ×250 mm,5μm)色谱柱,以水-四氢呋喃-甲酸(650∶350∶1)为流动相,流速:1.0 mL·min-1,检测波长:245nm,柱温:30℃,进样体积:20 μL.结果:琥珀酸甲泼尼龙在0.01 ~0.69 mg·mL-1浓度范围内呈良好线性关系(r =0.9999);平均回收率(n=9)为98.3%,RSD为0.3%.结论:本法简便、准确、重复性好,可用于注射用甲泼尼龙琥珀酸钠的含量测定.

  14. Alpha-tocopheryl polyethylene glycol succinate-emulsified poly(lactic-co-glycolic acid) nanoparticles for reversal of multidrug resistance in vitro

    Wang, Ying; Guo, Miao; Lu, Yu; Ding, Li-Ying; Ron, Wen-Ting; Liu, Ya-Qing; Song, Fei-Fei; Yu, Shu-Qin

    2012-12-01

    Multidrug resistance (MDR) is one of the factors in the failure of anticancer chemotherapy. In order to enhance the anticancer effect of P-glycoprotein (P-gp) substrates, inhibition of the P-gp efflux pump on MDR cells is a good tactic. We designed novel multifunctional drug-loaded alpha-tocopheryl polyethylene glycol succinate (TPGS)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPGS/PLGA/SN-38 NPs; SN-38 is 7-ethyl-10-hydroxy-camptothecin), with TPGS-emulsified PLGA NPs as the carrier and modulator of the P-gp efflux pump and SN-38 as the model drug. TPGS/PLGA/SN-38 NPs were prepared using a modified solvent extraction/evaporation method. Physicochemical characterizations of TPGS/PLGA/SN-38 NPs were in conformity with the principle of nano-drug delivery systems (nDDSs), including a diameter of about 200 nm, excellent spherical particles with a smooth surface, narrow size distribution, appropriate surface charge, and successful drug-loading into the NPs. The cytotoxicity of TPGS/PLGA/SN-38 NPs to MDR cells was increased by 3.56 times compared with that of free SN-38. Based on an intracellular accumulation study relative to the time-dependent uptake and efflux inhibition, we suggest novel mechanisms of MDR reversal of TPGS/PLGA NPs. Firstly, TPGS/PLGA/SN-38 NPs improved the uptake of the loaded drug by clathrin-mediated endocytosis in the form of unbroken NPs. Simultaneously, intracellular NPs escaped the recognition of P-gp by MDR cells. After SN-38 was released from TPGS/PLGA/SN-38 NPs in MDR cells, TPGS or/and PLGA may modulate the efflux microenvironment of the P-gp pump, such as mitochondria and the P-gp domain with an ATP-binding site. Finally, the controlled-release drug entered the nucleus of the MDR cell to induce cytotoxicity. The present study showed that TPGS-emulsified PLGA NPs could be functional carriers in nDDS for anticancer drugs that are also P-gp substrates. More importantly, to enhance the therapeutic effect of P-gp substrates, this work

  15. Alpha-tocopheryl polyethylene glycol succinate-emulsified poly(lactic-co-glycolic acid) nanoparticles for reversal of multidrug resistance in vitro

    Multidrug resistance (MDR) is one of the factors in the failure of anticancer chemotherapy. In order to enhance the anticancer effect of P-glycoprotein (P-gp) substrates, inhibition of the P-gp efflux pump on MDR cells is a good tactic. We designed novel multifunctional drug-loaded alpha-tocopheryl polyethylene glycol succinate (TPGS)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPGS/PLGA/SN-38 NPs; SN-38 is 7-ethyl-10-hydroxy-camptothecin), with TPGS-emulsified PLGA NPs as the carrier and modulator of the P-gp efflux pump and SN-38 as the model drug. TPGS/PLGA/SN-38 NPs were prepared using a modified solvent extraction/evaporation method. Physicochemical characterizations of TPGS/PLGA/SN-38 NPs were in conformity with the principle of nano-drug delivery systems (nDDSs), including a diameter of about 200 nm, excellent spherical particles with a smooth surface, narrow size distribution, appropriate surface charge, and successful drug-loading into the NPs. The cytotoxicity of TPGS/PLGA/SN-38 NPs to MDR cells was increased by 3.56 times compared with that of free SN-38. Based on an intracellular accumulation study relative to the time-dependent uptake and efflux inhibition, we suggest novel mechanisms of MDR reversal of TPGS/PLGA NPs. Firstly, TPGS/PLGA/SN-38 NPs improved the uptake of the loaded drug by clathrin-mediated endocytosis in the form of unbroken NPs. Simultaneously, intracellular NPs escaped the recognition of P-gp by MDR cells. After SN-38 was released from TPGS/PLGA/SN-38 NPs in MDR cells, TPGS or/and PLGA may modulate the efflux microenvironment of the P-gp pump, such as mitochondria and the P-gp domain with an ATP-binding site. Finally, the controlled-release drug entered the nucleus of the MDR cell to induce cytotoxicity. The present study showed that TPGS-emulsified PLGA NPs could be functional carriers in nDDS for anticancer drugs that are also P-gp substrates. More importantly, to enhance the therapeutic effect of P-gp substrates, this work

  16. Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation.

    Liying Hou

    Full Text Available Vitamin E succinate (VES, a potential cancer therapeutic agent, potently induces apoptosis and inhibits the growth of various cancer cells. Autophagy has been supposed to promote cancer cell survival or trigger cell death, depending on particular cancer types and tumor microenvironments. The role of autophagy in the growth suppressive effect of VES on gastric cancer cell is basically unknown. We aimed to determine whether and how autophagy affected the VES-induced inhibition of SGC-7901 human gastric carcinoma cell growth. SGC-7901 cells were treated with VES or pre-treated with autophagy inhibitor, chloroquine (CQ and 3-methyladenine (3-MA. Electron microscopy, fluorescence microscopy and Western blot were used to study whether VES induced autophagy reaction in SGC-7901 cells. Western blot evaluated the activities of the mammalian target of rapamycin (mTOR axis. Then we used 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and flow cytometry to detect the level of cell viability and apoptosis. Collectively, our data indeed strongly support our hypothesis that VES treatment produced cytological variations that depict autophagy, increased the amount of intracellular green fluorescent protein-microtubule associated protein 1 light chain 3 (GFP-LC3 punctate fluorescence and the number of autophagic vacuoles. It altered the expression of endogenous autophagy marker LC3. VES activated the suppression of mTOR through inhibiting upstream regulators p38 MAPK and Akt. mTOR suppression consequently inhibited the activation of mTOR downstream targets p70S6K and 4E-BP-1. The activation of the upstream mTOR inhibitor AMPK had been up-regulated by VES. The results showed that pre-treatment SGC-7901 with autophagy inhibitors before VES treatment could increase the capacity of VES to reduce cell viability and to provoke apoptosis. In conclusion, VES-induced autophagy participates in SGC-7901 cell protection by inhibiting mTOR axis

  17. Vitamin E analogue, D-alpha tocopherol succinate, enhances x-ray induced growth delay of human adenocarcinoma cancer cell line

    The purpose of this study was to assess the effects of d-alpha Tocopherol succinate (alpha-TS) in modifying radiation-induced viability reduction and apoptosis occurrence in the model for normal and cancer cells. Our hypothesis was that alpha-TS enhances the growth-inhibitory effect of x-irradiation in cancer cells and that the effect is more pronounced in these cells than in normal cells. Murine NIH 3T3 Swiss albino embryonic cells and HT29 human Caucasian colon adenocarcinoma cells were used in the experiments. Alpha-TS was added to the cultures 1 h prior to irradiation with doses of 2 or 5Gy of x-ray. After irradiation cells were incubated for 73 h. Trypan blue exclusion viability test and estimation of apoptosis and necrosis were made. Apoptotic and necrotic cells were counted in fluorescence microscope using fluorescence dyes: propidium iodide and Hoechst 33342. For experiments with the dose of 5 Gy at least five series of experiments were performed. At lower doses (up to approximately 25μM/ml) treatment with alpha-TS alone enhanced growth of both cell lines. At higher doses treatment with alpha-TS alone delayed the growth of the cell cultures, accompanied by 20-25% necrosis. At the concentrations higher than 25μM/mL alpha-TS alone caused growth delay of both cell cultures, being much more pronounced for the cancer cell line HT29. At the concentrations of 50 μM/mL, responsible for about 30-60% of growth delay, there was observed a synergy effect for x-rays and alpha-TS for both cell lines. The effect was more pronounced for HT29 cells (DMF=0.48 for HT29 versus DMF=0.73 for NIH 3T3). These results may confirm the views of the literature reports suggesting that use of vitamin E together with radiation could be favorable for colon cancer treatment; however, more experiments using more advanced techniques are needed

  18. Essential hypertension treatment with metoprolol succinate sustained-release tablets: an analysis of 60 cases%琥珀酸美托洛尔缓释片治疗原发性高血压60例分析

    张峰

    2011-01-01

    Aim To observe the effects of metoprolol succinate sustained-release tablets in treating mild to moderate essential hypertension. Methods 60 adults with mild and moderate essential hypertension were randomly divided into two groups of 30 patients:the treatment group metoprolol succinate sustained-release tablets oral 47.5 mg once a day,one time follow-up a week. Two weeks if no change to ineffective use of metoprolol succinate sustained-release tablets,95 mg was given orally once a day,4 weeks a course of treatment;the control group,amlodipine besylate tablets 2.5 ~ 5 mg once a day,one time follow-up a week,4 weeks a course of treatment. Results In the treatment group,4 weeks after treating with metoprolol succinate sustained-release tablets, blood pressure and heart rate were compared with that before treatment,which had with a significant difference (P < 0.05). In the control group, the blood pressure and heart rate before and after treatment were compared,with statistically significant difference(P <0.05). Changes in heart rate before and after the treatment were compared between the treatment group and the control group,the former better than the latter. The difference was statistically significant(P <0.05). Conclusion The metoprolol succinate sustained-release tablets can decrease blood pressure over 24h,which is one of the effective drugs to treat essential hypertension.%目的 应用琥珀酸美托洛尔缓释片治疗轻、中度原发性高血压,观察其疗效.方法 将60位轻、中度原发性高血压病人随机分为两组,每组30人.治疗组用琥珀酸美托洛尔缓释片47.5 mg,每日1次口服,每周随访1次,若2周无效者改用95 mg,每日1次口服,4周为1个疗程;对照组采用苯磺酸氨氯地平2.5~5 mg每日1次口服,每周随访1次,4周为1个疗程.结果 治疗组患者,琥珀酸美托洛尔缓释片治疗4周末,治疗前、后血压值及心率比较,差异有统计学著意义(P<0.05);对照组患者治疗前

  19. Simultaneous determination of clobutinol hydrochloride and doxylamine succinate from syrups by RP HPLC using a new stationary phase containing embedded urea polar groups

    Paulo Cesar Pires Rosa

    2012-06-01

    Full Text Available A new, simple, fast, reproducible and sensitive reversed phase HPLC method, using a new stationary phase containing embedded urea polar groups, has been developed and validated for the simultaneous determination of clobutinol hydrochloride (CLO and doxylamine succinate (DOX in syrups. The determination was carried out on a C8 urea column (125 mm x 3.9 mm i.d., 5 µm particle size synthetized at the Liquid Chomatography Laboratory (LabCrom of the Chemistry Institute of Unicamp. The mobile phase consisted of a mixture of acetonitrile:methanol:phosphate buffer (pH 2.5 in the gradient mode. The diode array detector (DAD was operated at 230 nm for CLO and 262 nm for DOX. The method showed adequate precision, with relative standard deviations (RSD less than 1%. The presence of the excipients did not interfere in the results of the analysis. Accuracy was determined by adding standards of the drugs to a placebo and good recovery values were obtained. The analytical curves were linear (r² 0.9999 for CLO and 0.9998 for DOX over a wide concentration range (2.4-336 µg mL-1 for CLO and 2.3-63 µg mL-1 for DOX. The solutions were stable for at least 72 hours at room temperature. The criteria for validation using the ICH guidelines were fulfilled.Um novo método simples, fácil e reprodutível, de fase reversa para CLAE, usando uma fase estacionária contendo um grupo polar, uréia, embutido, foi desenvolvido e validado para determinação simultânea de cloridrato de clobutinol (CLO e succinato de doxilamina (DOX em xarope. A determinação foi realizada em uma coluna C8 uréia (125 mm x 3,9 mm d.i., 5 µm tamanho de partícula sintetizada em nosso laboratório (LabCrom. A fase móvel consistiu de mistura de acetonitrila:metanol:tampão fosfato pH 2,5, em eluição por gradiente. O detector por arranjos de diodo (DAD foi utilizado a 230 nm para CLO e a 262 nm para DOX. O método apresentou precisão adequada, com desvio padrão relativo menor que 1%. A

  20. 7-(4-Fluorobenzylamino-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-amine methanol disolvatePart 19 in the series Fused heterocyclic systems with an s-triazine ring, for Part 18 see Dolzhenko et al. (2011a.

    Anton V. Dolzhenko

    2011-05-01

    Full Text Available The 1,2,4-triazolo[1,5-a][1,3,5]triazine system in the title compound, C17H14FN7·2CH3OH, is essentially planar, with an r.m.s. deviation of 0.0215 Å. The attached phenyl ring lies almost in the mean plane of the heterocyclic core [dihedral angle = 3.56 (4°]. In the crystal, centrosymmetric inversion dimers connected via intermolecular N—H...N hydrogen bonds between H atom of the primary amino group and the triazine N atom [R22(8 graph-set motif] form sheets parallel to (010. A second set of dimers connected via N—H...F hydrogen bonds between the other H atom of the primary amino group and the F atom forms an R22(24 graph-set motif linking the sheets. Methanol solvent molecules are packed in channels running along the [010] direction.

  1. Effect of potassium sodium dehydroandroan drographolide succinate combined with sodium thiosulfate in the treatment of eczema%炎琥宁联合硫代硫酸钠治疗湿疹的效果

    崔乐

    2014-01-01

    Objective To explore the effect of potassium sodium dehydroandroan drographolide succinate combined with sodium thiosulfate in the treatment of eczema. Methods 80 patients with eczema were randomly allocated to the control group receiving sodium thiosulfate and the observation group receiving potassium sodium dehydroandroan dro-grapholide succinate combined with sodium thiosulfate,with 40 patients in each group. Clinical efficacy and incidence of side effect of drugs were compared between the two groups. Results Score of clinical symptoms,score of area of skin rash and total score of clinical symptom before treatment in the two groups were not statistically different (P>0.05).The above-mentiond score after treatment in the two groups significantly improved (P0.05). Conclusion Potassium sodium dehydroandroan drographolide succinate combined with sodium thiosulfate can significantly improve the curative effect in the treatment of eczema,and at the same time it does not increase the incidence rate of side effect of drugs.%目的:探讨炎琥宁联合硫代硫酸钠治疗湿疹的效果。方法随机将80例湿疹患者分为接受硫代硫酸钠治疗的对照组及接受炎琥宁联合硫代硫酸钠治疗的观察组,每组各40例。对比两组的临床疗效及药物副作用发生率。结果两组治疗前的临床症状计分、皮疹面积计分及临床症状总积分比较,差异无统计学意义(P>0.05),治疗后,两组的上述评分均明显改善(P0.05)。结论炎琥宁联合硫代硫酸钠可显著改善治疗湿疹的效果,且不增高药物副作用发生率。

  2. Preparation of nanocomposites based on poly(Butylene Succinate) and montmorillonite organoclay via in situ polymerization; Preparo de nanocompositos de poli(succinato de butileno) (PDS) e argila motmorilonita organofilica via polimerizaco in situ

    Ferreira, Leticia P.; Moreira, Andrei N.; Souza Junior, Fernando G. de, E-mail: fgsj@ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Inst. de Macromoleculas; Pinto, Jose Carlos Costa da Silva [Coordenacao dos Cursos de Pos-Graduacao em Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Quimica

    2014-09-15

    Nanocomposites based on poly(butylene succinate) (PBS) and organophilic montmorillonite were synthesized via in situ polymerization using three different clay compositions (4, 6 and 8 wt%). The products were characterized by several different techniques. X-ray diffraction was useful to confirm the increase of the interlayer spacing of the clay due to the presence of the polymer chains among layers. Thermal analysis indicated that the polymerization method chosen led to materials with lower thermal stability compared to the pure PBS, due to the difficulty of chain growth in the presence of the clay. Low-field NMR technique was used to assess clay dispersion in the polymer, with exfoliated structures predominating in the nanocomposites. (author)

  3. Study on the properties of cassava hydroxypropyl and octenyl succinic anhydride compound modified starch%木薯羟丙基化辛烯基琥珀酸酯化复合改性淀粉的性质研究

    雷欣欣; 张本山; 周雪

    2012-01-01

    以木薯淀粉为原料制备木薯羟丙基化辛烯基琥珀酸酯化复合改性淀粉,采用傅里叶变换红外谱仪、扫描电镜、X射线衍射仪和Brabender黏度仪等对木薯羟丙基化辛烯基琥珀酸酯化复合改性淀粉的物化性质进行了测定和分析.并与木薯原淀粉和木薯辛烯基琥珀酸淀粉酯进行对比。结果表明,木薯淀粉经复合改性后,在1550-1610cm-1出现新的吸收峰.与原木薯淀粉和木薯SSOS相比,在940、880、730、570cm-1处呈现较弱的吸收峰;复合改性后颗粒表面受损严重.颗粒的形状也发生明显改变,但晶体类型没有发生改变;乳化性能和透明度得到提高;起糊温度、峰值温度降低.糊粘度增大;与单一的辛烯基琥珀酸酯化改性淀粉相比,热糊稳定性升高,凝沉性增强。%The cassava starch was used to prepare cassava hydroxypropyl and octenyl succinic anhydride compound modified starch. The physical properties of cassava hydroxypropyl and octenyl succinic anhydride compound modified starch were investigated by Fourier transform infrared spectrometer(FT-IR),Scanning electron microscop,X-ray diffraction(XRD),Brabender viscometer and so on with the comparison of the native cassava starch and octenyl succinic anhydride(OSA)-modified cassava starch. The results indicated that the FT-IR spectrum of compound modified cassava starch showed new absorption peaks at 1550-1610cm-1. and weaken absorption peak at the 940,880,730 and 570cm-1,compared with the native cassava starch and OSA- modified cassava starch. The starch granule exhibited rougher surface,more irregular shape significantly but the crystalline was not changed. The product showed good emulsifiability and transparency. That gelatinization temperature and the peak temperature all decreased,and paste viscosity was higher as well.The setback capacity was weaker,and hot paste stability increased,compared with single octenyl succinic anhydride

  4. Burst of succinate dehydrogenase and α-ketoglutarate dehydrogenase activity in concert with the expression of genes coding for respiratory chain proteins underlies short-term beneficial physiological stress in mitochondria.

    Zakharchenko, Marina V; Zakharchenko, A V; Khunderyakova, N V; Tutukina, M N; Simonova, M A; Vasilieva, A A; Romanova, O I; Fedotcheva, N I; Litvinova, E G; Maevsky, E I; Zinchenko, V P; Berezhnov, A V; Morgunov, I G; Gulayev, A A; Kondrashova, M N

    2013-01-01

    Conditions for the realization in rats of moderate physiological stress (PHS) (30-120 min) were selected, which preferentially increase adaptive restorative processes without adverse responses typical of harmful stress (HST). The succinate dehydrogenase (SDH) and α-ketoglutarate dehydrogenase (KDH) activity and the formation of reactive oxygen species (ROS) in mitochondria were measured in lymphocytes by the cytobiochemical method, which detects the regulation of mitochondria in the organism with high sensitivity. These mitochondrial markers undergo an initial 10-20-fold burst of activity followed by a decrease to a level exceeding the quiescent state 2-3-fold by 120 min of PHS. By 30-60 min, the rise in SDH activity was greater than in KDH activity, while the activity of KDH prevailed over that of SDH by 120 min. The attenuation of SDH hyperactivity during PHS occurs by a mechanism other than oxaloacetate inhibition developed under HST. The dynamics of SDH and KDH activity corresponds to the known physiological replacement of adrenergic regulation by cholinergic during PHS, which is confirmed here by mitochondrial markers because their activity reflects these two types of nerve regulation, respectively. The domination of cholinergic regulation provides the overrestoration of expenditures for activity. In essence, this phenomenon corresponds to the training of the organism. It was first revealed in mitochondria after a single short-time stress episode. The burst of ROS formation was congruous with changes in SDH and KDH activity, as well as in ucp2 and cox3 expression, while the activity of SDH was inversely dependent on the expression of the gene of its catalytic subunit in the spleen. As the SDH activity enhanced, the expression of the succinate receptor decreased with subsequent dramatic rise when the activity was becoming lower. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaption and therapy. PMID:22814171

  5. Soluble aldehyde dehydrogenase and metabolism of aldehydes by soybean bacteroids.

    Peterson, J. B.; LaRue, T A

    1982-01-01

    A soluble aldehyde dehydrogenase (EC 1.2.1.3) was partially purified from Rhizobium japonicum bacteroids and from free-living R. japonicum 61A76. The enzyme was activated by NAD+, NADH, and dithiothreitol, and it reduced NAD(P)+. Acetaldehyde, propionaldehyde, butyraldehyde, benzaldehyde, and succinic semialdehyde were substrates. The Km for straight-chain aldehydes decreased with increasing carbon chain length. The aldehyde dehydrogenase was inhibited by 6-cyanopurine, but not by metronidazo...

  6. 琥珀酸美托洛尔缓释微丸型片剂的制备与体外释放度考察%Preparation and in vitro Release of Metoprolol Succinate Sustained-release Pellet Tablets

    谢向阳; 邢传峰; 李银科; 李旸; 陈鹰

    2014-01-01

    Objective To prepare metoprolol succinate sustained-release pellet tablets,and to investigate their in vitro drug release behavior. Methods Metoprolol succinate sustained-release pellets were prepared by fluid bed coating technology,while the sustained-release pellet tablets were prepared by direct compression of sustained-release pellets and suitable excipients. The release behavior similarity was investigated between the reference and self-prepared tablets in release media. Similar factor( F 2 )was used to evaluate the similarity of release curves. Re-sults The size of blank sugar pellets was 250-350 μm. With Kollicoat SR 30D as the coating material,the coating level was 20%,the plasticizer content was 20%,the anti-tacking agent content was 50%,and the tableting pressure was 80 kN. The value of F 2 was more than 50,and the release behavior was similar. Conclusion The release behav-ior of metoprolol succinate sustained-release pellet tablets is quite satisfactory. This method of preparation may be used in industrial production.%目的:制备琥珀酸美托洛尔缓释微丸型片剂,并对其体外释放度进行考察。方法采用流化床包衣法制备琥珀酸美托洛尔缓释微丸,将缓释微丸与适合的辅料混合后采用直接压片法制备琥珀酸美托洛尔微丸型片剂,并采用F2相似因子法评价自制制剂和参比制剂在释放介质中的体外释放行为。结果选用空白蔗糖丸芯粒径为250~350μm,以Kollicoat SR 30D为微丸的衣膜材料,包衣增重为20%,增塑剂用量为20%,滑石粉用量为50%,压片压力为80 kN时,自制制剂和参比制剂F 2相似因子值大于50,说明2种制剂体外释放行为相似。结论制备的琥珀酸美托洛尔缓释微丸型片剂的释药行为较好,有望应用于工业生产。

  7. Novel MgCl2-supported Catalysts Containing Succinate Donors for Propylene Polymerization%琥珀酸酯为内给电子体的新型MgCl2载体催化剂用于丙烯聚合

    姜涛; 陈伟; 赵峰; 刘月祥

    2005-01-01

    A novel MgCl2-supported Ziegler-Natta catalyst containing diethyl diisopropylsuccinate donor was prepared and propylene polymerizations with the combination of such catalyst and four external donors were investigated in detail. The catalyst was compared with a commercial one with phthalate as internal donor in terms of catalytic activity, hydrogen sensitivity and stereospecificity in propylene polymerization. The molecular weight,molecular weight distribution and microstructure of the produced polypropylenes were compared also. It was found that the novel catalyst containing succinate internal donor showed higher activity and higher stereospecificity than those with phthalate as internal donor. Consequently, polypropylenes obtained by the succinate-based catalyst showed high molecular weight, high melting temperature, high isotactic index and broad molecular weight distribution than those obtained with the commercial catalyst.

  8. Influence of long-term hyper-gravity on the reactivity of succinic acid dehydrogenase and NADPH-diaphorase in the central nervous system of fish: a histochemical study

    Anken, R. H.; Rahmann, H.

    In the course of a densitometric evaluation, the histochemically demonstrated reactivity of succinic acid dehydrogenase (SDH) and of NADPH-diaphorase (NADPHD) was determined in different brain nuclei of two teleost fish (cichlid fish Oreochromis mossambicus, swordtail fish Xiphophorus helleri), which had been kept under 3g hyper-gravity for 8 days. SDH was chosen since it is a rate limiting enzyme of the Krebs cycle and therefore it is regarded as a marker for metabolic and neuronal activity. NADPHD reactivity reflects the activity of nitric oxide synthase. Nitric oxide (NO) is a gaseous intercellular messenger that has been suggested to play a major role in several different in vivo models of neuronal plasticity including learning. Within particular vestibulum-connected brain centers, significant effects of hyper-gravity were obtained, e.g., in the magnocellular nucleus, a primary vestibular relay ganglion of the brain stem octavolateralis area, in the superior rectus subdivision of the oculomotoric nucleus and within cerebellar eurydendroid cells, which in teleosts possibly resemble the deep cerebellar nucleus of higher vertebrates. Non-vestibulum related nuclei did not respond to hypergravity in a significant way. The effect of hyper-gravity found was much less distinct in adult animals as compared to the circumstances seen in larval fish (Anken et al., Adv. Space Res. 17, 1996), possibly due to a development correlated loss of neuronal plasticity.

  9. Biodegradation of poly(butylene succinate) powder in a controlled compost at 58°C evaluated by naturally-occurring carbon 14 amounts in evolved CO(2) based on the ISO 14855-2 method.

    Kunioka, Masao; Ninomiya, Fumi; Funabashi, Masahiro

    2009-10-01

    The biodegradabilities of poly(butylene succinate) (PBS) powders in a controlled compost at 58 degrees C have been studied using a Microbial Oxidative Degradation Analyzer (MODA) based on the ISO 14855-2 method, entitled "Determination of the ultimate aerobic biodegradability of plastic materials under controlled composting conditions-Method by analysis of evolved carbon dioxide-Part 2: Gravimetric measurement of carbon dioxide evolved in a laboratory-scale test". The evolved CO(2) was trapped by an additional aqueous Ba(OH)(2) solution. The trapped BaCO(3) was transformed into graphite via a serial vaporization and reduction reaction using a gas-tight tube and vacuum manifold system. This graphite was analyzed by accelerated mass spectrometry (AMS) to determine the percent modern carbon [pMC (sample)] based on the (14)C radiocarbon concentration. By using the theory that pMC (sample) was the sum of the pMC (compost) (109.87%) and pMC (PBS) (0%) as the respective ratio in the determined period, the CO(2) (respiration) was calculated from only one reaction vessel. It was found that the biodegradabilities determined by the CO(2) amount from PBS in the sample vessel were about 30% lower than those based on the ISO method. These differences between the ISO and AMS methods are caused by the fact that part of the carbons from PBS are changed into metabolites by the microorganisms in the compost, and not changed into CO(2). PMID:20057944

  10. Dissolution determination of solid dispersion particles of sumatriptan succinate%琥珀酸舒马曲坦固体分散体颗粒溶出度的测定

    徐俊; 闫启东; 石雷

    2016-01-01

    To establish a method to determine the dissolution of sumatriptan succinate (SS)solid disper-sions.The dissolution rate of SS was determined by UV,detection wavelength at 228 nm,and ethanol aqueous solution as blank control.Results showed that the linear range was 0.4 ~20 μg/mL (R =0.999 95),the average recovery rate was 99.80% (n =9,RSD =0.21%),the drug dissolution was above 85%.The method can be used for dissolution test of solid dispersion particles of SS or tablet.%建立琥珀酸舒马曲坦固体分散体颗粒溶出度的测定方法。运用紫外分光光度法测定溶出度,检测波长228 nm,以乙醇水溶液为空白对照。结果表明,舒马曲坦的线性范围为0.4~20μg/mL时(R=0.99995),平均回收率99.80%(n=9,RSD=0.21%),溶出度>85%。本方法可用于舒马曲坦片剂或颗粒溶出度的测定。

  11. The Influence of Green Surface Modification of Oil Palm Mesocarp Fiber by Superheated Steam on the Mechanical Properties and Dimensional Stability of Oil Palm Mesocarp Fiber/Poly(butylene succinate Biocomposite

    Yoon Yee Then

    2014-08-01

    Full Text Available In this paper, superheated steam (SHS was used as cost effective and green processing technique to modify oil palm mesocarp fiber (OPMF for biocomposite applications. The purpose of this modification was to promote the adhesion between fiber and thermoplastic. The modification was carried out in a SHS oven at various temperature (200–230 °C and time (30–120 min under normal atmospheric pressure. The biocomposites from SHS-treated OPMFs and poly(butylene succinate (PBS at a weight ratio of 70:30 were prepared by melt blending technique. The mechanical properties and dimensional stability of the biocomposites were evaluated. This study showed that the SHS treatment increased the roughness of the fiber surface due to the removal of surface impurities and hemicellulose. The tensile, flexural and impact properties, as well as dimensional stability of the biocomposites were markedly enhanced by the presence of SHS-treated OPMF. Scanning electron microscopy analysis showed improvement of interfacial adhesion between PBS and SHS-treated OPMF. This work demonstrated that SHS could be used as an eco-friendly and sustainable processing method for modification of OPMF in biocomposite fabrication.

  12. Biodegradation of poly(lactic acid, poly(hydroxybutyrate-co-hydroxyvalerate, poly(butylene succinate and poly(butylene adipate-co-terephthalate under anaerobic and oxygen limited thermophilic conditions

    Jutakan Boonmee

    2016-01-01

    Full Text Available In order to study the biodegradation behavior of biodegradable plastics in landfill conditions, four types of biodegradable plastics including poly(lactic acid (PLA, poly(hydroxybutyrate-co-hydroxyvalerate (PHBV, poly(butylene succinate (PBS, and poly(butylene adipate-co-terephthalate (PBAT were tested by burying in sludge mixed soil medium under anaerobic and oxygen limited conditions. The experiments were operated at 52 ± 2ºC in dark conditions according to ISO15985. The degree of biodegradation after 75 days was investigated by weight loss determination, visual examination, and surface appearance by scanning electronic microscopy (SEM. Under both anaerobic and oxygen limited conditions, the complete degradation (100% weight loss was found only in PHBV after 75 days. The plastic degradations were ranked in the order of PHBV> PLA> PBS> PBAT. The percentage of weight losses were significantly different at p ≤ 0.05. However, for all studied plastics, the degradation under anaerobic and oxygen limited conditions did not significantly different at 95% confidence.

  13. Succinic acid dihydrazide: a convenient N,N-double block for the synthesis of symmetrical and non-symmetrical succinyl-bis[5-trifluoro(chloro)methyl-1H-pyrazoles

    This paper describes the conventional regioselective synthesis of a series of new succinyl spacer bis-(3,5-substituted 2-pyrazolines and 1H-pyrazoles), namely; 1,4-bis[5-(trifluoromethyl)-5- hydroxy-4,5-dihydro-1H-pyrazol-1-yl]butane-1,4-diones (46-88%) and the respective dehydrated system (60-78%), new 1-[5-(trifluoromethyl)-5-hydroxy-4,5-dihydro-1H-pyrazol-1-yl]-4- oxobutane hydrazides (52-81%) and the non-symmetrical 2-pyrazolines derivatives thereof as 1-[5-(trifluoromethyl)- 5-hydroxy-4,5-dihydro-1H-pyrazol-1-yl)-4-(5-(trichloromethyl)-5-hydroxy- 4,5-dihydro-1H-pyrazol-1-yl]butane-1,4-diones (75-91%). All succinyl substituted bispyrazoles were obtained from the cyclocondensation reactions of 4-substituted 4-alkoxy-1,1,1-trihaloalk-3- en-2-ones, where the 4-substituents are H, Me, Ph, 4-FC6H4, 4-ClC6H4, 4-OMeC6H4, 4-NO2C6H4, 1-naphthyl and 2-furyl, with succinic acid dihydrazide in ethanol as solvent under controlled reaction conditions. (author)

  14. The influence of green surface modification of oil palm mesocarp fiber by superheated steam on the mechanical properties and dimensional stability of oil palm mesocarp fiber/poly(butylene succinate) biocomposite.

    Then, Yoon Yee; Ibrahim, Nor Azowa; Zainuddin, Norhazlin; Ariffin, Hidayah; Yunus, Wan Md Zin Wan; Chieng, Buong Woei

    2014-01-01

    In this paper, superheated steam (SHS) was used as cost effective and green processing technique to modify oil palm mesocarp fiber (OPMF) for biocomposite applications. The purpose of this modification was to promote the adhesion between fiber and thermoplastic. The modification was carried out in a SHS oven at various temperature (200-230 °C) and time (30-120 min) under normal atmospheric pressure. The biocomposites from SHS-treated OPMFs and poly(butylene succinate) (PBS) at a weight ratio of 70:30 were prepared by melt blending technique. The mechanical properties and dimensional stability of the biocomposites were evaluated. This study showed that the SHS treatment increased the roughness of the fiber surface due to the removal of surface impurities and hemicellulose. The tensile, flexural and impact properties, as well as dimensional stability of the biocomposites were markedly enhanced by the presence of SHS-treated OPMF. Scanning electron microscopy analysis showed improvement of interfacial adhesion between PBS and SHS-treated OPMF. This work demonstrated that SHS could be used as an eco-friendly and sustainable processing method for modification of OPMF in biocomposite fabrication. PMID:25177865

  15. Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

    Brandon H. Cline

    2015-02-01

    Full Text Available Central insulin receptor-mediated signalling is attracting the growing attention of researchers because of rapidly accumulating evidence implicating it in the mechanisms of plasticity, stress response and neuropsychiatric disorders including depression. Dicholine succinate (DS, a mitochondrial complex II substrate, was shown to enhance insulin-receptor mediated signaling in neurons and is regarded as a sensitizer of the neuronal insulin receptor. Compounds enhancing neuronal insulin receptor-mediated transmission exert an antidepressant-like effect in several pre-clinical paradigms of depression; similarly, such properties for DS were found with a stress-induced anhedonia model. Here, we additionally studied the effects of DS on several variables which were ameliorated by other insulin receptor sensitizers in mice. Pre-treatment with DS of chronically stressed C57BL6 mice rescued normal contextual fear conditioning, hippocampal gene expression of NMDA receptor subunit NR2A, the NR2A/NR2B ratio and increased REM sleep rebound after acute predation. In 18-month-old C57BL6 mice, a model of elderly depression, DS restored normal sucrose preference and activated the expression of neural plasticity factors in the hippocampus as shown by Illumina microarray. Finally, young naïve DS-treated C57BL6 mice had reduced depressive- and anxiety-like behaviours and, similarly to imipramine-treated mice, preserved hippocampal levels of the phosphorylated (inactive form of GSK3 beta that was lowered by forced swimming in pharmacologically naïve animals. Thus, DS can ameliorate behavioural and molecular outcomes under a variety of stress- and depression-related conditions. This further highlights neuronal insulin signalling as a new factor of pathogenesis and a potential pharmacotherapy of affective pathologies.

  16. Biodegradation of Poly(butylene succinate Powder in a Controlled Compost at 58 °C Evaluated by Naturally-Occurring Carbon 14 Amounts in Evolved CO2 Based on the ISO 14855-2 Method

    Masahiro Funabashi

    2009-09-01

    Full Text Available The biodegradabilities of poly(butylene succinate (PBS powders in a controlled compost at 58 °C have been studied using a Microbial Oxidative Degradation Analyzer (MODA based on the ISO 14855-2 method, entitled “Determination of the ultimate aerobic biodegradability of plastic materials under controlled composting conditions—Method by analysis of evolved carbon dioxide—Part 2: Gravimetric measurement of carbon dioxide evolved in a laboratory-scale test”. The evolved CO2 was trapped by an additional aqueous Ba(OH2 solution. The trapped BaCO3 was transformed into graphite via a serial vaporization and reduction reaction using a gas-tight tube and vacuum manifold system. This graphite was analyzed by accelerated mass spectrometry (AMS to determine the percent modern carbon [pMC (sample] based on the 14C radiocarbon concentration. By using the theory that pMC (sample was the sum of the pMC (compost (109.87% and pMC (PBS (0% as the respective ratio in the determined period, the CO2 (respiration was calculated from only one reaction vessel. It was found that the biodegradabilities determined by the CO2 amount from PBS in the sample vessel were about 30% lower than those based on the ISO method. These differences between the ISO and AMS methods are caused by the fact that part of the carbons from PBS are changed into metabolites by the microorganisms in the compost, and not changed into CO2.

  17. Antitumor efficiency of D-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-caprolactone-ran-lactide) nanoparticle-based delivery of docetaxel in mice bearing cervical cancer.

    Wang, Zhongyuan; Zeng, Xiaowei; Ma, Yaping; Liu, Jian; Tang, Xiaolong; Gao, Yongfeng; Liu, Kewei; Zhang, Jinxie; Ming, Pinghong; Huang, Laiqiang; Mei, Lin

    2014-08-01

    Pharmaceutical nanotechnology holds potential in cancer chemotherapy. In this research, the docetaxel-loaded D-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-caprolactone-ran-lactide) (TPGS-b-(PCL-ran-PLA)) nanoparticles were prepared by a modified nanoprecipitation method and then the particle size, surface morphology, nanoparticle stability, in vitro drug release and cellular uptake of nanoparticles were characterized. Finally, we evaluated the therapeutic effects of nanoparticle formulation in comparison with Taxotere both in vitro and in vivo. The size of TPGS-b-(PCL-ran-PLA) nanoparticles was about 150 nm and much smaller than PCL nanoparticles (about 185 nm) and the absolute value of zeta potential was higher than PCL nanoparticles (16.49 mV vs. 13.17 mV). FESEM images further confirmed the morphology and size of nanoparticles. The drug-loaded nanoparticles were considered to be stable, showing no change in the particle size and surface charge during three-month storage of its aqueous solution. In vitro drug release of TPGS-b-(PCL-ran-PLA) nanoparticles was much faster than PCL and PCL-TPGS nanoparticles. The cumulative drug release of docetaxel-loaded TPGS-b-(PCL-ran-PLA), PCL-TPGS, and PCL NPs were 38.00%, 34.48% and 29.04%, respectively. TPGS-b-(PCL-ran-PLA) nanoparticles showed an obvious increase of cellular uptake. Due to the advantages of TPGS-b-(PCL-ran-PLA) nanoparticles, it could achieve significantly higher level of cytotoxicity in vitro and better inhibition effect of tumor growth on xenograft BALB/c nude mice tumor model than commercial Taxotere at the same dose (1.49-fold more effective). The TPGS-b-(PCL-ran-PLA) could be used as a novel and potential biodegradable polymeric material for nanoformulation in cervical cancer chemotherapy. PMID:25016651

  18. Catalytic Effects Comparison of Several Catalysts Used to Synthesize Poly (Butylene Succinate)%几种合成聚丁二酸丁二酯用催化剂的催化效果比较

    高艳; 赖仕全; 刘兴南; 岳莉; 赵雪飞

    2014-01-01

    Poly(butylene succinate) (PBS) was synthesized respectively from 1,4-succinic acid and 1,4-butanediol using SnCl2,Sn(Oct)2,ZnCl2,Zn(OAc)2,Sb2O3 or SO42-/ZrO2 as catalyst by direct melt polycondensation method. The catalytic effects of the 6 kinds of catalysts in the polymerization reaction of PBS were compared by measuring liquid yield in the esterification reaction stage,yield and properties of PBS,such as intrinsic viscosity,molecular weight and melting temperature. Taking SnCl2 as example, the structure and thermal stability of PBS synthesized by SnCl2 were studied with FTIR and TG. The results show that the synthesized product is hydroxyl-capped PBS. The 6 kinds of catalysts all can promote dehydration esterification reaction of 1,4-succinic acid and 1,4-butanedio. Except for Sn(Oct)2,several other catalysts can effectively reduce the formation of tetrahydrofuran by-product. Overall,the catalytic effects of stannum compound are best among these catalyst and when SnCl2 is used as catalyst,the yield, intrinsic viscosity,number average molecular weight and original melting temperature of the synthesized PBS are best and it’s decomposition temperature is 280℃. Taking molecular weight of PBS as index,the order of the catalytic effects of the 6 catalysts is SnCl2>Sn(Oct)2>Sb2O3>SO42-/ZrO2>ZnCl2>Zn(OAc)2.%以1,4-丁二酸和1,4-丁二醇为原料,分别以SnCl2,异辛酸亚锡[Sn(Oct)2],ZnCl2,乙酸锌[Zn(OAc)2], Sb2O3和SO42-/ZrO2固体超强酸为催化剂,采用直接熔融缩聚法合成了聚丁二酸丁二酯(PBS)。通过测试酯化反应阶段的出液量、PBS的收率及其特性黏度、数均分子量和熔融温度等性质,比较了6种催化剂在PBS聚合反应中的催化效果。以SnCl2为例,利用傅立叶变换红外光谱和热重分析研究了由其催化合成的PBS的结构和热稳定性能。结果表明,实验合成的产物为羟基封端PBS;6种催化剂都能促进1,4-丁二酸和1,4-丁二醇分子间

  19. Pharmacokinetic Dose Proportionality Between Two Strengths (12.5 mg and 25 mg) of Doxylamine Hydrogen Succinate Film-Coated Tablets in Fasting State: A Single-Dose, Randomized, Two-Period Crossover Study in Healthy Volunteers

    Videla, Sebastián; Cebrecos, Jesús; Lahjou, Mounia; Wagner, France; Guibord, Pascal; Xu, Zhengguo; Cabot, Anna; Encabo, Mercedes; Encina, Gregorio; Sicard, Eric; Sans, Artur

    2013-01-01

    Background Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose proportionality of the pharmacokinetics of doxylamine are available, although this drug has been marketed in European countries for more than 50 years. Objective The objective of this study was to evaluate and compare the dose proportionality between two marketed strengths (12.5 mg and 25 mg) of doxylamine hydrogen succinat...

  20. HPLC法检测丁二酸发酵液中的有机酸和水溶性维生素%Analysis of organic acids and hydrosoluble vitamins in succinic acid fernmentation broth by high performance liquid chromatography

    赵文君; 屠春燕; 马海宁; 姜珉; 韦萍

    2011-01-01

    An innovative system of RP-HPLC method was proposed and optimized for detecting the organic acids and hydrosoluble vitamins in succinic acid fermentation broth. Under the optimal conditions, a Hedera ODS-2column (5μm, 4.6 mm × 250 mm) was used, the detection wavelength was 210 nm. Flow rate was 1.0 mL/min; Mobile phase A:20 mmol/L sodium dihydrogen phosphate(pH2.9), Mobile phase B: ACN; the gradient protocol was applied. All compounds were completely eluted in 15 min. All the correlation coefficients (r) of regression equations were above 0.9989, and the recoveries ranged from 92.5% to 100.3%. The relative standard deviations were in the range from 0.9% to 1.9%. By this method, organic acids and vitamins can be easily, rapidly and effectively determined.%采用高效液相色谱法(HPLC)同时检测丁二酸发酵液中的有机酸和水溶性维生素.以RP-HPLC为分离模式,选用Hedera ODS-2色谱柱(5μm,4.6×250mm),20mmol/L的磷酸盐缓冲溶液(pH 2.9)和乙腈为流动相,梯度洗脱,检测波长为210nm,建立了同时测定分析8种水溶性维生素和3种有机酸的方法,15min内所有组分都洗脱完全.8种水溶性维生素和3种有机酸在线性范围内峰面积与浓度呈良好的线性关系,相关系数为0.9989~0.9997;加标回收率在92.5%~100.3%之间;RSD(n=5):0.9%~1.9%.本方法采用同一种流动相既可以测定发酵液中的有机酸又可以测定水溶性维生素的含量.