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Sample records for conquers palmitate oxidation

  1. Substrate overload: Glucose oxidation in human myotubes conquers palmitate oxidation through anaplerosis

    DEFF Research Database (Denmark)

    Gaster, Michael

    2009-01-01

    of citrate was increased which could be abolished by phenylacetic acid (inhibitor of pyruvate carboxylase (PC)). The present data challenges above preconceptions. Although they operate at low-moderate substrate levels additional two principles determine substrate oxidation at higher substrate concentrations...

  2. Defective [U-14 C] palmitic acid oxidation in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Carroll, J.E.; Norris, B.J.; Brooke, M.H.

    1985-01-01

    Compared with normal skeletal muscle, muscle from patients with Duchenne dystrophy had decreased [U-14 C] palmitic acid oxidation. [1-14 C] palmitic acid oxidation was normal. These results may indicate a defect in intramitochondrial fatty acid oxidation

  3. Defective (U-14 C) palmitic acid oxidation in Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, J.E.; Norris, B.J.; Brooke, M.H.

    1985-01-01

    Compared with normal skeletal muscle, muscle from patients with Duchenne dystrophy had decreased (U-14 C) palmitic acid oxidation. (1-14 C) palmitic acid oxidation was normal. These results may indicate a defect in intramitochondrial fatty acid oxidation.

  4. Ascorbyl palmitate, gamma-tocopherol, and EDTA affect lipid oxidation in fish oil enriched salad dressing differently

    DEFF Research Database (Denmark)

    Let, M.B.; Jacobsen, Charlotte; Meyer, Anne S.

    2007-01-01

    The aim of the study was to investigate the ability of γ-tocopherol, ethylenediaminetetraacetate (EDTA), and ascorbyl palmitate to protect fish oil enriched salad dressing against oxidation during a 6 week storage period at room temperature. The lipid-soluble γ-tocopherol (220 and 880 µg g-1...

  5. Antioxidant effect of mogrosides against oxidative stress induced by palmitic acid in mouse insulinoma NIT-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Q.; Chen, S.Y.; Deng, L.D.; Feng, L.P.; Huang, L.Z.; Yu, R.R. [Department of Pharmacy, Guilin Medical University, Guilin (China)

    2013-11-18

    Excessive oxidative stress in pancreatic β cells, caused by glucose and fatty acids, is associated with the pathogenesis of type 2 diabetes. Mogrosides have shown antioxidant and antidiabetic activities in animal models of diabetes, but the underlying mechanisms remain unclear. This study evaluated the antioxidant effect of mogrosides on insulinoma cells under oxidative stress caused by palmitic acid, and investigated the underlying molecular mechanisms. Mouse insulinoma NIT-1 cells were cultured in medium containing 0.75 mM palmitic acid, mimicking oxidative stress. The effects of 1 mM mogrosides were determined with the dichlorodihydrofluorescein diacetate assay for intracellular reactive oxygen species (ROS) and FITC-Annexin V/PI assay for cell apoptosis. Expression of glucose transporter-2 (GLUT2) and pyruvate kinase was determined by semi-quantitative reverse-transcription polymerase chain reaction. Palmitic acid significantly increased intracellular ROS concentration 2-fold (P<0.05), and decreased expression of GLUT2 (by 60%, P<0.05) and pyruvate kinase (by 80%, P<0.05) mRNAs in NIT-1 cells. Compared with palmitic acid, co-treatment with 1 mM mogrosides for 48 h significantly reduced intracellular ROS concentration and restored mRNA expression levels of GLUT2 and pyruvate kinase. However, mogrosides did not reverse palmitic acid-induced apoptosis in NIT-1 cells. Our results indicate that mogrosides might exert their antioxidant effect by reducing intracellular ROS and regulating expression of genes involved in glucose metabolism. Further research is needed to achieve a better understanding of the signaling pathway involved in the antioxidant effect of mogrosides.

  6. Effect of artichoke extract (Cynara scolymus L.) on palmitic-1-14C acid oxidation in rats.

    Science.gov (United States)

    Juzyszyn, Zygmunt; Czerny, Boguslaw; Pawlik, Andrzej; Drozdzik, Marek

    2008-05-01

    Studies on the effect of the artichoke extract (AE) on oxidation of palmitic-1-14C acid administered intravenously to rats at a dose 25 and 50 mg/kg bw demonstrated marked enhancement of both 14CO2 expiration rate and 14CO2 recovery in the expired air. The extract suppressed accumulation of palmitic-1-14C acid in serum lipids and epididymal fat pad tissue as well. The effects of the extract on 14CO2 expiration rate, 14CO2 recovery, as well as accumulation of palmitic-1-14C acid were dose dependent. Total14CO2 recovery in expired air during 60 min was elevated by 17.3% (p < 0.05) and 52.1% (p < 0.001) in rats administered the extract at a dose of 25 and 50 mg/kg, respectively. The rats supplemented with the AE at a dose of 25 and 50 mg/kg bw were characterized by 10.0% (not significant) and 19% (p < 0.05) decrease in( 14)C radioactivity of serum lipids as well as reduction of epididymal fat tissue 14C radioactivity by 8.7 and 17.5% (p < 0.05), respectively, in comparison with the control rats. Thus, the results demonstrate that the AE possess stimulatory properties with respect to oxidation of palmitic acid administered to rats, and provide new information on the mechanism of antilipemic activity of the extract associated with activation of lipid oxidation in the organism.

  7. Preparation and properties of highly conductive palmitic acid/graphene oxide composites as thermal energy storage materials

    International Nuclear Information System (INIS)

    Mehrali, Mohammad; Latibari, Sara Tahan; Mehrali, Mehdi; Indra Mahlia, Teuku Meurah; Cornelis Metselaar, Hendrik Simon

    2013-01-01

    PA/GO (palmitic acid/graphene oxide) as PCMs (phase change materials) prepared by vacuum impregnation method, have high thermal conductivity. The GO (graphene oxide) composite was used as supporting material to improve thermal conductivity and shape stabilization of composite PCM (phase change material). SEM (Scanning electronic microscope), FT-IR (Fourier transformation infrared spectroscope) and XRD (X-ray diffractometer) were applied to determine microstructure, chemical structure and crystalloid phase of palmitic acid/GO composites, respectively. DSC (Differential scanning calorimeter) test was done to investigate thermal properties which include melting and solidifying temperatures and latent heat. FT-IR analysis represented that the composite instruction of porous palmitic acid and GO were physical. The temperatures of melting, freezing and latent heats of the composite measured through DSC analysis were 60.45, 60.05 °C, 101.23 and 101.49 kJ/kg, respectively. Thermal cycling test showed that the form-stable composite PCM has good thermal reliability and chemical stability. Thermal conductivity of the composite PCM was improved by more than three times from 0.21 to 1.02. As a result, due to their acceptable thermal properties, good thermal reliability, chemical stability and great thermal conductivities, we can consider the prepared form-stable composites as highly conductive PCMs for thermal energy storage applications. - Highlights: • Novel composite PCM with high thermal conductivity and latent heat storage. • New thermal cycling test for thermal reliability of composite PCMs. • Increasing thermal conductivity of composite PCM with graphene oxide. • Increasing thermal stability of phase change material by adding graphene oxide

  8. Resveratrol Ameliorates Palmitate-Induced Inflammation in Skeletal Muscle Cells by Attenuating Oxidative Stress and JNK/NF-κB Pathway in a SIRT1-Independent Mechanism.

    Science.gov (United States)

    Sadeghi, Asie; Seyyed Ebrahimi, Shadi Sadat; Golestani, Abolfazl; Meshkani, Reza

    2017-09-01

    Resveratrol has been shown to exert anti-inflammatory and anti-oxidant effects in a variety of cell types, however, its role in prevention of inflammatory responses mediated by palmitate in skeletal muscle cells remains unexplored. In the present study, we investigated the effects of resveratrol on palmitate-induced inflammation and elucidated the underlying mechanisms in skeletal muscle cells. The results showed that palmitate significantly enhanced TNF-α and IL-6 mRNA expression and protein secretion from C2C12 cells at 12, 24, and 36 h treatments. Increased expression of cytokines was accompanied by an enhanced phosphorylation of JNK, P38, ERK1/2, and IKKα/IKKβ. In addition, JNK and P38 inhibitors could significantly attenuate palmitate-induced mRNA expression of TNF-α and IL-6, respectively, whereas NF-κB inhibitor reduced the expression of both cytokines in palmitate-treated cells. Resveratrol pretreatment significantly prevented palmitate-induced TNF-α and IL-6 mRNA expression and protein secretion in C2C12 cells. Importantly, pre-treatment of the cells with resveratrol completely abrogated the phosphorylation of ERK1/2, JNK, and IKKα/IKKβ in palmitate treated cells. The protection from palmitate-induced inflammation by resveratrol was accompanied by a decrease in the generation of reactive oxygen species (ROS). N-acetyl cysteine (NAC), a known scavenger of ROS, could protect palmitate-induced expression of TNF-α and IL-6. Furthermore, inhibition of SIRT1 by shRNA or sirtinol demonstrated that the anti-inflammatory effect of resveratrol in muscle cells is mediated through a SIRT1-independent mechanism. Taken together, these findings suggest that resveratrol may represent a promising therapy for prevention of inflammation in skeletal muscle cells. J. Cell. Biochem. 118: 2654-2663, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Preparation and thermal properties of form-stable palmitic acid/active aluminum oxide composites as phase change materials for latent heat storage

    International Nuclear Information System (INIS)

    Fang, Guiyin; Li, Hui; Cao, Lei; Shan, Feng

    2012-01-01

    Form-stable palmitic acid (PA)/active aluminum oxide composites as phase change materials were prepared by adsorbing liquid palmitic acid into active aluminum oxide. In the composites, the palmitic acid was used as latent heat storage materials, and the active aluminum oxide was used as supporting material. Fourier transformation infrared spectroscope (FT-IR), X-ray diffractometer (XRD) and scanning electronic microscope (SEM) were used to determine the chemical structure, crystalloid phase and microstructure of the composites, respectively. The thermal properties and thermal stability were investigated by a differential scanning calorimeter (DSC) and a thermogravimetry analyzer (TGA). The FT-IR analyses results indicated that there is no chemical interaction between the palmitic acid and active aluminum oxide. The SEM results showed that the palmitic acid was well adsorbed into porous network of the active aluminum oxide. The DSC results indicated that the composites melt at 60.25 °C with a latent heat of 84.48 kJ kg −1 and solidify at 56.86 °C with a latent heat of 78.79 kJ kg −1 when the mass ratio of the PA to active aluminum oxide is 0.9:1. Compared with that of the PA, the melting and solidifying time of the composites CPCM5 was reduced by 20.6% and 21.4% because of the increased heat transfer rate through EG addition. The TGA results showed that the active aluminum oxide can improve the thermal stability of the composites. -- Highlights: ► Form-stable PA/active aluminum oxide composites as PCMs were prepared. ► Chemical structure, crystalloid phase and microstructure of composites were determined. ► Thermal properties and thermal stability of the composites were investigated. ► Expanded graphite can improve thermal conductivity of the composites.

  10. The combination of ascorbic acid 6-palmitate and [Fe III 3(µ3-O)]7+ as a catalyst for the oxidation of unsaturated lipids

    NARCIS (Netherlands)

    Micciche, F.; Long, G.J.; Shahin, A.M.; Grandjean, F.; Ming, W.; Haveren, van J.; Linde, van der R.

    2007-01-01

    Recently, iron 2-ethylhexanoate (Fe-eh, 1) in combination with ascorbic acid 6-palmitate (AsA6p) has been reported as a good catalytic system for the oxidation of ethyl linoleate (EL), an unsaturated lipid. In response to the fascinating chemistry of this bio-inspired iron-based catalyst the

  11. Varying effects of calcium on the oxidation of palmitate and alpha-ketoglutarate in isolated rat liver mitochondria incubated in KCl-based and sucrose-based media.

    Science.gov (United States)

    Borrebaek, B; Dolva, K; Singh, B

    1984-01-01

    Isolated mitochondria from rat liver were incubated in the presence of [U-14C]palmitate, ATP, CoA, carnitine, EGTA (ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid) and varying amounts of calcium. When a KC1-based incubation medium was used, the oxidation of palmitate was inhibited when the concentration of free calcium was increased from about 0.1-10 microM. When a sucrose-based incubation medium was used, the basal rate of palmitate oxidation was about half of that observed with the KC1-medium and calcium had a stimulatory effect. With the KC1-medium the rate of oxygen consumption was inhibited by calcium with alpha-ketoglutarate as well as palmitate as the respiratory substrate. No inhibitory effect of calcium was observed with succinate or beta-hydroxybutyrate. With the KC1-medium and with alpha-ketoglutarate as the respiratory substrate, state 3 respiration but not state 4 respiration was inhibited by calcium. When the sucrose-medium was used, state 3 respiration was first inhibited by calcium, but this inhibition was gradually relieved and the respiratory rate finally became higher than it was before calcium addition.

  12. Additions of caffeic acid, ascorbyl palmitate or gamma-tocopherol to fish oil-enriched energy bars affect lipid oxidation differently

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

    2009-01-01

    The objectives of the study were to investigate the effects of caffeic acid, ascorbyl palmitate and gamma-tocopherol on protection of fish oil-enriched energy bars against lipid oxidation during storage for 10 weeks at room temperature. The lipophilic gamma-tocopherol reduced lipid oxidation during...... storage when added at a concentration above 440 mu g/g fish oil. However, the best antioxidative effect was observed when it was added at a concentration of 660 mu g/g fish oil. In contrast, prooxidative effects were observed when using either gamma-tocopherol at concentrations below 220 mu g/g fish oil......, or the hydrophilic caffeic acid, or the amphiphilic ascorbyl palmitate at concentrations of 75, 150 and 300 mu g/g fish oil. Prooxidative effects were observed as an increase in the formation of lipid hydroperoxides and volatile secondary oxidation products, as well as the development of rancid off...

  13. Oxidative stability of a heme iron-fortified bakery product: Effectiveness of ascorbyl palmitate and co-spray-drying of heme iron with calcium caseinate.

    Science.gov (United States)

    Alemán, Mercedes; Bou, Ricard; Tres, Alba; Polo, Javier; Codony, Rafael; Guardiola, Francesc

    2016-04-01

    Fortification of food products with iron is a common strategy to prevent or overcome iron deficiency. However, any form of iron is a pro-oxidant and its addition will cause off-flavours and reduce a product's shelf life. A highly bioavailable heme iron ingredient was selected to fortify a chocolate cream used to fill sandwich-type cookies. Two different strategies were assessed for avoiding the heme iron catalytic effect on lipid oxidation: ascorbyl palmitate addition and co-spray-drying of heme iron with calcium caseinate. Oxidation development and sensory acceptability were monitored in the cookies over one-year of storage at room temperature in the dark. The addition of ascorbyl palmitate provided protection against oxidation and loss of tocopherols and tocotrienols during the preparation of cookies. In general, ascorbyl palmitate, either alone or in combination with the co-spray-dried heme iron, prevented primary oxidation and hexanal formation during storage. The combination of both strategies resulted in cookies that were acceptable from a sensory point of view after 1year of storage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Effect of temperature on thermal oxidation of palmitic acid studied by combination of EPR spin trapping technique and SPME-GC-MS/MS.

    Science.gov (United States)

    Chen, Hongjian; Wang, Yong; Cao, Peirang; Liu, Yuanfa

    2017-11-01

    Effect of temperatures on thermal oxidation of palmitic acid was studied by the combination of EPR and GC-MS/MS. DMPO was used as the spin trap. The experimental spectrum was simulated with alkyl and alkoxyl spin adducts. Total amount of spins, a parameter to indicate radical concentrations, detected at 180°C was nearly 10 times higher than that at 175°C. Besides, total amounts of spins detected at 180°C decreased rapidly because of the reaction between radical adducts and newly formed radicals. Signal intensities of alkyl radical adducts increased rapidly from 0.405 to 4.785 from 175°C to 180°C. Besides, more palmitic acid degraded to oxidized compounds from 175°C to 180°C than that of other temperature ranges. The C-C linkages between carbons 2 to 6 were easier to be oxidized at 180°C. The results all implied that oxidation rates of palmitic acid samples increased rapidly from 175°C to 180°C. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Inhibition of bacterial growth by iron oxide nanoparticles with and without attached drug: Have we conquered the antibiotic resistance problem?

    Science.gov (United States)

    Armijo, Leisha M.; Jain, Priyanka; Malagodi, Angelina; Fornelli, F. Zuly; Hayat, Allison; Rivera, Antonio C.; French, Michael; Smyth, Hugh D. C.; Osiński, Marek

    2015-03-01

    Pseudomonas aeruginosa is among the top three leading causative opportunistic human pathogens, possessing one of the largest bacterial genomes and an exceptionally large proportion of regulatory genes therein. It has been known for more than a decade that the size and complexity of the P. aeruginosa genome is responsible for the adaptability and resilience of the bacteria to include its ability to resist many disinfectants and antibiotics. We have investigated the susceptibility of P. aeruginosa bacterial biofilms to iron oxide (magnetite) nanoparticles (NPs) with and without attached drug (tobramycin). We also characterized the susceptibility of zero-valent iron NPs, which are known to inactivate microbes. The particles, having an average diameter of 16 nm were capped with natural alginate, thus doubling the hydrodynamic size. Nanoparticle-drug conjugates were produced via cross-linking drug and alginate functional groups. Drug conjugates were investigated in the interest of determining dosage, during these dosage-curve experiments, NPs unbound to drug were tested in cultures as a negative control. Surprisingly, we found that the iron oxide NPs inhibited bacterial growth, and thus, biofilm formation without the addition of antibiotic drug. The inhibitory dosages of iron oxide NPs were investigated and the minimum inhibitory concentrations are presented. These findings suggest that NP-drug conjugates may overcome the antibiotic drug resistance common in P. aeruginosa infections.

  16. Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Jun; Jiang, Li; Lue, Qingguo; Ke, Linqiu [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China); Li, Xiaoyu [State Key Laboratory of Oral Diseases, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, Sichuan 610041 (China); Tong, Nanwei, E-mail: buddyjun@hotmail.com [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China)

    2010-01-15

    Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

  17. Synthesis and preliminary evaluation of {sup 18}F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation

    Energy Technology Data Exchange (ETDEWEB)

    DeGrado, Timothy R. E-mail: trd@petsparc.mc.duke.edu; Wang Shuyan; Holden, James E.; Nickles, R. Jerome; Taylor, Michael; Stone, Charles K

    2000-04-01

    Interest remains strong for the development of a noninvasive technique for assessment of regional fatty acid oxidation rate in the myocardium. {sup 18}F-labeled 4-thia palmitate (FTP, 16-[{sup 18}F]fluoro-4-thia-hexadecanoic acid) has been synthesized and preliminarily evaluated as a metabolically trapped probe of myocardial fatty acid oxidation for positron emission tomography (PET). The radiotracer is synthesized by Kryptofix 2.2.2/K{sub 2}CO{sub 3} assisted nucleophilic radiofluorination of an iodo-ester precursor, followed by alkaline hydrolysis and by purification by reverse phase high performance liquid chromatography. Biodistribution studies in rats showed high uptake and long retention of FTP in heart, liver, and kidneys consistent with relatively high fatty acid oxidation rates in these tissues. Inhibition of carnitine palmitoyl-transferase-I caused an 80% reduction in myocardial uptake, suggesting the dependence of trapping on the transport of tracer into the mitochondrion. Experiments with perfused rat hearts showed that the estimates of the fractional metabolic trapping rate (FR) of FTP tracked inhibition of oxidation rate of palmitate with hypoxia, whereas the FR of the 6-thia analog 17-[{sup 18}F]fluoro-6-thia-heptadecanoic acid was insensitive to hypoxia. In vivo defluorination of FTP in the rat was evidenced by bone uptake of radioactivity. A PET imaging study with FTP in normal swine showed excellent myocardial images, prolonged myocardial retention, and no bone uptake of radioactivity up to 3 h, the last finding suggesting a species dependence for defluorination of the omega-labeled fatty acid. The results support further investigation of FTP as a potential PET tracer for assessing regional fatty acid oxidation rate in the human myocardium.

  18. Synthesis and preliminary evaluation of 18F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation

    International Nuclear Information System (INIS)

    DeGrado, Timothy R.; Wang Shuyan; Holden, James E.; Nickles, R. Jerome; Taylor, Michael; Stone, Charles K.

    2000-01-01

    Interest remains strong for the development of a noninvasive technique for assessment of regional fatty acid oxidation rate in the myocardium. 18 F-labeled 4-thia palmitate (FTP, 16-[ 18 F]fluoro-4-thia-hexadecanoic acid) has been synthesized and preliminarily evaluated as a metabolically trapped probe of myocardial fatty acid oxidation for positron emission tomography (PET). The radiotracer is synthesized by Kryptofix 2.2.2/K 2 CO 3 assisted nucleophilic radiofluorination of an iodo-ester precursor, followed by alkaline hydrolysis and by purification by reverse phase high performance liquid chromatography. Biodistribution studies in rats showed high uptake and long retention of FTP in heart, liver, and kidneys consistent with relatively high fatty acid oxidation rates in these tissues. Inhibition of carnitine palmitoyl-transferase-I caused an 80% reduction in myocardial uptake, suggesting the dependence of trapping on the transport of tracer into the mitochondrion. Experiments with perfused rat hearts showed that the estimates of the fractional metabolic trapping rate (FR) of FTP tracked inhibition of oxidation rate of palmitate with hypoxia, whereas the FR of the 6-thia analog 17-[ 18 F]fluoro-6-thia-heptadecanoic acid was insensitive to hypoxia. In vivo defluorination of FTP in the rat was evidenced by bone uptake of radioactivity. A PET imaging study with FTP in normal swine showed excellent myocardial images, prolonged myocardial retention, and no bone uptake of radioactivity up to 3 h, the last finding suggesting a species dependence for defluorination of the omega-labeled fatty acid. The results support further investigation of FTP as a potential PET tracer for assessing regional fatty acid oxidation rate in the human myocardium

  19. Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate β-oxidation in symptomatic patients with ACADS gene susceptibility variants.

    Science.gov (United States)

    Dessein, Anne-Frédérique; Fontaine, Monique; Joncquel-Chevalier Curt, Marie; Briand, Gilbert; Sechter, Claire; Mention-Mulliez, Karine; Dobbelaere, Dries; Douillard, Claire; Lacour, Arnaud; Redonnet-Vernhet, Isabelle; Lamireau, Delphine; Barth, Magalie; Minot-Myhié, Marie-Christine; Kuster, Alice; de Lonlay, Pascale; Gregersen, Niels; Acquaviva, Cécile; Vianey-Saban, Christine; Vamecq, Joseph

    2017-08-01

    Despite ACADS (acyl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C>T and c.625G>A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics. Whether or not, they might affect overall fatty acid β-oxidation still remains, however, unclear. De novo biosynthesis of acylcarnitines by whole blood samples incubated with deuterated palmitate (16- 2 H 3 ,15- 2 H 2 -palmitate) is suitable as a fluxomic exploration to distinguish between normal and disrupted β-oxidation, abnormal profiles and ratios of acylcarnitines with different chain-lengths being indicative of the site for enzymatic blockade. Determinations in 301 control subjects of ratios between deuterated butyrylcarnitine and sum of deuterated C2 to C14 acylcarnitines served here as reference values to state specifically functional SCAD impairment in patients addressed for clinical and/or biological suspicion of a β-oxidation disorder. Functional SCAD impairment was found in 39 patients. The 27 patients accepting subsequent gene studies were all positive for ACADS mutations. Twenty-six of 27 patients were positive for c.625G>A variant. Twenty-three of 27 patients harbored susceptibility variants as sole ACADS alterations (18 homozygous and 3 heterozygous for c.625G>A, 2 compound heterozygous for c.625G>A/c.511C>T). Our present fluxomic assessment of SCAD suggests a link between ACADS susceptibility variants and abnormal β-oxidation consistent with known altered kinetics of these variants. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. ORIGIN OF PALMITIC ACID CARBON IN PALMITATES FORMED FROM HEXADECANE-1-C14 AND TETRADECANE-1-C14 BY MICROCOCCUS CERIFICANS

    Science.gov (United States)

    Finnerty, W. R.; Kallio, R. E.

    1964-01-01

    Finnerty, W. R. (University of Iowa, Iowa City), and R. E. Kallio. Origin of palmitic acid carbon in palmitates formed from hexadecane-1-C14 and tetradecane-1-C14 by Micrococcus cerificans. J. Bacteriol. 87:1261–1265. 1964.—Degradation of the palmitic acid moiety of cetyl palmitate and myristyl palmitate formed from hexadecane-1-C14 and tetradecane-1-C14 by Micrococcus cerificans was carried out. The patterns of C14 labeling in palmitic acid from cetyl palmitate showed that hexadecane is oxidized at the C1 position, and cetyl alcohol and palmitic acid thus formed are directly esterified. Palmitic acid arising from tetradecane and esterified to tetradecanol appeared to have been synthesized by the addition of two carbon atoms to an existing 14-carbon atom skeleton. Considerable mixing of C14 occurred in the C1 and C2 positions of palmitic acid thus synthesized. PMID:14188700

  1. CPT1α over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

    International Nuclear Information System (INIS)

    Jambor de Sousa, Ulrike L.; Koss, Michael D.; Fillies, Marion; Gahl, Anja; Scheeder, Martin R.L.; Cardoso, M. Cristina; Leonhardt, Heinrich; Geary, Nori; Langhans, Wolfgang; Leonhardt, Monika

    2005-01-01

    To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1α (CPT1α). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1α transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1α over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1α over-expressing cells in a concentration-dependent manner. Both, PA and CPT1α over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1α, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo

  2. Oxidation of linoleic and palmitic acid in pre-hibernating and hibernating common noctule bats revealed by 13C breath testing.

    Science.gov (United States)

    Rosner, Elisabeth; Voigt, Christian C

    2018-02-19

    Mammals fuel hibernation by oxidizing saturated and unsaturated fatty acids from triacylglycerols in adipocytes, yet the relative importance of these two categories as an oxidative fuel may change during hibernation. We studied the selective use of fatty acids as an oxidative fuel in noctule bats ( Nyctalus noctula ). Pre-hibernating noctule bats that were fed 13 C-enriched linoleic acid (LA) showed 12 times higher tracer oxidation rates compared with conspecifics fed 13 C-enriched palmitic acid (PA). After this experiment, we supplemented the diet of bats with the same fatty acids on five subsequent days to enrich their fat depots with the respective tracer. We then compared the excess 13 C enrichment (excess atom percentage, APE) in breath of bats for torpor and arousal events during early and late hibernation. We observed higher APE values in breath of bats fed 13 C-enriched LA than in bats fed 13 C-enriched PA for both states (torpor and arousal), and also for both periods. Thus, hibernating bats selectively oxidized endogenous LA instead of PA, probably because of faster transportation rates of polyunsaturated fatty acids compared with saturated fatty acids. We did not observe changes in APE values in the breath of torpid animals between early and late hibernation. Skin temperature of torpid animals increased by 0.7°C between early and late hibernation in bats fed PA, whereas it decreased by -0.8°C in bats fed LA, highlighting that endogenous LA may fulfil two functions when available in excess: serving as an oxidative fuel and supporting cell membrane functionality. © 2018. Published by The Company of Biologists Ltd.

  3. Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

    International Nuclear Information System (INIS)

    Thomas, G.; Pepin, D.; Loriette, C.; Chambaz, J.; Bereziat, G.; Vidal, M.; Apparu, M.; Coornaert, S.

    1989-01-01

    The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be β oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be β oxidized only after an initial α oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me 2 ) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me 2 ) which cannot be β oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1- 14 C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethyl-branched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[ 125 I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1- 14 C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched palmitic acids were found in hepatocyte or secreted phospholipids as compared with palmitic acid. (orig.)

  4. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells.

    Science.gov (United States)

    Yeh, Lee-Chuan C; Ford, Jeffery J; Lee, John C; Adamo, Martin L

    2014-07-18

    Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Paliperidone palmitate-induced sialorrhoea

    Directory of Open Access Journals (Sweden)

    Cengiz Cengisiz

    2016-03-01

    Full Text Available Extrapyramidal, metabolic, and cardiac side effects were reported for atypical antipsychotics; although a few resources show paliperidone-induced sialorrhea, there are no resources that show paliperidone palmitate-induced sialorrhea. In this paper, we present the paliperidone palmitate-induced sialorrhea side effects of a patient who applied on our clinic [Cukurova Med J 2016; 41(0.100: 8-13

  6. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Lee-Chuan C.; Ford, Jeffery J. [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); Lee, John C. [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX (United States); Adamo, Martin L., E-mail: adamo@biochem.uthscsa.edu [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX (United States)

    2014-07-18

    Highlights: • Palmitate inhibits osteoblast differentiation. • Fatty acid synthase. • PPARγ. • Acetyl Co-A carboxylase inhibitor TOFA. • Fetal rat calvarial cell culture. - Abstract: Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects.

  7. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells

    International Nuclear Information System (INIS)

    Yeh, Lee-Chuan C.; Ford, Jeffery J.; Lee, John C.; Adamo, Martin L.

    2014-01-01

    Highlights: • Palmitate inhibits osteoblast differentiation. • Fatty acid synthase. • PPARγ. • Acetyl Co-A carboxylase inhibitor TOFA. • Fetal rat calvarial cell culture. - Abstract: Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects

  8. Enzymatic Cellulose Palmitate Synthesis Using Immobilized Lipase

    Directory of Open Access Journals (Sweden)

    Anna Roosdiana

    2017-06-01

    Full Text Available Bacterial cellulose can be modified by esterification using palmitic acid and Mucor miehei  lipase  as catalyst. The purpose of this research was to determine the optimum conditions of esterification reaction of cellulose and palmitic acid . The esterification reaction was carried out at the time variation  of  6, 12, 18, 24 and 30 hours and the mass ratio of cellulose: palmitic acid (1: 11: 2, 1: 3, 1: 4, 1: 5,1:6 at 50 °C. The   cellulose palmitate  was examined  its  physical and chemical properties by using FTIR spectrophotometer, XRD, bubble point test and saponification  apparatus. The results showed that the optimum reaction time of esterification reaction of cellulose and palmitic acid occurred within 24 hours and the mass ratio of cellulose: palmitic acid was 1: 3 resulting in DS of  0.376 with  swelling index of 187 %, crystallinity index of 61.95%,  and Φ porous of 2.40 μm. Identification of functional groups using FTIR spectrophotometer showed that C=O ester group  was observed at 1737.74 cm-1 and strengthened  by  the appearance of C-O ester peak at 1280 cm-1. The conclusion of this study is reaction time and reactant ratio influence significantly the DS of cellulose ester.

  9. Comparison of palmitic acid kinetics during glucose or ketone body infusions

    Energy Technology Data Exchange (ETDEWEB)

    Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

    1986-03-05

    Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of (1-/sup 14/C) palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat.

  10. Comparison of palmitic acid kinetics during glucose or ketone body infusions

    International Nuclear Information System (INIS)

    Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

    1986-01-01

    Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of [1- 14 C] palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat

  11. Conquering Credibility for Monetary Policy Under Sticky Confidence

    Directory of Open Access Journals (Sweden)

    Jaylson Jair da Silveira

    2015-06-01

    Full Text Available We derive a best-reply monetary policy when the confidence by price setters on the monetary authority’s commitment to price level targeting may be both incomplete and sticky. We find that complete confidence (or full credibility is not a necessary condition for the achievement of a price level target even when heterogeneity in firms’ price level expectations is endogenously time-varying and may emerge as a long-run equilibrium outcome. In fact, in the absence of exogenous perturbations to the dynamic of confidence building, it is the achievement of a price level target for long enough that, due to stickiness in the state of confidence, rather ensures the conquering of full credibility. This result has relevant implications for the conduct of monetary policy in pursuit of price stability. One implication is that setting a price level target matters more as a means to provide monetary policy with a sharper focus on price stability than as a device to conquer credibility. As regards the conquering of credibility for monetary policy, it turns out that actions speak louder than words, as the continuing achievement of price stability is what ultimately performs better as a confidence-building device.

  12. Learning strategies of public health nursing students: conquering operational space.

    Science.gov (United States)

    Hjälmhult, Esther

    2009-11-01

    To develop understanding of how public health nursing students learn in clinical practice and explore the main concern for the students and how they acted to resolve this main concern. How professionals perform their work directly affects individuals, but knowledge is lacking in understanding how learning is connected to clinical practice in public health nursing and in other professions. Grounded theory. Grounded theory was used in gathering and analysing data from 55 interviews and 108 weekly reports. The participants were 21 registered nurses who were public health nursing students. The grounded theory of conquering operational space explains how the students work to resolve their main concern. A social process with three identified phases, positioning, involving and integrating, was generated from analysing the data. Their subcategories and dimensions are related to the student role, relations with a supervisor, student activity and the consequences of each phase. Public health nursing students had to work towards gaining independence, often working against 'the system' and managing the tension by taking a risk. Many of them lost, changed and expanded their professional identity during practical placements. Public health nursing students' learning processes in clinical training are complex and dynamic and the theory of 'Conquering operational space' can assist supervisors in further developing their role in relation to guiding students in practice. Relationships are one key to opening or closing access to situations of learning and directly affect the students' achievement of mastering. The findings are pertinent to supervisors and educators as they prepare students for practice. Good relationships are elementary and supervisors can support students in conquering the field by letting students obtain operational space and gain independence. This may create a dialectical process that drives learning forward.

  13. Divide and conquer approach to quantum Hamiltonian simulation

    Science.gov (United States)

    Hadfield, Stuart; Papageorgiou, Anargyros

    2018-04-01

    We show a divide and conquer approach for simulating quantum mechanical systems on quantum computers. We can obtain fast simulation algorithms using Hamiltonian structure. Considering a sum of Hamiltonians we split them into groups, simulate each group separately, and combine the partial results. Simulation is customized to take advantage of the properties of each group, and hence yield refined bounds to the overall simulation cost. We illustrate our results using the electronic structure problem of quantum chemistry, where we obtain significantly improved cost estimates under very mild assumptions.

  14. Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.

    Science.gov (United States)

    Jung, Jong Gab; Choi, Sung-E; Hwang, Yoon-Jung; Lee, Sang-A; Kim, Eun Kyoung; Lee, Min-Seok; Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Kang, Yup; Lee, Kwan-Woo

    2011-10-15

    Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and α-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest that pyruvate depletion plays a critical role in PIGR and PIIGU; thus, pyruvate supplementation may help prevent obesity-induced insulin resistance in muscle cells. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Covalent modification of platelet proteins by palmitate

    International Nuclear Information System (INIS)

    Muszbek, L.; Laposata, M.

    1989-01-01

    Covalent attachment of fatty acid to proteins plays an important role in association of certain proteins with hydrophobic membrane structures. In platelets, the structure of many membrane glycoproteins (GPs) has been examined in detail, but the question of fatty acid acylation of platelet proteins has not been addressed. In this study, we wished to determine (a) whether platelet proteins could be fatty acid acylated; and, if so, (b) whether these modified proteins were present in isolated platelet membranes and cytoskeletal fractions; and (c) if the pattern of fatty acid acylated proteins changed on stimulation of the platelets with the agonist thrombin. We observed that in platelets allowed to incorporate 3H-palmitate, a small percentage (1.37%) of radioactivity incorporated into the cells became covalently bound to protein. Selective cleavage of thioester, thioester plus O-ester, and amide-linked 3H-fatty acids from proteins, and their subsequent analysis by high-performance liquid chromatography (HPLC) indicated that the greatest part of 3H-fatty acid covalently bound to protein was thioester-linked 3H-palmitate. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography, at least ten major radiolabeled proteins were detected. Activation of platelets by thrombin greatly increased the quantity of 3H-palmitoylated proteins associated with the cytoskeleton. Nearly all radiolabeled proteins were recovered in the membrane fraction, indicating that these proteins are either integral or peripheral membrane proteins or proteins tightly associated to membrane constituents. Components of the GPIIb-IIIa complex were not palmitoylated. Thus, platelet proteins are significantly modified posttranslationally by 3H-palmitate, and incorporation of palmitoylated proteins into the cytoskeleton is a prominent component of the platelet response to thrombin stimulation

  16. Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis.

    Science.gov (United States)

    Pillon, Nicolas J; Azizi, Paymon M; Li, Yujin E; Liu, Jun; Wang, Changsen; Chan, Kenny L; Hopperton, Kathryn E; Bazinet, Richard P; Heit, Bryan; Bilan, Philip J; Lee, Warren L; Klip, Amira

    2015-07-01

    Obesity is associated with inflammation and immune cell recruitment to adipose tissue, muscle and intima of atherosclerotic blood vessels. Obesity and hyperlipidemia are also associated with tissue insulin resistance and can compromise insulin delivery to muscle. The muscle/fat microvascular endothelium mediates insulin delivery and facilitates monocyte transmigration, yet its contribution to the consequences of hyperlipidemia is poorly understood. Using primary endothelial cells from human adipose tissue microvasculature (HAMEC), we investigated the effects of physiological levels of fatty acids on endothelial inflammation and function. Expression of cytokines and adhesion molecules was measured by RT-qPCR. Signaling pathways were evaluated by pharmacological manipulation and immunoblotting. Surface expression of adhesion molecules was determined by immunohistochemistry. THP1 monocyte interaction with HAMEC was measured by cell adhesion and migration across transwells. Insulin transcytosis was measured by total internal reflection fluorescence microscopy. Palmitate, but not palmitoleate, elevated the expression of IL-6, IL-8, TLR2 (Toll-like receptor 2), and intercellular adhesion molecule 1 (ICAM-1). HAMEC had markedly low fatty acid uptake and oxidation, and CD36 inhibition did not reverse the palmitate-induced expression of adhesion molecules, suggesting that inflammation did not arise from palmitate uptake/metabolism. Instead, inhibition of TLR4 to NF-κB signaling blunted palmitate-induced ICAM-1 expression. Importantly, palmitate-induced surface expression of ICAM-1 promoted monocyte binding and transmigration. Conversely, palmitate reduced insulin transcytosis, an effect reversed by TLR4 inhibition. In summary, palmitate activates inflammatory pathways in primary microvascular endothelial cells, impairing insulin transport and increasing monocyte transmigration. This behavior may contribute in vivo to reduced tissue insulin action and enhanced tissue

  17. Palmitate and insulin synergistically induce IL-6 expression in human monocytes

    Directory of Open Access Journals (Sweden)

    Lumpkin Charles K

    2010-11-01

    Full Text Available Abstract Background Insulin resistance is associated with a proinflammatory state that promotes the development of complications such as type 2 diabetes mellitus (T2DM and atherosclerosis. The metabolic stimuli that initiate and propagate proinflammatory cytokine production and the cellular origin of proinflammatory cytokines in insulin resistance have not been fully elucidated. Circulating proinflammatory monocytes show signs of enhanced inflammation in obese, insulin resistant subjects and are thus a potential source of proinflammatory cytokine production. The specific, circulating metabolic factors that might stimulate monocyte inflammation in insulin resistant subjects are poorly characterized. We have examined whether saturated nonesterified fatty acids (NEFA and insulin, which increase in concentration with developing insulin resistance, can trigger the production of interleukin (IL-6 and tumor necrosis factor (TNF-α in human monocytes. Methods Messenger RNA and protein levels of the proinflammatory cytokines IL-6 and TNF-α were measured by quantitative real-time PCR (qRT-PCR and Luminex bioassays. Student's t-test was used with a significance level of p Results Esterification of palmitate with coenzyme A (CoA was necessary, while β-oxidation and ceramide biosynthesis were not required, for the induction of IL-6 and TNF-α in THP-1 monocytes. Monocytes incubated with insulin and palmitate together produced more IL-6 mRNA and protein, and more TNF-α protein, compared to monocytes incubated with palmitate alone. Incubation of monocytes with insulin alone did not affect the production of IL-6 or TNF-α. Both PI3K-Akt and MEK/ERK signalling pathways are important for cytokine induction by palmitate. MEK/ERK signalling is necessary for synergistic induction of IL-6 by palmitate and insulin. Conclusions High levels of saturated NEFA, such as palmitate, when combined with hyperinsulinemia, may activate human monocytes to produce

  18. Fabrication of shape memory natural rubber using palmitic acid

    Directory of Open Access Journals (Sweden)

    Jeff Sze-Hua Wee

    2017-10-01

    Full Text Available This paper investigates the practicability of fabricating a shape memory natural rubber with the use of palmitic acid as the swelling agent. Strips of natural rubber samples were swollen in molten palmitic acid at 75 °C. Equilibrium swelling of natural rubber with palmitic acid was found to occur at approximately 50 min of swelling time. Under cooling effect, the palmitic acid crystallized to form a percolated crystalline platelet network. These networks allow fabricated shape memory natural rubber (SMNR to deform and recover its shape at a temperature above the melting point of palmitic acid. Under controlled uniaxial stress, the natural rubber sample with 0 parts per hundred rubber (phr carbon black loading exhibits fixity and recovery of 80 ± 10%. Motivation of this research is primarily on practicability of palmitic acid to be used as a swelling agent for shape memory properties. Results show that palmitic acid is a relatively good swelling agent to induce shape memory properties into natural rubber.

  19. Anti-inflammatory and antifibrotic effects of methyl palmitate

    International Nuclear Information System (INIS)

    El-Demerdash, Ebtehal

    2011-01-01

    Methyl palmitate (MP) has been shown earlier to inhibit Kupffer cells and rat peritoneal macrophages. To evaluate the potential of MP to inhibit the activation of other macrophages, RAW cells (macrophages of alveolar origin) were treated with varying concentrations of MP (0.25, 0.5, 1 mM). Assessment of cytotoxicity using MTT assay revealed that 0.25 and 0.5 mM are not toxic to RAW cells. MP was able to inhibit the phagocytic function of RAW cells. Treatment of cells with MP 24 hours prior to LPS stimulation significantly decreased nitric oxide release and altered the pattern of cytokines release; there was a significant decrease in TNF-α and a significant increase in IL-10 compared to the controls. However, there is a non-significant change in IL-6 level. Furthermore, phosphorylation of inhibitory kappa B (IκBα) protein was significantly decreased in RAW cells treated with 0.5 mM MP after LPS stimulation. Based upon the in-vitro results, it was examined whether MP treatment will be effective in preventing bleomycin-induced lung inflammation and fibrosis in-vivo. Bleomycin given by itself caused destruction of the lung architecture characterized by pulmonary fibrosis with collapse of air alveoli and emphysematous. Bleomycin induced a significant increase in hydroxyproline level and activated NF-κB, p65 expression in the lung. MP co-treatment significantly ameliorated bleomycin effects. These results suggest that MP has a potential of inhibiting macrophages in general. The present study demonstrated for the first time that MP has anti-inflammatory and antifibrotic effect that could be through NF-kB inhibition. Thus MP like molecule could be a promising anti-inflammatory and antifibrotic drug. - Research highlights: →Methyl palmitate is a universal macrophage inhibitor. →It could be a promising nucleus of anti-inflammatory and antifibrotic drugs. →The underlying mechanism of these effects could be through NF-kB inhibition.

  20. Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate.

    Science.gov (United States)

    Liu, Ning; Wu, Jichao; Zhang, Linxue; Gao, Zhaopeng; Sun, Yu; Yu, Miao; Zhao, Yajun; Dong, Shiyun; Lu, Fanghao; Zhang, Weihua

    2017-12-01

    Endothelial cell dysfunction is one of the main reasons for type II diabetes vascular complications. Hydrogen sulphide (H 2 S) has antioxidative effect, but its regulation on mitochondrial dynamics and mitophagy in aortic endothelial cells under hyperglycaemia and hyperlipidaemia is unclear. Rat aortic endothelial cells (RAECs) were treated with 40 mM glucose and 200 μM palmitate to imitate endothelium under hyperglycaemia and hyperlipidaemia, and 100 μM NaHS was used as an exogenous H 2 S donor. Firstly, we demonstrated that high glucose and palmitate decreased H 2 S production and CSE expression in RAECs. Then, the antioxidative effect of H 2 S was proved in RAECs under high glucose and palmitate to reduce mitochondrial ROS level. We also showed that exogenous H 2 S inhibited mitochondrial apoptosis in RAECs under high glucose and palmitate. Using Mito Tracker and transmission electron microscopy assay, we revealed that exogenous H 2 S decreased mitochondrial fragments and significantly reduced the expression of p-Drp-1/Drp-1 and Fis1 compared to high-glucose and high-palmitate group, whereas it increased mitophagy by transmission electron microscopy assay. We demonstrated that exogenous H 2 S facilitated Parkin recruited by PINK1 by immunoprecipitation and immunostaining assays and then ubiquitylated mitofusin 2 (Mfn2), which illuminated the mechanism of exogenous H 2 S on mitophagy. Parkin siRNA suppressed the expression of Mfn2, Nix and LC3B, which revealed that it eliminated mitophagy. In summary, exogenous H 2 S could protect RAECs against apoptosis under high glucose and palmitate by suppressing oxidative stress, decreasing mitochondrial fragments and promoting mitophagy. Based on these results, we proposed a new mechanism of H 2 S on protecting endothelium, which might provide a new strategy for type II diabetes vascular complication. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for

  1. Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium

    International Nuclear Information System (INIS)

    Schwaiger, M.; Schelbert, H.R.; Keen, R.; Vinten-Johansen, J.; Hansen, H.; Selin, C.; Barrio, J.; Huang, S.C.; Phelps, M.E.

    1985-01-01

    Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury

  2. Systemic treatment of seborrheic dermatitis with retinol palmitate

    OpenAIRE

    O. V. Kalinina; V. I. Albanova; T. A. Belousova; V. I. Nozdrin

    2014-01-01

    The goal of the study. Evaluating of the effectiveness of treatment of men with a diagnosis «Seborrheic dermatitis of the scalp» by the system using of retinol palmitate. Material and methods. 36 patients every day for 2 months received overnight per os 200000 ME of retinol palmitate, and in the comparison group (39 people) antiseborrheic shampoos have been used. The dynamics of severity of skin oiliness, pruritis, erythema, peeling, infiltration, excoriations has been evaluated in points. Be...

  3. Death: a foe to be conquered? Questioning the paradigm.

    Science.gov (United States)

    Gellie, Anthea; Mills, Amber; Levinson, Michele; Stephenson, Gemma; Flynn, Eleanor

    2015-01-01

    There are few certainties in life-death is one of them. Yet death is often thought of today as the 'loss of the battle' against illness, where in traditional societies it was the natural, meaningful, end to life. Medical knowledge and technologies have extended the possibilities of medical care and increased our life span. People living in most developed countries today can expect to survive to an advanced age and die in hospital rather than at home as in the past. Owing to these and other historical, cultural and social factors, our views on death have been skewed. Medical technology provides an arsenal of weapons to launch against death and the 'war against disease' has entrenched itself in medical philosophy. We now primarily experience death through the lens of a camera. Representations of 'death as spectacle' distort our perceptions and leave us ill-prepared for the reality. Additionally, death as a natural consequence of life has become much less visible than it was in the past due to our longer life expectancies and lack of infectious disease. The continued thrust for treatment, wedded with a failure to recognise the dying process, can rob individuals of a peaceful, dignified death. Progress being made in Advance Care Planning and palliative care is limited by the existing paradigm of death as a 'foe to be conquered'. It is time for a shift in this paradigm. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Spike sorting for polytrodes: a divide and conquer approach

    Directory of Open Access Journals (Sweden)

    Nicholas V. Swindale

    2014-02-01

    Full Text Available In order to determine patterns of neural activity, spike signals recorded by extracellular electrodes have to be clustered (sorted with the aim of ensuring that each cluster represents all the spikes generated by an individual neuron. Many methods for spike sorting have been proposed but few are easily applicable to recordings from polytrodes which may have 16 or more recording sites. As with tetrodes, these are spaced sufficiently closely that signals from single neurons will usually be recorded on several adjacent sites. Although this offers a better chance of distinguishing neurons with similarly shaped spikes, sorting is difficult in such cases because of the high dimensionality of the space in which the signals must be classified. This report details a method for spike sorting based on a divide and conquer approach. Clusters are initially formed by assigning each event to the channel on which it is largest. Each channel-based cluster is then sub-divided into as many distinct clusters as possible. These are then recombined on the basis of pairwise tests into a final set of clusters. Pairwise tests are also performed to establish how distinct each cluster is from the others. A modified gradient ascent clustering (GAC algorithm is used to do the clustering. The method can sort spikes with minimal user input in times comparable to real time for recordings lasting up to 45 minutes. Our results illustrate some of the difficulties inherent in spike sorting, including changes in spike shape over time. We show that some physiologically distinct units may have very similar spike shapes. We show that RMS measures of spike shape similarity are not sensitive enough to discriminate clusters that can otherwise be separated by principal components analysis. Hence spike sorting based on least-squares matching to templates may be unreliable. Our methods should be applicable to tetrodes and scaleable to larger multi-electrode arrays (MEAs.

  5. Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models

    Energy Technology Data Exchange (ETDEWEB)

    Saeed, Noha M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); El-Demerdash, Ebtehal [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); Abdel-Rahman, Hanaa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); Algandaby, Mardi M. [Department of Biology (Botany), Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Al-Abbasi, Fahad A. [Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Abdel-Naim, Ashraf B., E-mail: abnaim@pharma.asu.edu.eg [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-10-01

    Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS. Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ► Efficacy of MP and EP in combating inflammation was displayed in several models. ► MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ► MP and EP decreased TNF-α and IL-6 levels in experimental endotoxemia. ► MP and EP reduced NF-κB expression and histological changes in rat liver and lung. ► MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.

  6. Knowledge Reduction Based on Divide and Conquer Method in Rough Set Theory

    Directory of Open Access Journals (Sweden)

    Feng Hu

    2012-01-01

    Full Text Available The divide and conquer method is a typical granular computing method using multiple levels of abstraction and granulations. So far, although some achievements based on divided and conquer method in the rough set theory have been acquired, the systematic methods for knowledge reduction based on divide and conquer method are still absent. In this paper, the knowledge reduction approaches based on divide and conquer method, under equivalence relation and under tolerance relation, are presented, respectively. After that, a systematic approach, named as the abstract process for knowledge reduction based on divide and conquer method in rough set theory, is proposed. Based on the presented approach, two algorithms for knowledge reduction, including an algorithm for attribute reduction and an algorithm for attribute value reduction, are presented. Some experimental evaluations are done to test the methods on uci data sets and KDDCUP99 data sets. The experimental results illustrate that the proposed approaches are efficient to process large data sets with good recognition rate, compared with KNN, SVM, C4.5, Naive Bayes, and CART.

  7. Determination of Fatty Acid Metabolism with Dynamic [11C]Palmitate Positron Emission Tomography of Mouse Heart In Vivo

    Directory of Open Access Journals (Sweden)

    Yinlin Li

    2015-09-01

    Full Text Available The goal of this study was to establish a quantitative method for measuring fatty acid (FA metabolism with partial volume (PV and spill-over (SP corrections using dynamic [11C]palmitate positron emission tomographic (PET images of mouse heart in vivo. Twenty-minute dynamic [11C]palmitate PET scans of four 18- to 20-week-old male C57BL/6 mice under isoflurane anesthesia were performed using a Focus F-120 PET scanner. A model-corrected blood input function, by which the input function with SP and PV corrections and the metabolic rate constants (k1–k5 are simultaneously estimated from the dynamic [11C]palmitate PET images of mouse hearts in a four-compartment tracer kinetic model, was used to determine rates of myocardial fatty acid oxidation (MFAO, myocardial FA esterification, myocardial FA use, and myocardial FA uptake. The MFAO thus measured in C57BL/6 mice was 375.03 ± 43.83 nmol/min/g. This compares well to the MFAO measured in perfused working C57BL/6 mouse hearts ex vivo of about 350 nmol/g/min and 400 nmol/min/g. FA metabolism was measured for the first time in mouse heart in vivo using dynamic [11C]palmitate PET in a four-compartment tracer kinetic model. MFAO obtained with this model was validated by results previously obtained with mouse hearts ex vivo.

  8. Kinematic Identification of Parallel Mechanisms by a Divide and Conquer Strategy

    DEFF Research Database (Denmark)

    Durango, Sebastian; Restrepo, David; Ruiz, Oscar

    2010-01-01

    using the inverse calibration method. The identification poses are selected optimizing the observability of the kinematic parameters from a Jacobian identification matrix. With respect to traditional identification methods the main advantages of the proposed Divide and Conquer kinematic identification...... strategy are: (i) reduction of the kinematic identification computational costs, (ii) improvement of the numerical efficiency of the kinematic identification algorithm and, (iii) improvement of the kinematic identification results. The contributions of the paper are: (i) The formalization of the inverse...... calibration method as the Divide and Conquer strategy for the kinematic identification of parallel symmetrical mechanisms and, (ii) a new kinematic identification protocol based on the Divide and Conquer strategy. As an application of the proposed kinematic identification protocol the identification...

  9. Metabolism of U14C palmitic and 1-14C caproic acids by lettuce seeds during early germination

    International Nuclear Information System (INIS)

    Salon, C.; Raymond, P.; Pradet, A.

    1986-01-01

    Germinating lettuce embryos (before radicule emergence) were fed with either U 14 C palmitic acid or 1 14 C caproic acid until a metabolic steady state was reached. The bulk of labelled caproate was evolved as respiratory CO 2 (52%) and incorporated into organic and amino acids (38%) and only a small part incorporated into lipids whereas most of labelled palmitic acid was found into lipids (92%) and only 8% evolved as CO 2 and incorporated into organic and amino acids. The label distribution at steady state in intermediates linked to the T.C.A. cycle was interpreted using a metabolic model. They found that the two fatty acids were degraded by β-oxidation and incorporated into the T.C.A. cycle as acetylCoA suggesting that β-oxidation is located in the mitochondria. The results also indicate that lipids contribute for at least 90% to the carbon supply to respiration

  10. Switching away from pipotiazine palmitate: a naturalistic study.

    Science.gov (United States)

    Mustafa, Feras Ali

    2017-01-01

    In March 2015, pipotiazine palmitate depot antipsychotic was globally withdrawn due to the shortage of its active ingredient. Thus, all patients receiving this medication had to be switched to an alternative antipsychotic drug. In this study we set to evaluate the process of switching away from pipotiazine palmitate within our clinical service, and its impact on hospitalization. Demographic and clinical data on patients who were receiving pipotiazine palmitate in Northamptonshire at the time of its withdrawal were anonymously extracted from their electronic records and analyzed using descriptive statistics. A total of 17 patients were switched away from pipotiazine palmitate at the time of its withdrawal, all of whom had a prior history of nonadherence with oral treatment. A total of 14 patients were switched to another depot antipsychotic drug, while three patients chose an oral alternative which they subsequently discontinued resulting in relapse and hospitalization. There was a five-fold increase in mean hospitalization among patients who completed a year after the switch. Switching away from pipotiazine palmitate was associated with significant clinical deterioration in patients who switched to an oral antipsychotic, whereas most patients who switched to another depot treatment maintained stability. Clinicians should exercise caution when switching patients with schizophrenia away from depot antipsychotic drugs, especially in cases of patients with a history of treatment nonadherence who prefer to switch to oral antipsychotics.

  11. Systemic treatment of seborrheic dermatitis with retinol palmitate

    Directory of Open Access Journals (Sweden)

    O. V. Kalinina

    2014-01-01

    Full Text Available The goal of the study. Evaluating of the effectiveness of treatment of men with a diagnosis «Seborrheic dermatitis of the scalp» by the system using of retinol palmitate. Material and methods. 36 patients every day for 2 months received overnight per os 200000 ME of retinol palmitate, and in the comparison group (39 people antiseborrheic shampoos have been used. The dynamics of severity of skin oiliness, pruritis, erythema, peeling, infiltration, excoriations has been evaluated in points. Before and after the treatment a histological and morphometric study of biopsy material from the affected areas has been carried.The terms of relapses have been set. Results. Retinol palmitate treatment efficiency - 91.7%, antiseborrheic shampoos - 84.6%. Along with the regression of symptoms of the disease in both groups after retinol palmitate treatment significantly declined oiliness of skin; the sizes of sebaceous glands acini and the presence of differentiated sebocytes, the squares of lymphocytic-macrophage clusters in the dermis, the number of keratinocytes with vacuolated cytoplasm have been reduced. Relapses of the disease during a year occured more rare - in 21 patients out of 32 (in the comparison group- in 25 out of 31 and at a later date (in the first 3 months in 2 patients out of 32, in comparison group in 10 out of 31. Identified effects were due to the action of retinol palmitate on the morphogenesis of the sebaceous glands.

  12. Control of bovine hepatic fatty acid oxidation

    International Nuclear Information System (INIS)

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-01-01

    Fatty acid oxidation by bovine liver slices and mitochondria was examined to determine potential regulatory sites of fatty acid oxidation. Conversion of 1-[ 14 C]palmitate to 14 CO 2 and total [ 14 C]acid-soluble metabolites was used to measure fatty acid oxidation. Oxidation of palmitate (1 mM) was linear in both liver slice weight and incubation time. Carnitine stimulated palmitate oxidation; 2 mM dl-carnitine produced maximal stimulation of palmitate oxidation to both CO 2 and acid-soluble metabolites. Propionate (10 mM) inhibited palmitate oxidation by bovine liver slices. Propionate (.5 to 10 mM) had no effect on palmitate oxidation by mitochondria, but malonyl Coenzyme A, the first committed intermediate of fatty acid synthesis, inhibited mitochondrial palmitate oxidation (inhibition constant = .3 μM). Liver mitochonndrial carnitine palmitoyltransferase exhibited Michaelis constants for palmitoyl Coenzyme A and l-carnitine of 11.5 μM and .59 mM, respectively. Long-chain fatty acid oxidation in bovine liver is regulated by mechanisms similar to those in rats but adapted to the unique digestive physiology of the bovine

  13. Practical guidelines on the use of paliperidone palmitate in schizophrenia.

    Science.gov (United States)

    Newton, Richard; Hustig, Harry; Lakshmana, Raju; Lee, Joseph; Motamarri, Balaji; Norrie, Peter; Parker, Robert; Schreiner, Andreas

    2012-04-01

    Paliperidone palmitate is an atypical long-acting injectable (LAI) antipsychotic that has been approved for use in the US, EU, Australia and numerous other countries for acute and maintenance therapy of schizophrenia. LAI antipsychotics are often viewed as a 'last-resort' treatment for difficult-to-treat patients, however this article considers their role more broadly in the management of partial or non-adherence in schizophrenia. A search of MedLine, CTR and PsychInfo was conducted to identify relevant publications and clinical trials (search term 'paliperidone palmitate', up to December 2010). The findings were discussed in a number of teleconferences and the manuscript was finalized with a face-to-face meeting of the authors group. Relapse prevention in schizophrenia requires a comprehensive approach to treatment, which includes antipsychotic medication and psychosocial measures as well as family and/or carer involvement. Good symptom control and the interconnected issue of treatment adherence are arguably the most crucial factors for success. Carer and patient feedback should be carefully considered. Negotiation about commencing LAI therapy done early in course of disease is easier than many clinicians believe, although it is not often attempted in practice. Paliperidone palmitate is useful in both the acute and maintenance phases of treatment. A case-based approach is presented to suggest various opportunities where use of paliperidone palmitate could be considered within the disease course of schizophrenia. Paliperidone palmitate offers some advantages in terms of tolerability, simplicity of treatment initiation and long duration between injections. The consensus of the authors is that rather than reserving paliperidone palmitate for use in difficult-to-treat or refractory patients, it could be used to promote adherence and prevent relapse earlier in the course of the illness.

  14. Mechanisms of palmitate-induced cell death in human osteoblasts

    Science.gov (United States)

    Gunaratnam, Krishanthi; Vidal, Christopher; Boadle, Ross; Thekkedam, Chris; Duque, Gustavo

    2013-01-01

    Summary Lipotoxicity is an overload of lipids in non-adipose tissues that affects function and induces cell death. Lipotoxicity has been demonstrated in bone cells in vitro using osteoblasts and adipocytes in coculture. In this condition, lipotoxicity was induced by high levels of saturated fatty acids (mostly palmitate) secreted by cultured adipocytes acting in a paracrine manner. In the present study, we aimed to identify the underlying mechanisms of lipotoxicity in human osteoblasts. Palmitate induced autophagy in cultured osteoblasts, which was preceded by the activation of autophagosomes that surround palmitate droplets. Palmitate also induced apoptosis though the activation of the Fas/Jun kinase (JNK) apoptotic pathway. In addition, osteoblasts could be protected from lipotoxicity by inhibiting autophagy with the phosphoinositide kinase inhibitor 3-methyladenine or by inhibiting apoptosis with the JNK inhibitor SP600125. In summary, we have identified two major molecular mechanisms of lipotoxicity in osteoblasts and in doing so we have identified a new potential therapeutic approach to prevent osteoblast dysfunction and death, which are common features of age-related bone loss and osteoporosis. PMID:24285710

  15. Biosysthesis of Corn Starch Palmitate by Lipase Novozym 435

    Directory of Open Access Journals (Sweden)

    Kai Lin

    2012-06-01

    Full Text Available Esterification of starch was carried out to expand the usefulness of starch for a myriad of industrial applications. Lipase B from Candida antarctica, immobilized on macroporous acrylic resin (Novozym 435, was used for starch esterification in two reaction systems: micro-solvent system and solvent-free system. The esterification of corn starch with palmitic acid in the solvent-free system and micro-solvent system gave a degree of substitution (DS of 1.04 and 0.0072 respectively. Esterification of corn starch with palmitic acid was confirmed by UV spectroscopy and IR spectroscopy. The results of emulsifying property analysis showed that the starch palmitate with higher DS contributes to the higher emulsifying property (67.6% and emulsion stability (79.6% than the native starch (5.3% and 3.9%. Modified starch obtained by esterification that possesses emulsifying properties and has long chain fatty acids, like palmitic acid, has been widely used in the food, pharmaceutical and biomedical applications industries.

  16. Enzymatic formation of hexadecenoic acid from palmitic acid

    International Nuclear Information System (INIS)

    Nakano, Masao; Fujino, Yasuhiko

    1975-01-01

    Desaturation of palmitic acid was investigated in an enzyme system prepared from rat liver. 2-trans-Hexadecenoic acid as well as 9-cis-gexadecenoic acid (palmitoleic acid) were found to be formed as monoenoic acid in this system. (author)

  17. Reduced levels of SCD1 accentuate palmitate-induced stress in insulin-producing β-cells

    Directory of Open Access Journals (Sweden)

    Hovsepyan Meri

    2010-09-01

    Full Text Available Abstract Background Stearoyl-CoA desaturase 1 (SCD1 is an ER resident enzyme introducing a double-bond in saturated fatty acids. Global knockout of SCD1 in mouse increases fatty acid oxidation and insulin sensitivity which makes the animal resistant to diet-induced obesity. Inhibition of SCD1 has therefore been proposed as a potential therapy of the metabolic syndrome. Much of the work has focused on insulin target tissue and very little is known about how reduced levels of SCD1 would affect the insulin-producing β-cell, however. The aim of the present study was therefore to investigate how reduced levels of SCD1 affect the β-cell. Results Insulin-secreting MIN6 cells with reduced levels of SCD1 were established by siRNA mediated knockdown. When fatty acid oxidation was measured, no difference between cells with reduced levels of SCD1 and mock-transfected cells were found. Also, reducing levels of SCD1 did not affect insulin secretion in response to glucose. To investigate how SCD1 knockdown affected cellular mechanisms, differentially regulated proteins were identified by a proteomic approach. Cells with reduced levels of SCD1 had higher levels of ER chaperones and components of the proteasome. The higher amounts did not protect the β-cell from palmitate-induced ER stress and apoptosis. Instead, rise in levels of p-eIF2α and CHOP after palmitate exposure was 2-fold higher in cells with reduced levels of SCD1 compared to mock-transfected cells. Accordingly, apoptosis rose to higher levels after exposure to palmitate in cells with reduced levels of SCD1 compared to mock-transfected cells. Conclusions In conclusion, reduced levels of SCD1 augment palmitate-induced ER stress and apoptosis in the β-cell, which is an important caveat when considering targeting this enzyme as a treatment of the metabolic syndrome.

  18. Efficient Divide-And-Conquer Classification Based on Feature-Space Decomposition

    OpenAIRE

    Guo, Qi; Chen, Bo-Wei; Jiang, Feng; Ji, Xiangyang; Kung, Sun-Yuan

    2015-01-01

    This study presents a divide-and-conquer (DC) approach based on feature space decomposition for classification. When large-scale datasets are present, typical approaches usually employed truncated kernel methods on the feature space or DC approaches on the sample space. However, this did not guarantee separability between classes, owing to overfitting. To overcome such problems, this work proposes a novel DC approach on feature spaces consisting of three steps. Firstly, we divide the feature ...

  19. High Beta-Palmitate Fat Controls the Intestinal Inflammatory Response and Limits Intestinal Damage in Mucin Muc2 Deficient Mice

    NARCIS (Netherlands)

    Lu, Peng; Bar-Yoseph, Fabiana; Levi, Liora; Lifshitz, Yael; Witte-Bouma, Janneke; de Bruijn, Adrianus C. J. M.; Korteland-van Male, Anita M.; van Goudoever, Johannes B.; Renes, Ingrid B.

    2013-01-01

    Background: Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position

  20. High Beta-Palmitate Fat Controls the Intestinal Inflammatory Response and Limits Intestinal Damage in Mucin Muc2 Deficient Mice

    NARCIS (Netherlands)

    P. Lu (Peng); F. Bar-Yoseph (Fabiana); L. Levi (Liora); Y. Lifshitz (Yael); J. Witte-Bouma (Janneke); A.C.J.M. de Bruijn (Adrianus); A.M. Korteland-van Male (Anita); J.B. van Goudoever (Hans); I.B. Renes (Ingrid)

    2013-01-01

    textabstractBackground: Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the

  1. A case of paliperidone-palmitate-induced tardive dyskinesia.

    LENUS (Irish Health Repository)

    Lally, John

    2012-06-13

    OBJECTIVES: This is one of the first cases reported in the literature of paliperidone-palmitate-induced prolonged dyskinesia. METHOD: Case report. RESULTS: We report the case of a 49-year-old woman with paranoid schizophrenia who developed orofacial dyskinesia some 4 months after the commencement of paliperidone long-acting injection. CONCLUSION: This case serves as a clinical reminder that dyskinesia can occur with all antipsychotic medications.

  2. Conquering the electron the geniuses, visionaries, egomaniacs, and scoundrels who built our electronic age

    CERN Document Server

    Cheung, Derek

    2014-01-01

    Conquering the Electron offers readers a true and engaging history of the world of electronics. Beginning with the discoveries of static electricity and magnetism and ending with the creation of the smartphone and the iPad, this book shows the interconnection of each advance to the next one on the long journey to our modern day technologies. Want to know how AT&T's Bell Labs developed semiconductor technology--and how its leading scientists almost came to blows in the process? Want to understand how radio and television work--and why RCA drove their inventors to financial ruin and an early grave? Conquering the Electron offers these stories and more, presenting each revolutionary technological advance right alongside the blow-by-blow personal battles that all too often took place. By exploring the combination of genius, infighting, and luck that powered the creation of the electronic age we inhabit today, Conquering the Electron shows the interconnection of each advance to the next while also pulling bac...

  3. Optimization of α-tocopherol and ascorbyl palmitate addition for the stabilization of sardine oil

    Directory of Open Access Journals (Sweden)

    Morales-Medina, R.

    2015-06-01

    Full Text Available The purpose of the present work was to optimize the addition of natural antioxidants (α- tocopherol and ascorbyl palmitate for the stabilization of sardine oil rich in omega-3 PUFA. The optimal values for peroxide value (PV, which minimizes primary oxidation products, were obtained at low concentrations of α-tocopherol (50–207 ppm, high content of ascorbyl palmitate (450 ppm and 50 ppm citric acid. On the other hand, optimal values for p-anisidine value (AV, which minimizes secondary oxidation products, were found at medium concentrations of α-tocopherol (478–493 ppm, high contents of ascorbyl palmitate (390–450 ppm and 50 ppm citric acid. The conflicting effect of α-tocopherol on the individual optimization of PV and AV motivated the generation of a Pareto front (set of non inferior solutions employing the weighted-sum multi-objective optimization technique.El objetivo de este trabajo fue optimizar la adición de antioxidantes naturales (α-tocoferol y palmitato de ascorbilo para la estabilización de aceite de sardina rico en omega-3 PUFA. Bajas concentraciones de α-tocoferol (50–207 ppm combinadas con la adicción de antioxidantes secundarios como palmitato de ascorbilo (450 ppm y ácido cítrico (50 ppm, minimizaron la formación de hidroperóxidos en el aceite de sardina estudiado. Sin embargo, los productos secundarios de oxidación se redujeron para concentraciones medias de α-tocoferol (478–493 ppm, altas de palmitato de ascorbilo (390–450 ppm y 50 ppm de ácido cítrico. El efecto contradictorio de la concentración de α-tocoferol en la optimización individual del índice de peróxidos e índice de p-anisidina motivó la realización de una optimización simultánea que permite satisfacer la optimización de cada una de las variables individuales en el grado deseado.

  4. Metabolic fate of radiolabeled palmitate in ischemic canine myocardium: implications for positron emission tomography

    International Nuclear Information System (INIS)

    Rosamond, T.L.; Abendschein, D.R.; Sobel, B.E.; Bergmann, S.R.; Fox, K.A.

    1987-01-01

    Interpretation of dynamic and integrated myocardial tomograms requires elucidation of the biochemical fate of the tracer and characterization of its tissue distribution and rate of efflux. The fate of [1- 11 C] and [1- 14 C]palmitate was studied in 13 open-chest dogs during control or ischemic extracorporeal perfusion of the left circumflex coronary artery. Residue detection of myocardial radioactivity, and radio-biochemical analyses of sequential transmural biopsies and arterial and coronary venous effluent were performed for 30 min after intracoronary bolus administration of tracer. In control hearts, 10.3% of initially extracted tracer was retained in tissue (2.9% in triglyceride, 3.5% in phospholipid, and 3.9% in other lipid and aqueous fractions), 73.7% was oxidized, and 16.1% back-diffused unaltered. With ischemia (pump flow 10% of normal), 28.1% was retained (18% in triglyceride, 6.0% in phospholipid, and 4.1% in other lipid and aqueous fractions), 27.2% was oxidized, and 44.4% back diffused (p less than 0.05 compared to control). Throughout the 30-min study interval, triglyceride, diglyceride, and nonesterified fatty acid comprised a significantly greater fraction of initially extracted radioactivity in ischemic than in control hearts. Thus, during ischemia externally detected clearance rates cannot be used as a direct measure of fatty acid metabolism because of marked influences on efflux of nonmetabolized radiolabeled palmitate and the distribution of tracer retained in tissue. Quantitative measurements of specific metabolic processes by tomography will require development and validation of tracers confined to individual metabolic pathways or pools

  5. Selection and Characterization of Palmitic Acid Responsive Patients with an OXPHOS Complex I Defect

    Directory of Open Access Journals (Sweden)

    Tom E. J. Theunissen

    2017-10-01

    Full Text Available Mitochondrial disorders are genetically and clinically heterogeneous, mainly affecting high energy-demanding organs due to impaired oxidative phosphorylation (OXPHOS. Currently, effective treatments for OXPHOS defects, with complex I deficiency being the most prevalent, are not available. Yet, clinical practice has shown that some complex I deficient patients benefit from a high-fat or ketogenic diet, but it is unclear how these therapeutic diets influence mitochondrial function and more importantly, which complex I patients could benefit from such treatment. Dietary studies in a complex I deficient patient with exercise intolerance showed increased muscle endurance on a high-fat diet compared to a high-carbohydrate diet. We performed whole-exome sequencing to characterize the genetic defect. A pathogenic homozygous p.G212V missense mutation was identified in the TMEM126B gene, encoding an early assembly factor of complex I. A complementation study in fibroblasts confirmed that the p.G212V mutation caused the complex I deficiency. The mechanism turned out to be an incomplete assembly of the peripheral arm of complex I, leading to a decrease in the amount of mature complex I. The patient clinically improved on a high-fat diet, which was supported by the 25% increase in maximal OXPHOS capacity in TMEM126B defective fibroblast by the saturated fatty acid palmitic acid, whereas oleic acid did not have any effect in those fibroblasts. Fibroblasts of other patients with a characterized complex I gene defect were tested in the same way. Patient fibroblasts with complex I defects in NDUFS7 and NDUFAF5 responded to palmitic acid, whereas ACAD9, NDUFA12, and NDUFV2 defects were non-responding. Although the data are too limited to draw a definite conclusion on the mechanism, there is a tendency that protein defects involved in early assembly complexes, improve with palmitic acid, whereas proteins defects involved in late assembly, do not. Our data show at

  6. Identification of Lipoproteins Using Globomycin and Radioactive Palmitate.

    Science.gov (United States)

    Buddelmeijer, Nienke

    2017-01-01

    Bacterial lipoproteins are characterized by fatty acids that are covalently attached to their amino terminus via posttranslational modification in the cytoplasmic membrane. Three enzymatic steps are involved in the synthesis of mature triacylated lipoprotein: prolipoprotein converts into diacylglyceryl-prolipoprotein that in turn converts into apolipoprotein, which is finally converted into mature triacylated lipoprotein. Here we describe the detection of one of these intermediate forms of lipoprotein, diacylglyceryl-prolipoprotein, using 3 H-palmitate labeling and inhibition by globomycin and detection by fluorography.

  7. Localization of viable, ischemic myocardium by positron-emission tomography with 11C-palmitate

    International Nuclear Information System (INIS)

    Lerch, R.A.; Ambos, H.D.; Bergmann, S.R.; Welch, M.J.; Ter-Pogossian, M.M.; Sobel, B.E.

    1981-01-01

    A study was performed to determine whether viable, but ischemic, tissue could be detected and localized in vivo based on external detection of impaired fatty acid metabolism. Accordingly, regional clearance of 11 C-palmitate was assessed by sequential PET in 15 anesthetized dogs. Clearance was consistently monoexponential from 5-15 minutes after administration of the tracer. In the absence of coronary stenosis (n = 7), clearance was homogeneous throughout the heart, with an average rate constant (k) of -0.060 +/- 0.005 min -1 (+/- SEM) and a coefficient of variation (CV) of 11.1 +/- 2.1% in each heart. Homogeneity persisted when the heart rate was increased from 84.4 +/- 6.0 to 202.7 +/- 11.5 beats/min with atropine (CV 13.2 +/- 3.5%). With left circumflex coronary stenosis (less than or equal to70% reduction in vessel diameter), homogeneity of 11 C-clearance under control conditions and with tachycardia did not differ from clearance in hearts without coronary stenosis. However, with stenosis >70% sufficient to induce ischemia without gross infarction, regional clearance of 11 C became markedly heterogeneous under control conditions (CV 28.1 +/- 5.5%, p 11 C in regions supplied by the stenotic vessel (k = -0.044 +/- 0.011 min -1 ) compared with clearance in well perfused regions (k = -0.064 +/- 0.011 min -1 , p 11 C-palmitate delineates zones of viable, ischemic myocardium that characteristically exhibit impaired oxidation of extracted fatty acid

  8. Conquer Chiari

    Science.gov (United States)

    ... on the Web Chiari Facebook Page Pediatric Chiari Facebook Page Upcoming Events Community Fundraising Efforts ABOUT US C&S Patient Education Foundation Mission History & Accomplishments Team Financial Disclosure Forms (990's) Get Involved ...

  9. Estimation of transcapillary transport of palmitate by the multiple indicator dilution technique

    International Nuclear Information System (INIS)

    Little, S.E.; van der Vusse, G.J.; Bassingthwaighte, J.B.

    1986-01-01

    From the outflow concentration-time curves for 14 C-palmitate, intravascular ( 131 I-albumin) and extracellular ( 3 H-sucrose) tracers, palmitate extraction was estimated in rabbit hearts Langendorff-perfused at a constant flow with nonrecirculated palmitate-albumin Kreb's Ringer buffer. Contamination of 131 I-albumin with free 13 $ 1 I - (typically 1%) or aggregated albumin (typically 0.1 to 0.5%) greatly alters the shapes of the tails of the curves after 2 albumin transit times, vitiating accurate estimation of cellular permeability or reactions. Buffers were prepared by adding K + -palmitate (made using K 2 CO 3 ) to albumin solutions. The final concentrations (after dialysing twice and filtering through a 1.2 μ filter) of K + , HCO 3 , and CO 3 were 5.0 mM, 23.5 mM and 0.5 mM respectively, pH was between 7.35 and 7.40 for several hours. The bolus of tracers was prepared by mixing 131 I-albumin (dialysed to remove I - , and filtered through a 0.2 μM filter to remove aggregates), K + [U- 14 C]palmitate (high specific activity) and 3 H-sucrose. Before injection the radioactive bolus is preequilibrated with the perfusate at bolus:perfusate ratio of 1:10. Glacial acetic acid is added to the outflow samples to remove the 14 CO 2 which, if present in the sample, would be interpreted as increased palmitate back diffusion. The peak extractions of palmitate were about 40% at perfusate palmitate concentrations of 0.02 to 1.0 mM, 0.4 mM albumin, at a flow of 5 mlg -1 2] 1 , showing capillary permeability-surface area product to be roughly constant. This suggests either than transcapillary palmitate transport is passive or that a transporter interacts with the albumin-palmitate complex

  10. PHYSICAL AND CHEMICAL STABILITY ANALYSIS OF COSMETIC MULTI- PLE EMULSIONS LOADED WITH ASCORBYL PALMITATE AND SODIUM ASCORBYL PHOSPHATE SALTS.

    Science.gov (United States)

    Khan, Hira; Akhtar, Naveed; Ali, Atif; Khan, Haji M Shoaib; Sohail, Muhammad; Naeem, Muhammad; Nawaz, Zarqa

    2016-09-01

    Stability of hydrophilic and lipophilic vitamin C derivatives for quenching synergistic antioxidant activities and to treat oxidative related diseases is a major issue. This study was aimed to encapsulate hydrophilic and lipophilic vitamin C derivatives (ascorbyl palmitate and sodium ascorbyl phosphate) as functional ingredients in a newly formulated multiple emulsion of the W//W type to attain the synergistic antioxidant effects and the resultant system's long term physical and chemical stability. Several multiple emulsions using the same concentration of emulsifiers but different concentrations of ascorbyl palmitate and sodium ascorbyl phosphate were developed. Three finally selected multiple emulsions (ME₁, ME₂ and ME₃) were evaluated for physical stability in terms of rheology, microscopy, conductivity, pH, and organoleptic characteristics under different storage conditions for 3 months. Chemical stability was determined by HPLC on Sykam GmbH HPLC system (Germany), equipped with a variable UV detector. Results showed that at accelerated storage conditions all the three multiple emulsions had shear thinning behavior of varying shear stress with no influence of location of functional ingredients in a carrier system. Conductivity values increased and pH values remained within the skin pH range for 3 months. Microscopic analysis showed an increase in globule size with the passage of time, especially at higher temperatures while decreased at low temperatures. Centrifugation test did not cause phase separation till the 45th day, but little effects after 2 months. Chemical stability analysis by HPLC at the end of 3 months showed that ascorbyl palmitate and sodium ascorbyl phosphate were almost stable in all multiple emulsions with no influence of their location in a carrier system. Multiple emulsions were found a stable carrier for hydrophilic and lipophilic vitamin C derivatives to enhance their desired effects. Considering that many topical formulations

  11. Aspects of the regulation of long-chain fatty acid oxidation in bovine liver

    International Nuclear Information System (INIS)

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-01-01

    Factors involved in regulation of bovine hepatic fatty acid oxidation were examined using liver slices. Fatty acid oxidation was measured as the conversion of l-[ 14 C] palmitate to 14 CO 2 and total [ 14 C] acid-soluble metabolites. Extended (5 to 7 d) fasting of Holstein cows had relatively little effect on palmitate oxidation to acid-soluble metabolites by liver slices, although oxidation to CO 2 was decreased. Feeding a restricted roughage, high concentrate ration to lactating cows resulted in inhibition of palmitate oxidation. Insulin, glucose, and acetate inhibited palmitate oxidation by bovine liver slices. The authors suggest the regulation of bovine hepatic fatty acid oxidation may be less dependent on hormonally induced alterations in enzyme activity as observed in rat liver and more dependent upon action of rumen fermentation products or their metabolites on enzyme systems involved in fatty acid oxidation

  12. Randomized Trial of ConquerFear: A Novel, Theoretically Based Psychosocial Intervention for Fear of Cancer Recurrence

    NARCIS (Netherlands)

    Butow, P.N.; Turner, J.; Gilchrist, J.; Sharpe, L.; Smith, A.B.; Fardell, J.E.; Tesson, S.; O'Connell, R.; Girgis, A.; Gebski, V.J.; Asher, R.; Mihalopoulos, C.; Bell, M.L.; Zola, K.G.; Beith, J.; Thewes, B.

    2017-01-01

    Purpose Fear of cancer recurrence (FCR) is prevalent, distressing, and long lasting. This study evaluated the impact of a theoretically/empirically based intervention (ConquerFear) on FCR. Methods Eligible survivors had curable breast or colorectal cancer or melanoma, had completed treatment (not

  13. LAMBERSART "LES CONQUERANTS" (DEULE VALLEY, NORTH OF FRANCE) : A WEICHSELIAN EARLY-PLENIGLACIAL SLOPE-BOTTOM VALLEY TRANSITION

    NARCIS (Netherlands)

    Deschodt, Laurent; Munaut, Andre-Valentin; Limondin-Lozouet, Nicole; Boulen, Muriel

    2008-01-01

    The Lambersart "les Conquerants" trench sequence is made of a Shelly loam topped by coarse alluviums. The whole is covered by several meters thick pleniglacial loess. The palynological and malacological data shows that this Shelly loam deposit occured during Early Glacial, in cold and moist

  14. A divide-conquer-recombine algorithmic paradigm for large spatiotemporal quantum molecular dynamics simulations

    Science.gov (United States)

    Shimojo, Fuyuki; Hattori, Shinnosuke; Kalia, Rajiv K.; Kunaseth, Manaschai; Mou, Weiwei; Nakano, Aiichiro; Nomura, Ken-ichi; Ohmura, Satoshi; Rajak, Pankaj; Shimamura, Kohei; Vashishta, Priya

    2014-05-01

    We introduce an extension of the divide-and-conquer (DC) algorithmic paradigm called divide-conquer-recombine (DCR) to perform large quantum molecular dynamics (QMD) simulations on massively parallel supercomputers, in which interatomic forces are computed quantum mechanically in the framework of density functional theory (DFT). In DCR, the DC phase constructs globally informed, overlapping local-domain solutions, which in the recombine phase are synthesized into a global solution encompassing large spatiotemporal scales. For the DC phase, we design a lean divide-and-conquer (LDC) DFT algorithm, which significantly reduces the prefactor of the O(N) computational cost for N electrons by applying a density-adaptive boundary condition at the peripheries of the DC domains. Our globally scalable and locally efficient solver is based on a hybrid real-reciprocal space approach that combines: (1) a highly scalable real-space multigrid to represent the global charge density; and (2) a numerically efficient plane-wave basis for local electronic wave functions and charge density within each domain. Hybrid space-band decomposition is used to implement the LDC-DFT algorithm on parallel computers. A benchmark test on an IBM Blue Gene/Q computer exhibits an isogranular parallel efficiency of 0.984 on 786 432 cores for a 50.3 × 106-atom SiC system. As a test of production runs, LDC-DFT-based QMD simulation involving 16 661 atoms is performed on the Blue Gene/Q to study on-demand production of hydrogen gas from water using LiAl alloy particles. As an example of the recombine phase, LDC-DFT electronic structures are used as a basis set to describe global photoexcitation dynamics with nonadiabatic QMD (NAQMD) and kinetic Monte Carlo (KMC) methods. The NAQMD simulations are based on the linear response time-dependent density functional theory to describe electronic excited states and a surface-hopping approach to describe transitions between the excited states. A series of techniques

  15. A divide-conquer-recombine algorithmic paradigm for large spatiotemporal quantum molecular dynamics simulations

    International Nuclear Information System (INIS)

    Shimojo, Fuyuki; Hattori, Shinnosuke; Kalia, Rajiv K.; Mou, Weiwei; Nakano, Aiichiro; Nomura, Ken-ichi; Rajak, Pankaj; Vashishta, Priya; Kunaseth, Manaschai; Ohmura, Satoshi; Shimamura, Kohei

    2014-01-01

    We introduce an extension of the divide-and-conquer (DC) algorithmic paradigm called divide-conquer-recombine (DCR) to perform large quantum molecular dynamics (QMD) simulations on massively parallel supercomputers, in which interatomic forces are computed quantum mechanically in the framework of density functional theory (DFT). In DCR, the DC phase constructs globally informed, overlapping local-domain solutions, which in the recombine phase are synthesized into a global solution encompassing large spatiotemporal scales. For the DC phase, we design a lean divide-and-conquer (LDC) DFT algorithm, which significantly reduces the prefactor of the O(N) computational cost for N electrons by applying a density-adaptive boundary condition at the peripheries of the DC domains. Our globally scalable and locally efficient solver is based on a hybrid real-reciprocal space approach that combines: (1) a highly scalable real-space multigrid to represent the global charge density; and (2) a numerically efficient plane-wave basis for local electronic wave functions and charge density within each domain. Hybrid space-band decomposition is used to implement the LDC-DFT algorithm on parallel computers. A benchmark test on an IBM Blue Gene/Q computer exhibits an isogranular parallel efficiency of 0.984 on 786 432 cores for a 50.3 × 10 6 -atom SiC system. As a test of production runs, LDC-DFT-based QMD simulation involving 16 661 atoms is performed on the Blue Gene/Q to study on-demand production of hydrogen gas from water using LiAl alloy particles. As an example of the recombine phase, LDC-DFT electronic structures are used as a basis set to describe global photoexcitation dynamics with nonadiabatic QMD (NAQMD) and kinetic Monte Carlo (KMC) methods. The NAQMD simulations are based on the linear response time-dependent density functional theory to describe electronic excited states and a surface-hopping approach to describe transitions between the excited states. A series of

  16. The mystery of the seven spheres how homo sapiens will conquer space

    CERN Document Server

    Bignami, Giovanni F

    2015-01-01

    In this book, Giovanni Bignami, the outstanding Italian scientist and astronomer, takes the reader on a journey through the “seven spheres”, from our own planet to neighboring stars. The author offers a gripping account of the evolution of Homo Sapiens to the stage where our species is developing capabilities, in the form of new energy propulsion systems, that will enable us to conquer space. The reader will learn how we first expanded our activities to reach beyond our planet, to the Moon, and how nuclear energy, nuclear fusion, and matter–antimatter annihilation will enable us to extend our exploration. After Mars and Jupiter we shall finally reach the nearest stars, which we now know are surrounded by numerous planets, some of which are bound to be habitable. The book includes enticing descriptions of such newly discovered planets and also brings alive key historical characters in our story, such as Jules Verne and Werner von Braun.

  17. Toward a High Performance Tile Divide and Conquer Algorithm for the Dense Symmetric Eigenvalue Problem

    KAUST Repository

    Haidar, Azzam

    2012-01-01

    Classical solvers for the dense symmetric eigenvalue problem suffer from the first step, which involves a reduction to tridiagonal form that is dominated by the cost of accessing memory during the panel factorization. The solution is to reduce the matrix to a banded form, which then requires the eigenvalues of the banded matrix to be computed. The standard divide and conquer algorithm can be modified for this purpose. The paper combines this insight with tile algorithms that can be scheduled via a dynamic runtime system to multicore architectures. A detailed analysis of performance and accuracy is included. Performance improvements of 14-fold and 4-fold speedups are reported relative to LAPACK and Intel\\'s Math Kernel Library.

  18. First principles calculations using density matrix divide-and-conquer within the SIESTA methodology

    International Nuclear Information System (INIS)

    Cankurtaran, B O; Gale, J D; Ford, M J

    2008-01-01

    The density matrix divide-and-conquer technique for the solution of Kohn-Sham density functional theory has been implemented within the framework of the SIESTA methodology. Implementation details are provided where the focus is on the scaling of the computation time and memory use, in both serial and parallel versions. We demonstrate the linear-scaling capabilities of the technique by providing ground state calculations of moderately large insulating, semiconducting and (near-) metallic systems. This linear-scaling technique has made it feasible to calculate the ground state properties of quantum systems consisting of tens of thousands of atoms with relatively modest computing resources. A comparison with the existing order-N functional minimization (Kim-Mauri-Galli) method is made between the insulating and semiconducting systems

  19. A divide and conquer approach to determine the Pareto frontier for optimization of protein engineering experiments

    Science.gov (United States)

    He, Lu; Friedman, Alan M.; Bailey-Kellogg, Chris

    2016-01-01

    In developing improved protein variants by site-directed mutagenesis or recombination, there are often competing objectives that must be considered in designing an experiment (selecting mutations or breakpoints): stability vs. novelty, affinity vs. specificity, activity vs. immunogenicity, and so forth. Pareto optimal experimental designs make the best trade-offs between competing objectives. Such designs are not “dominated”; i.e., no other design is better than a Pareto optimal design for one objective without being worse for another objective. Our goal is to produce all the Pareto optimal designs (the Pareto frontier), in order to characterize the trade-offs and suggest designs most worth considering, but to avoid explicitly considering the large number of dominated designs. To do so, we develop a divide-and-conquer algorithm, PEPFR (Protein Engineering Pareto FRontier), that hierarchically subdivides the objective space, employing appropriate dynamic programming or integer programming methods to optimize designs in different regions. This divide-and-conquer approach is efficient in that the number of divisions (and thus calls to the optimizer) is directly proportional to the number of Pareto optimal designs. We demonstrate PEPFR with three protein engineering case studies: site-directed recombination for stability and diversity via dynamic programming, site-directed mutagenesis of interacting proteins for affinity and specificity via integer programming, and site-directed mutagenesis of a therapeutic protein for activity and immunogenicity via integer programming. We show that PEPFR is able to effectively produce all the Pareto optimal designs, discovering many more designs than previous methods. The characterization of the Pareto frontier provides additional insights into the local stability of design choices as well as global trends leading to trade-offs between competing criteria. PMID:22180081

  20. Test Time Reduction for BIST by Parallel Divide-and-Conquer Method

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Byung Gu; Kim, Dong Wook [Kwangwoon University (Korea)

    2000-06-01

    BIST(Built-in Self Test) has been considered as the most promising DFT(design-for-test) scheme for the present and future test strategy. The most serious problem in applying BIST(Built-in Self Test) into a large circuit is the excessive increase in test time. This paper is focused on this problem. We proposed a new BIST construction scheme which uses a parallel divide-and-conquer method. The circuit division is performed with respect to some internal nodes called test points. The test points are selected by considering the nodal connectivity of the circuit rather than the testability of each node. The test patterns are generated by only one linear feedback shift register(LFSR) and they are shared by all the divided circuits. Thus, the test for each divided circuit is performed in parallel. Test responses are collected from the test point as well as the primary outputs. Even though the divide-and-conquer scheme is used and test patterns are generated in one LFSR, the proposed scheme does not lose its pseudo-exhaustive property. We proposed a selection procedure to find the test points and it was implemented with C/C{sup ++} language. Several example circuits were applied to this procedure and the results showed that test time was reduced upto 1/2{sup 1}51 but the increase in the hardware overhead or the delay increase was not much high. Because the proposed scheme showed a tendency that the increasing rates in hardware overhead and delay overhead were less than that in test time reduction as the size of circuit increases, it is expected to be used efficiently for large circuits as VLSI and ULSI. (author). 15 refs., 7 figs., 5 tabs.

  1. The dynamic of lipid oxidation in human myotubes

    DEFF Research Database (Denmark)

    Gaster, Michael

    2009-01-01

    Both endogenous and exogenous lipid levels may be regulators of total lipid oxidation in skeletal muscles. We studied the dynamics of lipid oxidation in human myotubes established from healthy, lean subjects exposed to acutely and chronically increased palmitate concentrations. The intramyocellular...... triacylglycerol content increased with chronic palmitate exposure. Both, ectopically increased intracellular and extracellular lipid levels were simultaneously oxidized and could partly suppress each other's oxidation. Overall, the highest acute palmitate treatments stimulated fatty acid oxidation whilst...... the highest chronic treatments decreased total lipid oxidation. Intracellular lipids showed a more complete oxidation than exogenous lipids. Endogenous lipids reduced insulin-mediated glucose oxidation. Thus, both endogenous and exogenous lipid concentrations regulated each other's oxidation and total lipid...

  2. Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis.

    Science.gov (United States)

    Villa, P; Demitri, M T; Meazza, C; Sironi, M; Gnocchi, P; Ghezzi, P

    1996-12-01

    The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.

  3. Nanocarrier with self-antioxidative property for stabilizing and delivering ascorbyl palmitate into skin.

    Science.gov (United States)

    Janesirisakule, Sirinapa; Sinthusake, Tarit; Wanichwecharungruang, Supason

    2013-08-01

    The concept of a nanocarrier with a self-antioxidative property to deliver and stabilize a labile drug while at the same time providing a free radical scavenging activity is demonstrated. Curcumin was grafted onto a poly(vinyl alcohol) [PV(OH)] chain, and the nanocarriers fabricated from the obtained curcumin-grafted PV(OH) polymer [CUR-PV(OH)] showed a good free radical scavenging activity. Ascorbyl palmitate (AP) could be effectively loaded into the CUR-PV(OH) at 29% by weight. The CUR-PV(OH)-encapsulated AP was 77% more stable than the free (unencapsulated) AP, and 47% more stable than AP encapsulated in the control nanocarrier with no antioxidative property [cinnamoyl-grafted PV(OH); CIN-PV(OH)]. Although coencapsulation of curcumin and AP into CIN-PV(OH) showed some improvement on the AP stability, AP was more stable when encapsulated in CUR-PV(OH). Compared with the free AP, encapsulated AP within the CUR-PV(OH) nanocarriers showed not only a better penetration into pig skin dermis via hair follicle pathway followed by the release and diffusion of the AP, but also a greater AP stability after skin application. Although a proof of principle is shown for CUR-PV(OH) and AP, it is likely that other carriers of the same principal could be designed and applied to different oxidation-sensitive drugs. Copyright © 2013 Wiley Periodicals, Inc.

  4. Molecular dynamics of palmitic acid and lead palmitate in cross-linked linseed oil films: Implications from deuterium magnetic resonance for lead soap formation in traditional oil paintings.

    Science.gov (United States)

    Catalano, Jaclyn; Murphy, Anna; Yao, Yao; Zumbulyadis, Nicholas; Centeno, Silvia A; Dybowski, Cecil

    2018-02-01

    Many oil paintings, dating from the 15th century to the present, are affected by the formation of heavy-metal carboxylates (soaps) that alter the structural integrity and appearance of the works. Through transport phenomena not yet understood, free fatty acids formed from oils used as binders migrate through the paint film and react with heavy-metal ions that are constituents of pigments and/or driers, forming metal carboxylates. The local molecular dynamics of fatty acids and metal carboxylates are factors influencing material transport in these systems. We report temperature-dependent 2 H NMR spectra of palmitic acid and lead palmitate as pure materials, in cross-linked linseed oil films, and in a lead white linseed oil paint film as part of our broader research into metal soap formation. Local dynamics at the α carbon, at the terminal methyl group, and at the middle of the fatty acid chain were observed in specifically deuterated materials. Changes in the dynamic behavior with temperature were observed by the appearance of two species, a solid-like material and a liquid-like material. The relative amounts of the two phases and their deuterium NMR parameters indicate that the amount of liquid-like material and the local dynamics at that site increase with temperature. At the three locations along the chain and at all temperatures, there is a larger percentage of acyl chains of both palmitic acid and lead palmitate that are "mobile" or liquid-like in linseed oil films than there are in the pure materials. However, the percentage of liquid-like species is decreased in a lead white paint film, as compared to a linseed oil matrix. In addition, these experiments indicate that there is a larger percentage of liquid-like acyl chains of palmitic acid than of lead palmitate under identical conditions in these model paint systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Biological and Nutritional Properties of Palm Oil and Palmitic Acid: Effects on Health.

    Science.gov (United States)

    Mancini, Annamaria; Imperlini, Esther; Nigro, Ersilia; Montagnese, Concetta; Daniele, Aurora; Orrù, Stefania; Buono, Pasqualina

    2015-09-18

    A growing body of evidence highlights the close association between nutrition and human health. Fat is an essential macronutrient, and vegetable oils, such as palm oil, are widely used in the food industry and highly represented in the human diet. Palmitic acid, a saturated fatty acid, is the principal constituent of refined palm oil. In the last few decades, controversial studies have reported potential unhealthy effects of palm oil due to the high palmitic acid content. In this review we provide a concise and comprehensive update on the functional role of palm oil and palmitic acid in the development of obesity, type 2 diabetes mellitus, cardiovascular diseases and cancer. The atherogenic potential of palmitic acid and its stereospecific position in triacylglycerols are also discussed.

  6. Effects of substrate availability on myocardial C-11 palmitate kinetics by positron emission tomography in normal subjects and patients with ventricular dysfunction

    International Nuclear Information System (INIS)

    Schelbert, H.R.; Henze, E.; Sochor, H.; Grossman, R.G.; Huang, S.C.; Barrio, J.R.; Schwaiger, M.; Phelps, M.E.

    1986-01-01

    The possibility of demonstrating noninvasively with C-11 palmitate and positron emission tomography (PET) changes in myocardial substrate metabolism in normal and diseased human myocardium in response to altered substrate availability in blood and disease-related abnormalities was examined in five normal volunteers and 16 patients with ventricular dysfunction. C-11 palmitate injection and serial PET imaging were performed after an overnight fast (control period) and again 2 hours later after oral glucose (50 gm). Myocardial C-11 time-activity curves from serial PET images revealed a biexponential clearance pattern. An early rapid phase, defined by relative size and clearance half-time, reflects C-11 palmitate oxidation and the late slow phase tracer deposition in the endogenous lipid pool. During the control period, the tracer fraction entering the early rapid phase averaged 47 +/- 13% (SD) in normal subjects and 45 +/- 12% in patients. Corresponding clearance half-times were 19 +/- 7 and 20 +/- 5 minutes, respectively. Heart rate and blood pressure remained unchanged after glucose, but plasma glucose levels rose by 72.5% in normal subjects and by 98.9% in patients, while free fatty acid levels fell by 72% and 42% respectively. In normal subjects, the tracer fraction in the early rapid phase fell by 43% (p less than 0.005) and the clearance half-time increased by 46%. In patients, the response of C-11 palmitate tissue kinetics to glucose was variable. In nine patients, it was similar to normal subjects while in the other seven patients, the tracer fraction entering the rapid clearance phase increased after glucose by 30% (p less than 0.05) associated with a 36% (p less than 0.05) decline in clearance half-times. This was unrelated to disease etiology or plasma substrate levels but occurred mostly in left ventricles with more severely depressed function

  7. Manic Symptoms during a Switch from Paliperidone ER to Paliperidone Palmitate in a Patient with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Kadir Demirci

    2015-01-01

    Full Text Available Some antipsychotic drugs have treatment efficacy for mania and bipolar disorder. However, these drugs may rarely cause manic symptoms in some schizophrenic patients. We hereby report a 22-year-old female patient with schizophrenia who experienced a manic episode during a switch from paliperidone ER to paliperidone palmitate. This case is an important reminder that an abrupt switch from oral paliperidone to paliperidone palmitate may predispose certain patients to hypomanic or manic symptoms.

  8. Uncoupling effect of palmitate is exacerbated in skeletal muscle mitochondria of sea-acclimatized king penguins (Aptenodytes patagonicus).

    Science.gov (United States)

    Rey, Benjamin; Duchamp, Claude; Roussel, Damien

    2017-09-01

    In king penguin juveniles, the environmental transition from a terrestrial to a marine habitat, occurring at fledging, drastically stimulates lipid catabolism and the remodelling of muscle mitochondria to sustain extensive swimming activity and thermoregulation in the cold circumpolar oceans. However, the exact nature of these mechanisms remains only partially resolved. Here we investigated, in vitro, the uncoupling effect of increasing doses of fatty acids in pectoralis muscle intermyofibrillar mitochondria isolated, either from terrestrial never-immersed or experimentally cold water immersed pre-fledging king penguins or from sea-acclimatized fledged penguins. Mitochondria exhibited much greater palmitate-induced uncoupling respiration and higher maximal oxidative capacity after acclimatization to marine life. Such effects were not reproduced experimentally after repeated immersions in cold water, suggesting that the plasticity of mitochondrial characteristics may not be primarily driven by cold exposure per se but by other aspects of sea acclimatization. Copyright © 2017. Published by Elsevier Inc.

  9. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-09

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  10. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    International Nuclear Information System (INIS)

    Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  11. Randomized Trial of ConquerFear: A Novel, Theoretically Based Psychosocial Intervention for Fear of Cancer Recurrence.

    Science.gov (United States)

    Butow, Phyllis N; Turner, Jane; Gilchrist, Jemma; Sharpe, Louise; Smith, Allan Ben; Fardell, Joanna E; Tesson, Stephanie; O'Connell, Rachel; Girgis, Afaf; Gebski, Val J; Asher, Rebecca; Mihalopoulos, Cathrine; Bell, Melanie L; Zola, Karina Grunewald; Beith, Jane; Thewes, Belinda

    2017-12-20

    Purpose Fear of cancer recurrence (FCR) is prevalent, distressing, and long lasting. This study evaluated the impact of a theoretically/empirically based intervention (ConquerFear) on FCR. Methods Eligible survivors had curable breast or colorectal cancer or melanoma, had completed treatment (not including endocrine therapy) 2 months to 5 years previously, were age > 18 years, and had scores above the clinical cutoff on the FCR Inventory (FCRI) severity subscale at screening. Participants were randomly assigned at a one-to-one ratio to either five face-to-face sessions of ConquerFear (attention training, metacognitions, acceptance/mindfulness, screening behavior, and values-based goal setting) or an attention control (Taking-it-Easy relaxation therapy). Participants completed questionnaires at baseline (T0), immediately post-therapy (T1), and 3 (T2) and 6 months (T3) later. The primary outcome was FCRI total score. Results Of 704 potentially eligible survivors from 17 sites and two online databases, 533 were contactable, of whom 222 (42%) consented; 121 were randomly assigned to intervention and 101 to control. Study arms were equivalent at baseline on all measured characteristics. ConquerFear participants had clinically and statistically greater improvements than control participants from T0 to T1 on FCRI total ( P psychological distress, and triggers) as well as in general anxiety, cancer-specific distress (total), and mental quality of life and metacognitions (total). Differences in FCRI psychological distress and cancer-specific distress (total) remained significantly different at T3. Conclusion This randomized trial demonstrated efficacy of ConquerFear compared with attention control (Taking-it-Easy) in reduction of FCRI total scores immediately post-therapy and 3 and 6 months later and in many secondary outcomes immediately post-therapy. Cancer-specific distress (total) remained more improved at 3- and 6-month follow-up.

  12. Isosteviol has beneficial effects on palmitate-induced α-cell dysfunction and gene expression.

    Directory of Open Access Journals (Sweden)

    Xiaoping Chen

    Full Text Available BACKGROUND: Long-term exposure to high levels of fatty acids impairs insulin secretion and exaggerates glucagon secretion. The aim of this study was to explore if the antihyperglycemic agent, Isosteviol (ISV, is able to counteract palmitate-induced α-cell dysfunction and to influence α-cell gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Long-term incubation studies with clonal α-TC1-6 cells were performed in the presence of 0.5 mM palmitate with or without ISV. We investigated effects on glucagon secretion, glucagon content, cellular triglyceride (TG content, cell proliferation, and expression of genes involved in controlling glucagon synthesis, fatty acid metabolism, and insulin signal transduction. Furthermore, we studied effects of ISV on palmitate-induced glucagon secretion from isolated mouse islets. Culturing α-cells for 72-h with 0.5 mM palmitate in the presence of 18 mM glucose resulted in a 56% (p<0.01 increase in glucagon secretion. Concomitantly, the TG content of α-cells increased by 78% (p<0.01 and cell proliferation decreased by 19% (p<0.05. At 18 mM glucose, ISV (10(-8 and 10(-6 M reduced palmitate-stimulated glucagon release by 27% (p<0.05 and 27% (p<0.05, respectively. ISV (10(-6 M also counteracted the palmitate-induced hypersecretion of glucagon in mouse islets. ISV (10(-6 M reduced α-TC1-6 cell proliferation rate by 25% (p<0.05, but ISV (10(-8 and 10(-6 M had no effect on TG content in the presence of palmitate. Palmitate (0.5 mM increased Pcsk2 (p<0.001, Irs2 (p<0.001, Fasn (p<0.001, Srebf2 (p<0.001, Acaca (p<0.01, Pax6 (p<0.05 and Gcg mRNA expression (p<0.05. ISV significantly (p<0.05 up-regulated Insr, Irs1, Irs2, Pik3r1 and Akt1 gene expression in the presence of palmitate. CONCLUSIONS/SIGNIFICANCE: ISV counteracts α-cell hypersecretion and apparently contributes to changes in expression of key genes resulting from long-term exposure to palmitate. ISV apparently acts as a glucagonostatic drug with potential as a

  13. Monocyte adhesion induced by multi-walled carbon nanotubes and palmitic acid in endothelial cells and alveolar-endothelial co-cultures

    DEFF Research Database (Denmark)

    Cao, Yi; Roursgaard, Martin; Jacobsen, Nicklas Raun

    2016-01-01

    Free palmitic acid (PA) is a potential pro-atherogenic stimulus that may aggravate particle-mediated cardiovascular health effects. We hypothesized that the presence of PA can aggravate oxidative stress and endothelial activation induced by multi-walled carbon nanotube (MWCNT) exposure in vitro. We...... measured in the lower chamber on HUVECs and THP-1 cells. The exposure to MWCNTs, including a short (NM400) and long (NM402) type of entangled fibers, was associated with elevated levels of reactive oxygen species as well as a decrease in the intracellular glutathione concentration in HUVEC and A549...

  14. An Efficient Similarity Digests Database Lookup - A Logarithmic Divide & Conquer Approach

    Directory of Open Access Journals (Sweden)

    Frank Breitinger

    2014-09-01

    Full Text Available Investigating seized devices within digital forensics represents a challenging task due to the increasing amount of data. Common procedures utilize automated file identification, which reduces the amount of data an investigator has to examine manually. In the past years the research field of approximate matching arises to detect similar data. However, if n denotes the number of similarity digests in a database, then the lookup for a single similarity digest is of complexity of O(n. This paper presents a concept to extend existing approximate matching algorithms, which reduces the lookup complexity from O(n to O(log(n. Our proposed approach is based on the well-known divide and conquer paradigm and builds a Bloom filter-based tree data structure in order to enable an efficient lookup of similarity digests. Further, it is demonstrated that the presented technique is highly scalable operating a trade-off between storage requirements and computational efficiency. We perform a theoretical assessment based on recently published results and reasonable magnitudes of input data, and show that the complexity reduction achieved by the proposed technique yields a 220-fold acceleration of look-up costs.

  15. Modeling of Failure Prediction Bayesian Network with Divide-and-Conquer Principle

    Directory of Open Access Journals (Sweden)

    Zhiqiang Cai

    2014-01-01

    Full Text Available For system failure prediction, automatically modeling from historical failure dataset is one of the challenges in practical engineering fields. In this paper, an effective algorithm is proposed to build the failure prediction Bayesian network (FPBN model with data mining technology. First, the conception of FPBN is introduced to describe the state of components and system and the cause-effect relationships among them. The types of network nodes, the directions of network edges, and the conditional probability distributions (CPDs of nodes in FPBN are discussed in detail. According to the characteristics of nodes and edges in FPBN, a divide-and-conquer principle based algorithm (FPBN-DC is introduced to build the best FPBN network structures of different types of nodes separately. Then, the CPDs of nodes in FPBN are calculated by the maximum likelihood estimation method based on the built network. Finally, a simulation study of a helicopter convertor model is carried out to demonstrate the application of FPBN-DC. According to the simulations results, the FPBN-DC algorithm can get better fitness value with the lower number of iterations, which verified its effectiveness and efficiency compared with traditional algorithm.

  16. "Divide-and-conquer" semiclassical molecular dynamics: An application to water clusters

    Science.gov (United States)

    Di Liberto, Giovanni; Conte, Riccardo; Ceotto, Michele

    2018-03-01

    We present an investigation of vibrational features in water clusters performed by means of our recently established divide-and-conquer semiclassical approach [M. Ceotto, G. Di Liberto, and R. Conte, Phys. Rev. Lett. 119, 010401 (2017)]. This technique allows us to simulate quantum vibrational spectra of high-dimensional systems starting from full-dimensional classical trajectories and projection of the semiclassical propagator onto a set of lower dimensional subspaces. The potential energy surface employed is a many-body representation up to three-body terms, in which monomers and two-body interactions are described by the high level Wang-Huang-Braams-Bowman (WHBB) water potential, while, for three-body interactions, calculations adopt a fast permutationally invariant ab initio surface at the same level of theory of the WHBB 3-body potential. Applications range from the water dimer up to the water decamer, a system made of 84 vibrational degrees of freedom. Results are generally in agreement with previous variational estimates in the literature. This is particularly true for the bending and the high-frequency stretching motions, while estimates of modes strongly influenced by hydrogen bonding are red shifted, in a few instances even substantially, as a consequence of the dynamical and global picture provided by the semiclassical approach.

  17. Divide and Conquer-Based 1D CNN Human Activity Recognition Using Test Data Sharpening.

    Science.gov (United States)

    Cho, Heeryon; Yoon, Sang Min

    2018-04-01

    Human Activity Recognition (HAR) aims to identify the actions performed by humans using signals collected from various sensors embedded in mobile devices. In recent years, deep learning techniques have further improved HAR performance on several benchmark datasets. In this paper, we propose one-dimensional Convolutional Neural Network (1D CNN) for HAR that employs a divide and conquer-based classifier learning coupled with test data sharpening. Our approach leverages a two-stage learning of multiple 1D CNN models; we first build a binary classifier for recognizing abstract activities, and then build two multi-class 1D CNN models for recognizing individual activities. We then introduce test data sharpening during prediction phase to further improve the activity recognition accuracy. While there have been numerous researches exploring the benefits of activity signal denoising for HAR, few researches have examined the effect of test data sharpening for HAR. We evaluate the effectiveness of our approach on two popular HAR benchmark datasets, and show that our approach outperforms both the two-stage 1D CNN-only method and other state of the art approaches.

  18. Divide and Conquer-Based 1D CNN Human Activity Recognition Using Test Data Sharpening

    Directory of Open Access Journals (Sweden)

    Heeryon Cho

    2018-04-01

    Full Text Available Human Activity Recognition (HAR aims to identify the actions performed by humans using signals collected from various sensors embedded in mobile devices. In recent years, deep learning techniques have further improved HAR performance on several benchmark datasets. In this paper, we propose one-dimensional Convolutional Neural Network (1D CNN for HAR that employs a divide and conquer-based classifier learning coupled with test data sharpening. Our approach leverages a two-stage learning of multiple 1D CNN models; we first build a binary classifier for recognizing abstract activities, and then build two multi-class 1D CNN models for recognizing individual activities. We then introduce test data sharpening during prediction phase to further improve the activity recognition accuracy. While there have been numerous researches exploring the benefits of activity signal denoising for HAR, few researches have examined the effect of test data sharpening for HAR. We evaluate the effectiveness of our approach on two popular HAR benchmark datasets, and show that our approach outperforms both the two-stage 1D CNN-only method and other state of the art approaches.

  19. Divide and Conquer-Based 1D CNN Human Activity Recognition Using Test Data Sharpening †

    Science.gov (United States)

    Yoon, Sang Min

    2018-01-01

    Human Activity Recognition (HAR) aims to identify the actions performed by humans using signals collected from various sensors embedded in mobile devices. In recent years, deep learning techniques have further improved HAR performance on several benchmark datasets. In this paper, we propose one-dimensional Convolutional Neural Network (1D CNN) for HAR that employs a divide and conquer-based classifier learning coupled with test data sharpening. Our approach leverages a two-stage learning of multiple 1D CNN models; we first build a binary classifier for recognizing abstract activities, and then build two multi-class 1D CNN models for recognizing individual activities. We then introduce test data sharpening during prediction phase to further improve the activity recognition accuracy. While there have been numerous researches exploring the benefits of activity signal denoising for HAR, few researches have examined the effect of test data sharpening for HAR. We evaluate the effectiveness of our approach on two popular HAR benchmark datasets, and show that our approach outperforms both the two-stage 1D CNN-only method and other state of the art approaches. PMID:29614767

  20. Palmitate induces VSMC apoptosis via toll like receptor (TLR)4/ROS/p53 pathway.

    Science.gov (United States)

    Zhang, Yuanjun; Xia, Guanghao; Zhang, Yaqiong; Liu, Juxiang; Liu, Xiaowei; Li, Weihua; Lv, Yaya; Wei, Suhong; Liu, Jing; Quan, Jinxing

    2017-08-01

    Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yi, E-mail: yi.luo@pfizer.com; Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated

  3. The Effects of plasticizers and palmitic acid toward the properties of the carrageenan Film

    Science.gov (United States)

    Heru Wibowo, Atmanto; Listiyawati, Oktaviana; Purnawan, Candra

    2016-02-01

    Varied plasticizers and palmitic acid additive have been added in the carrageenan film. The film was made by mixing of the carrageenan and plasticizers (glycerol, polyethylene glycol, polyvinyl alcohol) with composition of 92:3, 90:6, 87:9, 84:12, 81:15(%w/w) and in the presence of palmitic acid as additive with 1%, 2%, 3%, 4%, 5% of total weight. Casting method was used for the film molding and drying at 60oC with the oven for 12 hours. To investigate the effects of plasticizers and additive, some mechanical tests on film were performed. The test result concludes that plasticizers in the film decreased the tensile strength and increased the elongation break of the carrageenan film. The additive of palmitic acid decreased the tensile strength of the carrageenan film and also decreased the-the water absorbance of the film. The highest tensile strength of films made was with the formulation of carrageenan: PEG with composition of 92:3 (% w/w). The highest elongation break of the film was for carrageenan:PVA with the composition of 81: 15 (%w/w) and carrageenan:palmitic acid:PEG with the composition of 92: 3: 1 (%w/w). The lowest water absorption of the film was achieved for carrageenan:PVA:palmitic acid with the composition of 87: 3: 5 (%w/w).

  4. Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKβ pathways.

    Science.gov (United States)

    Zhao, Wenwen; Wu, Chuanhong; Li, Shaojing; Chen, Xiuping

    2016-12-01

    Endothelial inflammation and insulin resistance (IR) has been closely associated with endothelial dysfunction. Adiponectin (APN), an adipocyte-secreted hormone from adipose tissues, showed cardioprotective effects. Here, the protective effect of APN on palmitic acid (PA)-induced endothelial inflammation and IR was investigated. Cultured human umbilical vein endothelial cells (HUVECs) were treated with PA without or without APN pretreatment. The expression of inflammatory cytokines TNF-α, IL-6, adhesion molecule ICAM-1 were determined by western blotting, ELISA, and real-time PCR. The protein expression and protein-protein interaction were determined by western blotting and immunoprecipitation. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) production were monitored with fluorescence probes. PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1 at protein and mRNA levels, which was significantly inhibited by APN. PA treatment caused increase of ROS generation, NOX2, p-IKKβ, p-IκBα, p-p65 expression, and p-IκBα-IKKβ interaction, which were all partly reversed by APN. ROS scavenger N-acetylcysteine (NAC) and NF-κB inhibitor PDTC showed similar effect on PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1. Furthermore, APN and NAC pretreatment restored PA-induced increase of p-IRS-1(S307), decrease of p-IRS-1(Tyr). In addition, insulin-triggered expression of p-IRS-1(Tyr), p-PI3K, p-AKT, p-eNOS and NO generation were inhibited by PA, which were also restored by both APN and NAC. These results suggested that APN ameliorated endothelial inflammation and IR through ROS/IKKβ pathway. This study shed new insights into the mechanisms of APN's cardiovascular protective effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Stevioside counteracts the alpha cell hypersecretion caused by long-term palmitate exposure

    DEFF Research Database (Denmark)

    Hong, Jing; Chen, Jianguo; Jeppesen, Per Bendix

    2006-01-01

    Long-term exposure to fatty acids impairs beta-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on alpha-cells. We therefore studied the prolonged impact of palmitate on alpha-cell function and on the expression of genes related to fuel metabolism. We......-activated receptor-gamma, and stearoyl-CoA desaturase gene expressions in the presence of palmitate (Pacids leads to a hypersecretion of glucagon and an accumulation of TG content in clonal alpha-TC1-6 cells. Stevioside was able to counteract the alpha......-cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes....

  6. Calculating orthologs in bacteria and Archaea: a divide and conquer approach.

    Directory of Open Access Journals (Sweden)

    Mihail R Halachev

    Full Text Available Among proteins, orthologs are defined as those that are derived by vertical descent from a single progenitor in the last common ancestor of their host organisms. Our goal is to compute a complete set of protein orthologs derived from all currently available complete bacterial and archaeal genomes. Traditional approaches typically rely on all-against-all BLAST searching which is prohibitively expensive in terms of hardware requirements or computational time (requiring an estimated 18 months or more on a typical server. Here, we present xBASE-Orth, a system for ongoing ortholog annotation, which applies a "divide and conquer" approach and adopts a pragmatic scheme that trades accuracy for speed. Starting at species level, xBASE-Orth carefully constructs and uses pan-genomes as proxies for the full collections of coding sequences at each level as it progressively climbs the taxonomic tree using the previously computed data. This leads to a significant decrease in the number of alignments that need to be performed, which translates into faster computation, making ortholog computation possible on a global scale. Using xBASE-Orth, we analyzed an NCBI collection of 1,288 bacterial and 94 archaeal complete genomes with more than 4 million coding sequences in 5 weeks and predicted more than 700 million ortholog pairs, clustered in 175,531 orthologous groups. We have also identified sets of highly conserved bacterial and archaeal orthologs and in so doing have highlighted anomalies in genome annotation and in the proposed composition of the minimal bacterial genome. In summary, our approach allows for scalable and efficient computation of the bacterial and archaeal ortholog annotations. In addition, due to its hierarchical nature, it is suitable for incorporating novel complete genomes and alternative genome annotations. The computed ortholog data and a continuously evolving set of applications based on it are integrated in the xBASE database, available

  7. Classification of lung sounds using higher-order statistics: A divide-and-conquer approach.

    Science.gov (United States)

    Naves, Raphael; Barbosa, Bruno H G; Ferreira, Danton D

    2016-06-01

    Lung sound auscultation is one of the most commonly used methods to evaluate respiratory diseases. However, the effectiveness of this method depends on the physician's training. If the physician does not have the proper training, he/she will be unable to distinguish between normal and abnormal sounds generated by the human body. Thus, the aim of this study was to implement a pattern recognition system to classify lung sounds. We used a dataset composed of five types of lung sounds: normal, coarse crackle, fine crackle, monophonic and polyphonic wheezes. We used higher-order statistics (HOS) to extract features (second-, third- and fourth-order cumulants), Genetic Algorithms (GA) and Fisher's Discriminant Ratio (FDR) to reduce dimensionality, and k-Nearest Neighbors and Naive Bayes classifiers to recognize the lung sound events in a tree-based system. We used the cross-validation procedure to analyze the classifiers performance and the Tukey's Honestly Significant Difference criterion to compare the results. Our results showed that the Genetic Algorithms outperformed the Fisher's Discriminant Ratio for feature selection. Moreover, each lung class had a different signature pattern according to their cumulants showing that HOS is a promising feature extraction tool for lung sounds. Besides, the proposed divide-and-conquer approach can accurately classify different types of lung sounds. The classification accuracy obtained by the best tree-based classifier was 98.1% for classification accuracy on training, and 94.6% for validation data. The proposed approach achieved good results even using only one feature extraction tool (higher-order statistics). Additionally, the implementation of the proposed classifier in an embedded system is feasible. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Divide and Conquer (DC BLAST: fast and easy BLAST execution within HPC environments

    Directory of Open Access Journals (Sweden)

    Won Cheol Yim

    2017-06-01

    Full Text Available Bioinformatics is currently faced with very large-scale data sets that lead to computational jobs, especially sequence similarity searches, that can take absurdly long times to run. For example, the National Center for Biotechnology Information (NCBI Basic Local Alignment Search Tool (BLAST and BLAST+ suite, which is by far the most widely used tool for rapid similarity searching among nucleic acid or amino acid sequences, is highly central processing unit (CPU intensive. While the BLAST suite of programs perform searches very rapidly, they have the potential to be accelerated. In recent years, distributed computing environments have become more widely accessible and used due to the increasing availability of high-performance computing (HPC systems. Therefore, simple solutions for data parallelization are needed to expedite BLAST and other sequence analysis tools. However, existing software for parallel sequence similarity searches often requires extensive computational experience and skill on the part of the user. In order to accelerate BLAST and other sequence analysis tools, Divide and Conquer BLAST (DCBLAST was developed to perform NCBI BLAST searches within a cluster, grid, or HPC environment by using a query sequence distribution approach. Scaling from one (1 to 256 CPU cores resulted in significant improvements in processing speed. Thus, DCBLAST dramatically accelerates the execution of BLAST searches using a simple, accessible, robust, and parallel approach. DCBLAST works across multiple nodes automatically and it overcomes the speed limitation of single-node BLAST programs. DCBLAST can be used on any HPC system, can take advantage of hundreds of nodes, and has no output limitations. This freely available tool simplifies distributed computation pipelines to facilitate the rapid discovery of sequence similarities between very large data sets.

  9. Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells.

    Science.gov (United States)

    Haywood, J; Yammani, R R

    2016-05-01

    Obesity is the major risk factor for the development of osteoarthritis (OA); however, the mechanisms involved are not clearly understood. Obesity is associated with increased production of adipokine and elevated levels of circulating free fatty acids (FFA). A recent study has shown that saturated fatty acid palmitate induced pro-inflammatory and pro-apoptotic pathways in chondrocytes. Meniscus has been shown to be more susceptible than articular cartilage to catabolic stimuli. Thus, the aim of this study was to determine the effect of FFA (specifically, palmitate) on meniscus cells. Cultured primary porcine meniscus cells were stimulated with 500 μM FFA (palmitate and oleate) for 24 h to induce endoplasmic reticulum (ER) stress. After treatment, cell lysates were prepared and immunoblotted for C/EBP homologous protein (CHOP). To determine the activation of unfolded protein response (UPR) signaling, cell lysates were probed for cJun n-terminal kinase (JNK), cleaved caspase -3 and Xbp-1s, an alternative mRNA splicing product generated due to Ire1α activation. Treatment of isolated primary meniscus cells with palmitate but not oleate induced expression of CHOP and Xbp-1s. Palmitate treatment of meniscus cells also activated JNK and increased expression of caspase-3, thus promoting apoptosis in meniscus cells. Palmitate induces ER stress and promotes apoptotic pathways in meniscus cells. This is the first study to establish ER stress as a key metabolic mechanistic link between obesity and OA, in addition to (or operating with) biomechanical factors. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. How can a place conquer a position in the mind of potential business investors? : A case study on Dubai

    OpenAIRE

    Kindblom, Henrik; Karlsson, David

    2006-01-01

    Abstract In the age of globalization it has become more and more common that places – cities, regions and nations – work actively to attract business investors; all with the aim to support economic development. Nevertheless, the competition is tough and it is hard to get through the information clutter and conquer a position in the mind of the business investors. Dubai, one of the seven Emirates that form the nation United Arab Emirates, was for many years a general unknown place for business...

  11. Saturated fatty acid palmitate negatively regulates autophagy by promoting ATG5 protein degradation in meniscus cells.

    Science.gov (United States)

    Mallik, Aritra; Yammani, Raghunatha R

    2018-07-20

    Obesity and associated metabolic factors are major risk factors for the development of osteoarthritis. Previously, we have shown that the free fatty acid palmitate induces endoplasmic reticulum (ER) stress and induces apoptosis in meniscus cells. However, the molecular mechanisms involved in these effects are not clearly understood. In our current study, we found that palmitate inhibits autophagy by modulating the protein levels of autophagy-related genes-5 (ATG5) that is associated with decreased lipidation of LC3 and increased activation of cleaved caspase 3. Pretreatment of meniscus cells with 4-phenyl butyric acid, a small molecule chemical chaperone that alleviates ER stress, or with MG-132, a proteasome inhibitor, restored normal levels of ATG5 and autophagosome formation, and decreased expression of cleaved caspase 3. Thus, our data suggest that palmitate downregulates autophagy in meniscus cells by degrading ATG5 protein via ER-associated protein degradation, and thus promotes apoptosis. This is the first study to demonstrate that palmitate-induced endoplasmic reticulum stress negatively regulates autophagy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Palmitate and stearate binding to human serum albumin. Determination of relative binding constants

    DEFF Research Database (Denmark)

    Vorum, H; Fisker, K; Honoré, B

    1997-01-01

    Multiple binding equilibria of two apparently insoluble ligands, palmitate and stearate, to defatted human serum albumin were studied in a 66 mM sodium phosphate buffer (pH 7.4) at 37 degrees C, by determination of dialytic exchange rates of ligands among identical equilibrium solutions. The expe...

  13. The effect of vitamin A palmitate eye gel on ocular surface recovery after LASIK

    Directory of Open Access Journals (Sweden)

    Yan Lu

    2013-04-01

    Full Text Available AIM: To study the effect of vitamin A palmitate eye gel on ocular surface reconstruction after laser in situ keratomileusis(LASIK, and to evaluate the efficacy and safety. METHODS: One hundred and twenty patients(240 eyesperforming LASIK were enrolled in this study. The right and left eyes were randomly divided into experimental group and control group. The experimental group were treated with vitamin A palmitate eye gel for 1 month, four times a day after LASIK, and the same as control group in other treatments. The SchirmerⅠ test, break-up time(BUTand corneal sensation were detect at preoperation and the postoperative 1st day, 1st month, 3rd month in two groups. RESULTS: There were significant difference in BUT and tear secretion quantity between the experimental group and the control group at the postoperative 1st month and 3rd month(P0.05, which revealed that vitamin A palmitate eye gel had no obvious effect on recovery of corneal sensation after LASIK. During the treatment, there was no adverse drug event occurred. CONCLUSION: Early use of vitamin A palmitate eye gel postoperatively is applicable for ocular surface reconstruction, but has no obvious effect on the regeneration of corneal sensation.

  14. Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils

    Energy Technology Data Exchange (ETDEWEB)

    Tone, O.; Miller, J.C.; Bell, J.M.; Rapoport, S.I.

    1987-11-01

    (/sup 14/C)Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion.

  15. Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils

    International Nuclear Information System (INIS)

    Tone, O.; Miller, J.C.; Bell, J.M.; Rapoport, S.I.

    1987-01-01

    [ 14 C]Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion

  16. Synthesis and characterization of arabinose-palmitic acid esters by enzymatic esterification

    NARCIS (Netherlands)

    Pappalardo, Valeria M.; Boeriu, Carmen G.; Zaccheria, Federica; Ravasio, Nicoletta

    2017-01-01

    The direct esterification of palmitic acid with L-(+)-arabinose has been carried out. The use of Candida antartica lipase B as the catalyst and the choice of suitable solvent and experimental conditions allowed carrying out the reaction successfully. In particular 10% dimethyl-sulfoxide in

  17. HDO of Methyl Palmitate over Silica-Supported Ni Phosphides: Insight into Ni/P Effect

    Directory of Open Access Journals (Sweden)

    Irina V. Deliy

    2017-10-01

    Full Text Available Two sets of silica-supported nickel phosphide catalysts with a nickel content of about 2.5 and 10 wt % and Ni/P molar ratio 2/1, 1/1 and 1/2 in each set, were prepared by way of a temperature-programmed reduction method using (Ni(CH3COO2 and ((NH42HPO4 as a precursor. The NixPy/SiO2 catalysts were characterized using chemical analysis N2 physisorption, XRD, TEM, 31P MAS NMR. Methyl palmitate hydrodeoxygenation (HDO was performed in a trickle-bed reactor at 3 MPa and 290 °C with LHSV ranging from 0.3 to 16 h−1. The Ni/P ratio was found to affect the nickel phosphide phase composition, POx groups content and catalytic properties in methyl palmitate HDO with the TOF increased along with a decline of Ni/P ratio and a growth of POx groups’ content. Taking into account the possible routes of methyl palmitate conversion (metal-catalyzed hydrogenolysis or acid-catalyzed hydrolysis, we proposed that the enhancement of acid POx groups’ content with the Ni/P ratio decrease provides an enhancement of the rate of methyl palmitate conversion through the acceleration of acid-catalyzed hydrolysis.

  18. Palmitate Antagonizes Wnt/Beta-catenin Signaling in 3T3-L1 Pre-adipocytes

    Science.gov (United States)

    Long chain saturated free fatty acids such as palmitate (PA) produce insulin resistance, endoplasmic reticulum stress, and apoptosis in mature adipocytes and pre-adipocytes. In pre-adipocytes, saturated free fatty acids also promote adipogenic induction in the presence of adipogenic hormones. Wnt/be...

  19. Esterification of Palmitic Acid with Methanol in the Presence of Macroporous Ion Exchange Resin as Catalyst

    Directory of Open Access Journals (Sweden)

    Amelia Qarina Yaakob and Subhash Bhatia

    2012-10-01

    Full Text Available The esterification of palmitic acid with methanol was studied in a batch reactor using macro porous ion exchange resin Amberlyst 15 as a catalyst. Methyl palmitate was produced from the reaction between palmitic acid and methanol in the presence of catalyst. The effects of processing parameters, molar ratio of alcohol to acid M, (4-10, catalyst loading (0-10 g cat/liter, water inhibition (0-2 mol/liter, agitator speed (200-800 rpm and reaction temperature (343-373K were studied. The experimental kinetic data were correlated using homogenous as well as heterogeneous models (based on single as well as dual site mechanisms. The activation energy of the reaction was 11.552 kJ/mol for forward reaction whilst 5.464 kJ/mol for backward reaction. The experimental data fitted well with the simulated data obtained from the kinetic models. Keywords: Palmitic Acid, Methanol, Esterification, Ion Exchange Resin, Kinetics.

  20. Impact of palmitic acid coating on the water uptake and loss of ammonium sulfate particles

    Directory of Open Access Journals (Sweden)

    R. M. Garland

    2005-01-01

    Full Text Available While water insoluble organics are prevalent in the atmosphere, it is not clear how the presence of such species alters the chemical and physical properties of atmospheric aerosols. Here we use a combination of FTIR spectroscopy, Transmission Electron Microscopy (TEM and Aerosol Mass Spectrometry (AMS to characterize ammonium sulfate particles coated with palmitic acid. Coated aerosols were generated by atomizing pure ammonium sulfate, mixing the particles with a heated flow of nitrogen with palmitic acid vapor, and then flowing the mixture through an in-line oven to create internally mixed particles. The mixing state of the particles was probed using the AMS data and images from the TEM. Both of these probes suggest that the particles were internally mixed. Water uptake by the mixed particles was then probed at 273 K. It was found that for ammonium sulfate containing ~20 wt% palmitic acid the deliquescence relative humidity (DRH was the same as for pure ammonium sulfate (80±3% RH. For particles with ~50 wt% palmitic acid however, the mixed particles began to take up water at relative humidities as low at 69% and continued to slowly take up water to 85% RH without fully deliquescing. In addition to studies of water uptake, water loss was also investigated. Here coatings of up to 50 wt% had no impact on the efflorescence relative humidity. These studies suggest that even if insoluble substances coat salt particles in the atmosphere, there may be relatively little effect on the resulting water uptake and loss.

  1. Improved hydroxypropyl methylcellulose (HPMC) films through incorporation of amylose-sodium palmitate inclusion complexes

    Science.gov (United States)

    Polymer film blends of hydroxypropyl methylcellulose (HPMC) and amylose-sodium palmitate inclusion complexes (Na-Palm) were produced with no plasticizer, and were observed to have improved physical and gas barrier properties as compared with pure HPMC. The crystalline amylose helices incorporating t...

  2. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

    Science.gov (United States)

    Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

    2009-01-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-θ to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-θ nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-θ attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-θ activation, resulting in reduced insulin activity. PMID:19726875

  3. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents.

    Science.gov (United States)

    Benoit, Stephen C; Kemp, Christopher J; Elias, Carol F; Abplanalp, William; Herman, James P; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G; Holland, William L; Clegg, Deborah J

    2009-09-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-theta nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-theta attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activity.

  4. Paliperidone Palmitate for Schizoaffective Disorder: A Review of the Clinical Evidence.

    Science.gov (United States)

    Greenberg, William M; Citrome, Leslie

    2015-12-01

    Despite being frequently diagnosed, there has been very limited study of efficacious treatments for schizoaffective disorder. Paliperidone had been approved for the treatment of schizoaffective disorder, and a recently completed relapse prevention study of the use of a once-monthly injectable paliperidone formulation has also led to an indication for that preparation to treat schizoaffective disorder. To review the efficacy and tolerability of paliperidone for schizoaffective disorder, we conducted a systematic literature search of studies of paliperidone in the treatment of schizoaffective disorder, and briefly reviewed evidence regarding the somewhat controversial nature of that diagnostic entity. We located several studies of the use of paliperidone extended release in the treatment of schizoaffective disorder, but only one completed study of the use of paliperidone palmitate, which demonstrated efficacy in preventing relapse. Three other studies are currently recruiting participants. Efficacy and tolerability were similar to the profile of oral paliperidone in the treatment of individuals with schizophrenia. These results were similar for both individuals treated with paliperidone palmitate alone, and for those treated with paliperidone palmitate with adjunctive mood stabilizers and/or antidepressants. The use of paliperidone palmitate does not require initial co-administration of oral paliperidone, has relatively little risk of drug-drug interactions, and its pharmacokinetics are favorable for once-monthly administration, an important treatment option for individuals with psychotic disorders, who may often be non-adherent to effective medication regimens. Paliperidone palmitate is an approved treatment for schizoaffective disorder, and can be efficacious with or without commonly employed adjunctive treatments.

  5. Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Cho Hyunju

    2013-01-01

    Full Text Available Abstract Background Palmitic acid, the most common saturated free fatty acid, has been implicated in ER (endoplasmic reticulum stress-mediated apoptosis. This lipoapotosis is dependent, in part, on the upregulation of the activating transcription factor-4 (ATF4. To better understand the mechanisms by which palmitate upregulates the expression level of ATF4, we integrated literature information on palmitate-induced ER stress signaling into a discrete dynamic model. The model provides an in silico framework that enables simulations and predictions. The model predictions were confirmed through further experiments in human hepatocellular carcinoma (HepG2 cells and the results were used to update the model and our current understanding of the signaling induced by palmitate. Results The three key things from the in silico simulation and experimental results are: 1 palmitate induces different signaling pathways (PKR (double-stranded RNA-activated protein kinase, PERK (PKR-like ER kinase, PKA (cyclic AMP (cAMP-dependent protein kinase A in a time dependent-manner, 2 both ATF4 and CREB1 (cAMP-responsive element-binding protein 1 interact with the Atf4 promoter to contribute to a prolonged accumulation of ATF4, and 3 CREB1 is involved in ER-stress induced apoptosis upon palmitate treatment, by regulating ATF4 expression and possibly Ca2+ dependent-CaM (calmodulin signaling pathway. Conclusion The in silico model helped to delineate the essential signaling pathways in palmitate-mediated apoptosis.

  6. Acidolysis of terebinth fruit oil with palmitic and caprylic acids in a recirculating packed bed reactor: optimization using response surface methodology

    Energy Technology Data Exchange (ETDEWEB)

    Koçak, D.; Keskin, H.; Fadiloglu, S.; Gögüs, F.

    2016-07-01

    The acidolysis reaction of terebinth fruit oil with caprylic and palmitic acid has been investigated. The reaction was catalyzed by lipase (Lipozyme IM from Rhizomucormiehei) and carried out in recirculating packed bed reactor. The effects of reaction parameters have been analyzed using response surface methodology. Reaction time (3.5–6.5 h), enzyme load (10–20%), substrate flow rate (4–8 mL·min−1 ) and substrate mole ratios (Terebinth oil : Palmitic acid : Caprylic acid, 1:1.83:1.22–1:3.07:2.05) were evaluated. The optimum reaction conditions were 5.9 h reaction time, 10% enzyme load, 4 mL·min−1 substrate flow rate and 1:3.10:2.07 substrate mole ratio. The structured lipid obtained at these optimum conditions had 52.23% desired triacylglycerols and a lower caloric value than that of terebinth fruit oil. The melting characteristics and microstructure of the structured lipid were similar to those of commercial margarine fat extracts. The results showed that the structured lipid had the highest oxidative stability among the studied fats. (Author)

  7. Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Mlejnek, Petr; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Šilhavý, Jan; Strnad, Hynek; Eigner, Sebastian; Eigner-Henke, Kateřina; Škop, V.; Malínská, H.; Trnovská, J.; Kazdová, L.; Drahota, Zdeněk; Mráček, Tomáš; Houštěk, Josef

    2016-01-01

    Roč. 48, č. 6 (2016), s. 420-427 ISSN 1094-8341 R&D Projects: GA MŠk(CZ) LL1204; GA ČR(CZ) GB14-36804G; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 ; RVO:61389005 Keywords : brown adipose tissue * autocrine * transgenic * spontaneously hypertensive rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.044, year: 2016

  8. Efficient dermal delivery of retinyl palmitate: Progressive polarimetry and Raman spectroscopy to evaluate the structure and efficacy.

    Science.gov (United States)

    Lee, Jun Bae; Lee, Dong Ryeol; Choi, Nak Cho; Jang, Jihui; Park, Chun Ho; Yoon, Moung Seok; Lee, Miyoung; Won, Kyoungae; Hwang, Jae Sung; Kim, B Moon

    2015-10-12

    Over the past decades, there has been a growing interest in dermal drug delivery. Although various novel delivery devices and methods have been developed, dermal delivery is still challenging because of problems such as poor drug permeation, instability of vesicles and drug leakage from vesicles induced by fusion of vesicles. To solve the vesicle instability problems in current dermal delivery systems, we developed materials comprised of liquid crystals as a new delivery vehicle of retinyl palmitate and report the characterization of the liquid crystals using a Mueller matrix polarimetry. The stability of the liquid-crystal materials was evaluated using the polarimeter as a novel evaluation tool along with other conventional methods. The dermal delivery of retinyl palmitate was investigated through the use of confocal Raman spectroscopy. The results indicate that the permeation of retinyl palmitate was enhanced by up to 106% compared to that using an ordinary emulsion with retinyl palmitate. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Large-scale atomistic simulations of nanostructured materials based on divide-and-conquer density functional theory

    Directory of Open Access Journals (Sweden)

    Vashishta P.

    2011-05-01

    Full Text Available A linear-scaling algorithm based on a divide-and-conquer (DC scheme is designed to perform large-scale molecular-dynamics simulations, in which interatomic forces are computed quantum mechanically in the framework of the density functional theory (DFT. This scheme is applied to the thermite reaction at an Al/Fe2O3 interface. It is found that mass diffusion and reaction rate at the interface are enhanced by a concerted metal-oxygen flip mechanism. Preliminary simulations are carried out for an aluminum particle in water based on the conventional DFT, as a target system for large-scale DC-DFT simulations. A pair of Lewis acid and base sites on the aluminum surface preferentially catalyzes hydrogen production in a low activation-barrier mechanism found in the simulations

  10. Computerized implementation of higher-order electron-correlation methods and their linear-scaling divide-and-conquer extensions.

    Science.gov (United States)

    Nakano, Masahiko; Yoshikawa, Takeshi; Hirata, So; Seino, Junji; Nakai, Hiromi

    2017-11-05

    We have implemented a linear-scaling divide-and-conquer (DC)-based higher-order coupled-cluster (CC) and Møller-Plesset perturbation theories (MPPT) as well as their combinations automatically by means of the tensor contraction engine, which is a computerized symbolic algebra system. The DC-based energy expressions of the standard CC and MPPT methods and the CC methods augmented with a perturbation correction were proposed for up to high excitation orders [e.g., CCSDTQ, MP4, and CCSD(2) TQ ]. The numerical assessment for hydrogen halide chains, polyene chains, and first coordination sphere (C1) model of photoactive yellow protein has revealed that the DC-based correlation methods provide reliable correlation energies with significantly less computational cost than that of the conventional implementations. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

    OpenAIRE

    Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

    2009-01-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of ...

  12. Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane palmitate accumulation.

    Directory of Open Access Journals (Sweden)

    Laurie-Anne Payet

    Full Text Available The F508del-CFTR mutation, responsible for Cystic Fibrosis (CF, leads to the retention of the protein in the endoplasmic reticulum (ER. The mistrafficking of this mutant form can be corrected by pharmacological chaperones, but these molecules showed limitations in clinical trials. We therefore hypothesized that important factors in CF patients may have not been considered in the in vitro assays. CF has also been associated with an altered lipid homeostasis, i. e. a decrease in polyunsaturated fatty acid levels in plasma and tissues. However, the precise fatty acyl content of membrane phospholipids from human CF bronchial epithelial cells had not been studied to date. Since the saturation level of phospholipids can modulate crucial membrane properties, with potential impacts on membrane protein folding/trafficking, we analyzed this parameter for freshly isolated bronchial epithelial cells from CF patients. Interestingly, we could show that Palmitate, a saturated fatty acid, accumulates within Phosphatidylcholine (PC in CF freshly isolated cells, in a process that could result from hypoxia. The observed PC pattern can be recapitulated in the CFBE41o(- cell line by incubation with 100 µM Palmitate. At this concentration, Palmitate induces an ER stress, impacts calcium homeostasis and leads to a decrease in the activity of the corrected F508del-CFTR. Overall, these data suggest that bronchial epithelial cells are lipointoxicated by hypoxia-related Palmitate accumulation in CF patients. We propose that this phenomenon could be an important bottleneck for F508del-CFTR trafficking correction by pharmacological agents in clinical trials.

  13. High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes.

    Science.gov (United States)

    Nazli, S A; Loeser, R F; Chubinskaya, S; Willey, J S; Yammani, R R

    2017-09-01

    Insulin-like growth factor-1 (IGF-1) promotes matrix synthesis and cell survival in cartilage. Chondrocytes from aged and osteoarthritic cartilage have a reduced response to IGF-1. The purpose of this study was to determine the effect of free fatty acids (FFA) present in a high-fat diet on IGF-1 function in cartilage and the role of endoplasmic reticulum (ER) stress. C57BL/6 male mice were maintained on either a high-fat (60% kcal from fat) or a low-fat (10% kcal from fat) diet for 4 months. Mice were then sacrificed; femoral head cartilage caps were collected and treated with IGF-1 to measure proteoglycan (PG) synthesis. Cultured human chondrocytes were treated with 500 μM FFA palmitate or oleate, followed by stimulation with (100 ng/ml) IGF-1 overnight to measure CHOP (a protein marker for ER stress) and PG synthesis. Human chondrocytes were pre-treated with palmitate or 1 mM 4-phenyl butyric acid (PBA) or 1 μM C-Jun N terminal Kinase (JNK) inhibitor, and IGF-1 function (PG synthesis and signaling) was measured. Cartilage explants from mice on the high fat-diet showed reduced IGF-1 mediated PG synthesis compared to a low-fat group. Treatment of human chondrocytes with palmitate induced expression of CHOP, activated JNK and inhibited IGF-1 function. PBA, a small molecule chemical chaperone that alleviates ER stress rescued IGF-1 function and a JNK inhibitor rescued IGF-1 signaling. Palmitate-induced ER stress inhibited IGF-1 function in chondrocytes/cartilage via activating the mitogen-activated protein (MAP) kinase JNK. This is the first study to demonstrate that ER stress is metabolic factor that regulates IGF-1 function in chondrocytes. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult

    OpenAIRE

    Zhangyang Qi; Meihao Wu; Yun Fu; Tengfei Huang; Tingting Wang; Yanjie Sun; Zhibo Feng; Changzheng Li

    2017-01-01

    Background/Aims: The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer’s disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane...

  15. A Case of Ileus in a Patient with Schizophrenia Under Paliperidone Palmitate Treatment

    OpenAIRE

    Can, Serdar S?leyman; Kabaday?, Esra

    2016-01-01

    Constipation is a side effect of antipsychotic drugs that have high affinity for muscarinic cholinergic receptors. In addition, ileus is an important side effect of antipsychotic treatment, with potentially morbid and mortal consequences if early detection fails. In this report, a colonic ileus case is described in a patient with schizophrenia under the treatment of paliperidone palmitate. Consequently, complete physical examination and close screening of side effects are recommended when ant...

  16. A divide-and-conquer approach to determine the Pareto frontier for optimization of protein engineering experiments.

    Science.gov (United States)

    He, Lu; Friedman, Alan M; Bailey-Kellogg, Chris

    2012-03-01

    In developing improved protein variants by site-directed mutagenesis or recombination, there are often competing objectives that must be considered in designing an experiment (selecting mutations or breakpoints): stability versus novelty, affinity versus specificity, activity versus immunogenicity, and so forth. Pareto optimal experimental designs make the best trade-offs between competing objectives. Such designs are not "dominated"; that is, no other design is better than a Pareto optimal design for one objective without being worse for another objective. Our goal is to produce all the Pareto optimal designs (the Pareto frontier), to characterize the trade-offs and suggest designs most worth considering, but to avoid explicitly considering the large number of dominated designs. To do so, we develop a divide-and-conquer algorithm, Protein Engineering Pareto FRontier (PEPFR), that hierarchically subdivides the objective space, using appropriate dynamic programming or integer programming methods to optimize designs in different regions. This divide-and-conquer approach is efficient in that the number of divisions (and thus calls to the optimizer) is directly proportional to the number of Pareto optimal designs. We demonstrate PEPFR with three protein engineering case studies: site-directed recombination for stability and diversity via dynamic programming, site-directed mutagenesis of interacting proteins for affinity and specificity via integer programming, and site-directed mutagenesis of a therapeutic protein for activity and immunogenicity via integer programming. We show that PEPFR is able to effectively produce all the Pareto optimal designs, discovering many more designs than previous methods. The characterization of the Pareto frontier provides additional insights into the local stability of design choices as well as global trends leading to trade-offs between competing criteria. Copyright © 2011 Wiley Periodicals, Inc.

  17. High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Peng Lu

    Full Text Available BACKGROUND: Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate, the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate, the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF diet and high beta-palmitate fat (HBPF diet on colitis development in Muc2 deficient (Muc2(-/- mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. METHODS: Muc2(-/- mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. RESULTS: Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/- mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1, genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. CONCLUSIONS: This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/- mice by inducing an immunosuppressive Treg cell response.

  18. High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.

    Science.gov (United States)

    Lu, Peng; Bar-Yoseph, Fabiana; Levi, Liora; Lifshitz, Yael; Witte-Bouma, Janneke; de Bruijn, Adrianus C J M; Korteland-van Male, Anita M; van Goudoever, Johannes B; Renes, Ingrid B

    2013-01-01

    Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate), the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF) diet and high beta-palmitate fat (HBPF) diet on colitis development in Muc2 deficient (Muc2(-/-)) mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. Muc2(-/-) mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/-) mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg) cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1), genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/-) mice by inducing an immunosuppressive Treg cell response.

  19. Modification of Turen Bentonite with AlCl3 for Esterification of Palmitic Acid

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    Abdulloh Abdulloh

    2014-03-01

    Full Text Available Natural Turen bentonite has been modified and applied as catalyst for palmitic acid esterification. Modification of natural Turen bentonite was conducted by cation exchange method using AlCl3 solution. Catalyst characterization was performed on X-ray Fluoroscence, X-ray Diffraction, nitrogen adsorption-desorption and infrared spectroscopy techniques. The catalytic activity test in the esterification reaction of palmitic acid with methanol was conducted by bath at 65 °C with a variation of reaction time of 1, 2, 3, 4 and 5 h. Catalytic activity has been observed qualitatively using GC-MS and quantitatively by changes in acid number. The analysis showed the formation of Al3+-bentonite. Observation on the elements has shown that the presence of calcium decreased from 10.2% to 4.17%, with an increase of aluminium content from 9.9% to 13%. Diffraction line at 2θ 5.7379º became 5.6489º, along with changes in d-spacing of 15.3895 Å to 15.6319 Å. The surface area increased from 83.78 m2/g to 91.26 m2/g, while Brönsted acid sites increased from 10.2 µmol/g to 67.5 µmol/g and Lewis acid sites increased from 94.9 µmol/g to 132 µmol/g. Furthermore, Al3+-bentonite has showed as active catalyst in the esterification reaction of palmitic acid with palmitic acid with conversion of 78.78% for 5 h. © 2014 BCREC UNDIP. All rights reservedReceived: 24th September 2013; Revised: 31st December 2013; Accepted: 26th January 2014[How to Cite: Abdulloh, A., Maryam, S., Aminah, N.S., Triyono, T., Trisunaryanti, W., Mudasir, M., Prasetyoko, D. (2014. Modification of Turen’s Bentonite with AlCl3 for Esterification of Palmitic Acid. Bulletin of Chemical Reaction Engineering & Catalysis, 9 (1: 66-73. (doi:10.9767/bcrec.9.1.5513.66-73][Permalink/DOI: http://dx.doi.org/10.9767/bcrec.9.1.5513.66-73

  20. Oleate ameliorates palmitate-induced reduction of NAMPT activity and NAD levels in primary human hepatocytes and hepatocarcinoma cells.

    Science.gov (United States)

    Penke, Melanie; Schuster, Susanne; Gorski, Theresa; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

    2017-10-03

    Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) levels are crucial for liver function. The saturated fatty acid palmitate and the unsaturated fatty acid oleate are the main free fatty acids in adipose tissue and human diet. We asked how these fatty acids affect cell survival, NAMPT and NAD levels in HepG2 cells and primary human hepatocytes. HepG2 cells were stimulated with palmitate (0.5mM), oleate (1mM) or a combination of both (0.5mM/1mM) as well as nicotinamide mononucleotide (NMN) (0.5 mM) or the specific NAMPT inhibitor FK866 (10nM). Cell survival was measured by WST-1 assay and Annexin V/propidium iodide staining. NAD levels were determined by NAD/NADH Assay or HPLC. Protein and mRNA levels were analysed by Western blot analyses and qPCR, respectively. NAMPT enzyme activity was measured using radiolabelled 14 C-nicotinamide. Lipids were stained by Oil red O staining. Palmitate significantly reduced cell survival and induced apoptosis at physiological doses. NAMPT activity and NAD levels significantly declined after 48h of palmitate. In addition, NAMPT mRNA expression was enhanced which was associated with increased NAMPT release into the supernatant, while intracellular NAMPT protein levels remained stable. Oleate alone did not influence cell viability and NAMPT activity but ameliorated the negative impact of palmitate on cell survival, NAMPT activity and NAD levels, as well as the increased NAMPT mRNA expression and secretion. NMN was able to normalize intracellular NAD levels but did not ameliorate cell viability after co-stimulation with palmitate. FK866, a specific NAMPT inhibitor did not influence lipid accumulation after oleate-treatment. Palmitate targets NAMPT activity with a consequent cellular depletion of NAD. Oleate protects from palmitate-induced apoptosis and variation of NAMPT and NAD levels. Palmitate-induced cell stress leads to an increase of NAMPT mRNA and accumulation in the supernatant. However

  1. Astragalus Polysaccharide Improves Palmitate-Induced Insulin Resistance by Inhibiting PTP1B and NF-κB in C2C12 Myotubes

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    Yong Li

    2012-06-01

    Full Text Available We investigated the effects of Astragalus polysaccharide (APS on palmitate-induced insulin resistance in C2C12 skeletal muscle myotubes. Palmitate-reduced glucose uptake was restored by APS. APS prevented palmitate-induced C2C12 myotubes from impaired insulin signaling by inhibiting Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 and increasing Ser473 phosphorylation of Akt. Moreover, the increases in protein-tyrosine phosphatase-1B (PTP1B protein level and NF-κB activation associated with palmitate treatment were also prevented by APS. However the treatment with APS didn’t change AMP-activated protein kinase (AMPK activation in palmitate-induced myotubes. The results of the present study suggest that Astragalus polysaccharide inhibits palmitate-induced insulin resistance in C2C12 myotubes by inhibiting expression of PTP1B and regulating NF-κB but not AMPK pathway.

  2. Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

    Science.gov (United States)

    Perry, Ben D; Rahnert, Jill A; Xie, Yang; Zheng, Bin; Woodworth-Hobbs, Myra E; Price, S Russ

    2018-01-01

    Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4). Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory indicators of TLR4 activation (IL-6 and TNFα) and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

  3. Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

    Directory of Open Access Journals (Sweden)

    Ben D Perry

    Full Text Available Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4. Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides, palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242. Inflammatory indicators of TLR4 activation (IL-6 and TNFα and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

  4. Conquering the Mesoscale of Africa's Landscapes: deciphering the Genomic Record of Individuating Landforms with Geoecodynamics

    Science.gov (United States)

    Cotterill, Fenton P. D.

    2016-04-01

    through to continental scales). Our ability to reconstruct narratives of landscape dynamics of encompassing - mega-geomorphic - patterns can only be as good as the details of individual events we can discern in Earth history. Obviously, recognizing the centrality of "Conquering the Mesoscale" as the intrinsic prerequisite to test competing hypotheses of landscape dynamics, in the earth system context, calls for innovative research approaches. This is where Africa holds vast potential. The continent is the most remarkable natural laboratory to explore and tackle these challenges where we seek to build the composite mega-geomorphic chronicle informed in the detail of mesoscale process and form. But how does geomorphology, embedded in an earth system framework, advance beyond the established approaches in process and mega-geomorphology? The latter's limitations to reconstruct the tempo and mode of African landforms and palaeoenviroments reveal the stark limits for researchers. This is where a geobiological approach brings interesting opportunities, especially for Africa. Consider, for one, the interlinking patterns of high endemism and geographical heterogeneity of extant biodiversity across the continent, and moreover the interplay in biotic turnovers since the Mesozoic that shaped these regional and more local patterns. These individuated biotic assemblages making up the continent's biomes and ecoregions reveal strident congruence with physiographic controls: especially relief, drainage and edaphic variables. Calibrated by molecular clocks, resolved with DNA evidence, timetrees of this phylogenetic diversity reveal a richness of evolutionary signals; the spectrum of these spectacular biotic radiations of African biodiversity range from the Late Mesozoic to Recent. The temporal spread of this phylogenetic diversity is exemplified, for example, in the extant mammal fauna: witness the Afrotheria compared to the Bovidae (Kingdon J et al. 2013. Mammals of Africa. Bloomsbury

  5. Phase equilibrium measurements and thermodynamic modelling for the system (CO2 + ethyl palmitate + ethanol) at high pressures

    International Nuclear Information System (INIS)

    Gaschi, Priscilla S.; Mafra, Marcos R.; Ndiaye, Papa M.; Corazza, Marcos L.

    2013-01-01

    Graphical abstract: Ethyl palmitate and biodiesel comparison in a pressure–composition diagram for the systems (CO 2 + ethyl palmitate + biodiesel), at different temperatures. Highlights: ► We measured VLE, LLE, and VLLE for the system (CO 2 + ethyl palmitate + ethanol). ► The saturation pressures were obtained using a variable-volume view cell. ► Phase envelope of (CO 2 + ethyl palmitate) is different that (CO 2 + soybean oil biodiesel). ► The experimental data were modeled using PR-vdW2 and PR–WS equations of state. - Abstract: This work reports phase equilibrium measurements for the binary {CO 2 (1) + ethyl palmitate(2)} and ternary {CO 2 (1) + ethyl palmitate(2) + ethanol(3)} systems at high pressures. There is currently great interest in biodiesel production processes involving supercritical and/or pressurized solvents, such as non-catalytic supercritical biodiesel production and enzyme-catalysed biodiesel production. Also, supercritical CO 2 can offer an interesting alternative for glycerol separation in the biodiesel purification step in a water-free process. In this context, the main goal of this work was to investigate the phase behaviour of binary and ternary systems involving CO 2 , a pure constituent of biodiesel ethyl palmitate and ethanol. Experiments were carried out in a high-pressure variable-volume view cell with operating temperatures ranging from (303.15 to 353.15) K and pressures up to 21 MPa. The CO 2 mole fraction ranged from 0.5033 to 0.9913 for the binary {CO 2 (1) + ethyl palmitate(2)} system and from 0.4436 to 0.9712 for ternary system {CO 2 (1) + ethyl palmitate(2) + ethanol(3)} system with ethyl ester to ethanol molar ratios of (1:6), (1:3), and (1:1). For the systems investigated, vapour–liquid (VL), liquid–liquid (LL) and vapour–liquid–liquid (VLL) phase transitions were observed. The experimental data sets were successfully modeled using the Peng–Robinson equation of state with the classical van der Waals

  6. The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanol encapsulated in solid lipid nanoparticles.

    Science.gov (United States)

    Ruktanonchai, Uracha; Limpakdee, Surachai; Meejoo, Siwaporn; Sakulkhu, Usawadee; Bunyapraphatsara, Nuntavan; Junyaprasert, Varaporn; Puttipipatkhachorn, Satit

    2008-03-05

    This present study was aimed at investigating the effect of the crystallinity of cetyl palmitate based solid lipid nanoparticles (SLNs) on the physical properties of γ-oryzanol-loaded SLNs. SLNs consisting of varying ratios of cetyl palmitate and γ-oryzanol were prepared. Their hydrodynamic diameters were in the range 210-280 nm and the zeta potentials were in the range -27 to -35 mV. The size of SLNs increased as the amount of cetyl palmitate decreased whereas no significant change of zeta potentials was found. Atomic force microscopy pictures indicated the presence of disc-like particles. The crystallinity of SLNs, determined by differential scanning calorimetry and powder x-ray diffraction, was directly dependent on the ratio of cetyl palmitate to γ-oryzanol and decreased with decreasing cetyl palmitate content in the lipid matrix. Varying this ratio in the lipid mix resulted in a shift in the melting temperature and enthalpy, although the SLN structure remained unchanged as an orthorhombic lamellar lattice. This has been attributed to a potential inhibition by γ-oryzanol during lipid crystal growth as well as a less ordered structure of the SLNs. The results revealed that the crystallinity of the SLNs was mainly dependent on the solid lipid, and that the crystallinity has an important impact on the physical characteristics of active-loaded SLNs.

  7. The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanol encapsulated in solid lipid nanoparticles

    International Nuclear Information System (INIS)

    Ruktanonchai, Uracha; Sakulkhu, Usawadee; Limpakdee, Surachai; Meejoo, Siwaporn; Bunyapraphatsara, Nuntavan; Junyaprasert, Varaporn; Puttipipatkhachorn, Satit

    2008-01-01

    This present study was aimed at investigating the effect of the crystallinity of cetyl palmitate based solid lipid nanoparticles (SLNs) on the physical properties of γ-oryzanol-loaded SLNs. SLNs consisting of varying ratios of cetyl palmitate and γ-oryzanol were prepared. Their hydrodynamic diameters were in the range 210-280 nm and the zeta potentials were in the range -27 to -35 mV. The size of SLNs increased as the amount of cetyl palmitate decreased whereas no significant change of zeta potentials was found. Atomic force microscopy pictures indicated the presence of disc-like particles. The crystallinity of SLNs, determined by differential scanning calorimetry and powder x-ray diffraction, was directly dependent on the ratio of cetyl palmitate to γ-oryzanol and decreased with decreasing cetyl palmitate content in the lipid matrix. Varying this ratio in the lipid mix resulted in a shift in the melting temperature and enthalpy, although the SLN structure remained unchanged as an orthorhombic lamellar lattice. This has been attributed to a potential inhibition by γ-oryzanol during lipid crystal growth as well as a less ordered structure of the SLNs. The results revealed that the crystallinity of the SLNs was mainly dependent on the solid lipid, and that the crystallinity has an important impact on the physical characteristics of active-loaded SLNs

  8. Palmitic acid follows a different metabolic pathway than oleic acid in human skeletal muscle cells; lower lipolysis rate despite an increased level of adipose triglyceride lipase.

    Science.gov (United States)

    Bakke, Siril S; Moro, Cedric; Nikolić, Nataša; Hessvik, Nina P; Badin, Pierre-Marie; Lauvhaug, Line; Fredriksson, Katarina; Hesselink, Matthijs K C; Boekschoten, Mark V; Kersten, Sander; Gaster, Michael; Thoresen, G Hege; Rustan, Arild C

    2012-10-01

    Development of insulin resistance is positively associated with dietary saturated fatty acids and negatively associated with monounsaturated fatty acids. To clarify aspects of this difference we have compared the metabolism of oleic (OA, monounsaturated) and palmitic acids (PA, saturated) in human myotubes. Human myotubes were treated with 100μM OA or PA and the metabolism of [(14)C]-labeled fatty acid was studied. We observed that PA had a lower lipolysis rate than OA, despite a more than two-fold higher protein level of adipose triglyceride lipase after 24h incubation with PA. PA was less incorporated into triacylglycerol and more incorporated into phospholipids after 24h. Supporting this, incubation with compounds modifying lipolysis and reesterification pathways suggested a less influenced PA than OA metabolism. In addition, PA showed a lower accumulation than OA, though PA was oxidized to a relatively higher extent than OA. Gene set enrichment analysis revealed that 24h of PA treatment upregulated lipogenesis and fatty acid β-oxidation and downregulated oxidative phosphorylation compared to OA. The differences in lipid accumulation and lipolysis between OA and PA were eliminated in combination with eicosapentaenoic acid (polyunsaturated fatty acid). In conclusion, this study reveals that the two most abundant fatty acids in our diet are partitioned toward different metabolic pathways in muscle cells, and this may be relevant to understand the link between dietary fat and skeletal muscle insulin resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. A Divide-and-Conquer Approach for Solving Fuzzy Max-Archimedean t-Norm Relational Equations

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    Jun-Lin Lin

    2014-01-01

    Full Text Available A system of fuzzy relational equations with the max-Archimedean t-norm composition was considered. The relevant literature indicated that this problem can be reduced to the problem of finding all the irredundant coverings of a binary matrix. A divide-and-conquer approach is proposed to solve this problem and, subsequently, to solve the original problem. This approach was used to analyze the binary matrix and then decompose the matrix into several submatrices such that the irredundant coverings of the original matrix could be constructed using the irredundant coverings of each of these submatrices. This step was performed recursively for each of these submatrices to obtain the irredundant coverings. Finally, once all the irredundant coverings of the original matrix were found, they were easily converted into the minimal solutions of the fuzzy relational equations. Experiments on binary matrices, with the number of irredundant coverings ranging from 24 to 9680, were also performed. The results indicated that, for test matrices that could initially be partitioned into more than one submatrix, this approach reduced the execution time by more than three orders of magnitude. For the other test matrices, this approach was still useful because certain submatrices could be partitioned into more than one submatrix.

  10. Hierarchical Artificial Bee Colony Optimizer with Divide-and-Conquer and Crossover for Multilevel Threshold Image Segmentation

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    Maowei He

    2014-01-01

    Full Text Available This paper presents a novel optimization algorithm, namely, hierarchical artificial bee colony optimization (HABC, for multilevel threshold image segmentation, which employs a pool of optimal foraging strategies to extend the classical artificial bee colony framework to a cooperative and hierarchical fashion. In the proposed hierarchical model, the higher-level species incorporates the enhanced information exchange mechanism based on crossover operator to enhance the global search ability between species. In the bottom level, with the divide-and-conquer approach, each subpopulation runs the original ABC method in parallel to part-dimensional optimum, which can be aggregated into a complete solution for the upper level. The experimental results for comparing HABC with several successful EA and SI algorithms on a set of benchmarks demonstrated the effectiveness of the proposed algorithm. Furthermore, we applied the HABC to the multilevel image segmentation problem. Experimental results of the new algorithm on a variety of images demonstrated the performance superiority of the proposed algorithm.

  11. Synthesis of Renewable Diesel Range Alkanes by Hydrodeoxygenation of Palmitic Acid over 5% Ni/CNTs under Mild Conditions

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    Yanan Duan

    2017-03-01

    Full Text Available Recently, the catalytic upgrading of bio-oil to renewable diesel has been attracting more and more attention. In the current paper, carbon nanotube (CNT-supported nickel catalysts, namely, 5% Ni/CNTs, were prepared for liquid hydrocarbon production through the deoxygenation of palmitic acid, the model compound of bio-oil under a mild condition of 240 °C reaction temperature and 2 MPa H2 pressure. The experimental results revealed that the main reaction product was pentadecane (yield of 89.64% at an optimum palmitic acid conversion of 97.25% via the hydrodecarbonylation (HDC process. The deoxygenation mechanism for palmitic acid conversion was also investigated. This study provides technical parameters and a theoretical basis for further industrialization in the bio-oil upgrading process.

  12. Beta Palmitate Improves Bone Length and Quality during Catch-Up Growth in Young Rats

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    Meytal Bar-Maisels

    2017-07-01

    Full Text Available Palmitic acid (PA is the most abundant saturated fatty acid in human milk, where it is heavily concentrated in the sn-2-position (termed beta palmitate, BPA and as such is conserved in all women, regardless of their diet or ethnicity, indicating its physiological and metabolic importance. We hypothesized that BPA improves the efficiency of nutrition-induced catch up growth as compared to sn-1,3 PA, which is present in vegetable oil. Pre-pubertal male rats were subjected to a 17 days food restriction followed by re-feeding for nine days with 1,3 PA or BPA-containing diets. We measured bone length, epiphyseal growth plate height (EGP, histology, bone quality (micro-CT and 3-point bending assay, and gene expression (Affymetrix. The BPA-containing diet improved most growth parameters: humeri length and EGP height were greater in the BPA-fed animals. Further analysis of the EGP revealed that the hypertrophic zone was significantly higher in the BPA group. In addition, Affymetrix analysis revealed that the diet affected the expression of several genes in the liver and EGP. Despite the very subtle difference between the diets and the short re-feeding period, we found a small but significant improvement in most growth parameters in the BPA-fed rats. This pre-clinical study may have important implications, especially for children with growth disorders and children with special nutritional needs.

  13. Paliperidone Palmitate Improves and Maintains Functioning in Asia-Pacific Patients with Schizophrenia.

    Science.gov (United States)

    Zhang, Hongyan; Turkoz, Ibrahim; Zhuo, Jianmin; Mathews, Maju; Tan, Wilson; Feng, Yu

    2017-11-01

    Post hoc analyses (two single-arm studies) were conducted to determine the impact of once-monthly injection of paliperidone palmitate on functioning in adult patients with schizophrenia in the Asia-Pacific region. Study 1 enrolled hospitalized patients with acute exacerbation of schizophrenia, and study 2 enrolled patients with recently diagnosed schizophrenia unsatisfactorily treated with oral antipsychotics. Patients received paliperidone palmitate, 150 mg eq. on day 1, 100 mg eq. on day 8, then once monthly (50-150 mg eq.) (study 1, days 36 and 64; study 2, 18 months). Functional status was evaluated by Personal and Social Performance score in both studies and employment only in study 2. In study 1, 54 of 184 patients (29.4%) with an unfavorable level of functioning at the baseline improved to a favorable level (Personal and Social Performance score greater than 70) at day 92. This improvement was significantly greater among patients with recently diagnosed schizophrenia (5 years or less) compared with patients with chronic schizophrenia (more than 5 years): 40% versus 22% (p schizophrenia. Janssen-Cilag Asia-Pacific Medical Affairs.

  14. Lauric and palmitic acids eutectic mixture as latent heat storage material for low temperature heating applications

    International Nuclear Information System (INIS)

    Tuncbilek, Kadir; Sari, Ahmet; Tarhan, Sefa; Erguenes, Gazanfer; Kaygusuz, Kamil

    2005-01-01

    Palmitic acid (PA, 59.8 deg. C) and lauric acid (LA, 42.6 deg. C) are phase change materials (PCM) having quite high melting temperatures which can limit their use in low temperature solar applications such as solar space heating and greenhouse heating. However, their melting temperatures can be tailored to appropriate value by preparing a eutectic mixture of the lauric and the palmitic acids. In the present study, the thermal analysis based on differential scanning calorimetry (DSC) technique shows that the mixture of 69.0 wt% LA and 31 wt% PA forms a eutectic mixture having melting temperature of 35.2 deg. C and the latent heat of fusion of 166.3 J g -1 . This study also considers the experimental determination of the thermal characteristics of the eutectic mixture during the heat charging and discharging processes. Radial and axial temperature distribution, heat transfer coefficient between the heat transfer fluid (HTF) pipe and the PCM, heat recovery rate and heat charging and discharging fractions were experimentally established employing a vertical concentric pipe-in-pipe energy storage system. The changes of these characteristics were evaluated with respect to the effect of inlet HTF temperature and mass flow rate. The DSC thermal analysis and the experimental results indicate that the LA-PA eutectic mixture can be a potential material for low temperature thermal energy storage applications in terms of its thermo-physical and thermal characteristics

  15. Palmitic acid/polypyrrole composites as form-stable phase change materials for thermal energy storage

    International Nuclear Information System (INIS)

    Silakhori, Mahyar; Metselaar, Hendrik Simon Cornelis; Mahlia, Teuku Meurah Indra; Fauzi, Hadi; Baradaran, Saeid; Naghavi, Mohammad Sajad

    2014-01-01

    Highlights: • A novel phase change composite of palmitic acid–polypyrrole(PA–PPy) was fabricated. • Thermal properties of PA–PPy are characterized in different mass ratios of PA–PPy. • Thermal cycling test showed that form stable PCM had a favorable thermal reliability. - Abstract: In this study a novel palmitic acid (PA)/polypyrrole (PPy) form-stable PCMs were readily prepared by in situ polymerization method. PA was used as thermal energy storage material and PPy was operated as supporting material. Form-stable PCMs were investigated by SEM (scanning electron microscopy) and FTIR (Fourier transform infrared spectrometer) analysis that illustrated PA Particles were wrapped by PPy particles. XRD (X-ray diffractometer) was used for crystalline phase of PA/PPy composites. Thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC) were used for investigating Thermal stability and thermal energy storage properties of prepared form-stable PCMs. According to the obtained results the form stable PCMs exhibited favorable thermal stability in terms of their phase change temperature. The form-stable PCMs (79.9 wt% loading of PA) were considered as the highest loading PCM with desirable latent heat storage of 166.3 J/g and good thermal stability. Accelerated thermal cycling tests also showed that form stable PCM had an acceptable thermal reliability. As a consequence of acceptable thermal properties, thermal stability and chemical stability, we can consider the new kind of form stable PCMs for low temperature solar thermal energy storage applications

  16. Preparation and Characterization of a Solid Acid Catalyst from Macro Fungi Residue for Methyl Palmitate Production

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    Min Wang

    2015-07-01

    Full Text Available During the process of fungal polysaccharide extraction for health care products and food factories, a large quantity of macro-fungi residues are produced, but most of the residues are abandoned and become environmental pollutants. A solid acid catalyst, prepared by sulfonating carbonized Phellinus igniarius residue, was shown to be an efficient and environmentally benign catalyst for the esterification of palmitate acid (PA and methanol. As a comparison, two types of common biomass catalysts, wheat straws and wood chips, were prepared. In this study, characterizations, including scanning electron microscopy, thermo-gravimetric analysis, Fourier transform infrared spectrometry, Brunauer-Emmett-Teller assays and elemental analysis, and reaction conditions for the synthesis of methyl palmitate (MP using solid acid catalysts were investigated. Experiments showed that the solid acid catalyst prepared from P. igniarius residue had a higher catalytic activity than the other two catalysts, and the highest yield of MP catalyzed by P. igniarius residue solid acid catalyst was 91.5% under the following optimum conditions: molar ratio of methanol/PA of 10:1, reaction temperature of 60 °C, mass ratio of catalyst/substrate of 2%, and a reaction time of 1.5 h. Thus, the use of this catalyst offers a method for producing MP.

  17. Metabolic reserve in normal myocardium assessed by positron emission tomography with C-11 palmitate

    International Nuclear Information System (INIS)

    Tamaki, Nagara; Kawamoto, Masahide; Takahashi, Norio; Yonekura, Yoshiharu; Magata, Yasuhiro; Nohara, Ryuji; Kambara, Hirofumi; Kawai, Chuichi; Konishi, Junji

    1991-01-01

    Positron emission tomography (PET) with C-11 palmitate has been used in estimating the myocardial utilization of free fatty acid. To assess the metabolic reserve in normal subjects, a PET study was performed at control and during dobutamine infusion at 2 hour intervals in 5 normal subjects. Following monoexponential curve fitting of the time activity curve of the myocardium, the clearance half time (min) and residual fraction (%) were calculated as indices of β-oxydation of free fatty acid. A significant increase in the heart rate and systolic blood pressure were observed during dobutamine infusion (65±5 vs 100±29 bpm, p<0.05 and 119±12 vs 144±16 mmHg, p<0.01, respectively). The clearance half-time and the residual fraction were significantly decreased (23.4±2.6 vs 15.8±2.3 min and 67.0±2.5 vs 58.6±4.0%, p<0.05, each). When the left ventricular myocardium was divided into 4 segments, these indices were similar at control and uniformly decreased without regional differences during dobutamine infusion. These data suggest that β-oxydation of free fatty acid may be uniformly increased in the left ventricular myocardium in relation to the increase in cardiac work in normal subjects. PET with C-11 palmitate at control and during dobutamine infusion is considered to be promising in assessing metabolic reserve in the myocardium. (author)

  18. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

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    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  19. D-isoascorbyl palmitate: lipase-catalyzed synthesis, structural characterization and process optimization using response surface methodology.

    Science.gov (United States)

    Sun, Wen-Jing; Zhao, Hong-Xia; Cui, Feng-Jie; Li, Yun-Hong; Yu, Si-Lian; Zhou, Qiang; Qian, Jing-Ya; Dong, Ying

    2013-07-08

    Isoascorbic acid is a stereoisomer of L-ascorbic acid, and widely used as a food antioxidant. However, its highly hydrophilic behavior prevents its application in cosmetics or fats and oils-based foods. To overcome this problem, D-isoascorbyl palmitate was synthesized in the present study for improving the isoascorbic acid's oil solubility with an immobilized lipase in organic media. The structural information of synthesized product was clarified using LC-ESI-MS, FT-IR, 1H and 13C NMR analysis, and process parameters for high yield of D-isoascorbyl palmitate were optimized by using One-factor-at-a-time experiments and response surface methodology (RSM). The synthesized product had the purity of 95% and its structural characteristics were confirmed as isoascorbyl palmitate by LC-ESI-MS, FT-IR, 1H, and 13C NMR analysis. Results from "one-factor-at-a-time" experiments indicated that the enzyme load, reaction temperature and D-isoascorbic-to-palmitic acid molar ratio had a significant effect on the D-isoascorbyl palmitate conversion rate. 95.32% of conversion rate was obtained by using response surface methodology (RSM) under the the optimized condition: enzyme load of 20% (w/w), reaction temperature of 53°C and D- isoascorbic-to-palmitic acid molar ratio of 1:4 when the reaction parameters were set as: acetone 20 mL, 40 g/L of molecular sieves content, 200 rpm speed for 24-h reaction time. The findings of this study can become a reference for developing industrial processes for the preparation of isoascorbic acid ester, which might be used in food additives, cosmetic formulations and for the synthesis of other isoascorbic acid derivatives.

  20. Palmitate diet-induced loss of cardiac caveolin-3: a novel mechanism for lipid-induced contractile dysfunction.

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    Catherine J Knowles

    Full Text Available Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate, and MCT diet (21% medium-chain triglycerides, no palmitate. We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release.

  1. Ultrasound-assisted lipase-catalyzed synthesis of D-isoascorbyl palmitate: process optimization and Kinetic evaluation.

    Science.gov (United States)

    Cui, Feng-Jie; Zhao, Hong-Xia; Sun, Wen-Jing; Wei, Zhuan; Yu, Si-Lian; Zhou, Qiang; Dong, Ying

    2013-12-09

    D-isoascorbic acid is a food antioxidant additive and used in accordance with Good Manufacturing Practice (GMP). High solubility in water (about 150 g/L at 25°C) reduces its effectiveness in stabilizing fats and oils. Our research group had successfully synthesized D-isoascorbyl palmitate using immobilized lipase Novozym 435 as a biocatalyst. Low production efficiency of D-isoascorbyl palmitate is still a problem for industrial production due to the long reaction time of over 24 h. In the present work, ultrasonic treatment was applied for accelerating the reaction process. The operation parameters were optimized to obtain the maximum D-isoascorbyl palmitate conversion rate by using a 5-level-4-factor Central Composite Design (CCD) and Response Surface Methdology (RSM). The reaction apparent kinetic parameters under the ultrasound treatment and mechanical shaking conditions were also determined and compared. Results showed that ultrasound treatment decreased the reaction time by over 50%. D-isoascorbyl palmitate yielded to 94.32 ± 0.17% and the productivity reached to 8.67 g L-1 h-1 under the optimized conditions as: 9% of enzyme load (w/w), 61°C of reaction temperature, 1:5 of D- isoascorbic-to-palmitic acid molar ratio, and 137 W of the ultrasound power. The immobilized lipase Novozym 435 could be reused for 7 times with 65% of the remained D-isoascorbyl palmitate conversion rate. The reaction kinetics showed that the maximum apparent reaction rate (vmax) of the ultrasound-assisted reaction was 2.85 times higher than that of the mechanical shaking, which proved that ultrasound treatment significantly enhanced the reaction efficiency. A systematic study on ultrasound-assisted enzymatic esterification for D-isoascorbyl palmitate production is reported. The results show a promising perspective of the ultrasound technique to reduce the reaction time and improve the production efficiency. The commercial D-isoascorbyl palmitate synthesis will be potentially

  2. Bactericidal activity of self-assembled palmitic and stearic fatty acid crystals on highly ordered pyrolytic graphite.

    Science.gov (United States)

    Ivanova, Elena P; Nguyen, Song Ha; Guo, Yachong; Baulin, Vladimir A; Webb, Hayden K; Truong, Vi Khanh; Wandiyanto, Jason V; Garvey, Christopher J; Mahon, Peter J; Mainwaring, David E; Crawford, Russell J

    2017-09-01

    The wings of insects such as cicadas and dragonflies have been found to possess nanostructure arrays that are assembled from fatty acids. These arrays can physically interact with the bacterial cell membranes, leading to the death of the cell. Such mechanobactericidal surfaces are of significant interest, as they can kill bacteria without the need for antibacterial chemicals. Here, we report on the bactericidal effect of two of the main lipid components of the insect wing epicuticle, palmitic (C16) and stearic (C18) fatty acids. Films of these fatty acids were re-crystallised on the surface of highly ordered pyrolytic graphite. It appeared that the presence of two additional CH 2 groups in the alkyl chain resulted in the formation of different surface structures. Scanning electron microscopy and atomic force microscopy showed that the palmitic acid microcrystallites were more asymmetric than those of the stearic acid, where the palmitic acid microcrystallites were observed to be an angular abutment in the scanning electron micrographs. The principal differences between the two types of long-chain saturated fatty acid crystallites were the larger density of peaks in the upper contact plane of the palmitic acid crystallites, as well as their greater proportion of asymmetrical shapes, in comparison to that of the stearic acid film. These two parameters might contribute to higher bactericidal activity on surfaces derived from palmitic acid. Both the palmitic and stearic acid crystallite surfaces displayed activity against Gram-negative, rod-shaped Pseudomonas aeruginosa and Gram-positive, spherical Staphylococcus aureus cells. These microcrystallite interfaces might be a useful tool in the fabrication of effective bactericidal nanocoatings. Nanostructured cicada and dragonfly wing surfaces have been discovered to be able physically kill bacterial cells. Here, we report on the successful fabrication of bactericidal three-dimensional structures of two main lipid

  3. The conquered conqueror Álvar Núñez Cabeza de Vaca and the conquered conqueror Sor Juana Inés de la Cruz. Analysis of two divergent identities from two brief works

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    Alejandro Rodríguez Díaz del Real

    2017-11-01

    Full Text Available Starting from two recent critical publications against the fatalism of the traditional discourse of the (anti-Spanish Black Legend, which do not pretend to be revisionist but instead point out certain positive aspects to the conquest of the Americas, the article contrasts two works that illustrate the permeability of two minds who wanted to open up to diversity: Álvar Núnez Cabeza de Vaca with his Shipwrecks (Naufragios on the one hand, and Sor Juana Inés de la Cruz with his Allegorical Neptune (Neptuno alegórico on the other. Only half a century after the discovery of America, and in the exact year of the New Laws of Charles V, which reflect the spirit of Las Casas critics and a defence of the Indian that later landed in the anti-Spanish Black Legend, Cabeza de Vaca presents a case of self-discovery as a fascinated conqueror who ends up conquered by the very environment that he is supposed to dominate; by a world that is too different and mysterious not to arouse his curiosity. The article contrasts this adventure of empathy and knowledge towards the other with an original work by Sor Juana Inés de la Cruz, Neptuno alegórico (1680, which represents another kind of journey, more a literary than autobiographical one, of the American world towards a Baroque or European “otherness”. In spite of the considerable time that separates each case, and of the logical and predictable divergences in terms of literary genre, both works are united by a willingness to be carried away by cultural spheres and aesthetic guidelines that are far from the known world, doing what today we would call “leaving one’s comfort zone”, but achieving an enrichment of the authors’ own lived and creative experience, as well as the literary horizon of the reader.

  4. Clinical effect of vitamin A palmitate eye gel on early ocular surface reconstruction after thermal or chemical injuries

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    Fen-Dui Zhang

    2015-11-01

    Full Text Available AIM: To evaluate the clinical effect of vitamin A palmitate eye gel on early ocular surface reconstruction after thermal or chemical injuries. METHODS: Seventy-eight cases with thermal or chemical injuries to eyes were selected and divided into two groups by randomized, double-blind, positive drug parallel controlled method: group A(40 cases were treated with vitamin A palmitate eye geland group B \\〖38 cases were treated with basic fibroblast growth factor(bFGF\\〗. The bFGF and vitamin A palmitate eye gel were used 4 times a day. The treatment course was 14d. Restoration of epithelial defect, Schirmer's test values, tear break-up time(BUT, and subjective assessment of symptoms and signs were observed on D1, D3, D5, D7, D10 and D14.RESULTS: In group A, 31 cases were cured, 5 cases were effective, with the cure rate of 76% and efficiency 90%. In group B, 32 cases were cured, 3 cases were effective, with the cure rate of 84% and efficiency 92%. There were no significant differences between the two groups(P>0.05. However, there were significant differences on the results of Schirmer's test and BUT(PPCONCLUSION: Vitamin A palmitate eye gel is valuable and safe on early ocular surface reconstruction of the eyes suffered from thermal or chemical injuries.

  5. Recovery outcomes of schizophrenia patients treated with paliperidone palmitate in a community setting: patient and provider perspectives on recovery.

    Science.gov (United States)

    Williams, Wesley; McKinney, Christopher; Martinez, Larry; Benson, Carmela

    2016-01-01

    This study evaluated the effect of paliperidone palmitate long-acting injectable (LAI) antipsychotic on recovery-oriented mental health outcomes from the perspective of healthcare providers and patients during the treatment of patients with schizophrenia or schizoaffective disorders. Archival data for patients with a primary diagnosis of schizophrenia or schizoaffective disorder receiving ≥6 months of paliperidone palmitate LAI were retrieved from the electronic medical records system at the Mental Health Center of Denver. Mental health recovery was assessed from both a provider's (Recovery Markers Inventory [RMI]) and patient's (Consumer Recovery Measure [CRM]) perspective. A three-level hierarchical linear model (HLM) was utilized to determine changes in CRM and RMI scores by including independent variables in the models: intercept, months from treatment (slope), treatment time period (pretreatment and treatment), age, gender, primary diagnosis, substance abuse diagnosis, concurrent medications, and adherence to paliperidone palmitate LAI. A total of 219 patients were identified and included in the study. Results of the final three-level HLMs indicated an overall increase in CRM scores (p a retrospective, non-comparative design, and did not adjust for multiplicity Conclusions: The current study demonstrates that changes in recovery-oriented mental health outcomes can be detected following the administration of a specific antipsychotic treatment in persons with schizophrenia or schizoaffective disorders. Furthermore, patients receiving paliperidone palmitate LAI can effectively improve recovery-oriented outcomes, thereby supporting the drug's use as schizophrenia treatment from a recovery-oriented perspective.

  6. Quantitative analysis of retinol and retinol palmitate in vitamin tablets using {sup 1}H-nuclear magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Hae; Kim, Hye Kyong; Wilson, Erica G.; Erkelens, Cornelis; Trijzelaar, Ben; Verpoorte, Robert

    2004-06-04

    {sup 1}H-NMR spectrometry was applied to the quantitative analysis of Vitamin A in four different types of vitamin tablets without any chromatographic purification or saponification. The experiment was performed analysing the H-15 resonance, which appears at {delta} 4.32 for retinol and {delta} 4.69 for retinol palmitate, well separated from other resonances in the {sup 1}H-NMR spectrum. Compounds were quantified using the relative ratio of the integral of the H-15 signal to that of a known amount of internal standard (200 {mu}g/ml), anthracene. In order to evaluate the feasibility of avoiding the saponification of retinol palmitate in the preparation of samples, several solvents such as dimethylsulfoxide, n-hexane, methanol, water, and 0.1 M of HCl were tested as possible extraction solvents. Among these, dimethylsulfoxide showed the best yield of retinol palmitate. This method, using dimethylsulfoxide extraction and {sup 1}H-NMR, allows rapid and simple quantitation of retinol palmitate in tablets avoiding tedious saponification.

  7. Quantitative analysis of retinol and retinol palmitate in vitamin tablets using 1H-nuclear magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Choi, Young Hae; Kim, Hye Kyong; Wilson, Erica G.; Erkelens, Cornelis; Trijzelaar, Ben; Verpoorte, Robert

    2004-01-01

    1 H-NMR spectrometry was applied to the quantitative analysis of Vitamin A in four different types of vitamin tablets without any chromatographic purification or saponification. The experiment was performed analysing the H-15 resonance, which appears at δ 4.32 for retinol and δ 4.69 for retinol palmitate, well separated from other resonances in the 1 H-NMR spectrum. Compounds were quantified using the relative ratio of the integral of the H-15 signal to that of a known amount of internal standard (200 μg/ml), anthracene. In order to evaluate the feasibility of avoiding the saponification of retinol palmitate in the preparation of samples, several solvents such as dimethylsulfoxide, n-hexane, methanol, water, and 0.1 M of HCl were tested as possible extraction solvents. Among these, dimethylsulfoxide showed the best yield of retinol palmitate. This method, using dimethylsulfoxide extraction and 1 H-NMR, allows rapid and simple quantitation of retinol palmitate in tablets avoiding tedious saponification

  8. Synergy analysis reveals association between insulin signaling and desmoplakin expression in palmitate treated HepG2 cells.

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    Xuewei Wang

    Full Text Available The regulation of complex cellular activities in palmitate treated HepG2 cells, and the ensuing cytotoxic phenotype, involves cooperative interactions between genes. While previous approaches have largely focused on identifying individual target genes, elucidating interacting genes has thus far remained elusive. We applied the concept of information synergy to reconstruct a "gene-cooperativity" network for palmititate-induced cytotoxicity in liver cells. Our approach integrated gene expression data with metabolic profiles to select a subset of genes for network reconstruction. Subsequent analysis of the network revealed insulin signaling as the most significantly enriched pathway, and desmoplakin (DSP as its top neighbor. We determined that palmitate significantly reduces DSP expression, and treatment with insulin restores the lost expression of DSP. Insulin resistance is a common pathological feature of fatty liver and related ailments, whereas loss of DSP has been noted in liver carcinoma. Reduced DSP expression can lead to loss of cell-cell adhesion via desmosomes, and disrupt the keratin intermediate filament network. Our findings suggest that DSP expression may be perturbed by palmitate and, along with insulin resistance, may play a role in palmitate induced cytotoxicity, and serve as potential targets for further studies on non-alcoholic fatty liver disease (NAFLD.

  9. Palmitate activates autophagy in INS-1E β-cells and in isolated rat and human pancreatic islets.

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    Luisa Martino

    Full Text Available We have investigated the in vitro effects of increased levels of glucose and free fatty acids on autophagy activation in pancreatic beta cells. INS-1E cells and isolated rat and human pancreatic islets were incubated for various times (from 2 to 24 h at different concentrations of glucose and/or palmitic acid. Then, cell survival was evaluated and autophagy activation was explored by using various biochemical and morphological techniques. In INS-1E cells as well as in rat and human islets, 0.5 and 1.0 mM palmitate markedly increased autophagic vacuole formation, whereas high glucose was ineffective alone and caused little additional change when combined with palmitate. Furthermore, LC3-II immunofluorescence co-localized with that of cathepsin D, a lysosomal marker, showing that the autophagic flux was not hampered in PA-treated cells. These effects were maintained up to 18-24 h incubation and were associated with a significant decline of cell survival correlated with both palmitate concentration and incubation time. Ultrastructural analysis showed that autophagy activation, as evidenced by the occurrence of many autophagic vacuoles in the cytoplasm of beta cells, was associated with a diffuse and remarkable swelling of the endoplasmic reticulum. Our results indicate that among the metabolic alterations typically associated with type 2 diabetes, high free fatty acids levels could play a role in the activation of autophagy in beta cells, through a mechanism that might involve the induction of endoplasmic reticulum stress.

  10. Mixed monolayers of dipalmitoyl phosphatidylcholine and ethyl palmitate at the air/water interface

    Energy Technology Data Exchange (ETDEWEB)

    Gzyl, Barbara [Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Cracow (Poland)]. E-mail: gzyl@chemia.uj.edu.pl; Paluch, Maria [Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Cracow (Poland)

    2005-06-30

    The behaviour of monolayers containing dipalmitoyl phosphatidylcholine and ethyl palmitate and their mixtures at different molar fraction, using surface pressure-molecular area results, was investigated. The negative deviation from additivity of the mean molecular areas as a function of the mixture composition indicates the miscibility. The miscibility was confirmed by applying the two-dimensional phase rule, since the collapse pressure values vary with the composition of the mixtures. Also the free energy of mixing {delta}G{sub mix} and the excess free energy of mixing {delta}G{sub mix}{sup E} were determined. The negative values of {delta}G{sub mix} and {delta}G{sub mix}{sup E} indicate that the mixed monolayers are thermodynamically more stable compared to the pure ones and that the compounds in the two dimensional state experience mainly attractive interactions.

  11. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

    Science.gov (United States)

    Nishiwaki, Satoshi; Nakayama, Takayuki; Murata, Makoto; Nishida, Tetsuya; Terakura, Seitaro; Saito, Shigeki; Kato, Tomonori; Mizuno, Hiroki; Imahashi, Nobuhiko; Seto, Aika; Ozawa, Yukiyasu; Miyamura, Koichi; Ito, Masafumi; Takeshita, Kyosuke; Kato, Hidefumi; Toyokuni, Shinya; Nagao, Keisuke; Ueda, Ryuzo; Naoe, Tomoki

    2014-01-01

    Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

  12. Thermal properties of silica-filled high density polyethylene composites compatibilized with glut palmitate

    Science.gov (United States)

    Samsudin, Dalina; Ismail, Hanafi; Othman, Nadras; Hamid, Zuratul Ain Abdul

    2017-07-01

    A study of thermal properties resulting from the utilization of Glut Palmitate (GP) on the silica filled high density polyethylene (HDPE) composites was carried out. The composites with the incorporation of GP at 0.5, 1.0, 2.0 and 3.0 phr were prepared by using an internal mixer at the temperature 180 °C and the rotor speed of 50 rpm. The thermal behaviours of the composites were then investigated using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). It was found that the crystallinity and the thermal stability of the composites increased with the incorporation of GP. The highest crystallinity contents and decomposition temperatures were observed at the 1 phr GP loading.

  13. Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate

    DEFF Research Database (Denmark)

    Green, C J; Bunprajun, T; Pedersen, B K

    2013-01-01

    in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance......  The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture...... and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism...

  14. KINETIC STUDY OF PALMITIC ACID ESTERIFICATION CATALYZED BY Rhizopus oryzae RESTING CELLS

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    JONH J MÉNDEZ

    2009-01-01

    Full Text Available ABSTRACT In the present study, a kinetic model for the biocatalytic synthesis of esters using Rhizopus oryzae resting cells is proposed. The kinetic study has been made in a range of 30-50 °C and atmospheric pressure. The Influence of operating variables, water content, pH, amount of mycelium was studied. Different values of temperature, initial mycelium concentration and acid/alcohol molar ratio were tested. Initial rates were estimated from the slope of the concentration of palmitic acid, or their corresponding ester at conversions of less than 10%, versus time and reported as mmol l-1 min -1. The values of kinetic constants were computed using the freeware program SIMFIT (http:\\\\www.simfit.man.ac.uk. Key words: bound lipase, esterification, fungal resting cells, Rhizopus oryzae, palmitic acid, propanol. RESUMEN En el presente estudio, un modelo cinético para la síntesis de esteres usando Rhizopus oryzae resting cells es propuesto. El estudio cinético fue realizado en un rango de temperatura de 30-50 ºC a presión atmosférica reducida. La influencia de las variables de operación tales como temperatura, pH y contenido de agua fueron estudiadas. Diferentes valores de concentración de micelio y relación molar de ácido/alcohol son ensayadas, Las velocidades iníciales se estimaron de la curva de concentración de acido palmítico, y su correspondiente conversión a ester en menos del 10%, frente a tiempo y reportadas en mmol I-1 min -1. Los valores de las constantes cinéticas fueron calculados usando el programa freeware SIMFIT (http:\\\\www.simfit.man.ac.uk. Palabras clave: Lipasas, esterificación, resting cells, Rhizopus oryzae, acido palmítico, propanol.

  15. PALMITIC AND OLEIC ACIDS AND THEIR ROLE IN PATHOGENESIS OF ATHEROSCLEROSIS

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    V. N. Titov

    2014-01-01

    Full Text Available On the basis of phylogenetic theory of general pathology, the cause of a noninfectious disease whose occurrence in a population is more than 5–7% is an impaired biological function or reaction to the environment. From the general biology viewpoint, high mortality rate related to cardio-vascular diseases and atherosclerosis (intercellular deficiency of polyenic fatty acids (PFA is just extinction of the Homo sapiens population upon adaptation to new environmental factors. The biological function of throphology (feeding and biological reaction of exotrophy (external feeding are impaired in several aspects, the major of which is nonphysiologically high dietary content of saturated fatty acids, primarily, of palmitic fatty acid (FA. The lipoprotein system formed at early stages of phylogenesis cannot transport and provide physiological deposition of great amounts of palmitic FA, which leads to the development of an adaption (compensatory and accumulation disease. This results in hypermipidemia, impaired bioavailability of PFA to cells, compesatory production of humoral mediators from ω-9 eicosatrienoic mead FA, disorders in physiological parameters of cell plasma membrane and integral proteins, nonphysiological conformation of apoВ-100 in lipoproteins, formation of ligandless lipoproteins (biological litter and impairments in the biological function of endoecology, utilization of ligandless lipoproteins in arterial intima by phylogenetically early macrophages that do not hydrolyze polyenic cholesterol esters, increase in the intensity of the biological reaction of inflammation, and destructive and inflammatory lesions in arterial intima of an atheromatosis or atherothrombosis type. Atheromatous masses are catabolites of PFA which were not internalized by phylogenetically late cells via receptor-mediated pathway.

  16. Palmitic acid-labeled lipids selectively incorporated into platelet cytoskeleton during aggregation

    International Nuclear Information System (INIS)

    Packham, M.A.; Guccione, M.A.; Bryant, N.L.; Livne, A.

    1990-01-01

    Previous experiments showed that during the early stages (20-30 seconds) of aggregation induced by adenosine diphosphate (ADP, 2 microM) or thrombin (0.1 U/mL) of rabbit or human platelets prelabeled with [3H]palmitic acid, labeled lipid became associated with the cytoskeleton isolated after lysis with 1% Triton X-100, 5 mM EGTA [ethylene glycol-bis-(beta-aminoethyl ether)]-N,N,N',N'-tetra-acetic acid. The association appeared to be related to the number of sites of contact and was independent of the release of granule contents. We have now investigated the nature of the labeled lipids by thin-layer and column chromatography and found differences between the distribution of the label in intact platelets (both stimulated and unstimulated) and the isolated cytoskeletons. In both species, and with either ADP or thrombin as aggregating agent, 70-85% of the label in both intact platelets and in the cytoskeletons was in phospholipids. The distribution of label among the phospholipids in the cytoskeletons was similar to that in intact platelets except that the percentage of label in phosphatidylcholine was significantly higher in the cytoskeletons of human platelets than in the intact platelets, and the percentage of label in phosphatidylserine/phosphatidylinositol was significantly lower in the cytoskeletons of rabbit platelets and thrombin-aggregated human platelets than in intact platelets. The cytoskeletons contained a lower percentage of label in triacylglycerol, diacylglycerol, and cholesterol ester than the intact platelets. Contrary to a report in the literature, we found no evidence for the incorporation of diacylglycerol and palmitic acid into the cytoskeleton

  17. ClC-3 deficiency protects preadipocytes against apoptosis induced by palmitate in vitro and in type 2 diabetes mice.

    Science.gov (United States)

    Huang, Yun-Ying; Huang, Xiong-Qin; Zhao, Li-Yan; Sun, Fang-Yun; Chen, Wen-Liang; Du, Jie-Yi; Yuan, Feng; Li, Jie; Huang, Xue-Lian; Liu, Jie; Lv, Xiao-Fei; Guan, Yong-Yuan; Chen, Jian-Wen; Wang, Guan-Lei

    2014-11-01

    Palmitate, a common saturated free fatty acid (FFA), has been demonstrated to induce preadipocyte apoptosis in the absence of adipogenic stimuli, suggesting that preadipocytes may be prone to apoptosis under adipogenic insufficient conditions, like type 2 diabetes mellitus (T2DM). ClC-3, encoding Cl(-) channel or Cl(-)/H(+) antiporter, is critical for cell fate choices of proliferation versus apoptosis under diseased conditions. However, it is unknown whether ClC-3 is related with preadipocyte apoptosis induced by palmitate or T2DM. Palmitate, but not oleate, induced apoptosis and increase in ClC-3 protein expression and endoplasmic reticulum (ER) stress in 3T3-L1 preadipocyte. ClC-3 specific siRNA attenuated palmitate-induced apoptosis and increased protein levels of Grp78, ATF4, CHOP and phosphorylation of JNK1/2, whereas had no effects on increased phospho-PERK and phospho-eIF2α protein expression. Moreover, the enhanced apoptosis was shown in preadipocytes from high-sucrose/fat, low-dose STZ induced T2DM mouse model with hyperglycemia, hyperlipidemia (elevated serum TG and FFA levels) and insulin resistance. ClC-3 knockout significantly attenuated preadipocyte apoptosis and the above metabolic disorders in T2DM mice. These data demonstrated that ClC-3 deficiency prevent preadipocytes against palmitate-induced apoptosis via suppressing ER stress, and also suggested that ClC-3 may play a role in regulating cellular apoptosis and disorders of glucose and lipid metabolism during T2DM.

  18. The French market of electrical equipment and installation. Control over energy consumption, environmental law and new markets to be conquered draw perspectives for the sector

    International Nuclear Information System (INIS)

    2012-12-01

    This article presents the content of a market study which aimed at identifying the size and dynamics of the French industry of electrical equipment and installation, at comparing financial performance of equipment manufacturers and of installation major companies, at analysing strategies developed by operators to take benefit of growth opportunities in the field of energy efficiency, at identifying new markets to be conquered, and at anticipating capitalistic evolutions. Fifteen companies are presented and analysed within this perspective: ABB, Alstom, Areva, ETDE, General Electric, GDF Suez, the Energy pole of Eiffage, Legrand, Nexans, Rexel, Schneider Electric, Siemens, Sonepar, Spie, and Vinci Energies

  19. CONQUERING A NEW CUSTOMER SEGMENT : INNOVATIVE MEDIA CONCEPT FOR THE PRE-LAUNCH COMMUNICATION OF THE NEW BMW 2 SERIES ACTIVE TOURER

    OpenAIRE

    Heidemann, Gerald

    2014-01-01

    The BMW 2 Series Active Tourer is a brand new car concept for the company and will be launched in Sweden at the end of September 2014. It will compete in the compact MPV (Multi Purpose Vehicles) segment with established competitors like the Mercedes Benz BClass. Therefore, BMW Sweden has the goal to win new customers and unknown target groups, in order to conquer the market. To support BMW in this matter, this research shows systematically, who the new customers are, what they prefer, how the...

  20. Perturbation of N-linked oligosaccharide structure results in an altered incorporation of [3H]palmitate into specific proteins in Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Wellner, R.B.; Ghosh, P.C.; Roecklein, B.; Wu, H.C.

    1987-01-01

    Increased [ 3 H]palmitate incorporation into specific cellular proteins has been reported to occur in Chinese hamster ovary and yeast mutant cells. In this paper we report studies concerning the relationship between N-linked oligosaccharide structure and [ 3 H]palmitate incorporation into proteins of Chinese hamster ovary (CHO) cells. We have compared the incorporation of [ 3 H]palmitate into proteins of wild-type and four different mutant CHO cell lines defective in various steps of N-linked protein glycosylation. Sodium dodecyl sulfate-gel electrophoretic analysis showed that three of the mutants exhibited increased [ 3 H]palmitate incorporation into several CHO cellular proteins (approximately 30,000-38,000 molecular weight) as compared to the wild-type cells. One of the affected mutants which accumulates the Man5Gn2Asn intermediate structure was examined in detail. In agreement with earlier reports, virtually all of the [ 3 H] palmitate-labeled proteins of both wild-type and mutant cell lines are membrane-bound. Pretreatment of the mutant cell line with tunicamycin blocked the increased [ 3 H]palmitate incorporation into the two specific proteins (both of approximately 30,000 molecular weight) observed in untreated cells; the decreased incorporation of [ 3 H]palmitate into the 30,000 molecular weight species was accompanied by a concomitant increase in the incorporation of [ 3 H]palmitate into two proteins of approximately 20,000 molecular weight. Pretreatment of wild-type cells with tunicamycin also caused increased [ 3 H]palmitate incorporation into the 20,000 molecular weight species

  1. A divide-and-conquer algorithm for large-scale de novo transcriptome assembly through combining small assemblies from existing algorithms.

    Science.gov (United States)

    Sze, Sing-Hoi; Parrott, Jonathan J; Tarone, Aaron M

    2017-12-06

    While the continued development of high-throughput sequencing has facilitated studies of entire transcriptomes in non-model organisms, the incorporation of an increasing amount of RNA-Seq libraries has made de novo transcriptome assembly difficult. Although algorithms that can assemble a large amount of RNA-Seq data are available, they are generally very memory-intensive and can only be used to construct small assemblies. We develop a divide-and-conquer strategy that allows these algorithms to be utilized, by subdividing a large RNA-Seq data set into small libraries. Each individual library is assembled independently by an existing algorithm, and a merging algorithm is developed to combine these assemblies by picking a subset of high quality transcripts to form a large transcriptome. When compared to existing algorithms that return a single assembly directly, this strategy achieves comparable or increased accuracy as memory-efficient algorithms that can be used to process a large amount of RNA-Seq data, and comparable or decreased accuracy as memory-intensive algorithms that can only be used to construct small assemblies. Our divide-and-conquer strategy allows memory-intensive de novo transcriptome assembly algorithms to be utilized to construct large assemblies.

  2. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult.

    Science.gov (United States)

    Qi, Zhangyang; Wu, Meihao; Fu, Yun; Huang, Tengfei; Wang, Tingting; Sun, Yanjie; Feng, Zhibo; Li, Changzheng

    2017-01-01

    The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer's disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF) fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin's ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin and P-curcumin was determined. The association

  3. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult

    Directory of Open Access Journals (Sweden)

    Zhangyang Qi

    2017-11-01

    Full Text Available Background/Aims: The generation of reactive oxygen species (ROS caused by amyloid-β (Aβ is considered to be one of mechanisms underlying the development of Alzheimer’s disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. Methods: P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR and high-resolution mass spectrometry (HRMS. An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. Results: A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin’s ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin

  4. Conquering the Physics GRE

    Science.gov (United States)

    Kahn, Yoni; Anderson, Adam

    2018-03-01

    Preface; How to use this book; Resources; 1. Classical mechanics; 2. Electricity and magnetism; 3. Optics and waves; 4. Thermodynamics and statistical mechanics; 5. Quantum mechanics and atomic physics; 6. Special relativity; 7. Laboratory methods; 8. Specialized topics; 9. Special tips and tricks for the Physics GRE; Sample exams and solutions; References; Equation index; Subject index; Problems index.

  5. Ignore and Conquer.

    Science.gov (United States)

    Conroy, Mary

    1989-01-01

    Discusses how teachers can deal with student misbehavior by ignoring negative behavior that is motivated by a desire for attention. Practical techniques are described for pinpointing attention seekers, enlisting classmates to deal with misbehaving students, ignoring misbehavior, and distinguishing behavior that responds to this technique from…

  6. Conquering Athletic Injuries.

    Science.gov (United States)

    Taylor, Paul M., Ed.; Taylor, Diane K., Ed.

    The purpose of this book is to be a source of complete, reliable, and practical sports medicine information. Experts from the American Running and Fitness Association describe in clear language how overuse injuries occur, how to recognize and self-treat them, when to seek professional help, and how to prevent future injuries. The book also…

  7. Conquering the Physics GRE

    CERN Document Server

    Kahn, Yoni

    2018-01-01

    The Physics GRE plays a significant role in deciding admissions to nearly all US physics Ph.D. programs, yet few exam prep books focus on the test's actual content and unique structure. Recognised as one of the best student resources available, this tailored guide has been thoroughly updated for the current Physics GRE. It contains more than 300 pages of review material carefully matched to all of the topics covered, as well as tips and tricks to help you solve problems under time pressure. It features three full-length practice exams, revised to accurately reflect the difficulty of the current test, with fully-worked solutions so that you can simulate taking the test, review your preparedness, and identify areas in which further study is needed. Written by working physicists who took the Physics GRE for their own graduate admissions to MIT, this self-contained reference guide will help you achieve your best score.

  8. Enhancement in electrical conductivity of pastes containing submicron Ag-coated Cu filler with palmitic acid surface modification

    Science.gov (United States)

    Choi, Eun Byeol; Lee, Jong-Hyun

    2017-09-01

    The fabrication and applied use of submicron Ag-coated Cu (Cu@Ag) particles as a filler material for epoxy-based conductive pastes having the advantages of a lower material cost and antioxidation behavior were studied. Submicron Cu@Ag particles were successfully prepared and surface-modified using palmitic acid. Diffuse reflectance infrared Fourier transform spectroscopy and thermogravimetric differential scanning calorimetry results indicated the formation of an organic layer by the chemical interaction between the Cu@Ag surface and palmitic acid and the survival of the organic layer after treatment at 160 °C for 3 h in air. The printed pastes containing both commercial micron Cu@Ag flakes and the fabricated submicron Cu@Ag particles showed a greatly reduced electrical resistivity (4.68 × 10-4 Ω cm) after surface modification compared to an initial value of 1.85 × 10-3 Ω cm when cured.

  9. Palmitate-induced ER stress increases trastuzumab sensitivity in HER2/neu-positive breast cancer cells

    International Nuclear Information System (INIS)

    Baumann, Jan; Wong, Jason; Sun, Yan; Conklin, Douglas S.

    2016-01-01

    HER2/neu-positive breast cancer cells have recently been shown to use a unique Warburg-like metabolism for survival and aggressive behavior. These cells exhibit increased fatty acid synthesis and storage compared to normal breast cells or other tumor cells. Disruption of this synthetic process results in apoptosis. Since the addition of physiological doses of exogenous palmitate induces cell death in HER2/neu-positive breast cancer cells, the pathway is likely operating at its limits in these cells. We have studied the response of HER2/neu-positive breast cancer cells to physiological concentrations of exogenous palmitate to identify lipotoxicity-associated consequences of this physiology. Since epidemiological data show that a diet rich in saturated fatty acids is negatively associated with the development of HER2/neu-positive cancer, this cellular physiology may be relevant to the etiology and treatment of the disease. We sought to identify signaling pathways that are regulated by physiological concentrations of exogenous palmitate specifically in HER2/neu-positive breast cancer cells and gain insights into the molecular mechanism and its relevance to disease prevention and treatment. Transcriptional profiling was performed to assess programs that are regulated in HER2-normal MCF7 and HER2/neu-positive SKBR3 breast cancer cells in response to exogenous palmitate. Computational analyses were used to define and predict functional relationships and identify networks that are differentially regulated in the two cell lines. These predictions were tested using reporter assays, fluorescence-based high content microscopy, flow cytometry and immunoblotting. Physiological effects were confirmed in HER2/neu-positive BT474 and HCC1569 breast cancer cell lines. Exogenous palmitate induces functionally distinct transcriptional programs in HER2/neu-positive breast cancer cells. In the lipogenic HER2/neu-positive SKBR3 cell line, palmitate induces a G2 phase cell cycle delay and

  10. Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Haffar, T. [Université de Montreal (Canada); Montreal Heart Institute (Canada); Bérubé-Simard, F. [Montreal Heart Institute (Canada); Bousette, N., E-mail: nicolas.bousette@umontreal.ca [Université de Montreal (Canada); Montreal Heart Institute (Canada)

    2015-12-04

    A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring {sup 14}C–CO{sub 2} production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. - Highlights: • Palmitate had a slower clearance rate from NCMs than oleate. • Palmitate caused a significant decrease in fatty acid oxidation in cardiomyocytes. • Impaired FAO was not due to loss of Cpt1b protein or mitochondrial integrity. • Enhancing FAO

  11. Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes

    International Nuclear Information System (INIS)

    Haffar, T.; Bérubé-Simard, F.; Bousette, N.

    2015-01-01

    A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring "1"4C–CO_2 production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. - Highlights: • Palmitate had a slower clearance rate from NCMs than oleate. • Palmitate caused a significant decrease in fatty acid oxidation in cardiomyocytes. • Impaired FAO was not due to loss of Cpt1b protein or mitochondrial integrity. • Enhancing FAO attenuated

  12. Gas chromatography-mass spectrometry of ethyl palmitate calibration and resolution with ethyl oleate as biomarker ethanol sub acute in urine application study

    Science.gov (United States)

    Suaniti, Ni Made; Manurung, Manuntun

    2016-03-01

    Gas Chromatography-Mass Spectrometry is used to separate two and more compounds and identify fragment ion specific of biomarker ethanol such as palmitic acid ethyl ester (PAEE), as one of the fatty acid ethyl esters as early detection through conyugated reaction. This study aims to calibrate ethyl palmitate and develop analysis with oleate acid. This methode can be used analysis ethanol and its chemistry biomarker in ethanol sub-acute consumption as analytical forensic toxicology. The result show that ethanol level in urine rats Wistar were 9.21 and decreased 6.59 ppm after 48 hours consumption. Calibration curve of ethyl palmitate was y = 0.2035 x + 1.0465 and R2 = 0.9886. Resolution between ethyl palmitate and oleate were >1.5 as good separation with fragment ion specific was 88 and the retention time was 18 minutes.

  13. An 11-bp insertion in Zea mays fatb reduces the palmitic acid content of fatty acids in maize grain.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available The ratio of saturated to unsaturated fatty acids in maize kernels strongly impacts human and livestock health, but is a complex trait that is difficult to select based on phenotype. Map-based cloning of quantitative trait loci (QTL is a powerful but time-consuming method for the dissection of complex traits. Here, we combine linkage and association analyses to fine map QTL-Pal9, a QTL influencing levels of palmitic acid, an important class of saturated fatty acid. QTL-Pal9 was mapped to a 90-kb region, in which we identified a candidate gene, Zea mays fatb (Zmfatb, which encodes acyl-ACP thioesterase. An 11-bp insertion in the last exon of Zmfatb decreases palmitic acid content and concentration, leading to an optimization of the ratio of saturated to unsaturated fatty acids while having no effect on total oil content. We used three-dimensional structure analysis to explain the functional mechanism of the ZmFATB protein and confirmed the proposed model in vitro and in vivo. We measured the genetic effect of the functional site in 15 different genetic backgrounds and found a maximum change of 4.57 mg/g palmitic acid content, which accounts for ∼20-60% of the variation in the ratio of saturated to unsaturated fatty acids. A PCR-based marker for QTL-Pal9 was developed for marker-assisted selection of nutritionally healthier maize lines. The method presented here provides a new, efficient way to clone QTL, and the cloned palmitic acid QTL sheds lights on the genetic mechanism of oil biosynthesis and targeted maize molecular breeding.

  14. Hibiscus sabdariffa polyphenols prevent palmitate-induced renal epithelial mesenchymal transition by alleviating dipeptidyl peptidase-4-mediated insulin resistance.

    Science.gov (United States)

    Huang, Chien-Ning; Wang, Chau-Jong; Yang, Yi-Sun; Lin, Chih-Li; Peng, Chiung-Huei

    2016-01-01

    Diabetic nephropathy has a significant socioeconomic impact, but its mechanism is unclear and needs to be examined. Hibiscus sabdariffa polyphenols (HPE) inhibited high glucose-induced angiotensin II receptor-1 (AT-1), thus attenuating renal epithelial mesenchymal transition (EMT). Recently, we reported HPE inhibited dipeptidyl-peptidase-4 (DPP-4, the enzyme degrades type 1 glucagon-like peptide (GLP-1)), which mediated insulin resistance signals leading to EMT. Since free fatty acids can realistically bring about insulin resistance, using the palmitate-stimulated cell model in contrast with type 2 diabetic rats, in this study we examined if insulin resistance causes renal EMT, and the preventive effect of HPE. Our findings reveal that palmitate hindered 30% of glucose uptake. Treatment with 1 mg mL(-1) of HPE and the DPP-4 inhibitor linagliptin completely recovered insulin sensitivity and palmitate-induced signal cascades. HPE inhibited DPP-4 activity without altering the levels of DPP-4 and the GLP-1 receptor (GLP-1R). HPE decreased palmitate-induced phosphorylation of Ser307 of insulin receptor substrate-1 (pIRS-1 (S307)), AT-1 and vimentin, while increasing phosphorylation of phosphatidylinositol 3-kinase (pPI3K). IRS-1 knockdown revealed its essential role in mediating downstream AT-1 and EMT. In type 2 diabetic rats, it suggests that HPE concomitantly decreased the protein levels of DPP-4, AT-1, vimentin, and fibronectin, but reversed the in vivo compensation of GLP-1R. In conclusion, HPE improves insulin sensitivity by attenuating DPP-4 and the downstream signals, thus decreasing AT-1-mediated tubular-interstitial EMT. HPE could be an adjuvant to prevent diabetic nephropathy.

  15. An 11-bp Insertion in Zea mays fatb Reduces the Palmitic Acid Content of Fatty Acids in Maize Grain

    Science.gov (United States)

    Li, Qing; Yang, Xiaohong; Zheng, Debo; Warburton, Marilyn; Chai, Yuchao; Zhang, Pan; Guo, Yuqiu; Yan, Jianbing; Li, Jiansheng

    2011-01-01

    The ratio of saturated to unsaturated fatty acids in maize kernels strongly impacts human and livestock health, but is a complex trait that is difficult to select based on phenotype. Map-based cloning of quantitative trait loci (QTL) is a powerful but time-consuming method for the dissection of complex traits. Here, we combine linkage and association analyses to fine map QTL-Pal9, a QTL influencing levels of palmitic acid, an important class of saturated fatty acid. QTL-Pal9 was mapped to a 90-kb region, in which we identified a candidate gene, Zea mays fatb (Zmfatb), which encodes acyl-ACP thioesterase. An 11-bp insertion in the last exon of Zmfatb decreases palmitic acid content and concentration, leading to an optimization of the ratio of saturated to unsaturated fatty acids while having no effect on total oil content. We used three-dimensional structure analysis to explain the functional mechanism of the ZmFATB protein and confirmed the proposed model in vitro and in vivo. We measured the genetic effect of the functional site in 15 different genetic backgrounds and found a maximum change of 4.57 mg/g palmitic acid content, which accounts for ∼20–60% of the variation in the ratio of saturated to unsaturated fatty acids. A PCR-based marker for QTL-Pal9 was developed for marker-assisted selection of nutritionally healthier maize lines. The method presented here provides a new, efficient way to clone QTL, and the cloned palmitic acid QTL sheds lights on the genetic mechanism of oil biosynthesis and targeted maize molecular breeding. PMID:21931818

  16. Palmitic Acid on Salt Subphases and in Mixed Monolayers of Cerebrosides: Application to Atmospheric Aerosol Chemistry

    Directory of Open Access Journals (Sweden)

    Ellen M. Adams

    2013-10-01

    Full Text Available Palmitic acid (PA has been found to be a major constituent in marine aerosols, and is commonly used to investigate organic containing atmospheric aerosols, and is therefore used here as a proxy system. Surface pressure-area isotherms (π-A, Brewster angle microscopy (BAM, and vibrational sum frequency generation (VSFG were used to observe a PA monolayer during film compression on subphases of ultrapure water, CaCl2 and MgCl2 aqueous solutions, and artificial seawater (ASW. π-A isotherms indicate that salt subphases alter the phase behavior of PA, and BAM further reveals that a condensation of the monolayer occurs when compared to pure water. VSFG spectra and BAM images show that Mg2+ and Ca2+ induce ordering of the PA acyl chains, and it was determined that the interaction of Mg2+ with the monolayer is weaker than Ca2+. π-A isotherms and BAM were also used to monitor mixed monolayers of PA and cerebroside, a simple glycolipid. Results reveal that PA also has a condensing effect on the cerebroside monolayer. Thermodynamic analysis indicates that attractive interactions between the two components exist; this may be due to hydrogen bonding of the galactose and carbonyl headgroups. BAM images of the collapse structures show that mixed monolayers of PA and cerebroside are miscible at all surface pressures. These results suggest that the surface morphology of organic-coated aerosols is influenced by the chemical composition of the aqueous core and the organic film itself.

  17. 3-MCPD 1-Palmitate Induced Tubular Cell Apoptosis In Vivo via JNK/p53 Pathways

    Science.gov (United States)

    Liu, Man; Huang, Guoren; Wang, Thomas T.Y.; Sun, Xiangjun; Yu, Liangli (Lucy)

    2016-01-01

    Fatty acid esters of 3-chloro-1, 2-propanediol (3-MCPD esters) are a group of processing induced food contaminants with nephrotoxicity but the molecular mechanism(s) remains unclear. This study investigated whether and how the JNK/p53 pathway may play a role in the nephrotoxic effect of 3-MCPD esters using 3-MCPD 1-palmitate (MPE) as a probe compound in Sprague Dawley rats. Microarray analysis of the kidney from the Sprague Dawley rats treated with MPE, using Gene Ontology categories and KEGG pathways, revealed that MPE altered mRNA expressions of the genes involved in the mitogen-activated protein kinase (JNK and ERK), p53, and apoptotic signal transduction pathways. The changes in the mRNA expressions were confirmed by qRT-PCR and Western blot analyses and were consistent with the induction of tubular cell apoptosis as determined by histopathological, TUNEL, and immunohistochemistry analyses in the kidneys of the Sprague Dawley rats. Additionally, p53 knockout attenuated the apoptosis, and the apoptosis-related protein bax expression and cleaved caspase-3 activation induced by MPE in the p53 knockout C57BL/6 mice, whereas JNK inhibitor SP600125 but not ERK inhibitor U0126 inhibited MPE-induced apoptosis, supporting the conclusion that JNK/p53 might play a critical role in the tubular cell apoptosis induced by MPE and other 3-MCPD fatty acid esters. PMID:27008853

  18. Calculation procedure for formulating lauric and palmitic fat blends based on the grouping of triacylglycerol melting points

    Directory of Open Access Journals (Sweden)

    B. P. Nusantoro

    2018-01-01

    Full Text Available A calculation procedure for formulating lauric and palmitic fat blends has been developed based on grouping TAG melting points. This procedure offered more flexibility in choosing the initial fats and oils and eventually gave deeper insight into the existing chemical compositions and better prediction on the physicochemical properties and microstructure of the fat blends. The amount of high, medium and low melting TAGs could be adjusted using the given calculation procedure to obtain the desired functional properties in the fat blends. Solid fat contents and melting behavior of formulated fat blends showed particular patterns with respect to ratio adjustments of the melting TAG groups. These outcomes also suggested that both TAG species and their quantity had a significant influence on the crystallization behavior of the fat blends. Palmitic fat blends, in general, were found to exhibit higher SFC values than those of Lauric fat blends. Instead of the similarity in crystal microstructure, lauric fat blends were stabilized at β polymorph while palmitic fat blends were stabilized at β’ polymorph.

  19. Optimization of 2-ethylhexyl palmitate production using lipozyme RM IM as catalyst in a solvent-free system.

    Science.gov (United States)

    Richetti, Aline; Leite, Selma G F; Antunes, Octávio A C; de Souza, Andrea L F; Lerin, Lindomar A; Dallago, Rogério M; Paroul, Natalia; Di Luccio, Marco; Oliveira, J Vladimir; Treichel, Helen; de Oliveira, Débora

    2010-04-01

    This work reports the application of a lipase in the 2-ethylhexyl palmitate esterification in a solvent-free system with an immobilized lipase (Lipozyme RM IM). A sequential strategy was used applying two experimental designs to optimize the 2-ethylhexyl palmitate production. An empirical model was then built so as to assess the effects of process variables on the reaction conversion. Afterwards, the operating conditions that optimized 2-ethylhexyl palmitate production were established as being acid/alcohol molar ratio 1:3, temperature of 70 degrees C, stirring rate of 150 rpm, 10 wt.% of enzyme, leading to a reaction conversion as high as 95%. From this point, a kinetic study was carried out evaluating the effect of acid:alcohol molar ratio, the enzyme concentration and the temperature on product conversion. The results obtained in this step permit to verify that an excess of alcohol (acid to alcohol molar ratio of 1:6), relatively low enzyme concentration (10 wt.%) and temperature of 70 degrees C, led to conversions next to 100%.

  20. Preparation and characterization Al3+-bentonite Turen Malang for esterification fatty acid (palmitic acid, oleic acid and linoleic acid)

    Science.gov (United States)

    Abdulloh, Abdulloh; Aminah, Nanik Siti; Triyono, Mudasir, Trisunaryanti, Wega

    2016-03-01

    Catalyst preparation and characterization of Al3+-bentonite for esterification of palmitic acid, oleic acid and linoleic acid has been done. Al3+-bentonite catalyst was prepared from natural bentonite of Turen Malang through cation exchange reaction using AlCl3 solution. The catalysts obtained were characterized by XRD, XRF, pyridine-FTIR and surface area analyser using the BET method. Catalyst activity test of Al3+-bentonite for esterification reaction was done at 65°C using molar ratio of metanol-fatty acid of 30:1 and 0.25 g of Al3+-bentonite catalyst for the period of ½, 1, 2, 3, 4 and 5 hours. Based on the characterization results, the Al3+-bentonite Turen Malang catalyst has a d-spacing of 15.63 Ǻ, acid sites of Brönsted and Lewis respectively of 230.79 µmol/g and 99.39 µmol/g, surface area of 507.3 m2/g and the average of radius pore of 20.09 Å. GC-MS analysis results of the oil phase after esterification reaction showed the formation of biodiesel (FAME: Fatty acid methyl ester), namely methyl palmitate, methyl oleate and methyl linoleate. The number of conversions resulted in esterification reaction using Al3+-bentonite Turen Malang catalyst was 74.61%, 37.75%, and 20, 93% for the esterification of palmitic acid, oleic acid and linoleic acid respectively.

  1. Calculation procedure for formulating lauric and palmitic fat blends based on the grouping of triacylglycerol melting points

    International Nuclear Information System (INIS)

    Nusantoro, B.P.; Yanty, N.A.M.; Van de Walle, D.; Hidayat, C.; Danthine, S.; Dewettinck, K.

    2017-01-01

    A calculation procedure for formulating lauric and palmitic fat blends has been developed based on grouping TAG melting points. This procedure offered more flexibility in choosing the initial fats and oils and eventually gave deeper insight into the existing chemical compositions and better prediction on the physicochemical properties and microstructure of the fat blends. The amount of high, medium and low melting TAGs could be adjusted using the given calculation procedure to obtain the desired functional properties in the fat blends. Solid fat contents and melting behavior of formulated fat blends showed particular patterns with respect to ratio adjustments of the melting TAG groups. These outcomes also suggested that both TAG species and their quantity had a significant influence on the crystallization behavior of the fat blends. Palmitic fat blends, in general, were found to exhibit higher SFC values than those of Lauric fat blends. Instead of the similarity in crystal microstructure, lauric fat blends were stabilized at β polymorph while palmitic fat blends were stabilized at β’ polymorph. [es

  2. Synthesis and characterization of microencapsulated myristic acid–palmitic acid eutectic mixture as phase change material for thermal energy storage

    International Nuclear Information System (INIS)

    Alva, Guruprasad; Huang, Xiang; Liu, Lingkun; Fang, Guiyin

    2017-01-01

    Highlights: •Myristic acid–palmitic acid eutectic was microencapsulated with silica shell. •Structure, morphology of microencapsulated phase change material were investigated. •Thermal capacity, stability of microencapsulated phase change material were analyzed. •Silica shell improved thermal stability of microencapsulated phase change material. -- Abstract: In this work microencapsulation of myristic acid–palmitic acid (MA–PA) eutectic mixture with silica shell using sol−gel method has been attempted. The core phase change material (PCM) for thermal energy storage was myristic acid−palmitic acid eutectic mixture and the shell material to prevent the PCM core from leakage was silica prepared from methyl triethoxysilane (MTES). Thermal properties of the microcapsules were measured by differential scanning calorimeter (DSC). The morphology and particle size of the microcapsules were examined by scanning electronic microscope (SEM). Fourier transformation infrared spectrophotometer (FT–IR) and X–ray diffractometer (XRD) were used to investigate the chemical structure and crystalloid phase of the microcapsules respectively. The DSC results indicated that microencapsulated phase change material (MPCM) melts at 46.08 °C with a latent heat of 169.69 kJ kg −1 and solidifies at 44.35 °C with a latent heat of 159.59 kJ kg −1 . The thermal stability of the microcapsules was analyzed by a thermogravimeter (TGA). The results indicated that the MPCM has good thermal stability and is suitable for thermal energy storage application.

  3. Number needed to treat and number needed to harm with paliperidone palmitate relative to long-acting haloperidol, bromperidol, and fluphenazine decanoate for treatment of patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Srihari Gopal

    2011-03-01

    Full Text Available Srihari Gopal1, Joris Berwaerts1, Isaac Nuamah1, Kasem Akhras2, Danielle Coppola1, Ella Daly1, David Hough1, Joseph Palumbo11Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ, USA; 2Johnson & Johnson Pharmaceutical Services, LLC, Raritan, NJ, USABackground: We analyzed data retrieved through a PubMed search of randomized, placebo-controlled trials of first-generation antipsychotic long-acting injectables (haloperidol decanoate, bromperidol decanoate, and fluphenazine decanoate, and a company database of paliperidone palmitate, to compare the benefit-risk ratio in patients with schizophrenia.Methods: From the eight studies that met our selection criteria, two efficacy and six safety parameters were selected for calculation of number needed to treat (NNT, number needed to harm (NNH, and the likelihood of being helped or harmed (LHH using comparisons of active drug relative to placebo. NNTs for prevention of relapse ranged from 2 to 5 for paliperidone palmitate, haloperidol decanoate, and fluphenazine decanoate, indicating a moderate to large effect size.Results: Among the selected maintenance studies, NNH varied considerably, but indicated a lower likelihood of encountering extrapyramidal side effects, such as akathisia, tremor, and tardive dyskinesia, with paliperidone palmitate versus placebo than with first-generation antipsychotic depot agents versus placebo. This was further supported by an overall higher NNH for paliperidone palmitate versus placebo with respect to anticholinergic use and Abnormal Involuntary Movement Scale positive score. LHH for preventing relapse versus use of anticholinergics was 15 for paliperidone palmitate and 3 for fluphenazine decanoate, favoring paliperidone palmitate.Conclusion: Overall, paliperidone palmitate had a similar NNT and a more favorable NNH compared with the first-generation long-acting injectables assessed.Keywords: long-acting injectables, first-generation antipsychotics

  4. Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPAR{sub β/δ} in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Guanghua; Shi, Yuanping; Zhang, Jun; Mu, Qinfeng; Qin, Li; Zheng, Lu; Feng, Yuehua [Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou 213003 (China); Berggren-Söderlund, Maria; Nilsson-Ehle, Peter [Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund (Sweden); Zhang, Xiaoying, E-mail: zhangxy6689996@163.com [Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003 (China); Xu, Ning, E-mail: ning.xu@med.lu.se [Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund (Sweden)

    2014-02-28

    Highlights: • Palmitic acid significantly inhibited APOM gene expression in HepG2 cells. • Palmitic acid could obviously increase PPARB/D mRNA levels in HepG2 cells. • PPAR{sub β/δ} antagonist, GSK3787, had no effect on APOM expression. • GSK3787 could reverse the palmitic acid-induced down-regulation of APOM expression. • Palmitic acid induced suppression of APOM expression is mediated via the PPAR{sub β/δ} pathway. - Abstract: It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important for further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPAR{sub β/δ}) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPAR{sub β/δ} pathway.

  5. Effect of α-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes

    Directory of Open Access Journals (Sweden)

    Dong Lei

    2011-07-01

    Full Text Available Abstract Background Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease (NAFLD. In this study, we investigated the effects of saturated and unsaturated fatty acids (FA on apoptosis in primary rat hepatocytes. Methods The primary rat hepatocytes were treated with palmitic acid and/or α-linolenic acid in vitro. The expression of proteins associated with endoplasmic reticulum (ER stress, apoptosis, caspase-3 levels were detected after the treatment. Results The treatment with palmitic acid produced a significant increase in cell death. The unfolded protein response (UPR-associated genes CHOP, GRP78, and GRP94 were induced to higher expression levels by palmitic acid. Co-treatment with α-linolenic acid reversed the apoptotic effect and levels of all three indicators of ER stress exerted by palmitic acid. Tunicamycin, which induces ER stress produced similar effects to those obtained using palmitic acid; its effects were also reversed by α-linolenic acid. Conclusions α-Linolenic acid may provide a useful strategy to avoid the lipotoxicity of dietary palmitic acid and nutrient overload accompanied with obesity and NAFLD.

  6. Sensitization of vascular smooth muscle cell to TNF-α-mediated death in the presence of palmitate

    International Nuclear Information System (INIS)

    Rho, Mun-Chual; Ah Lee, Kyeong; Mi Kim, Sun; Sik Lee, Chang; Jeong Jang, Min; Kook Kim, Young; Sun Lee, Hyun; Hyun Choi, Yung; Yong Rhim, Byung; Kim, Koanhoi

    2007-01-01

    Saturated free fatty acids (FFAs), including palmitate, can activate the intrinsic death pathway in cells. However, the relationship between FFAs and receptor-mediated death pathway is still unknown. In this study, we have investigated whether FFAs are able to trigger receptor-mediated death. In addition, to clarify the mechanisms responsible for the activation, we examined the biochemical changes in dying vascular smooth muscle cell (VSMC) and the effects of various molecules to the receptor-mediated VSMC death. Tumor necrosis factor (TNF)-α-mediated VSMC death occurred in the presence of sub-cytotoxic concentration of palmitate as determined by assessing viability and DNA degradation, while the cytokine did not influence VSMC viability in the presence of oleate. The VSMC death was inhibited by the gene transfer of a dominant-negative Fas-associated death domain-containing protein and the baculovirus p35, but not by the bcl-xL or the c-Jun N-terminal kinase (JNK) binding domain of JNK-interacting protein-1, in tests utilizing recombinant adenoviruses. The VSMC death was also inhibited by a neutralizing anti-TNF receptor 1 antibody, the caspase inhibitor z-VAD, and the cathepsin B inhibitor CA074, a finding indicative of the role of both caspases and cathepsin B in this process. Consistent with this finding, caspase-3 activation and an increase in cytosolic cathepsin B activity were detected in the dying VSMC. Palmitate inhibited an increase of TNF-α-mediated nuclear factor kappa B (NF-κB) activity, the survival pathway activated by the cytokine, by hindering the translocation of the NF-κB subunit of p65 from the cytosol into the nucleus. The gene transfer of inhibitor of NF-κB predisposed VSMC to palmitate-induced cell death. To the best of our knowledge, this study is the first report to demonstrate the activation of TNF-α-mediated cell death in the presence of palmitate. The current study proposes that FFAs would take part in deleterious vascular

  7. Hospitalizations and economic analysis in psychotic patients with paliperidone palmitate long-acting injection.

    Science.gov (United States)

    Mesones-Peral, Jesús E; Gurillo-Muñoz, Pedro; Sánchez-Sicilia, Mari Paz; Miller, Adam; Griñant-Fernández, Alejandra

    Prevent hospitalizations in psychotic disorders is an important aim, so long-acting antipsychotic is a good option that can control better the correct adherence. Moreover, in the current economic context pharmacoeconomic studies are necessary. We estimate the effect in prevention of paliperidone palmitate long-acting injection (PP-LAI) and calculate the economic cost in the 12 months preceding the start of treatment with PP-LAI and 12 months later. Mirror image study of 71 outpatients diagnosed with psychotic disorders and treated with PP-LAI. In a first analysis, we measured along one year: number of hospitalizations/year, number of hospitalization in days, number of emergency assists/year and if there is antipsychotics associated to long-acting treatment. After this phase, we applied Fees Act of Valencia for economic analysis and estimate of the cost per hospitalization (€ 5,640.41) and hospital emergency (€ 187.61). After one year of treatment with PP-LAI (mean dose=130.65mg/month), we obtained greater numbers in assistance variables: total hospitalizations decrease, 78.8% (P=.009); shortening in hospitalization days, 89.4% (P=.009); abridgement of number of emergency assists, 79.1% (P=.002); decrease of rate of antipsychotics associated to long-acting treatment, 21% (P<.0001); increase in monotherapy, 53.8% (P<.0001). Therefore, after 12 months of treatment with PP-LAI we obtained a reduction in inpatient spending (savings of € 175,766.54) and increased spending on antipsychotics 32% (equivalent to € 151,126.92). PP-LAI can be an effective therapy for the treatment of patients with severe psychotic disorders: improves symptomatic stability and can prevent hospitalizations with cost-effective symptom control. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Androgenic effect of honeybee drone milk in castrated rats: roles of methyl palmitate and methyl oleate.

    Science.gov (United States)

    Seres, A B; Ducza, E; Báthori, M; Hunyadi, A; Béni, Z; Dékány, M; Hajagos-Tóth, J; Verli, J; Gáspár, Róbert

    2014-04-28

    Numerous honeybee (Apis mellifera) products have been used in traditional medicine to treat infertility and to increase vitality in both men and women. Drone milk (DM) is a relatively little-known honeybee product with a putative sexual hormone effect. The oestrogenic effect of a fraction of DM has recently been reported in rats. However, no information is available on the androgenic effects of DM. The purpose of the present study was to determine the androgen-like effect of DM in male rats and to identify effective compounds. A modified Hershberger assay was used to investigate the androgenic effect of crude DM, and the plasma level of testosterone was measured. The prostatic mRNA and protein expression of Spot14-like androgen-inducible protein (SLAP) were also examined with real-time PCR and Western blot techniques. GC-MS and NMR spectroscopic investigations were performed to identify the active components gained by bioactivity-guided fractionation. The crude DM increased the relative weights of the androgen-dependent organs and the plasma testosterone level in castrated rats and these actions were flutamide-sensitive. DM increased the tissue mRNA and protein level of SLAP, providing further evidence of its androgen-like character. After bioactivity-guided fractionation, two fatty acid esters, methyl palmitate (MP) and methyl oleate (MO), were identified as active compounds. MP alone showed an androgenic effect, whereas MO increased the weight of androgen-sensitive tissues and the plasma testosterone level only in combination. The experimental data of DM and its active compounds (MO and MP) show androgenic activity confirming the traditional usage of DM. DM or MP or/and MO treatments may project a natural mode for the therapy of male infertility. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Determination of physicochemical properties and degradation kinetics of triamcinolone acetonide palmitate in vitro.

    Science.gov (United States)

    Peng, Cuilian; Liu, Cong; Tang, Xing

    2010-12-01

    Triamcinolone acetonide palmitate (TAP) is a lipophilic prodrug of triamcinolone acetonide (TAA) to improve the insoluble TAA physicochemical properties for the preparation of emulsions. This investigation has focused on the preformulation study of TAP, including its physicochemical properties and hydrolysis kinetics in vitro. The solubility of TAP in medium-chain triglyceride is about twice greater than that in soybean oil (long-chain triglyceride) (19.17 versus 9.55 mg/g) at 25°C, and in all investigated cases, lecithin (80, 160, and 240 mg/g) as solubilizer provided increased solubility of drugs in medium-chain triglyceride and long-chain triglyceride, whereas the maximum water solubility of TAP was 0.10 μg/mL. The partition coefficient (log P) of TAP was 5.79 irrespective of the pH conditions. The hydrolysis of TAP followed pseudo-first-order kinetics in aqueous solutions, and the stable pH range was from pH 5.0 to 9.0. The in vitro enzymolysis kinetics of TAP in rat plasma and liver homogenate was evaluated by measuring the decrease of TAP as well as the increase of TAA at 37°C for 96 hours. The results demonstrated that the TAP may be hydrolyzed mainly by rat plasma esterase and, to a minor extent, by liver esterase, and the hydrolysis half-life of TAP in 100% rat plasma was 17.53 ± 6.85 hours at pH 7.4. All these results indicated that TAP had successfully obtained higher lipid-soluble property for the preparation of intravenous emulsion and may be an effective prodrug for sustained release of TAA in vivo.

  10. Three pillars for achieving quantum mechanical molecular dynamics simulations of huge systems: Divide-and-conquer, density-functional tight-binding, and massively parallel computation.

    Science.gov (United States)

    Nishizawa, Hiroaki; Nishimura, Yoshifumi; Kobayashi, Masato; Irle, Stephan; Nakai, Hiromi

    2016-08-05

    The linear-scaling divide-and-conquer (DC) quantum chemical methodology is applied to the density-functional tight-binding (DFTB) theory to develop a massively parallel program that achieves on-the-fly molecular reaction dynamics simulations of huge systems from scratch. The functions to perform large scale geometry optimization and molecular dynamics with DC-DFTB potential energy surface are implemented to the program called DC-DFTB-K. A novel interpolation-based algorithm is developed for parallelizing the determination of the Fermi level in the DC method. The performance of the DC-DFTB-K program is assessed using a laboratory computer and the K computer. Numerical tests show the high efficiency of the DC-DFTB-K program, a single-point energy gradient calculation of a one-million-atom system is completed within 60 s using 7290 nodes of the K computer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. [11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

    International Nuclear Information System (INIS)

    Guiducci, Letizia; Jaervisalo, Mikko; Kiss, Jan; Nagren, Kjell; Viljanen, Antti; Naum, Alexandru G.; Gastaldelli, Amalia; Savunen, Timo; Knuuti, Juhani; Salvadori, Piero A.; Ferrannini, Ele; Nuutila, Pirjo; Iozzo, Patricia

    2006-01-01

    Purpose: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [ 11 C]palmitate injection during fasting and insulin stimulation. Methods: Plasma [ 11 C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. Results: At 10 min, plasma levels of unchanged [ 11 C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P≤.03), suggesting faster clearance. Levels of unmetabolized [ 11 C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [ 11 C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92±1% and 82±6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. Conclusion: The study indicates that the redistribution of [ 11 C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional

  12. [{sup 11}C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Guiducci, Letizia [SSSUP Medical Sciences Branch, Pisa 56100 (Italy); Turku PET Centre, University of Turku, Turku 20520 (Finland); PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Jaervisalo, Mikko [Turku PET Centre, University of Turku, Turku 20520 (Finland); Kiss, Jan [Turku PET Centre, University of Turku, Turku 20520 (Finland); Department of Surgery, University of Turku, Turku 20520 (Finland); Nagren, Kjell [Turku PET Centre, University of Turku, Turku 20520 (Finland); Viljanen, Antti [Turku PET Centre, University of Turku, Turku 20520 (Finland); Naum, Alexandru G. [Turku PET Centre, University of Turku, Turku 20520 (Finland); Gastaldelli, Amalia [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Savunen, Timo [Department of Surgery, University of Turku, Turku 20520 (Finland); Knuuti, Juhani [Turku PET Centre, University of Turku, Turku 20520 (Finland); Salvadori, Piero A. [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Ferrannini, Ele [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Department of Internal Medicine, University of Pisa School of Medicine, Pisa 56100 (Italy); Nuutila, Pirjo [Turku PET Centre, University of Turku, Turku 20520 (Finland); Department of Medicine, University of Turku, Turku 20520 (Finland); Iozzo, Patricia [Turku PET Centre, University of Turku, Turku 20520 (Finland) and PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy)]. E-mail: patricia.iozzo@ifc.cnr.it

    2006-05-15

    Purpose: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [{sup 11}C]palmitate injection during fasting and insulin stimulation. Methods: Plasma [{sup 11}C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. Results: At 10 min, plasma levels of unchanged [{sup 11}C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P{<=}.03), suggesting faster clearance. Levels of unmetabolized [{sup 11}C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [{sup 11}C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92{+-}1% and 82{+-}6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. Conclusion: The study indicates that the redistribution of [{sup 11}C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG

  13. Differences in partitioning of meal fatty acids into blood lipid fractions: a comparison of linoleate, oleate, and palmitate

    OpenAIRE

    Hodson, Leanne; McQuaid, Siobh?n E.; Karpe, Fredrik; Frayn, Keith N.; Fielding, Barbara A.

    2008-01-01

    There has been much interest in the health effects of dietary fat, but few studies have comprehensively compared the acute metabolic fate of specific fatty acids in vivo. We hypothesized that different classes of fatty acids would be variably partitioned in metabolic pathways and that this would become evident over 24 h. We traced the fate of fatty acids using equal amounts of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate given in a test breakfast meal in 12 healthy subjects. There wa...

  14. Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways.

    Science.gov (United States)

    Hao, Feng; Kang, Jinsen; Cao, Yajun; Fan, Shengjun; Yang, Haopeng; An, Yu; Pan, Yan; Tie, Lu; Li, Xuejun

    2015-11-01

    Lipotoxicity plays a vital role in development and progression of type 2 diabetes. Prolonged elevation of free fatty acids especially the palmitate leads to pancreatic β-cell dysfunction and apoptosis. Curcumin (diferuloylmethane), a polyphenol from the curry spice turmeric, is considered to be a broadly cytoprotective agent. The present study was designed to determine the protective effect of curcumin on palmitate-induced apoptosis in β-cells and investigate underlying mechanisms. Our results showed that curcumin improved cell viability and enhanced glucose-induced insulin secretory function in MIN6 pancreatic β-cells. Palmitate incubation evoked chromatin condensation, DNA nick end labeling and activation of caspase-3 and -9. Curcumin treatment inhibited palmitate-induced apoptosis, relieved mitochondrial depolarization and up-regulated Bcl-2/Bax ratio. Palmitate induced the generation of reactive oxygen species and inhibited activities of antioxidant enzymes, which could be neutralized by curcumin treatment. Moreover, curcumin could promote rapid phosphorylation of Akt and nuclear exclusion of FoxO1 in MIN6 cells under lipotoxic condition. Phosphatidylinositol 3-kinase and Akt specific inhibitors abolished the anti-lipotoxic effect of curcumin and stimulated FoxO1 nuclear translocation. These findings suggested that curcumin protected MIN6 pancreatic β-Cells against apoptosis through activation of Akt, inhibition of nuclear translocation of FoxO1 and mitochondrial survival pathway.

  15. Effects of Ursodeoxycholic Acid and Insulin on Palmitate-Induced ROS Production and Down-Regulation of PI3K/Akt Signaling Activity.

    Science.gov (United States)

    Yokoyama, Kunihiro; Tatsumi, Yasuaki; Hayashi, Kazuhiko; Goto, Hidemi; Ishikawa, Tetsuya; Wakusawa, Shinya

    2017-01-01

    In obese and diabetic patients, plasma free fatty acid (FFA) levels are often elevated and may play a causal role in insulin resistance and reactive oxygen species (ROS) production. We have previously shown that ursodeoxycholic acid (UDCA) has antioxidative activity through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling-mediated glutathione production. In this study, we investigated the effects of UDCA on insulin response by analyzing intracellular ROS and the activation of the PI3K/Akt signaling pathway in HepG2 cells treated with palmitate. The level of ROS was quantified using 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCFDA), and the activation of the PI3K/Akt signaling pathway was determined by Western blotting assay using appropriate antibodies. The intracellular ROS levels were increased by palmitate but were reduced by treatment with UDCA and insulin. Furthermore, insulin significantly stimulated the phosphorylation of Akt. When the cells were pre-treated with palmitate, insulin-induced Akt-phosphorylation was markedly inhibited. However, when the cells were treated with palmitate and UDCA, the effects of insulin were partially restored. UDCA may have protective effects against palmitate-induced decreases in responsiveness to insulin.

  16. Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions

    Directory of Open Access Journals (Sweden)

    Lingling Han

    2015-01-01

    Full Text Available This study aimed to study the effects of acylated ghrelin on glucose and triglyceride metabolism in rat myoblasts under palmitic acid- (PA- induced high fat conditions. Rat myoblasts were treated with 0, 10−11, 10−9, or 10−7 M acylated ghrelin and 0.3 mM PA for 12 h. Triglyceride accumulation was determined by Oil-Red-O staining and the glycerol phosphate dehydrogenase-peroxidase enzymatic method, and glucose uptake was determined by isotope tracer. The glucose transporter 4 (GLUT4, AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase (ACC, and uncoupling protein 3 (UCP3 were assessed by RT-PCR and western blot. Compared to 0.3 mM PA, ghrelin at 10−9 and 10−7 M reduced triglyceride content (5.855 ± 0.352 versus 5.030 ± 0.129 and 4.158 ± 0.254 mM, P<0.05 and prevented PA-induced reduction of glucose uptake (1.717 ± 0.264 versus 2.233 ± 0.333 and 2.333 ± 0.273 10−2 pmol/g/min, P<0.05. The relative protein expression of p-AMPKα/AMPKα, UCP3, and p-ACC under 0.3 mM PA was significantly reduced compared to controls (all P<0.05, but those in the 10−9 and 10−7 M ghrelin groups were significantly protected from 0.3 mM PA (all P<0.05. In conclusion, acylated ghrelin reduced PA-induced triglyceride accumulation and prevented the PA-induced decrease in glucose uptake in rat myoblasts. These effects may involve fatty acid oxidation.

  17. In Vitro Palmitate Treatment of Myotubes from Postmenopausal Women Leads to Ceramide Accumulation, Inflammation and Affected Insulin Signaling

    DEFF Research Database (Denmark)

    Abildgaard, Julie; Henstridge, Darren C; Pedersen, Anette Tønnes

    2014-01-01

    Menopause is associated with an increased incidence of insulin resistance and metabolic diseases. In a chronic palmitate treatment model, we investigated the role of skeletal muscle fatty acid exposure in relation to the metabolic deterioration observed with menopause. Human skeletal muscle......, post-myotubes showed a blunted insulin stimulated phosphorylation of AS160 in response to chronic palmitate treatment compared with pre-myotubes (p = 0.02). The increased intramyocellular ceramide content in the post-myotubes was associated with a significantly higher mRNA expression of Serine...... Palmitoyltransferase1 (SPT1) after one day of palmitate treatment (p = 0.03) in post-myotubes compared with pre-myotubes. Our findings indicate that post-myotubes are more prone to develop lipid accumulation and defective insulin signaling following chronic saturated fatty acid exposure as compared to pre-myotubes....

  18. Incorporation of [14C]-palmitate into lipids of Brassica cells during the induction of freezing tolerance

    International Nuclear Information System (INIS)

    Lynch, D.V.; Joseph, R.A.

    1989-01-01

    Changes in plasma membrane lipid composition have been causally related to increased freezing tolerance. Studies of lipid metabolism during ABA induction of freezing tolerance in Brassica napus suspension cultures were undertaken. Cells were labeled with [ 14 C]-palmitate four days after transfer to fresh medium (control) or medium containing ABA (which increases freezing tolerance). At times between one and 20 hrs after labeling, ABA-treated cells incorporated almost twice the amount of label as controls cells. Approximately 80% of the radioactivity was associated with neutral lipids in ABA-treated cells and controls. Incorporation of label into total cellular polar lipids was 4.9 x 10 5 dpm/mg protein for control cells and 1 x 10 6 dpm/mg protein for cells transferred to medium containing ABA. Analysis of lipids following alkaline hydrolysis indicated that incorporation of [ 14 C]-palmitate into glucosylceramide of ABA-treated cells was less than 60% of control values when expressed relative to that of the total polar lipids. Incorporation into ceramides was also depressed in ABA-treated cells

  19. Deoxygenation of Palmitic and Lauric Acids over Pt/ZIF-67 Membrane/Zeolite 5A Bead Catalysts.

    Science.gov (United States)

    Yang, Liqiu; Carreon, Moises A

    2017-09-20

    The deoxygenation of palmitic and lauric acids over 0.5 wt % Pt/ZIF-67 membrane/zeolite 5A bead catalysts is demonstrated. Almost complete conversion (% deoxygenation of ≥95%) of these two fatty acids was observed over both fresh and recycled catalyst after a 2 h reaction time. The catalysts displayed high selectivity to pentadecane and undecane via decarboxylation reaction pathway even at low 0.5 wt % Pt loading. Selectivity to pentadecane and undecane as high as ∼92% and ∼94% was observed under CO 2 atmosphere when palmitic and lauric acids were used respectively as reactants. Depending on the reaction gas atmosphere, two distinctive reaction pathways were observed: decarboxylation and hydrodeoxygenation. Specifically, it was found that decarboxylation reaction pathway was more favorable in the presence of helium and CO 2 , while hydrodeoxygenation pathway strongly competed against the decarboxylation pathway when hydrogen was employed during the deoxygenation reactions. Esters were identified as the key reaction intermediates leading to decarboxylation and hydrodeoxygenation pathways.

  20. Intestinal absorption and distribution of 14C-palmitic acid in an young Indian freshwater major carp, Labeo rohita (Hamilton)

    International Nuclear Information System (INIS)

    Sinha, G.M.; Chakrabarti, P.

    1983-01-01

    The mechanism of absorption and distribution of radioactive lipids in the various regions of the intestine and hepatopancreas of young Labeo rohita (Ham.) was investigated after feeding with small-sized earthworms (Pheretima posthuma), preinjected with 14 C-Palmitic acid. Dietary free fatty acids were mainly absorbed in the various regions (anterior, middle and posterior) of the intestine-the absorption capacity, however, varying greatly from region to region. The absorption of free fatty acids through the luminal brush border of the various regions of the intestine started at 24 hr of post-feeding (h.p.f.) with labelled diet and recorded its peak during 32 +- 2 h.p.f. However, middle intestine was found to be more active for such absorption than the other two regions (anterior and posterior). Incorporation of labelled Palmitic acid in the columnar epithelial cells and its subsequent transportation in the hepatic tissues, via lymphatic systems took place with in a short interval after absorption. However, absorption was completed within 40 h.p.f. when deposition of radioactive lipids was found to be maximum in the columnar epithelial cells of the various regions of the intestine and hepatic tissues. (author)

  1. Optimization of methanol crystallization for highly efficient separation of palmitic acid from palm fatty acid mixture using response surface methodology

    Directory of Open Access Journals (Sweden)

    A. A.W. Japir

    2018-01-01

    Full Text Available The objective of the current study was to develop parameters for the separation of palmitic acid (PA from a crude palm oil saturated fatty acid (SFAs mixture by using the methanol crystallization method. The conditions of methanol crystallization were optimized by the response surface methodology (RSM with the D-optimal design. The procedure of developing the solvent crystallization method was based on various different parameters. The fatty acid composition was carried out using a gas chromatography flame ionization detector (GC-FID as fatty acid methyl esters. The highest percentage of SFAs was more than 96% with the percentage yield of 87.5% under the optimal conditions of fatty acids-to-methanol ratio of 1: 20 (w/v, the crystallization temperature of -15 °C, and the crystallization time of 24 hours, respectively. The composition of separated SFAs in the solid fraction contains 96.7% of palmitic acid (C16:0 as a dominant component and 3.3% of stearic acid (C18:0. The results showed that utilizing methanol as a crystallization solvent is recommended because of its high efficiency, low cost, stability, availability, comparative ease of recovery and its ability to form needle-like crystals which have good filtering and washing characteristics.

  2. Optimization of methanol crystallization for highly efficient separation of palmitic acid from palm fatty acid mixture using response surface methodology

    International Nuclear Information System (INIS)

    Japir, A.A.W.; Salimon, J.; Derawi, D.; Yahaya, B.H.; Jamil, M.S.M.; Yusop, M.R.

    2017-01-01

    The objective of the current study was to develop parameters for the separation of palmitic acid (PA) from a crude palm oil saturated fatty acid (SFAs) mixture by using the methanol crystallization method. The conditions of methanol crystallization were optimized by the response surface methodology (RSM) with the D-optimal design. The procedure of developing the solvent crystallization method was based on various different parameters. The fatty acid composition was carried out using a gas chromatography flame ionization detector (GC-FID) as fatty acid methyl esters. The highest percentage of SFAs was more than 96% with the percentage yield of 87.5% under the optimal conditions of fatty acids-to-methanol ratio of 1: 20 (w/v), the crystallization temperature of -15 °C, and the crystallization time of 24 hours, respectively. The composition of separated SFAs in the solid fraction contains 96.7% of palmitic acid (C16:0) as a dominant component and 3.3% of stearic acid (C18:0). The results showed that utilizing methanol as a crystallization solvent is recommended because of its high efficiency, low cost, stability, availability, comparative ease of recovery and its ability to form needle-like crystals which have good filtering and washing characteristics. [es

  3. Improving the physical and moisture barrier properties of Lepidium perfoliatum seed gum biodegradable film with stearic and palmitic acids.

    Science.gov (United States)

    Seyedi, Samira; Koocheki, Arash; Mohebbi, Mohebbat; Zahedi, Younes

    2015-01-01

    Stearic and palmitic fatty acids (10%, 20% and 30%, W/W gum) were used to improve the barrier properties of Lepidium perfoliatum seed gum (LPSG) film. The impact of the incorporation of fatty acids into the film matrix was studied by investigating the physical, mechanical, and barrier properties of the films. Addition of stearic and palmitic fatty acids to LPSG films reduced their water vapor permeability (WVP), moisture content, water solubility and water adsorption. Increasing fatty acid concentration from 10% to 30%, reduced the elongation at break (EB). Lower values of tensile strength (TS) and elastic modulus (EM) were obtained in the presence of higher fatty acids concentrations. Incorporation of fatty acids led to production of opaque films and the opacity increased as function of fatty acids concentration. Results showed that moisture content, water solubility and WVP decreased as the chain length of fatty acid increased. Therefore, LPSG-fatty acids composite film could be used for packaging in which a low affinity toward water is needed. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a

    NARCIS (Netherlands)

    Bandsma, RHJ; Rake, JP; Visser, G; Neese, RA; Hellerstein, MK; van Duyvenvoorde, W; Princen, HMG; Stellaard, F; Smit, GPA; Kuipers, F

    We describe 2 patients with glycogen storage disease type la and severe hyperlipidemia without premature atherosclerosis. Susceptibility of low-density lipoproteins to oxidation was decreased, possibly related to the similar to40-fold increase in palmitate synthesis altering lipoprotein saturated

  5. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna Christina

    2017-01-01

    INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were...... performed in 2 pigs and 2 healthy volunteers by whole-body [11C]palmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions. Metabolites were estimated using 2 approaches and subsequently compared: Indirect [11C]CO2...

  6. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna Christina

    2017-01-01

    release and parent [11C]palmitate measured by a solid-phase extraction (SPE) method. Finally, myocardial fatty acid uptake was calculated in a patient cohort using input functions derived from individual metabolite correction compared with population-based metabolite correction. RESULTS: In humans, mean......INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were...

  7. Acidolysis of terebinth fruit oil with palmitic and caprylic acids in a recirculating packed bed reactor: optimization using response surface methodology

    Directory of Open Access Journals (Sweden)

    Koçak Yanık, D.

    2016-06-01

    Full Text Available The acidolysis reaction of terebinth fruit oil with caprylic and palmitic acid has been investigated. The reaction was catalyzed by lipase (Lipozyme IM from Rhizomucormiehei and carried out in recirculating packed bed reactor. The effects of reaction parameters have been analyzed using response surface methodology. Reaction time (3.5–6.5 h, enzyme load (10–20%, substrate flow rate (4–8 mL·min-1 and substrate mole ratios (Terebinth oil : Palmitic acid : Caprylic acid, 1:1.83:1.22–1:3.07:2.05 were evaluated. The optimum reaction conditions were 5.9 h reaction time, 10% enzyme load, 4 mL·min-1 substrate flow rate and 1:3.10:2.07 substrate mole ratio. The structured lipid obtained at these optimum conditions had 52.23% desired triacylglycerols and a lower caloric value than that of terebinth fruit oil. The melting characteristics and microstructure of the structured lipid were similar to those of commercial margarine fat extracts. The results showed that the structured lipid had the highest oxidative stability among the studied fats.Se ha investigado la reacción de acidolisis del aceite de pistacho con los ácidoscaprílico y palmítico. La reacción fue catalizada por la lipasa Lipozyme IM de Rhizomucormiehei y realizada mediante recirculación del reactor de lecho compacto. Los efectos de los parámetros de la reacción han sido analizados mediante el uso de la metodología de superficie de respuesta. El tiempo de reacción (3.5 hasta 6.5 h, la carga de enzima (10–20%, el caudal de sustrato (4–8 mL·min-1 relaciones molares de los sustrato (aceite de pistacho: ácido palmítico: ácido caprílico, 1: 1,83: 1,22–1: 3,07: 2,05 fueron evaluados. Las condiciones óptimas de reacción fueron 5,9 h de tiempo de reacción, el 10% de carga de la enzima, 4 mL·min-1 de caudal de sustrato y 1: 3,10: 2,07 de relación molar de sustratos. Los lípidos estructurados obtenidos en las condiciones óptimas tenías 52,23% de triacilgliceroles

  8. Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yunxia, E-mail: wwwdluyx@sina.com [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032 (China); Cheng, Jingjing [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Chen, Li [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Department of Medical Laboratory, Anhui Provincial Hospital, Hefei, Anhui 230001 (China); Li, Chaofei; Chen, Guanjun [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Gui, Li [The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032 (China); Shen, Bing [Department of Physiology, Anhui Medical University, Hefei, Anhui 230032 (China); Zhang, Qiu [Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022 (China)

    2015-02-27

    Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS. - Highlights: • Fenofibrate treatment improved pathological changes in thoracic aorta by chronic high-fat-diet feeding. • Fenofibrate pretreatment improved endothelium-dependent vasodilation impaired by different concentrations of palmitic acid. • The inhibition of proliferation in endothelial cells by palmitic acid were inverted by fenofibric

  9. Study on the metabolism of 15 p-131iodine phenyl pentadecanoic acid [p-iodine phenyl pentadecanoic acid] as a tracer of free fatty acids in comparison to 1-14C-palmitic acid (C-palmitic acid)

    International Nuclear Information System (INIS)

    Sauer, J.W.

    1986-01-01

    In an animal experiment under identical metabolic influences the metabolism of a new radiopharmaceutical, 15 p- 131 iodine phenyl pentadecanoic acid (IPPA), was compared to the marked physiological fatty acid, 1- 14 C-palmitic acid (PA). The pharmacological kinetics of both tracers in tissues with widely varied turnover rates of fatty acids (heart, lung, liver, kidney, spleen, small intestine, skeletal muscle) was studied. By alkali extraction of the tissue lipids and then a chromatographic separation of the lipid fractions quantitatively comparable statements about the metabolism of PA and IPPA were made possible. The analyses of autoradiographs of the chromatographically separated lipids show a qualitatively congruous assimilation of both markers in the major lipid fractions. The quantitative evaluation shows minor differences as a result of a preferred assimilation of IPPA in triglycerides and of PA in phospholipids. The fractionated separation of tissue lipids which had been marked with PA and IPPA in vivo agrees very well with values which have been determined by other authors using 14 C- or 3 H-marked fatty acids. The close correlation of the tissue-specific metabolism kinetics of both markers makes it clear that both fatty acids are metabolized by similar, respectively, primarily identical metabolic pathyways. In conclusion, this study makes clear the extensive congruence of the metabolism kinetics of IPPA and the kinetics of the physiological palmitic acid. As a result of the presented results of the γ-radiating radiopharmaceutical IPPA as a free fatty acid analog new possibilities for the non-invasive external comprehension of lipid metabolism are opened up, whose use especially in the diagnostic of heart diseases promises success. (orig./MG) [de

  10. Serotonin- and Dopamine-Related Gene Expression in db/db Mice Islets and in MIN6 β-Cells Treated with Palmitate and Oleate

    Directory of Open Access Journals (Sweden)

    L. R. Cataldo

    2016-01-01

    Full Text Available High circulating nonesterified fatty acids (NEFAs concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent β-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated β-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 β-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 β-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (−25%; p<0.0001 and oleate (−43%; p<0.0001 were detected in MIN6 β-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 β-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content.

  11. SIRT1 attenuates palmitate-induced endoplasmic reticulum stress and insulin resistance in HepG2 cells via induction of oxygen-regulated protein 150

    Science.gov (United States)

    Jung, T.W.; Lee, K.T.; Lee, M.W.; Ka, K.H.

    2012-01-01

    Endoplasmic reticulum (ER) stress has been implicated in the pathology of type 2 diabetes mellitus (T2DM). Although SIRT1 has a therapeutic effect on T2DM, the mechanisms by which SIRT1 ameliorates insulin resistance (IR) remain unclear. In this study, we investigated the impact of SIRT1 on palmitate-induced ER stress in HepG2 cells and its underlying signal pathway. Treatment with resveratrol, a SIRT1 activator significantly inhibited palmitate-induced ER stress, leading to the protection against palmitate-induced ER stress and insulin resistance. Resveratrol and SIRT1 overexpression induced the expression of oxygen-regulated protein (ORP) 150 in HepG2 cells. Forkhead box O1 (FOXO1) was involved in the regulation of ORP150 expression because suppression of FOXO1 inhibited the induction of ORP150 by SIRT1. Our results indicate a novel mechanism by which SIRT1 regulates ER stress by overexpression of ORP150, and suggest that SIRT1 ameliorates palmitate-induced insulin resistance in HepG2 cells via regulation of ER stress.

  12. Synergetic Effect of Ni2P/SiO2 and γ-Al2O3 Physical Mixture in Hydrodeoxygenation of Methyl Palmitate

    Directory of Open Access Journals (Sweden)

    Ivan V. Shamanaev

    2017-11-01

    Full Text Available The Ni2P/SiO2 catalyst, which was prepared by in situ temperature-programmed reduction and in the mixture with the inert (SiC, SiO2 or acidic (γ-Al2O3 material was studied in methyl palmitate hydrodeoxygenation (HDO. Methyl palmitate HDO was carried out at temperatures of 270–330 °C, H2/feed volume ratio of 600 Nm3/m3, and H2 pressure of 3.0 MPa. Ni2P/SiO2 catalyst, diluted with γ-Al2O3 showed a higher activity than Ni2P/SiO2 catalyst diluted with SiC or SiO2. The conversion of methyl palmitate increased significantly in the presence of γ-Al2O3 most probably due to the acceleration of the acid-catalyzed reaction of ester hydrolysis. The synergism of Ni2P/SiO2 and γ-Al2O3 in methyl palmitate HDO can be explained by the cooperation of the metal sites of Ni2P/SiO2 and the acid sites of γ-Al2O3 in consecutive metal-catalyzed and acid-catalyzed reactions of HDO. The obtained results let us conclude that the balancing of metal and acid sites plays an important role in the development of the efficient catalyst for the HDO of fatty acid esters over supported phosphide catalysts.

  13. Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Shrestha, Chandan [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Ito, Takashi [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kawahara, Ko-ichi [Department of Biomedical Engineering, Osaka Institute of Technology, Osaka (Japan); Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto [Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Maruyama, Ikuro, E-mail: rinken@m3.kufm.kagoshima-u.ac.jp [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan)

    2013-08-09

    Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis.

  14. Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

    International Nuclear Information System (INIS)

    Shrestha, Chandan; Ito, Takashi; Kawahara, Ko-ichi; Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto; Maruyama, Ikuro

    2013-01-01

    Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis

  15. Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial.

    Science.gov (United States)

    Toshida, Hiroshi; Funaki, Toshinari; Ono, Koichi; Tabuchi, Nobuhito; Watanabe, Sota; Seki, Tamotsu; Otake, Hiroshi; Kato, Takuji; Ebihara, Nobuyuki; Murakami, Akira

    2017-01-01

    The purpose of this study was to investigate the efficacy and safety of the administration of retinol palmitate (VApal) ophthalmic solution (500 IU/mL) for the treatment of patients with dry eye. This study included 66 patients with dry eye. After a 2-week washout period, patients were randomized (1:1) into either a VApal ophthalmic solution or a placebo group, and a single drop of either solution was administered six times daily for 4 weeks. Efficacy measures were 12 subjective symptoms, rose bengal (RB) and fluorescein staining scores, tear film breakup time, and tear secretion. Safety measures included clinical blood and urine analyses and adverse event recordings. In comparisons of the two groups, the mean change in RB staining score from baseline was significantly lower in the VApal group at 2 and 4 weeks ( P ophthalmic solution (500 IU/mL) is safe and effective for the treatment of patients with dry eye.

  16. Incorporation of [14C]-L-leucine in splenic and hepatic tissue of rats 'chemically splenectomized' by ethyl palmitate

    International Nuclear Information System (INIS)

    Sebestik, V.; Kselikova, M.; Freiova, M.; Potmesilova, I.

    1978-01-01

    In experiments with 'chemically splenectomized' rats by an i.v. application of ethyl palmitate (EP) emulsion and using [ 14 C]-L-leucine, the protein synthesis in spleen and liver was followed. Two hours following EP application protein synthesis in the spleen was significantly decreased; after 24 hrs and 4 days the incorporation increased moderately above normal values, and in the subsequent intervals protein synthesis was again lowered. In the liver a significant increase of protein synthesis 24 hrs and 4 days after EP injection was observed. Changes of proteins synthesis in the spleen are evidently related to damage of the tissue and its subsequent regeneration. Changes in the liver are manifestations rather of an increased metabolic load during EP degradation. (author)

  17. Polarized Raman and Infrared Spectroscopy and ab Initio Calculation of Palmitic and Stearic Acids in the Bm and C Forms.

    Science.gov (United States)

    L da Silva, L F; Andrade-Filho, T; Freire, P T C; Filho, J Mendes; da Silva Filho, J G; Saraiva, G D; Moreira, S G C; de Sousa, F F

    2017-06-29

    A complete experimental study on the vibrational properties of palmitic and stearic acids crystallized in the B m and C forms, both belonging to the monoclinic system with the P2 1 /a (C 2h 5 ) space group, through polarized Raman and infrared spectroscopy, is reported in this paper. Density functional theory calculations were also performed to assign the normal modes and to help in the interpretation of the experimental data. The different polarizations were compared and their influence on the spectral profiles, in both the lattice and the internal mode regions, was discussed. In general, the Raman and infrared spectra exhibit accentuated differences among the polymorphic forms, which are associated with the different molecular modifications, defined as gauche and all-trans conformations. Insights about interaction among different groups are also furnished.

  18. Thermal properties and heat storage analysis of palmitic acid-TiO_2 composite as nano-enhanced organic phase change material (NEOPCM)

    International Nuclear Information System (INIS)

    Sharma, R.K.; Ganesan, P.; Tyagi, V.V.; Metselaar, H.S.C.; Sandaran, S.C.

    2016-01-01

    Highlights: • Novel composite of palmitic acid and TiO_2 nanoparticles with enhanced thermal energy storage capabilities • The composite is thermally reliable and chemically stable. • Thermal conductivity of the composite increases significantly with the loading. - Graphical Abstract: - Abstract: In the present study, the phase change behavior of prepared novel composites of palmitic acid and solid nanoparticles of titanium dioxide (TiO_2) for thermal energy storage has been investigated. The nanoparticles are dispersed into the base fluid in various mass fractions (0.5, 1, 3, and 5%), and their effects on the thermo-physical properties have been investigated. Structural analysis has been carried out by using FESEM, and crystallography was checked by XRD technique. The chemical/functional groups of the base fluid and composite PCMs have been analyzed by using FT-IR spectrum. The observations showed that the TiO_2 nanoparticles do not affect the chemical structure of palmitic acid; however they improve the chemical stability. The phase transition temperature and latent heat of fusion has shown the significant stability with the increase in nanoparticle weight fractions. The accelerated thermal cycle test of the composite shows good thermal reliability for 1500 melt/freeze cycles. Thermal conductivity of palmitic acid increased gradually by 12.7, 20.6, 46.6, and 80% for the nanoparticle weight fractions of 0.5, 1, 3, and 5% respectively. Based on the results, it can be mentioned that the prepared palmitic acid based nano-enhanced organic phase change composite materials can be very well used as potential solar thermal energy storage materials.

  19. ShenFu Preparation Protects AML12 Cells Against Palmitic Acid-Induced Injury Through Inhibition of Both JNK/Nox4 and JNK/NFκB Pathways

    Directory of Open Access Journals (Sweden)

    Jia-Fu Ji

    2018-02-01

    Full Text Available Background/Aims: Nonalcoholic steatohepatitis includes steatosis along with liver inflammation, hepatocyte injury and fibrosis. In this study, we investigated the protective role and the potential mechanisms of a traditional Chinese medicine ShenFu (SF preparation in an in vitro hepatic steatosis model. Methods: In palmitic acid (PA-induced murine hepatic AML12 cell injury, effects of SF preparation on cellular apoptosis and intracellular triglyceride (iTG level were assessed using TUNEL and TG Colorimetric Assay. Reactive oxygen species (ROS and mitochondrial membrane potential (MMP levels were measured using DCF and JC-1 assay. Cytokine levels were evaluated using ELISA assay. Immunoblot was used to compare the activation level of c-Jun N terminal kinase (JNK, NADPH oxidase (Nox4, and NFκB pathways. Results: Addition of SF preparation prevented PA-mediated increase of apoptosis and iTG as well as IL-8 and IL-6. In PA-treated cell, SF preparation reduced the level of Nox4 and ROS, while increasing the level of MMP and the expression of manganese superoxide dismutase (MnSOD and catalase, indicating emendation of mitochondrial dysfunction. Nox4 inhibitor GKT137381 prevented PA-induced increase of ROS and apoptosis, while decreasing iTG slightly and not influencing the level of IL-8 and IL-6. SF preparation prevented PA-induced upregulation of phospho-JNK. JNK inhibitor SP600125 prevented PA-mediated increase of Nox4, IL-8, IL-6 and iTG. Nuclear translocation of NFκB/p65 was detected in PA-treated cells, which was prevented by SF preparation. An IκB degradation inhibitor, BAY11-7082, prevented PA-induced increase of IL-8 and IL-6 as well as iTG, whereas it only decreased ROS levels slightly and showed no influence on cellular apoptosis. Conclusion: SF preparation shows a beneficial role in prevention of hepatocyte injury by attenuating oxidative stress and cytokines production at least partially through inhibition of JNK/Nox4 and JNK

  20. Overcoming drug-tolerant cancer cell subpopulations showing AXL activation and epithelial–mesenchymal transition is critical in conquering ALK-positive lung cancer

    Science.gov (United States)

    Nakamichi, Shinji; Seike, Masahiro; Miyanaga, Akihiko; Chiba, Mika; Zou, Fenfei; Takahashi, Akiko; Ishikawa, Arimi; Kunugi, Shinobu; Noro, Rintaro; Kubota, Kaoru; Gemma, Akihiko

    2018-01-01

    Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) induce a dramatic response in non–small cell lung cancer (NSCLC) patients with the ALK fusion gene. However, acquired resistance to ALK-TKIs remains an inevitable problem. In this study, we aimed to discover novel therapeutic targets to conquer ALK-positive lung cancer. We established three types of ALK-TKI (crizotinib, alectinib and ceritinib)-resistant H2228 NSCLC cell lines by high exposure and stepwise methods. We found these cells showed a loss of ALK signaling, overexpressed AXL with epithelial-mesenchymal transition (EMT), and had cancer stem cell-like (CSC) properties, suggesting drug-tolerant cancer cell subpopulations. Similarly, we demonstrated that TGF-β1 treated H2228 cells also showed AXL overexpression with EMT features and ALK-TKI resistance. The AXL inhibitor, R428, or HSP90 inhibitor, ganetespib, were effective in reversing ALK-TKI resistance and EMT changes in both ALK-TKI-resistant and TGF-β1-exposed H2228 cells. Tumor volumes of xenograft mice implanted with established H2228-ceritinib-resistant (H2228-CER) cells were significantly reduced after treatment with ganetespib, or ganetespib in combination with ceritinib. Some ALK-positive NSCLC patients with AXL overexpression showed a poorer response to crizotinib therapy than patients with a low expression of AXL. ALK signaling-independent AXL overexpressed in drug-tolerant cancer cell subpopulations with EMT and CSC features may be commonly involved commonly involved in intrinsic and acquired resistance to ALK-TKIs. This suggests AXL and HSP90 inhibitors may be promising therapeutic drugs to overcome drug-tolerant cancer cell subpopulations in ALK-positive NSCLC patients for the reason that ALK-positive NSCLC cells do not live through ALK-TKI therapy. PMID:29930762

  1. Bezafibrate in skeletal muscle fatty acid oxidation disorders

    DEFF Research Database (Denmark)

    Ørngreen, Mette Cathrine; Madsen, Karen Lindhardt; Preisler, Nicolai

    2014-01-01

    OBJECTIVE: To assess whether bezafibrate increases fatty acid oxidation (FAO) and lowers heart rate (HR) during exercise in patients with carnitine palmitoyltransferase (CPT) II and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies. METHODS: This was a 3-month, randomized, double......, triglyceride, and free fatty acid concentrations; however, there were no changes in palmitate oxidation, FAO, or HR during exercise. CONCLUSION: Bezafibrate does not improve clinical symptoms or FAO during exercise in patients with CPT II and VLCAD deficiencies. These findings indicate that previous in vitro...

  2. Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Fu Dong-Jing

    2011-05-01

    Full Text Available Abstract Background Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal. These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability. Methods In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively or placebo (NCT#00590577. Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE rates and relative risks (RR with 95% confidence intervals (CI versus placebo were determined. Results Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS mean PANSS total score at Day 8 (p = 0.037. After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo and Day 36 (p Conclusions Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1 compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose

  3. Methodological challenges in indirect treatment comparisons: spotlight on a recent comparison of long-acting injectable aripiprazole versus paliperidone palmitate in the treatment of schizophrenia.

    Science.gov (United States)

    Singh, Arun; Gopal, Srihari; Kim, Edward; Mathews, Maju; Kern-Sliwa, Jennifer; Turkoz, Ibrahim; Wooller, Annette; Berlin, Jesse

    2018-03-01

    In a recent study, an indirect treatment comparison was performed to examine the relative efficacy and tolerability of aripiprazole once monthly and paliperidone palmitate once monthly. The authors concluded that the results may suggest relative advantages for aripiprazole once monthly over paliperidone palmitate once monthly in the short-term treatment of schizophrenia. However, the validity of the study is compromised as an indirect treatment comparison using extant data may violate important assumptions. Other methodological issues identified further highlight the challenges of performing indirect treatment comparisons.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

  4. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to beta-palmitate and increased calcium absorption pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following an application from IDACE, submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to beta...... (middle or beta) position of the glycerol backbone. Beta-palmitate is considered to be sufficiently characterised. The claimed effect is “beta palmitate enrichment contributes to increase calcium absorption”. The target population proposed by the applicant is infants from birth to 12 months of age......, the Panel took into account the biological plausibility of the mechanism by which beta-palmitate could exert the claimed effect and that three small human intervention studies in preterm and term infants provided some evidence that a higher degree of palmitic acid in the sn-2 position of formula...

  5. A simple and robust quantitative analysis of retinol and retinyl palmitate using a liquid chromatographic isocratic method

    Directory of Open Access Journals (Sweden)

    Satoshi Yokota

    2018-04-01

    Full Text Available Vitamin A is a vital nutritional substances that regulates biological activities including development, but is also associated with disease onset. The extent of vitamin A intake influences the retinoid content in the liver, the most important organ for the storage of vitamin A. Measurement of endogenous retinoid in biological samples is important to understand retinoid homeostasis. Here we present a reliable, highly sensitive, and robust method for the quantification of retinol and retinyl palmitate using a reverse-phase HPLC/UV isocratic method. We determined the impact of chronic dietary vitamin A on retinoid levels in livers of mice fed an AIN-93G semi-purified diet (4 IU/g compared with an excess vitamin A diet (1000 IU/g over a period from birth to 10 weeks of age. Coefficients of variation for intra-assays for both retinoids were less than 5%, suggesting a higher reproducibility than any other HPLC/UV gradient method. Limits of detection and quantification for retinol were 0.08 pmol, and 0.27 pmol, respectively, which are remarkably higher than previous results. Supplementation with higher doses of vitamin A over the study period significantly increased liver retinol and retinyl palmitate concentrations in adult mice. The assays described here provide a sensitive and rigorous quantification of endogenous retinol and retinyl palmitate, which can be used to help determine retinoid homeostasis in disease states, such as toxic hepatitis and liver cancer. Keywords: Vitamin A excess, Retinol, Retinyl palmitate, Liver

  6. Red palm oil-supplemented and biofortified cassava gari increase the carotenoid and retinyl palmitate concentrations of triacylglycerol-rich plasma in women.

    Science.gov (United States)

    Zhu, Chenghao; Cai, Yimeng; Gertz, Erik R; La Frano, Michael R; Burnett, Dustin J; Burri, Betty J

    2015-11-01

    Boiled biofortified cassava containing β-carotene can increase retinyl palmitate in triacylglycerol-rich plasma. Thus, it might alleviate vitamin A deficiency. Cassava requires extensive preparation to decrease its level of cyanogenic glucosides, which can be fatal. Garification is a popular method of preparing cassava that removes cyanogen glucosides. Our objective was to compare the effectiveness of biofortified gari to gari prepared with red palm oil. The study was a randomized crossover trial in 8 American women. Three gari preparations separated by 2-week washout periods were consumed. Treatments (containing 200-225.9 g gari) were as follows: biofortified gari (containing 1 mg β-carotene), red palm oil-fortified gari (1 mg β-carotene), and unfortified gari with a 0.3-mg retinyl palmitate reference dose. Blood was collected 6 times from -0.5 to 9.5 hours after ingestion. Triacylglycerol-rich plasma was separated by ultracentrifugation and analyzed by high-performance liquid chromatography (HPLC) with diode array detection. Area under the curve for β-carotene, α-carotene, and retinyl palmitate increased after the fortified meals were fed (P palm oil treatment was greater than that induced by the biofortified treatment (P palm oil and biofortified gari, respectively. These results show that both treatments increased β-carotene, α-carotene, and retinyl palmitate in triacylglycerol-rich plasma concentrations in healthy well-nourished adult women, supporting our hypothesis that both interventions could support efforts to alleviate vitamin A deficiency. Published by Elsevier Inc.

  7. Effects of inhibition of serine palmitoyltransferase (SPT and sphingosine kinase 1 (SphK1 on palmitate induced insulin resistance in L6 myotubes.

    Directory of Open Access Journals (Sweden)

    Agnieszka Mikłosz

    Full Text Available BACKGROUND: The objective of this study was to examine the effects of short (2 h and prolonged (18 h inhibition of serine palmitoyltransferase (SPT and sphingosine kinase 1 (SphK1 on palmitate (PA induced insulin resistance in L6 myotubes. METHODS: L6 myotubes were treated simultaneously with either PA and myriocin (SPT inhibitor or PA and Ski II (SphK1inhibitor for different time periods (2 h and 18 h. Insulin stimulated glucose uptake was measured using radioactive isotope. Expression of insulin signaling proteins was determined using Western blot analyses. Intracellular sphingolipids content [sphinganine (SFA, ceramide (CER, sphingosine (SFO, sphingosine-1-phosphate (S1P] were estimated by HPLC. RESULTS: Our results revealed that both short and prolonged time of inhibition of SPT by myriocin was sufficient to prevent ceramide accumulation and simultaneously reverse palmitate induced inhibition of insulin-stimulated glucose transport. In contrast, prolonged inhibition of SphK1 intensified the effect of PA on insulin-stimulated glucose uptake and attenuated further the activity of insulin signaling proteins (pGSK3β/GSK3β ratio in L6 myotubes. These effects were related to the accumulation of sphingosine in palmitate treated myotubes. CONCLUSION: Myriocin is more effective in restoration of palmitate induced insulin resistance in L6 myocytes, despite of the time of SPT inhibition, comparing to SKII (a specific SphK1 inhibitor. Observed changes in insulin signaling proteins were related to the content of specific sphingolipids, namely to the reduction of ceramide. Interestingly, inactivation of SphK1 augmented the effect of PA induced insulin resistance in L6 myotubes, which was associated with further inhibition of insulin stimulated PKB and GSK3β phosphorylation, glucose uptake and the accumulation of sphingosine.

  8. Estimated medical cost reductions for paliperidone palmitate vs placebo in a randomized, double-blind relapse-prevention trial of patients with schizoaffective disorder.

    Science.gov (United States)

    Joshi, K; Lin, J; Lingohr-Smith, M; Fu, D J

    2015-01-01

    The objective of this economic model was to estimate the difference in medical costs among patients treated with paliperidone palmitate once-monthly injectable antipsychotic (PP1M) vs placebo, based on clinical event rates reported in the 15-month randomized, double-blind, placebo-controlled, parallel-group study of paliperidone palmitate evaluating time to relapse in subjects with schizoaffective disorder. Rates of psychotic, depressive, and/or manic relapses and serious and non-serious treatment-emergent adverse events (TEAEs) were obtained from the long-term paliperidone palmitate vs placebo relapse prevention study. The total annual medical cost for a relapse from a US payer perspective was obtained from published literature and the costs for serious and non-serious TEAEs were based on Common Procedure Terminology codes. Total annual medical cost differences for patients treated with PP1M vs placebo were then estimated. Additionally, one-way and Monte Carlo sensitivity analyses were conducted. Lower rates of relapse (-18.3%) and serious TEAEs (-3.9%) were associated with use of PP1M vs placebo as reported in the long-term paliperidone palmitate vs placebo relapse prevention study. As a result of the reduction in these clinical event rates, the total annual medical cost was reduced by $7140 per patient treated with PP1M vs placebo. One-way sensitivity analysis showed that variations in relapse rates had the greatest impact on the estimated medical cost differences (range: -$9786, -$4670). Of the 10,000 random cycles of Monte Carlo simulations, 100% showed a medical cost difference schizoaffective disorder was associated with a significantly lower rate of relapse and a reduction in medical costs compared to placebo. Further evaluation in the real-world setting is warranted.

  9. Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid-induced insulin resistance.

    Science.gov (United States)

    Shinjo, Satoko; Jiang, Shuying; Nameta, Masaaki; Suzuki, Tomohiro; Kanai, Mai; Nomura, Yuta; Goda, Nobuhito

    2017-10-01

    The mitochondria-associated ER membrane (MAM) is a specialized subdomain of ER that physically connects with mitochondria. Although disruption of inter-organellar crosstalk via the MAM impairs cellular homeostasis, its pathological significance in insulin resistance in type 2 diabetes mellitus remains unclear. Here, we reveal the importance of reduced MAM formation in the induction of fatty acid-evoked insulin resistance in hepatocytes. Palmitic acid (PA) repressed insulin-stimulated Akt phosphorylation in HepG2 cells within 12h. Treatment with an inhibitor of the ER stress response failed to restore PA-mediated suppression of Akt activation. Mitochondrial reactive oxygen species (ROS) production did not increase in PA-treated cells. Even short-term exposure (3h) to PA reduced the calcium flux from ER to mitochondria, followed by a significant decrease in MAM contact area, suggesting that PA suppressed the functional interaction between ER and mitochondria. Forced expression of mitofusin-2, a critical component of the MAM, partially restored MAM contact area and ameliorated the PA-elicited suppression of insulin sensitivity with Ser473 phosphorylation of Akt selectively improved. These results suggest that loss of proximity between ER and mitochondria, but not perturbation of homeostasis in the two organelles individually, plays crucial roles in PA-evoked Akt inactivation in hepatic insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effect of Retinol Palmitate on Corneal and Conjunctival Mucin Gene Expression in a Rat Dry Eye Model After Injury.

    Science.gov (United States)

    Tabuchi, Nobuhito; Toshida, Hiroshi; Koike, Daisuke; Odaka, Akito; Suto, Chikako; Ohta, Toshihiko; Murakami, Akira

    We examined the wound-healing effect of retinol palmitate (VApal) on mucin gene and protein expressions in a rat dry eye model based on lacrimal gland (LG) resection after injury. The rat dry eye model was prepared by surgical resection of the main LG in male Long-Evans rats. After alkaline injury of the central part of the lower palpebral conjunctiva bilaterally, VApal eye drops at 1,500 IU/mL in one eye and a vehicle in the fellow eye were both administered 6 times a day for 7 days. The expression of mucin gene and protein was analyzed by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in the cornea and conjunctiva of MUC1, MUC4, MUC16, and MUC5AC after 1, 3, (5), and 7 days of treatment with VApal. Significant decreases in fluorescein-stained areas and rose bengal scores were observed in VApal-treated dry eyes compared with vehicle-treated dry eyes at both 3 (P dry eye model after injury. VApal also promoted conjunctival MUC16 expression. These results indicate that VApal has efficacy in improving keratoconjunctival epithelial damage associated with decreased tear production.

  11. Topical Application of Retinyl Palmitate-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

    Directory of Open Access Journals (Sweden)

    Marcela B. Oliveira

    2014-01-01

    Full Text Available The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS with and without retinyl palmitate (RP. LCS containing polyether functional siloxane (PFS as a surfactant, silicon glycol copolymer (SGC as oil phase, and water in the ratios 30 : 25 : 45 and 40 : 50 : 10 with (OLSv = RP-loaded opaque liquid system and TLSv = RP-loaded transparent liquid system, respectively and without (OLS and TLS, respectively RP were studied. Samples were characterized using polarized light microscopy (PLM and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging.

  12. Multivariate optimization of a synergistic blend of oleoresin sage (Salvia officinalis L.) and ascorbyl palmitate to stabilize sunflower oil.

    Science.gov (United States)

    Upadhyay, Rohit; Mishra, Hari Niwas

    2016-04-01

    The simultaneous optimization of a synergistic blend of oleoresin sage (SAG) and ascorbyl palmitate (AP) in sunflower oil (SO) was performed using central composite and rotatable design coupled with principal component analysis (PCA) and response surface methodology (RSM). The physicochemical parameters viz., peroxide value, anisidine value, free fatty acids, induction period, total polar matter, antioxidant capacity and conjugated diene value were considered as response variables. PCA reduced the original set of correlated responses to few uncorrelated principal components (PC). The PC1 (eigen value, 5.78; data variance explained, 82.53 %) was selected for optimization using RSM. The quadratic model adequately described the data (R (2) = 0. 91, p  0.05). The contour plot of PC 1 score indicated the optimal synergistic combination of 1289.19 and 218.06 ppm for SAG and AP, respectively. This combination of SAG and AP resulted in shelf life of 320 days at 25 °C estimated using linear shelf life prediction model. In conclusion, the versatility of PCA-RSM approach has resulted in an easy interpretation in multiple response optimizations. This approach can be considered as a useful guide to develop new oil blends stabilized with food additives from natural sources.

  13. Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Ji, Zhi-Hong; Xu, Zhong-Qi; Zhao, Hong; Yu, Xin-Yu

    2017-03-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Effect of vitamin A palmitate ophthalmic gel adjunctive therapy on tear film stability and inflammatory cytokines in patients with dry eye

    Directory of Open Access Journals (Sweden)

    Ya-Yuan Lu

    2018-06-01

    Full Text Available AIM:To investigate the effect of sodium hyaluronate eye drops combined with vitamin A palmitate ophthalmic gel on levels of tear film stability and inflammatory cytokines in patients with dry eye. METHODS: A total of 100 patients with dry eye treated in our hospital from January 2015 to February 2017 were randomly divided into control group and observation group, 50 cases in each group. Patients in the control group were treated with sodium hyaluronate eye drops. Patients in the observation group were given vitamin A palmitate ophthalmic gel on the basis of the control group, and then the clinical efficacy, tear film stability and the level of inflammatory cytokines were detected in the two groups. RESULTS: After treatment, the levels of BUT and SⅠt in both groups increased significantly compared with that before treatment, and FL was significantly lower than that before treatment. The levels of BUT and SⅠt in the observation group after treatment were 11.24±0.22s and 11.4±0.17mm/5min respectively, which was high than that of control groups(PPPPCONCLUSION: Sodium hyaluronate eye drops combined with vitamin A palmitate ophthalmic gel can relieve the symptoms of patients with dry eye effectively, increase the stability of tear film, and reduce the levels of inflammatory factors in tears, which is reliable in clinical application.

  15. Incorporation of radioactive labelled cholin and palmitate into lung lecithin of rabbits treated with high doses of bromcarbamides, barbiturates and diazepam

    International Nuclear Information System (INIS)

    Wichert, P. von; Schmidt, C.; Pomraenke, K.; Wiegers, U.

    1977-01-01

    Severe intoxications with bromcarbamides often show respiratory complications. To answer the question if there is a direct effect of the drug on lung tissue the incorporation of radioactive labelled choline and palmitate into lung lecithin was investigated. The phospholipid metabolism is in close relation to the surfactant system of the lung. Secondly the influence of bromcarbamides was compared with other hypnotic drugs. There was a reduction of palmitate incorporation into lung lecithin down to 40%, whereas the incorporation of choline increases in bromcarbamide intoxication. The relation between palmitate and choline incorporation was 6.77 in the controls and it decreases to 2-3 in the bromcarbamide group. The total phospholipid content in the lung/g wet weight remained unchanged in all experiments. From this data it is concluded, that these drugs cause a reduction of fatty acid exchange of the lecithin molecules of the lung. This might lead to the production of non surface active lecithin. The clinical and the morphological aspects of severe bromcarbamide intoxication are consistent with a perturbation of the surfactant function. (orig./MG) [de

  16. Click chemistry approach to functionalize two-dimensional macromolecules of graphene oxide nanosheets

    Institute of Scientific and Technical Information of China (English)

    Liang Kou; Hongkun He; Chao Gao

    2010-01-01

    A facile 'click chemistry' approach to functionalize 2D macromolecules of graphene oxide nanosheets with poly(ethylene glycol) of different molecular weights,polystyrene,palmitic acid and various amino acids was presented.FTIR,TGA,Raman spectroscopy,XPS,XRD,TEM,AFM and SEM were utilized to characterize the products.High degree of functionalization was achieved on the flat surfaces of graphene oxide,affording polymer-grafted 2D brushes and amino acids-immobilized nanosheets,which show improved solubility in organic solvents.The click chemistry strategy reported herein provides a facile and general method for functionalization of graphene oxide with macromolecules and desired biomolecules.

  17. Identification of a Substrate-binding Site in a Peroxisomal β-Oxidation Enzyme by Photoaffinity Labeling with a Novel Palmitoyl Derivative*

    OpenAIRE

    Kashiwayama, Yoshinori; Tomohiro, Takenori; Narita, Kotomi; Suzumura, Miyuki; Glumoff, Tuomo; Hiltunen, J. Kalervo; Van Veldhoven, Paul P.; Hatanaka, Yasumaru; Imanaka, Tsuneo

    2010-01-01

    Peroxisomes play an essential role in a number of important metabolic pathways including β-oxidation of fatty acids and their derivatives. Therefore, peroxisomes possess various β-oxidation enzymes and specialized fatty acid transport systems. However, the molecular mechanisms of these proteins, especially in terms of substrate binding, are still unknown. In this study, to identify the substrate-binding sites of these proteins, we synthesized a photoreactive palmitic acid analogue bearing a d...

  18. Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.

    Directory of Open Access Journals (Sweden)

    Joseph W McFadden

    Full Text Available Modification of hypothalamic fatty acid (FA metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1 and fatty acid oxidation (FAOx, exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS, and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism.

  19. Simultaneous determination of triamcinolone acetonide palmitate and triamcinolone acetonide in beagle dog plasma by UPLC-MS/MS and its application to a long-term pharmacokinetic study of triamcinolone acetonide palmitate lipid emulsion injection.

    Science.gov (United States)

    Liu, Hui; Yang, Mingjing; Wu, Panpan; Guan, Jiao; Men, Lei; Lin, Hongli; Tang, Xing; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid-liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C18 column (50 mm × 2.1mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5→397.3, 435.3→415.3 and 393.3→355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1-1,000 ng/ml for TAP and 0.5-500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of -8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7-104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Robots conquering local government services

    DEFF Research Database (Denmark)

    Nielsen, Jeppe Agger; Andersen, Kim Normann; Sigh, Anne

    2016-01-01

    labour-intensive services, the public administration research community is short on knowledge of the impact on the work processes carried out in public organizations and how staff and clients react toward robots. This case study investigates the implementation and use of robot vacuum cleaners in Danish......The movement of robots from the production line to the service sector provides a potentially radical solution to innovate and transform public service delivery. Although robots are increasingly being adopted in service delivery (e.g., health- and eldercare) to enhance and in some cases substitute...... eldercare, demonstrating how robot vacuums have proven to have considerable interpretive flexibility with variation in the perceived nature of technology, technology strategy, and technology use between key stakeholders in eldercare....

  1. CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Wei Hua

    Full Text Available Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN, respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated.The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20 by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5 and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software.CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO, the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid.CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.

  2. Reciprocal effects of 5-(tetradecyloxy)-2-furoic acid on fatty acid oxidation.

    Science.gov (United States)

    Otto, D A; Chatzidakis, C; Kasziba, E; Cook, G A

    1985-10-01

    Under certain incubation conditions 5-(tetradecyloxy)-2-furoic acid (TOFA) stimulated the oxidation of palmitate by hepatocytes, as observed by others. A decrease in malonyl-CoA concentration accompanied the stimulation of oxidation. Under other conditions, however, TOFA inhibited fatty acid oxidation. The observed effects of TOFA depended on the TOFA and fatty acid concentrations, the cell concentration, the time of TOFA addition relative to the addition of fatty acid, and the nutritional state of the animal (fed or starved). The data indicate that only under limited incubation conditions may TOFA be used as an inhibitor of fatty acid synthesis without inhibition of fatty acid oxidation. When rat liver mitochondria were preincubated with TOFA, ketogenesis from palmitate was slightly inhibited (up to 20%) at TOFA concentrations that were less than that of CoA, but the inhibition became almost complete (up to 90%) when TOFA was greater than or equal to the CoA concentration. TOFA had only slight or no inhibitory effects on the oxidation of palmitoyl-CoA, palmitoyl(-)carnitine, or butyrate. Since TOFA can be converted to TOFyl-CoA, the data suggest that the inhibition of fatty acid oxidation from palmitate results from the decreased availability of CoA for extramitochondrial activation of fatty acids. These data, along with previous data of others, indicate that inhibition of fatty acid oxidation by CoA sequestration is a common mechanism of a group of carboxylic acid inhibitors. A general caution is appropriate with regard to the interpretation of results when using TOFA in studies of fatty acid oxidation.

  3. Thermodynamic versus non-equilibrium stability of palmitic acid monolayers in calcium-enriched sea spray aerosol proxy systems.

    Science.gov (United States)

    Wellen Rudd, Bethany A; Vidalis, Andrew S; Allen, Heather C

    2018-04-16

    Of the major cations in seawater (Na+, Mg2+, Ca2+, K+), Ca2+ is found to be the most enriched in fine sea spray aerosols (SSA). In this work, we investigate the binding of Ca2+ to the carboxylic acid headgroup of palmitic acid (PA), a marine-abundant fatty acid, and the impact such binding has on the stability of PA monolayers in both equilibrium and non-equilibrium systems. A range of Ca2+ conditions from 10 μM to 300 mM was utilized to represent the relative concentration of Ca2+ in high and low relative humidity aerosol environments. The CO2- stretching modes of PA detected by surface-sensitive infrared reflection-absorption spectroscopy (IRRAS) reveal ionic binding motifs of the Ca2+ ion to the carboxylate group with varying degrees of hydration. Surface tensiometry was used to determine the thermodynamic equilibrium spreading pressure (ESP) of PA on the various aqueous CaCl2 subphases. Up to concentrations of 1 mM Ca2+, each system reached equilibrium, and Ca2+:PA surface complexation gave rise to a lower energy state revealed by elevated surface pressures relative to water. We show that PA films are not thermodynamically stable at marine aerosol-relevant Ca2+ concentrations ([Ca2+] ≥ 10 mM). IRRAS and vibrational sum frequency generation (VSFG) spectroscopy were used to investigate the surface presence of PA on high concentration Ca2+ aqueous subphases. Non-equilibrium relaxation (NER) experiments were also conducted and monitored by Brewster angle microscopy (BAM) to determine the effect of the Ca2+ ions on PA stability. At high surface pressures, the relaxation mechanisms of PA varied among the systems and were dependent on Ca2+ concentration.

  4. Stereochemistry of Endogenous Palmitic Acid Ester of 9-Hydroxystearic Acid and Relevance of Absolute Configuration to Regulation.

    Science.gov (United States)

    Nelson, Andrew T; Kolar, Matthew J; Chu, Qian; Syed, Ismail; Kahn, Barbara B; Saghatelian, Alan; Siegel, Dionicio

    2017-04-05

    Lipids have fundamental roles in the structure, energetics, and signaling of cells and organisms. The recent discovery of fatty acid esters of hydroxy fatty acids (FAHFAs), lipids with potent antidiabetic and anti-inflammatory activities, indicates that our understanding of the composition of lipidome and the function of lipids is incomplete. The ability to synthesize and test FAHFAs was critical in elucidating the roles of these lipids, but these studies were performed with racemic mixtures, and the role of stereochemistry remains unexplored. Here, we synthesized the R- and S- palmitic acid ester of 9-hydroxystearic acid (R-9-PAHSA, S-9-PAHSA). Access to highly enantioenriched PAHSAs enabled the development of a liquid chromatography-mass spectrometry (LC-MS) method to separate and quantify R- and S-9-PAHSA, and this approach identified R-9-PAHSA as the predominant stereoisomer that accumulates in adipose tissues from transgenic mice where FAHFAs were first discovered. Furthermore, biochemical analysis of 9-PAHSA biosynthesis and degradation indicate that the enzymes and pathways for PAHSA production are stereospecific, with cell lines favoring the production of R-9-PAHSA and carboxyl ester lipase (CEL), a PAHSA degradative enzyme, selectively hydrolyzing S-9-PAHSA. These studies highlight the role of stereochemistry in the production and degradation of PAHSAs and define the endogenous stereochemistry of 9-PAHSA in adipose tissue. This information will be useful in the identification and characterization of the pathway responsible for PAHSA biosynthesis, and access to enantiopure PAHSAs will elucidate the role of stereochemistry in PAHSA activity and metabolism in vivo.

  5. Intramuscular administration of paliperidone palmitate extended-release injectable microsuspension induces a subclinical inflammatory reaction modulating the pharmacokinetics in rats.

    Science.gov (United States)

    Darville, Nicolas; van Heerden, Marjolein; Vynckier, An; De Meulder, Marc; Sterkens, Patrick; Annaert, Pieter; Van den Mooter, Guy

    2014-07-01

    The present study aims at elucidating the intricate nature of the drug release and absorption following intramuscular (i.m.) injection of sustained-release prodrug nanocrystals/microcrystals. A paliperidone palmitate (PPP) long-acting suspension was characterized with regard to particle size (Dv,50 = 1.09 μm) and morphology prior to i.m. injection in rats. The local disposition was rigorously investigated by means of (immuno)histochemistry and transmission electron microscopy while the concurrent multiphasic pharmacokinetics was linked to the microanatomy. A transient (24 h) trauma-induced inflammation promptly evolved into a subclinical but chronic granulomatous inflammatory reaction initiated by the presence of solid material. The dense inflammatory envelope (CD68(+) macrophages) led to particle agglomeration with subsequent drop in dissolution rate beyond 24 h postinjection. This was associated with a decrease in apparent paliperidone (PP) absorption (near-zero order) until 96 h and a delayed time of occurrence of observed maximum drug plasma concentration (168 h). The infiltrating macrophages phagocytosed large fractions of the depot, thereby influencing the (pro)drug release. Radial angiogenesis (CD31(+)) was observed throughout the inflammatory rim from 72 h onwards and presumably contributed to the sustained systemic PP concentrations by maintaining a sufficient absorptive capacity. No solid-state transitions of the retrieved formulation were recorded with X-ray diffraction analysis. In summary, the initial formulation-driven prodrug (PPP) dissolution and drug (PP) absorption were followed by a complex phase determined by the relative contribution of formulation factors and dynamic physiological variables. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers.

    Science.gov (United States)

    Brezinova, Marie; Kuda, Ondrej; Hansikova, Jana; Rombaldova, Martina; Balas, Laurence; Bardova, Kristina; Durand, Thierry; Rossmeisl, Martin; Cerna, Marcela; Stranak, Zbynek; Kopecky, Jan

    2018-02-01

    To achieve optimal development of a newborn, breastfeeding is extensively recommended, but little is known about the role of non-nutritive bioactive milk components. We aimed to characterize the fatty acid esters of hydroxy fatty acids (FAHFAs), namely palmitic acid hydroxystearic acids (PAHSAs)-endogenous lipids with anti-inflammatory and anti-diabetic properties, in human breast milk. Breast milk samples from 30 lean (BMI=19-23) and 23 obese (BMI>30) women were collected 72h postpartum. Adipose tissue and milk samples were harvested from C57BL/6J mice. FAHFA lipid profiles were measured using reverse phase and chiral liquid chromatography-mass spectrometry method. PAHSA regioisomers as well as other FAHFAs were present in both human and murine milk. Unexpectedly, the levels of 5-PAHSA were higher relative to other regioisomers. The separation of both regioisomers and enantiomers of PAHSAs revealed that both R- and S-enantiomers were present in the biological samples, and that the majority of the 5-PAHSA signal is of R configuration. Total PAHSA levels were positively associated with weight gain during pregnancy, and 5-PAHSA as well as total PAHSA levels were significantly lower in the milk of the obese compared to the lean mothers. Our results document for the first time the presence of lipid mediators from the FAHFA family in breast milk, while giving an insight into the stereochemistry of PAHSAs. They also indicate the negative effect of obesity on 5-PAHSA levels. Future studies will be needed to explore the role and mechanism of action of FAHFAs in breast milk. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The role and mechanism of KCa3.1 channels in human monocyte migration induced by palmitic acid.

    Science.gov (United States)

    Ma, Xiao-Zhen; Pang, Zheng-Da; Wang, Jun-Hong; Song, Zheng; Zhao, Li-Mei; Du, Xiao-Jun; Deng, Xiu-Ling

    2018-05-21

    Monocyte migration into diseased tissues contributes to the pathogenesis of diseases. Intermediate-conductance Ca 2+ -activated K + (K Ca 3.1) channels play an important role in cell migration. However, the role of K Ca 3.1 channels in mediating monocyte migration induced by palmitic acid (PA) is still unclear. Using cultured THP-1 cells and peripheral blood mononuclear cells from healthy subjects, we investigated the role and signaling mechanisms of K Ca 3.1 channels in mediating the migration induced by PA. Using methods of Western blotting analysis, RNA interference, cell migration assay and ELISA, we found that PA-treated monocytes exhibited increment of the protein levels of K Ca 3.1 channel and monocyte chemoattractant protein-1 (MCP-1), and the effects were reversed by co-incubation of PA with anti-TLR2/4 antibodies or by specific inhibitors of p38-MAPK, or NF-κB. In addition, PA increased monocyte migration, which was abolished by a specific K Ca 3.1 channel blocker, TRAM-34, or K Ca 3.1 small interfering RNA (siRNA). The expression and secretion of MCP-1 induced by PA was also similarly prevented by TRAM-34 and K Ca 3.1 siRNA. These results demonstrate for the first time that PA upregulates K Ca 3.1 channels through TLR2/4, p38-MAPK and NF-κB pathway to promote the expression of MCP-1, and then induce the trans-endothelial migration of monocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

    Science.gov (United States)

    Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

    2016-05-01

    Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

  9. Rats and rabbits as pharmacokinetic screening tools for long acting intramuscular depots: case study with paliperidone palmitate suspension.

    Science.gov (United States)

    Patel, Harilal; Patel, Prakash; Modi, Nirav; Patel, Pinakin; Wagh, Yogesh; George, Alex; Desai, Nirmal; Srinivas, Nuggehally R

    2018-05-08

    Development of prodrug of 9-hydroxyrisperidone (paliperidone) long-acting intramuscular injection has enabled delivery over four-week time period with improved compliance. The key aim of this work was to establish a reliable preclinical model which may potentially serve as a screening tool for judging the pharmacokinetics of paliperidone formulation(s) prior to human clinical work. Sparse sampling composite study was used in rats, (Wistar/Sprague-Dawley (SD; n = 10)) and a serial blood sampling study design was used in rabbits (n = 4). Animals received intramuscular injection of paliperidone palmitate in the thigh muscle at dose of 16 (rats) and 4.5 mg/kg (rabbits). Samples were drawn in rats (retro-orbital sinus) and rabbits (central ear artery) and were analysed for paliperidone using liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) assay. The plasma data was subjected to pharmacokinetic analysis. Following intramuscular injection of depot formulation in Wistar/SD rats and rabbits, absorption of paliperidone was slow and gradual with median value of time to reach maximum concentration (T max ) occurring on day 7. The exposures (i.e. area under the curve (AUC; 0-28) days) were 18,597, 21,865 and 18,120 ng.h/mL, in Wistar, SD and rabbits, respectively. The clearance was slow and supported long half-life (8-10 days). Either one of the two models can serve as a research tool for establishing pharmacokinetics of paliperidone formulation(s).

  10. Palmitic acid induces neurotoxicity and gliatoxicity in SH-SY5Y human neuroblastoma and T98G human glioblastoma cells

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    Yee-Wen Ng

    2018-04-01

    Full Text Available Background Obesity-related central nervous system (CNS pathologies like neuroinflammation and reactive gliosis are associated with high-fat diet (HFD related elevation of saturated fatty acids like palmitic acid (PA in neurons and astrocytes of the brain. Methods Human neuroblastoma cells SH-SY5Y (as a neuronal model and human glioblastoma cells T98G (as an astrocytic model, were treated with 100–500 µM PA, oleic acid (OA or lauric acid (LA for 24 h or 48 h, and their cell viability was assessed by 3-(4,5-dimetylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. The effects of stable overexpression of γ-synuclein (γ-syn, a neuronal protein recently recognized as a novel regulator of lipid handling in adipocytes, and transient overexpression of Parkinson’s disease (PD α-synuclein [α-syn; wild-type (wt and its pathogenic mutants A53T, A30P and E46K] in SH-SY5Y and T98G cells, were also evaluated. The effects of co-treatment of PA with paraquat (PQ, a Parkinsonian pesticide, and leptin, a hormone involved in the brain-adipose axis, were also assessed. Cell death mode and cell cycle were analyzed by Annexin V/PI flow cytometry. Reactive oxygen species (ROS level was determined using 2′,7′-dichlorofluorescien diacetate (DCFH-DA assay and lipid peroxidation level was determined using thiobarbituric acid reactive substances (TBARS assay. Results MTT assay revealed dose- and time-dependent PA cytotoxicity on SH-SY5Y and T98G cells, but not OA and LA. The cytotoxicity was significantly lower in SH-SY5Y-γ-syn cells, while transient overexpression of wt α-syn or its PD mutants (A30P and E46K, but not A53T modestly (but still significantly rescued the cytotoxicity of PA in SH-SY5Y and T98G cells. Co-treatment of increasing concentrations of PQ exacerbated PA’s neurotoxicity. Pre-treatment of leptin, an anti-apoptotic adipokine, did not successfully rescue SH-SY5Y cells from PA-induced cytotoxicity—suggesting a mechanism of PA

  11. Effects of hypoxia and pyruvate infusion on myocardial fatty acid oxidation measured with 123I heptadecanoic acid

    International Nuclear Information System (INIS)

    Comans, E.F.I.; Visser, F.C.; Elzinga, Gijs

    1993-01-01

    Radio-iodinated fatty acids like 123 I heptadecanoic acid (HDA) can be used for the non-invasive delineation of myocardial non-esterified fatty acid (FA) metabolism. In this study the quantitative value of HDA was assessed for the measurement of myocardial FA oxidation. In an isolated saline perfused rat heart preparation myocardial time-activity curves were made during control perfusion and after inhibition of FA oxidation by hypoxia and infusion of 10.0 mM pyruvate, respectively. Control experiments were performed using 1- 14 C palmitate as the 'golden standard' for myocardial FA oxidation. Myocardial HDA oxidation was calculated from the amplitude of the third exponential term of the time-activity curve. During control perfusion no differences were observed between the calculated oxygen equivalents (from HDA oxidation) and the measured (A-V oxygen content difference) and the estimated ( 14 CO 2 production) values. Inhibition of palmitate oxidation with pyruvate was accurately detected with HDA. During hypoxic perfusion, an overestimation of palmitate oxidation was calculated on the basic of HDA oxidation. Infusion of pyruvate did not influence the time constants of the time-activity curves, whereas during hypoxic perfusion an increase of the time constant of the third exponential term was observed, probably caused by the presence of back-diffusion of non-metabolized HDA. We conclude that HDA can be used as a quantitative tool for the measurement of myocardial FA oxidation under various metabolic conditions. During periods of a decreased oxygen availability back-diffusion of FA needs to be taken into account for the interpretation of the myocardial time-activity curves. (author)

  12. Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism.

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    Kirsten Roomp

    Full Text Available Studies on the pathophysiology of type 2 diabetes mellitus (T2DM have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/ or confirm reported mechanisms of lipotoxicity. To this end isolated human pancreatic islets, exposed to chronically elevated palmitate concentrations for 0, 2 and 7 days, were functionally characterized and their levels of multiple targeted lipid and untargeted protein species determined. Glucose-stimulated insulin secretion from the islets increased on day 2 and decreased on day 7. At day 7 islet insulin content decreased and the proinsulin to insulin content ratio doubled. Amounts of cholesterol, stearic acid, C16 dihydroceramide and C24:1 sphingomyelin, obtained from the lipidomic screen, increased time-dependently in the palmitate-exposed islets. The proteomic screen identified matching changes in proteins involved in lipid biosynthesis indicating up-regulated cholesterol and lipid biosynthesis in the islets. Furthermore, proteins associated with immature secretory granules were decreased when palmitate exposure time was increased despite their high affinity for cholesterol. Proteins associated with mature secretory granules remained unchanged. Pathway analysis based on the protein and lipid expression profiles implicated autocrine effects of insulin in lipotoxicity. Taken together the study demonstrates that combining different omics approaches has potential in mapping of multiple simultaneous cellular events. However, it also shows that challenges exist for effectively combining lipidomics and proteomics in primary cells. Our

  13. , , , , , and Gene Expression in Single- and Co-cultured Bovine Satellite Cells and Intramuscular Preadipocytes Treated with Palmitic, Stearic, Oleic, and Linoleic Acid

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    S. H. Choi

    2015-03-01

    Full Text Available We previously demonstrated that bovine subcutaneous preadipocytes promote adipogenic gene expression in muscle satellite cells in a co-culture system. Herein we hypothesize that saturated fatty acids would promote adipogenic/lipogenic gene expression, whereas mono- and polyunsaturated fatty acids would have the opposite effect. Bovine semimembranosus satellite cells (BSC and intramuscular preadipocytes (IPA were isolated from crossbred steers and cultured with 10% fetal bovine serum (FBS/Dulbecco’s Modified Eagle Medium (DMEM and 1% antibiotics during the 3-d proliferation period. After proliferation, cells were treated for 3 d with 3% horse serum/DMEM (BSC or 5% FBS/DMEM (IPA with antibiotics. Media also contained 10 μg/mL insulin and 10 μg/mL pioglitazone. Subsequently, differentiating BSC and IPA were cultured in their respective media with 40 μM palmitic, stearic, oleic, or linoleic acid for 4 d. Finally, BSC and IPA were single- or co-cultured for an additional 2 h. All fatty acid treatments increased (p = 0.001 carnitine palmitoyltransferase-1 beta (CPT1β gene expression, but the increase in CPT1β gene expression was especially pronounced in IPA incubated with palmitic and stearic acid (6- to 17- fold increases. Oleic and linoleic acid decreased (p = 0.001 stearoyl-CoA desaturase (SCD gene expression over 80% in both BSC and IPA. Conversely, palmitic and stearic acid increased SCD gene expression three fold in co-cultured in IPA, and stearic acid increased AMPKα gene expression in single- and co-cultured BSC and IPA. Consistent with our hypothesis, saturated fatty acids, especially stearic acid, promoted adipogenic and lipogenic gene expression, whereas unsaturated fatty acids decreased expression of those genes associated with fatty acid metabolism.

  14. THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

    2013-06-07

    Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  15. Effect of hypoxia on the incorporation of [2-3H] glycerol and [1-14C[-palmitate into lipids of various brain regions

    International Nuclear Information System (INIS)

    Alberghina, M.; Giuffrida, A.M.

    1981-01-01

    The lipid metabolism in guinea pig brain after intermittent hypoxia, prolonged for 80 hrs, was markedly impaired. The in vivo incorporation of [2-3H] glycerol and [1-14C] palmitate into lipids of microsomes, mitochondria, myelin, and synaptosomes, purified form cerebral hemispheres, was significantly lower in the hypoxic animals than in the controls. The same effect was observed on the incorporation of labeled precursors into lipids of mitochondria purified from cerebellum and brainstem. In particular, the labeling of th major phospholipids present - ie, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) - in the mitochondria of the three brain regions examined decreased after hypoxic treatment

  16. Optimization of Palmitic Acid Composition in Crude Oleic Acid to Provide Specifications of Titer and Cloud Point of Distillate Oleic Acid using a Flash Distiller

    OpenAIRE

    Muhammad Yusuf Ritonga

    2010-01-01

    Titer and cloud point Distilled Oleic Acid’s higher than standard on feed composition palmitic acid (C15H31COOH) or C16 11.2 %. Feed composition C16, top temperature precut and bottom main distiller column were optimized to produce DOA. A factorial design 3 independent variables 3 X 2 X 3, twice repeating’s applied to observe effects of feed composition C16 to quality parameters. On the optimum C16 feed composition at 5.20 % was produced DOA with titer 6.8 oC, cloud point 5.0 oC (inside it...

  17. Optimization of Palmitic Acid Composition in Crude Oleic Acid to Provide Specifications of Titer and Cloud Point of Distillate Oleic Acid using a Flash Distiller

    Directory of Open Access Journals (Sweden)

    Muhammad Yusuf Ritonga

    2010-11-01

    Full Text Available Titer and cloud point of Distilled Oleic Acid is higher than is the standard on feed composition palmitic acid (C15H31COOH or C16 11.2 %. Feed composition C16, top temperature precut and bottom main distiller column were optimized to produce DOA. A factorial design with 3 independent variables, 3 X 2 X 3, repeated twice as much, is applied to observe effects of feed composition C16 to quality parameters. In the optimum C16, feed composition at 5.20 % produced DOA with titer 6.8 oC, cloud point 5.0 oC (inside its specification.

  18. Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial

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    Toshida H

    2017-06-01

    Full Text Available Hiroshi Toshida,1 Toshinari Funaki,2 Koichi Ono,3 Nobuhito Tabuchi,4 Sota Watanabe,4 Tamotsu Seki,5 Hiroshi Otake,6 Takuji Kato,7 Nobuyuki Ebihara,8 Akira Murakami2 1Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka, 2Department of Ophthalmology, Juntendo University Graduate School of Medicine, 3Department of Ophthalmology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, 4Pharmaceutical Research Laboratories, Lion Corporation, Kanagawa, 5Tamagawa Eye Clinic, Tokyo, 6Otake Eye Clinic, Kanagawa, 7Kato Eye Clinic, Tokyo, 8Department of Ophthalmology, Juntendo University Urayasu Hospital, Chiba, Japan Purpose: The purpose of this study was to investigate the efficacy and safety of the administration of retinol palmitate (VApal ophthalmic solution (500 IU/mL for the treatment of patients with dry eye. Patients and methods: This study included 66 patients with dry eye. After a 2-week washout period, patients were randomized (1:1 into either a VApal ophthalmic solution or a placebo group, and a single drop of either solution was administered six times daily for 4 weeks. Efficacy measures were 12 subjective symptoms, rose bengal (RB and fluorescein staining scores, tear film breakup time, and tear secretion. Safety measures included clinical blood and urine analyses and adverse event recordings. Results: In comparisons of the two groups, the mean change in RB staining score from baseline was significantly lower in the VApal group at 2 and 4 weeks (P<0.05 and P<0.01, respectively. Furthermore, the fluorescein clearance rate (fluorescein staining score was significantly higher in the VApal group at 4 weeks (P<0.05. The VApal group showed a significant improvement in blurred vision at 1 and 2 weeks (P<0.01 and P<0.05, respectively, and the mean change in the total score for subjective symptoms from baseline was significantly lower in the VApal group at 1 week (P<0.05. In before- and after-intervention comparisons, the

  19. A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema.

    Science.gov (United States)

    Daull, Philippe; Paterson, Christopher A; Kuppermann, Baruch D; Garrigue, Jean-Sébastien

    2013-03-01

    Dexamethasone palmitate (DXP) is a lipophilic prodrug of dexamethasone (DXM), a potent corticosteroid used to treat a variety of ophthalmic diseases. The aim of the study was to characterize the sustained release capacity (in rabbit), efficacy (in rat and rabbit), and safety (in rabbit, cat, and minipig) of intravitreal (IVT) DXP emulsions in preclinical models. Oil-in-water emulsions of DXP were administered by IVT injections in rats, rabbits, cats, or minipigs. Efficacy was assessed in rabbits by the inhibition of VEGF-induced vascular leakage and in rats by inhibition of laser-induced choroidal neovascularization. Concentrations of DXP and DXM in aqueous humor, vitreous, retina, choroid, and blood were determined to characterize the ocular and systemic pharmacokinetic (PK) profile. Complete ophthalmic examinations (indirect ophthalmoscopy, slit-lamp biomacroscopy, electroretinography, tonometry) were performed to assess the ocular safety of IVT DXP doses up to 2,600 μg in minipig, followed by histopathologic examinations. A validated feline model of DXM-induced elevated intraocular pressure (IOP) was used to assess the ocular hypertensive impact (i.e., the safety) of an IVT injection of DXP emulsion. Rat and rabbit efficacy data demonstrated that IVT injections of DXP emulsions were effective. Rabbit PK data demonstrated that following a single 1,280 μg IVT injection resulted in sustained DXM levels in the retina and choroid (1,179.6 and 577.7 ng/g with a half-life of 189 and 103 days, respectively) sufficient to inhibit VEGF-induced vascular hyper-permeability for up to 9 months. No adverse ocular findings were observed in the rabbit at the 1,280 μg DXP dose. Plasma levels of DXP and DXM were close to the lower limit of quantification (0.5 ng/mL). In minipigs, no systemic effects were observed at a dose up to 2,600 μg DXP. In steroid responsive cats, IVT DXP emulsions increased IOP to a lesser extent than triamcinolone acetonide with a more rapid return to

  20. Comparison of Medicaid spending in schizoaffective patients treated with once monthly paliperidone palmitate or oral atypical antipsychotics.

    Science.gov (United States)

    Xiao, Yongling; Muser, Erik; Fu, Dong-Jing; Lafeuille, Marie-Hélène; Pilon, Dominic; Emond, Bruno; Wu, Allen; Duh, Mei Sheng; Lefebvre, Patrick

    2016-01-01

    Compared to oral atypical antipsychotics (OAAs), long-acting injectable antipsychotics require less frequent administration, and thus may improve adherence and reduce risk of relapse in schizoaffective disorder (SAD) patients. To evaluate the impact of once monthly paliperidone palmitate (PP) versus OAAs on healthcare resource utilization, Medicaid spending, and hospital readmission among SAD patients. Using FL, IA, KS, MS, MO, and NJ Medicaid data (January 2009-December 2013), adults with ≥2 SAD diagnoses initiated on PP or OAA (index date) were identified. Baseline characteristics and outcomes were assessed during the 12month pre- and post-index periods, respectively. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to reduce confounding and compare the estimated treatment effect for PP versus OAA. A total of 10,778 OAA-treated patients and 876 PP-treated patients were selected. Compared to OAAs, PP was associated with significantly lower medical costs (PSM: mean monthly cost difference [MMCD] = -$383, p < 0.001; IPTW: MMCD = -$403, p = 0.016), which offset the higher pharmacy costs associated with PP (PSM: MMCD = $270, p < 0.001; IPTW: MMCD = $350, p < 0.001) and resulted in similar total healthcare cost (PSM: MMCD = -$113, p = 0.414; IPTW: MMCD = -$53, p = 0.697) for PP versus OAA. Reduced risk of hospitalization (PSM: incidence rate ratio [IRR] = 0.85, p = 0.128; IPTW: IRR = 0.96, p = 0.004) and fewer hospitalization days (PSM: IRR = 0.74, p = 0.008; IPTW: IRR = 0.85, p < 0.001) were observed in PP versus OAA patients. Among hospitalized patients, PP was associated with a lower risk of 30 day hospital readmission compared to OAA (IPTW: odds ratio = 0.89, p = 0.041). Limitations The Medicaid data may not be representative of the nation or other states, and includes pre-rebate pharmacy costs (potentially over-estimated). Also

  1. Reduced lipid oxidation in myotubes established from obese and type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Gaster, Michael

    2009-01-01

    To date, it is unknown whether reduced lipid oxidation of skeletal muscle of obese and obese type 2 diabetic (T2D) subjects partly is based on reduced oxidation of endogenous lipids. Palmitate (PA) accumulation, total oxidation and lipolysis were not different between myotubes established from lean...... both for endogenous and exogenous lipids. Thus myotubes established from obese and obese T2D subjects express a reduced complete oxidation of endogenous lipids. Two cardinal principles govern the reduced lipid oxidation in obese and diabetic myotubes; firstly, an impaired coupling between endogenous...... lipid and mitochondria in obese and obese diabetic myotubes and secondly, a mismatch between beta-oxidation and citric acid cycle in obese diabetic myotubes....

  2. Oxidative stability of structured lipids produced from sunflower oil and caprylic acid

    DEFF Research Database (Denmark)

    Timm Heinrich, Maike; Xu, Xuebing; Nielsen, Nina Skall

    2003-01-01

    Traditional sunflower oil (SO), randomized lipid (RL) and specific structured lipid (SL), both produced from SO and tricaprylin/caprylic acid, respectively, were stored for up to 12 wk to compare their oxidative stabilities by chemical and sensory analyses. Furthermore, the effect of adding...... a commercial antioxidant blend Grindox 117 (propyl gallate/citric acid/ascorbyl palmitate) or gallic acid to the SL was investigated. The lipid type affected the oxidative stability: SL was less stable than SO and RL. The reduced stability was most likely caused by both the structure of the lipid...

  3. Comparative evaluation of labelling patterns and turnover of lipids, tagged by 15 (p-123I-phenyl-)pentadecanoic and 1-14C-palmitic acid

    International Nuclear Information System (INIS)

    Reske, S.N.; Sauer, W.; Reichmann, K.; Winkler, C.; Machulla, H.J.; Knust, E.J.

    1984-01-01

    Uptake and turnover of chloroform/methanol extractable tissue lipids labelled in vivo simultaneously with 15(p- 123 I-phenyl-)pentadecanoic and 1- 14 C-palmitic acid were compared. Lipid turnover studies were performed in fasted pentobarbital-anaesthetized Wistar rats in tissues with highly varying free fatty acid turnover rates. In all tissues investigated, i.e. heart, lung, liver, spleen and kidney, both tracers labelled nearly identical lipid fractions. The main tracer uptake was found in free fatty acids, phospholipids, diglycerides and triglycerides. A highly significant correlation of uptake and turnover in main tissue lipid fractions indicated an essentially identical metabolic pathway of both tracers in intermediary tissue lipid metabolism. Concordant tracer uptake and turnover patterns in tissue of lipids with highly varying fatty acid metabolic rates suggested that intrinsic metabolic activity of the tissue and respective lipid fraction was the major determinant of metabolic handling of both iodophenyl fatty- and palmitic acid. Thus, the feasibility of iodophenylpentadecanoic acid as free fatty acid tracer for studying tissue lipid metabolism is demonstrated. (author)

  4. Comparative evaluation of labelling patterns and turnover of lipids, tagged by 15 (p-/sup 123/I-phenyl-)pentadecanoic and 1-/sup 14/C-palmitic acid

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Sauer, W.; Reichmann, K.; Winkler, C. (Bonn Univ. (Germany, F.R.). Inst. fuer Klinische und Experimentelle Nuklearmedizin); Machulla, H.J.; Knust, E.J. (Essen Univ. (Germany, F.R.). Inst. fuer Medizinische Strahlenphysik und Strahlenbiologie)

    1984-06-15

    Uptake and turnover of chloroform/methanol extractable tissue lipids labelled in vivo simultaneously with 15(p-/sup 123/I-phenyl-)pentadecanoic and 1-/sup 14/C-palmitic acid were compared. Lipid turnover studies were performed in fasted pentobarbital-anaesthetized Wistar rats in tissues with highly varying free fatty acid turnover rates. In all tissues investigated, i.e. heart, lung, liver, spleen and kidney, both tracers labelled nearly identical lipid fractions. The main tracer uptake was found in free fatty acids, phospholipids, diglycerides and triglycerides. A highly significant correlation of uptake and turnover in main tissue lipid fractions indicated an essentially identical metabolic pathway of both tracers in intermediary tissue lipid metabolism. Concordant tracer uptake and turnover patterns in tissue of lipids with highly varying fatty acid metabolic rates suggested that intrinsic metabolic activity of the tissue and respective lipid fraction was the major determinant of metabolic handling of both iodophenyl fatty- and palmitic acid. Thus, the feasibility of iodophenylpentadecanoic acid as free fatty acid tracer for studying tissue lipid metabolism is demonstrated. 21 refs.

  5. Fatty acid oxidation and ketogenesis in astrocytes

    International Nuclear Information System (INIS)

    Auestad, N.

    1988-01-01

    Astrocytes were derived from cortex of two-day-old rat brain and grown in primary culture to confluence. The metabolism of the fatty acids, octanoate and palmitate, to CO 2 in oxidative respiration and to the formation of ketone bodies was examined by radiolabeled tracer methodology. The net production of acetoacetate was also determined by measurement of its mass. The enzymes in the ketogenic pathway were examined by measuring enzymic activity and/or by immunoblot analyses. Labeled CO 2 and labeled ketone bodies were produced from the oxidation of fatty acids labeled at carboxy- and ω-terminal carbons, indicating that fatty acids were oxidized by β-oxidation. The results from the radiolabeled tracer studies also indicated that a substantial proportion of the ω-terminal 4-carbon unit of the fatty acids bypassed the β-ketothiolase step of the β-oxidation pathway. The [ 14 C]acetoacetate formed from the [1- 14 C]labeled fatty acids, obligated to pass through the acetyl-CoA pool, contained 50% of the label at carbon 3 and 50% at carbon 1. In contrast, the [ 14 C]acetoacetate formed from the (ω-1)labeled fatty acids contained 90% of the label at carbon 3 and 10% at carbon 1

  6. Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial beta-oxidation of fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Freneaux, E.; Fromenty, B.; Berson, A.; Labbe, G.; Degott, C.; Letteron, P.; Larrey, D.; Pessayre, D. (Unite de Recherches de Physiolopathologie Hepatique (INSERM U-24), Hopital Beaujon, Clichy (France))

    1990-11-01

    The effects of the R-(-) and S-(+)ibuprofen enantiomers were first studied in vitro with mouse liver mitochondria incubated in the presence of various concentrations of exogenous coenzyme A. In the presence of a low concentration of coenzyme A (2.5 microM), the R-(-)enantiomer (which forms an acylcoenzyme A) inhibited stereoselectively the beta oxidation of (1-{sup 14}C)palmitic acid but not that of (1-{sup 14}C)palmitoyl-L-carnitine (which can directly enter the mitochondria). In the presence, however, of a concentration of coenzyme A (50 microM) reproducing that present in liver cell cytosol, both enantiomers (2 mM) slightly inhibited the beta oxidation of (1-{sup 14}C)palmitic acid and markedly inhibited the beta oxidation of (1-{sup 14}C)octanoic acid and (1-{sup 14}C)butyric acid. In vivo, both enantiomers (1 mmol.kg-1) similarly inhibited the formation of ({sup 14}C)CO{sub 2} from (1-{sup 14}C)fatty acids. Both enantiomers similarly decreased plasma ketone bodies. Both similarly increased hepatic triglycerides, and both produced mild microvesicular steatosis of the liver. We conclude that both ibuprofen enantiomers inhibit beta oxidation of fatty acids in vitro and in vivo. In addition, the R-(-)enantiomer may stereoselectively sequester coenzyme A; at low concentrations of coenzyme A in vitro, this may stereoselectively inhibit the mitochondrial uptake and beta oxidation of long chain fatty acids.

  7. Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial beta-oxidation of fatty acids

    International Nuclear Information System (INIS)

    Freneaux, E.; Fromenty, B.; Berson, A.; Labbe, G.; Degott, C.; Letteron, P.; Larrey, D.; Pessayre, D.

    1990-01-01

    The effects of the R-(-) and S-(+)ibuprofen enantiomers were first studied in vitro with mouse liver mitochondria incubated in the presence of various concentrations of exogenous coenzyme A. In the presence of a low concentration of coenzyme A (2.5 microM), the R-(-)enantiomer (which forms an acylcoenzyme A) inhibited stereoselectively the beta oxidation of [1- 14 C]palmitic acid but not that of [1- 14 C]palmitoyl-L-carnitine (which can directly enter the mitochondria). In the presence, however, of a concentration of coenzyme A (50 microM) reproducing that present in liver cell cytosol, both enantiomers (2 mM) slightly inhibited the beta oxidation of [1- 14 C]palmitic acid and markedly inhibited the beta oxidation of [1- 14 C]octanoic acid and [1- 14 C]butyric acid. In vivo, both enantiomers (1 mmol.kg-1) similarly inhibited the formation of [ 14 C]CO 2 from [1- 14 C]fatty acids. Both enantiomers similarly decreased plasma ketone bodies. Both similarly increased hepatic triglycerides, and both produced mild microvesicular steatosis of the liver. We conclude that both ibuprofen enantiomers inhibit beta oxidation of fatty acids in vitro and in vivo. In addition, the R-(-)enantiomer may stereoselectively sequester coenzyme A; at low concentrations of coenzyme A in vitro, this may stereoselectively inhibit the mitochondrial uptake and beta oxidation of long chain fatty acids

  8. Nuclear factor-κB is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate

    Energy Technology Data Exchange (ETDEWEB)

    Hinoi, Eiichi; Iezaki, Takashi; Ozaki, Kakeru; Yoneda, Yukio, E-mail: yyoneda@p.kanazawa-u.ac.jp

    2014-10-03

    Highlights: • GDF5 expression is up-regulated by IL-1β, TNF-α and palmitate in brown pre-adipocytes. • NF-κB stimulates promoter activity and expression of GDF5 in brown pre-adipocytes. • Recruitment of NF-κB to the GDF5 promoter is facilitated in BAT from ob/ob mice. • An NF-κB inhibitor prevents upregulation of GDF5 expression in brown pre-adipocytes. - Abstract: We have previously demonstrated that genetic and acquired obesity similarly led to drastic upregulation in brown adipose tissue (BAT), rather than white adipose tissue, of expression of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promoting brown adipogenesis. In this study, we evaluated expression profiles of GDF5 in cultured murine brown pre-adipocytes exposed to pro-inflammatory cytokines and free fatty acids (FFAs), which are all shown to play a role in the pathogenesis of obesity. Both interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were effective in up-regulating GDF5 expression in a concentration-dependent manner, while similar upregulation was seen in cells exposed to the saturated FFA palmitate, but not to the unsaturated FFA oleate. In silico analysis revealed existence of the putative nuclear factor-κB (NF-κB) binding site in the 5′-flanking region of mouse GDF5, whereas introduction of NF-κB subunits drastically facilitated both promoter activity and expression of GDF5 in brown pre-adipocytes. Chromatin immunoprecipitation analysis confirmed significant facilitation of the recruitment of NF-κB to the GDF5 promoter in lysed extracts of BAT from leptin-deficient ob/ob obese mice. Upregulation o GDF5 expression was invariably inhibited by an NF-κB inhibitor in cultured brown pre-adipocytes exposed to IL-1β, TNF-α and palmitate. These results suggest that obesity leads to upregulation of GDF5 expression responsible for the promotion of brown adipogenesis through a mechanism

  9. Preparation and properties of palmitic-stearic acid eutectic mixture/expanded graphite composite as phase change material for energy storage

    International Nuclear Information System (INIS)

    Zhang, Nan; Yuan, Yanping; Du, Yanxia; Cao, Xiaoling; Yuan, Yaguang

    2014-01-01

    A novel composite PCM (phase change material) with PA-SA (palmitic-stearic acid) eutectic mixture as PCM and EG (expanded graphite) as supporting material was prepared. The optimum absorption ratio of PA-SA/EG (Palmitic-stearic acid/expanded graphite) composite PCM was determined as PA-SA:EG = 13:1 (by mass). Scanning electron microscope and Fourier transformation infrared spectroscopy results show that PA-SA was uniformly distributed in the porous network structure of EG due to the physical action. Thermal property and thermal stability of the PA-SA/EG composite PCM were characterized by DSC (differential scanning calorimetry) and TGA (thermogravimetric analysis). DSC results indicated that the melting and freezing temperatures and latent heats of PA-SA/EG were measured as 53.89 °C and 54.37 °C, and 166.27 J/g and 166.13 J/g. TGA test results revealed that PA-SA/EG had a good thermal stability in working temperature range. Thermal cycling test results showed PA-SA/EG had a good thermal reliability after 720 thermal cycles. Thermal conductivity of the composite PCM was measured as 2.51 W/m K, much higher than that of PA-SA. The thermal energy storage and release rates of PA-SA/EG were also increased due to the high thermal conductivity of EG. In conclusion, the prepared PA-SA/EG composite PCM can be acted as a potential material for thermal energy storage due to the acceptable thermal properties, good thermal reliability and stability, high thermal conductivity. - Highlights: • PA-SA/EG (Palmitic-stearic acid/expanded graphite) composite PCM was prepared. • Optimum absorption ratio of PA-SA in EG was obtained as 13:1 (by mass). • Thermal conductivity and performance of PA-SA/EG have been significate improved. • PA-SA/EG has a good thermal reliability and thermal stability

  10. Early growth response protein 1 (EGR1) regulates pro-inflammatory gene expression in response to palmitate and TNF alpha in human placenta cells and is induced in obese placenta

    Science.gov (United States)

    Maternal obesity has been hypothesized to induce a pro-inflammatory response in the placenta. However, the specific factors contributing to this pro-infalmmatory response are yet to be determined. Our objective was to examine the effects of palmitic acid (PA), tumor necrosis factor alpha (TNF alph...

  11. Digestibility of Fatty Acids in the Gastrointestinal Tract of Dairy Cows Fed with Tallow or Saturated Fats Rich in Stearic Acid or Palmitic Acid

    DEFF Research Database (Denmark)

    Weisbjerg, Martin Riis; Hvelplund, Torben; Børsting, Christian Friis

    1992-01-01

    Fatty acid digestibility was studied with five lactating cows fed three different fat sources in a 5 × 5 latin square experiment. The treatments were 500 g of tallow, 500 or 1000 g of saturated fat rich in stearic acid (C18:0) (SARF) or 500 or 1000 g of saturated fat rich in palmitic acid (C16......:0) (PARF) per day. The total daily fatty acid intake was about 1100 g in rations with the highest fat inclusion. The fatty acid digestibilities were 76% for tallow, 74 and 64% for 500 and 1000 g SARF, respectively, and 87 and 81% for 500 and 1000 g of PARF, respectively. When compared to fatty acid...... digestibility for tallow predicted from a model based on literature values, PARF had a higher fatty acid digestibility at both fat intakes, and SARF had a lower fatty acid digestibility, especially at high fat intake....

  12. Phase change and heat transfer characteristics of a eutectic mixture of palmitic and stearic acids as PCM in a latent heat storage system

    International Nuclear Information System (INIS)

    Baran, Guelseren; Sari, Ahmet

    2003-01-01

    The phase change and heat transfer characteristics of a eutectic mixture of palmitic and stearic acids as phase change material (PCM) during the melting and solidification processes were determined experimentally in a vertical two concentric pipes energy storage system. This study deals with three important subjects. First is determination of the eutectic composition ratio of the palmitic acid (PA) and stearic acid (SA) binary system and measurement of its thermophysical properties by differential scanning calorimetry (DSC). Second is establishment of the phase transition characteristics of the mixture, such as the total melting and solidification temperatures and times, the heat transfer modes in the melted and solidified PCM and the effect of Reynolds and Stefan numbers as initial heat transfer fluid (HTF) conditions on the phase transition behaviors. Third is calculation of the heat transfer coefficients between the outside wall of the HTF pipe and the PCM, the heat recovery rates and heat fractions during the phase change processes of the mixture and also discussion of the effect of the inlet HTF parameters on these characteristics. The DSC results showed that the PA-SA binary system in the mixture ratio of 64.2:35.8 wt% forms a eutectic, which melts at 52.3 deg. C and has a latent heat of 181.7 J g -1 , and thus, these properties make it a suitable PCM for passive solar space heating and domestic water heating applications with respect to climate conditions. The experimental results also indicated that the eutectic mixture of PA-SA encapsulated in the annulus of concentric double pipes has good phase change and heat transfer characteristics during the melting and solidification processes, and it is an attractive candidate as a potential PCM for heat storage in latent heat thermal energy storage systems

  13. Impact of time of initiation of once-monthly paliperidone palmitate in hospitalized Asian patients with acute exacerbation of schizophrenia: a post hoc analysis from the PREVAIL study.

    Science.gov (United States)

    Li, Huafang; Li, Yan; Feng, Yu; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson

    2018-01-01

    To evaluate the differences in efficacy and safety outcomes in acute exacerbating schizophrenia patients between 2 subgroups (≤1 week and >1 week), differing in time interval from hospitalization to time of initiation of once-monthly paliperidone palmitate. PREVAIL was a multicenter, single-arm, open-label, prospective Phase IV study in hospitalized Asian patients (either sex, aged 18-65 years) diagnosed with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition). Change from baseline to week 13 in primary (Positive and Negative Syndrome Scale [PANSS] total score), secondary endpoints (PANSS responder rate, PANSS subscale, PANSS Marder factor, Clinical Global Impression-Severity, and Personal and Social Performance scale scores, readiness for hospital discharge questionnaire) and safety were assessed in this post hoc analysis. Significant mean reduction from baseline to week 13 in the PANSS total score, 30% PANSS responder rates ( P ≤0.01), PANSS subscales (positive and general psychopathology; all P ≤0.01), PANSS Marder factor (positive symptoms, uncontrolled hostility, and excitement and anxiety/depression; all P ≤0.01), Personal and Social Performance scale scores ( P ≤0.05) and Clinical Global Impression-Severity categorical summary ( P ≤0.05) were significantly greater in the ≤1 week subgroup versus >1 week subgroup ( P ≤0.05). The readiness for hospital discharge questionnaire improved over time for the overall study population, but remained similar between subgroups at all-time points. Treatment-emergent adverse events were similar between the subgroups. Early initiation of once-monthly paliperidone palmitate in hospitalized patients with acute exacerbation of schizophrenia led to greater improvements in psychotic symptoms with comparable safety than treatment initiation following 1 week of hospitalization.

  14. Caffeine Promotes Conversion of Palmitic Acid to Palmitoleic Acid by Inducing Expression of fat-5 in Caenorhabditis elegans and scd1 in Mice.

    Science.gov (United States)

    Du, Xiaocui; Huang, Qin; Guan, Yun; Lv, Ming; He, Xiaofang; Fang, Chongye; Wang, Xuanjun; Sheng, Jun

    2018-01-01

    The synthesis and metabolism of fatty acids in an organism is related to many biological processes and is involved in several diseases. The effects of caffeine on fatty acid synthesis and fat storage in Caenorhabditis elegans and mice were studied. After 6 h of food deprivation, adult C. elegans were treated with 0.1 mg/mL caffeine for 24 h. Quantitative reverse-transcription polymerase chain reaction showed that, among all the genes involved in fat accumulation, the mRNA expression of fat-5 in caffeine-treated C. elegans was significantly higher than that of controls, whereas fat-6 and fat-7 displayed no significant difference. Gas chromatography-mass spectrometry was used to verify the fatty acid composition of C. elegans . Results showed that the ratio of palmitoleic acid (16:1) to that of palmitic acid (16:0) was higher in the caffeine-treated group. Several mutant strains, including those involved in the insulin-like growth factor-1, dopamine, and serotonin pathways, and nuclear hormone receptors ( nhrs ), were used to assess their necessity to the effects of caffeine. We found that mdt-15 was essential for the effects of caffeine, which was independent of nhr-49 and nhr -80. Caffeine may increase fat-5 expression by acting on mdt-15 . In high fat diet (HFD), but not in normal diet (ND) mice, caffeine induced expression of scd1 in both subcutaneous and epididymal white adipose tissue, which was consistent with the palmitoleic/palmitic ratio results by gas chromatograph analysis. In mature adipocytes, caffeine treatment induced both mRNA and protein expression of scd1 and pgc-1 α. Overall, our results provided a possible mechanism on how caffeine modulates metabolism homeostasis in vivo .

  15. The Deoxygenation Pathways of Palmitic Acid into Hydrocarbons on Silica-Supported Ni12P5 and Ni2P Catalysts

    Directory of Open Access Journals (Sweden)

    Wenjun Zhou

    2018-04-01

    Full Text Available Pure Ni12P5/SiO2 and pure Ni2P/SiO2 catalysts were obtained by adjusting the Ni and P molar ratios, while Ni/SiO2 catalyst was prepared as a reference against which the deoxygenation pathways of palmitic acid were investigated. The catalysts were characterized by N2 adsorption, X-ray diffraction (XRD, X-ray photoelectron spectroscopy (XPS, transmission election microscopy (TEM, infrared spectroscopy of pyridine adsorption (Py-IR, H2-adsorption and temperature-programmed desorption of hydrogen (H2-TPD. The crystallographic planes of Ni(111, Ni12P5(400, Ni2P(111 were found mainly exposed on the above three catalysts, respectively. It was found that the deoxygenation pathway of palmitic acid mainly proceeded via direct decarboxylation (DCO2 to form C15 on Ni/SiO2. In contrast, on the Ni12P5/SiO2 catalyst, there were two main competitive pathways producing C15 and C16, one of which mainly proceeded via the decarbonylation (DCO to form C15 accompanying water formation, and the other pathway produced C16 via the dehydration of hexadecanol intermediate, and the yield of C15 was approximately twofold that of C16. Over the Ni2P/SiO2 catalyst, two main deoxygenation pathways formed C15, one of which was mainly the DCO pathway and the other was dehydration accompanying the hexadecanal intermediate and then direct decarbonylation without water formation. The turn over frequency (TOF followed the order: Ni12P5/SiO2 > Ni/SiO2 > Ni2P/SiO2.

  16. Mapping the low palmitate fap1 mutation and validation of its effects in soybean oil and agronomic traits in three soybean populations.

    Science.gov (United States)

    Cardinal, Andrea J; Whetten, Rebecca; Wang, Sanbao; Auclair, Jérôme; Hyten, David; Cregan, Perry; Bachlava, Eleni; Gillman, Jason; Ramirez, Martha; Dewey, Ralph; Upchurch, Greg; Miranda, Lilian; Burton, Joseph W

    2014-01-01

    fap 1 mutation is caused by a G174A change in GmKASIIIA that disrupts a donor splice site recognition and creates a GATCTG motif that enhanced its expression. Soybean oil with reduced palmitic acid content is desirable to reduce the health risks associated with consumption of this fatty acid. The objectives of this study were: to identify the genomic location of the reduced palmitate fap1 mutation, determine its molecular basis, estimate the amount of phenotypic variation in fatty acid composition explained by this locus, determine if there are epistatic interactions between the fap1 and fap nc loci and, determine if the fap1 mutation has pleiotropic effects on seed yield, oil and protein content in three soybean populations. This study detected two major QTL for 16:0 content located in chromosome 5 (GmFATB1a, fap nc) and chromosome 9 near BARCSOYSSR_09_1707 that explained, with their interaction, 66-94 % of the variation in 16:0 content in the three populations. Sequencing results of a putative candidate gene, GmKASIIIA, revealed a single unique polymorphism in the germplasm line C1726, which was predicted to disrupt the donor splice site recognition between exon one and intron one and produce a truncated KASIIIA protein. This G to A change also created the GATCTG motif that enhanced gene expression of the mutated GmKASIIIA gene. Lines homozygous for the GmKASIIIA mutation (fap1) had a significant reduction in 16:0, 18:0, and oil content; and an increase in unsaturated fatty acids content. There were significant epistatic interactions between GmKASIIIA (fap1) and fap nc for 16:0 and oil contents, and seed yield in two populations. In conclusion, the fap1 phenotype is caused by a single unique SNP in the GmKASIIIA gene.

  17. Inhibition of SH2-domain-containing inositol 5-phosphatase (SHIP2) ameliorates palmitate induced-apoptosis through regulating Akt/FOXO1 pathway and ROS production in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorgani-Firuzjaee, Sattar [Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran (Iran, Islamic Republic of); Adeli, Khosrow [Division of Clinical Biochemistry, The Hospital for Sick Children, University of Toronto, Toronto (Canada); Meshkani, Reza, E-mail: rmeshkani@tums.ac.ir [Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran (Iran, Islamic Republic of)

    2015-08-21

    The serine–threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome c and poly (ADP-ribose) polymerase. Overexpression of the wild-type SHIP2 gene led to a massive apoptosis in HepG2 cells. The protection from palmitate-induced apoptosis by SHIP2 inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). In addition, SHIP2 inhibition was accompanied by an increased Akt and FOXO-1 phosphorylation, whereas overexpression of the wild-type SHIP2 gene had the opposite effects. Taken together, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipoapotosis and its inhibition can potentially be a target in treatment of hepatic lipoapoptosis in diabetic patients. - Highlights: • Lipoapoptosis is the major contributor to the development of NAFLD. • The PI3-K/Akt pathway regulates apoptosis in different cells. • The role of negative regulator of this pathway, SHIP2 in lipoapoptosis is unknown. • SHIP2 inhibition significantly reduces palmitate-induced apoptosis in HepG2 cells. • SHIP2 inhibition prevents palmitate induced-apoptosis by regulating Akt/FOXO1 pathway.

  18. Inhibition of SH2-domain-containing inositol 5-phosphatase (SHIP2) ameliorates palmitate induced-apoptosis through regulating Akt/FOXO1 pathway and ROS production in HepG2 cells

    International Nuclear Information System (INIS)

    Gorgani-Firuzjaee, Sattar; Adeli, Khosrow; Meshkani, Reza

    2015-01-01

    The serine–threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome c and poly (ADP-ribose) polymerase. Overexpression of the wild-type SHIP2 gene led to a massive apoptosis in HepG2 cells. The protection from palmitate-induced apoptosis by SHIP2 inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). In addition, SHIP2 inhibition was accompanied by an increased Akt and FOXO-1 phosphorylation, whereas overexpression of the wild-type SHIP2 gene had the opposite effects. Taken together, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipoapotosis and its inhibition can potentially be a target in treatment of hepatic lipoapoptosis in diabetic patients. - Highlights: • Lipoapoptosis is the major contributor to the development of NAFLD. • The PI3-K/Akt pathway regulates apoptosis in different cells. • The role of negative regulator of this pathway, SHIP2 in lipoapoptosis is unknown. • SHIP2 inhibition significantly reduces palmitate-induced apoptosis in HepG2 cells. • SHIP2 inhibition prevents palmitate induced-apoptosis by regulating Akt/FOXO1 pathway

  19. The effect of valinomycin in fibroblasts from patients with fatty acid oxidation disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ndukwe Erlingsson, Uzochi Chimdinma [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); Iacobazzi, Francesco [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); Department of Basic Medical Sciences, University of Bari, Piazza Giulio Cesare 11, Policlinico, I-70124 Bari (Italy); Liu, Aiping [ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Ardon, Orly; Pasquali, Marzia [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Department of Pathology, University of Utah, Salt Lake City, UT 84132 (United States); Longo, Nicola, E-mail: Nicola.Longo@hsc.utah.edu [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Department of Pathology, University of Utah, Salt Lake City, UT 84132 (United States)

    2013-08-09

    Highlights: •Valinomycin can cause mitochondrial stress and stimulate fatty acid oxidation. •Cells with VLCAD deficiency fail to increase fatty acid oxidation in response to valinomycin. •Response to valinomycin can help in the diagnosis of VLCAD deficiency. -- Abstract: Disorders of the carnitine cycle and of the beta oxidation spiral impair the ability to obtain energy from fats at time of fasting and stress. This can result in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic medical problems. The in vitro study of fibroblasts from patients with these conditions is impaired by their limited oxidative capacity. Here we evaluate the capacity of valinomycin, a potassium ionophore that increases mitochondrial respiration, to increase the oxidation of fatty acids in cells from patients with inherited fatty acid oxidation defects. The addition of valinomycin to fibroblasts decreased the accumulation of the lipophilic cation tetraphenylphosphonium (TPP{sup +}) at low concentrations due to the dissipation of the mitochondrial membrane potential. At higher doses, valinomycin increased TPP{sup +} accumulation due to the increased potassium permeability of the plasma membrane and subsequent cellular hyperpolarization. The incubation of normal fibroblasts with valinomycin increased [{sup 14}C]-palmitate oxidation (measured as [{sup 14}C]O{sub 2} release) in a dose-dependent manner. By contrast, valinomycin failed to increase palmitate oxidation in fibroblasts from patients with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This was not observed in fibroblasts from patients heterozygous for this condition. These results indicate that valinomycin can increase fatty acid oxidation in normal fibroblasts and could be useful to differentiate heterozygotes from patients affected with VLCAD deficiency.

  20. The effect of valinomycin in fibroblasts from patients with fatty acid oxidation disorders

    International Nuclear Information System (INIS)

    Ndukwe Erlingsson, Uzochi Chimdinma; Iacobazzi, Francesco; Liu, Aiping; Ardon, Orly; Pasquali, Marzia; Longo, Nicola

    2013-01-01

    Highlights: •Valinomycin can cause mitochondrial stress and stimulate fatty acid oxidation. •Cells with VLCAD deficiency fail to increase fatty acid oxidation in response to valinomycin. •Response to valinomycin can help in the diagnosis of VLCAD deficiency. -- Abstract: Disorders of the carnitine cycle and of the beta oxidation spiral impair the ability to obtain energy from fats at time of fasting and stress. This can result in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic medical problems. The in vitro study of fibroblasts from patients with these conditions is impaired by their limited oxidative capacity. Here we evaluate the capacity of valinomycin, a potassium ionophore that increases mitochondrial respiration, to increase the oxidation of fatty acids in cells from patients with inherited fatty acid oxidation defects. The addition of valinomycin to fibroblasts decreased the accumulation of the lipophilic cation tetraphenylphosphonium (TPP + ) at low concentrations due to the dissipation of the mitochondrial membrane potential. At higher doses, valinomycin increased TPP + accumulation due to the increased potassium permeability of the plasma membrane and subsequent cellular hyperpolarization. The incubation of normal fibroblasts with valinomycin increased [ 14 C]-palmitate oxidation (measured as [ 14 C]O 2 release) in a dose-dependent manner. By contrast, valinomycin failed to increase palmitate oxidation in fibroblasts from patients with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This was not observed in fibroblasts from patients heterozygous for this condition. These results indicate that valinomycin can increase fatty acid oxidation in normal fibroblasts and could be useful to differentiate heterozygotes from patients affected with VLCAD deficiency

  1. Terrorism/Criminalogy/Sociology via Magnetism-Hamiltonian ``Models''?!: Black Swans; What Secrets Lie Buried in Magnetism?; ``Magnetism Will Conquer the Universe?''(Charles Middleton, aka ``His Imperial Majesty The Emperior Ming `The Merciless!!!''

    Science.gov (United States)

    Carrott, Anthony; Siegel, Edward Carl-Ludwig; Hoover, John-Edgar; Ness, Elliott

    2013-03-01

    Terrorism/Criminalogy//Sociology : non-Linear applied-mathematician (``nose-to-the grindstone / ``gearheadism'') ''modelers'': Worden,, Short, ...criminologists/counter-terrorists/sociologists confront [SIAM Conf. on Nonlinearity, Seattle(12); Canadian Sociology Conf,. Burnaby(12)]. ``The `Sins' of the Fathers Visited Upon the Sons'': Zeno vs Ising vs Heisenberg vs Stoner vs Hubbard vs Siegel ''SODHM''(But NO Y!!!) vs ...??? Magntism and it turn are themselves confronted BY MAGNETISM,via relatively magnetism/metal-insulator conductivity / percolation-phase-transitions critical-phenomena -illiterate non-linear applied-mathematician (nose-to-the-grindstone/ ``gearheadism'')''modelers''. What Secrets Lie Buried in Magnetism?; ``Magnetism Will Conquer the Universe!!!''[Charles Middleton, aka ``His Imperial Majesty The Emperior Ming `The Merciless!!!']'' magnetism-Hamiltonian phase-transitions percolation-``models''!: Zeno(~2350 BCE) to Peter the Pilgrim(1150) to Gilbert(1600) to Faraday(1815-1820) to Tate (1870-1880) to Ewing(1882) hysteresis to Barkhausen(1885) to Curie(1895)-Weiss(1895) to Ising-Lenz(r-space/Localized-Scalar/ Discrete/1911) to Heisenberg(r-space/localized-vector/discrete/1927) to Priesich(1935) to Stoner (electron/k-space/ itinerant-vector/discrete/39) to Stoner-Wohlfarth (technical-magnetism hysteresis /r-space/ itinerant-vector/ discrete/48) to Hubbard-Longuet-Higgins (k-space versus r-space/

  2. Synergistic Effects of Zinc Oxide Nanoparticles and Fatty Acids on Toxicity to Caco-2 Cells

    DEFF Research Database (Denmark)

    Cao, Yi; Roursgaard, Martin; Kermanizadeh, Ali

    2015-01-01

    epithelial (Caco-2) cells. The ZnO NPs exposure concentration dependently induced cytotoxicity to Caco-2 cells showing as reduced proliferation and activity measured by 3 different assays. PA exposure induced cytotoxicity, and coexposure to ZnO NPs and PA showed the largest cytotoxic effects. The presence......Fatty acids exposure may increase sensitivity of intestinal epithelial cells to cytotoxic effects of zinc oxide (ZnO) nanoparticles (NPs). This study evaluated the synergistic effects of ZnO NPs and palmitic acid (PA) or free fatty acids (FFAs) mixture (oleic/PA 2:1) on toxicity to human colon...

  3. Impact of time of initiation of once-monthly paliperidone palmitate in hospitalized Asian patients with acute exacerbation of schizophrenia: a post hoc analysis from the PREVAIL study

    Directory of Open Access Journals (Sweden)

    Li H

    2018-04-01

    Full Text Available Huafang Li,1,2 Yan Li,1,2 Yu Feng,3 Jianmin Zhuo,4 Ibrahim Turkoz,5 Maju Mathews,5 Wilson Tan3 1Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China; 3Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 4Janssen China Research and Development, Shanghai, China; 5Janssen Research & Development LLC, Titusville, NJ, USA Purpose: To evaluate the differences in efficacy and safety outcomes in acute exacerbating schizophrenia patients between 2 subgroups (≤1 week and >1 week, differing in time interval from hospitalization to time of initiation of once-monthly paliperidone palmitate. Patients and methods: PREVAIL was a multicenter, single-arm, open-label, prospective Phase IV study in hospitalized Asian patients (either sex, aged 18–65 years diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Change from baseline to week 13 in primary (Positive and Negative Syndrome Scale [PANSS] total score, secondary endpoints (PANSS responder rate, PANSS subscale, PANSS Marder factor, Clinical Global Impression-Severity, and Personal and Social Performance scale scores, readiness for hospital discharge questionnaire and safety were assessed in this post hoc analysis. Results: Significant mean reduction from baseline to week 13 in the PANSS total score, 30% PANSS responder rates (P≤0.01, PANSS subscales (positive and general psychopathology; all P≤0.01, PANSS Marder factor (positive symptoms, uncontrolled hostility, and excitement and anxiety/depression; all P≤0.01, Personal and Social Performance scale scores (P≤0.05 and Clinical Global Impression-Severity categorical summary (P≤0.05 were significantly greater in the ≤1 week subgroup versus >1 week subgroup (P≤0.05. The readiness for hospital discharge questionnaire improved over time for the overall study population, but

  4. Nutrient digestibility and milk production responses to increasing levels of palmitic acid supplementation vary in cows receiving diets with or without whole cottonseed.

    Science.gov (United States)

    Rico, J E; de Souza, J; Allen, M S; Lock, A L

    2017-01-01

    Our study evaluated the dose-dependent effects of a palmitic acid-enriched supplement in basal diets with or without the inclusion of whole cottonseed on nutrient digestibility and production responses of dairy cows. Sixteen Holstein cows (149 ± 56 days in milk) were used in a split plot Latin square design experiment. Cows were blocked by 3.5% fat-corrected milk (FCM) and allocated to a main plot receiving either a basal diet with soyhulls (SH, = 8) or a basal diet with whole cottonseed (CS, = 8) that was fed throughout the experiment. A palmitic acid-enriched supplement (PA 88.5% C16:0) was fed at 0, 0.75, 1.50, or 2.25% of ration DM in a replicated 4 × 4 Latin Square design within each basal diet group. Periods were 14 d with the final 4 d used for data collection. PA dose increased milk fat content linearly, and cubically affected yields of milk fat and 3.5% FCM. The PA dose did not affect milk protein and lactose contents, BW, and BCS, but tended to increase yields of milk, milk protein, and milk lactose. Also, PA dose reduced DMI and 16-carbon fatty acid digestibility quadratically, and increased 18-carbon fatty acid digestibility quadratically. There were no effects of basal diet on the yield of milk or milk components, but DMI tended to decrease in CS compared with SH, increasing feed efficiency (3.5% FCM/DMI). Compared with SH, CS diets increased yield of preformed milk fatty acids and 16-carbon fatty acid digestibility, and tended to decrease 18-carbon fatty acid digestibility. We observed basal diet × PA dose interactions for yields of milk and milk protein and for 16-carbon and total fatty acid digestibility, as well as tendency for yields of milk fat and 3.5% FCM. Also, there was a tendency for an interaction between basal diet and PA dose for NDF digestibility, which increased more for CS with increasing PA than for SH. PA dose linearly decreased digestibility of total fatty acids in SH diets but did not affect it in CS diets Results demonstrate

  5. Influence of alcohol containing and alcohol free cosmetics on FAEE concentrations in hair. A performance evaluation of ethyl palmitate as sole marker, versus the sum of four FAEEs.

    Science.gov (United States)

    Dumitrascu, C; Paul, R; Kingston, R; Williams, Rachel

    2018-02-01

    Fatty acid ethyl esters (FAEE) are direct metabolites of ethanol and have been shown to be suitable markers for the evaluation of alcohol consumption. Previous research has suggested that the regular use of alcohol containing cosmetic products can influence the concentration of FAEE detected in hair. In this study we investigated the influence of alcohol containing and alcohol free hair cosmetics (hairspray and waxes) on the FAEE concentrations in hair. The effect of cosmetic treatment was measured against the impact on ethyl palmitate in isolation as compared to the sum of four esters. 10 volunteers treated part of their scalp with cosmetic products every day during a 2 month period (alcohol free hairspray n=2, hairspray containing alcohol (42% by volume) n=3, alcohol free wax n=2, wax containing alcohol (11% by volume) n=3). After the 2 month period of cosmetic application hair samples from volunteers were collected from both sides of the scalp. Hair samples were washed with n-heptane, and then cut finely into small pieces. All samples were subjected to clean-up by HS-SPME and then GC PCI-MS/MS for analysis of FAEEs. Comparison of FAEE concentrations between treated and untreated hair showed in some instances that application of hair spray or wax products caused an increase in FAEE levels. Products containing alcohol caused a more substantial increase in alcohol metabolite concentrations in hair when compared to alcohol free products. Three volunteers using an alcohol based hairspray in the study experienced a significant increase in FAEE levels (+27.4%, +205.5%, and +1287.5%), with one of the volunteers showing levels below the cut off for 'abstinence' in the untreated scalp portion, and levels above the cut off for 'chronic excessive consumption' in the treated scalp portion. Performance evaluation of ethyl palmitate as sole marker, compared to the sum of four esters approach suggested that the two quantification approaches react in a very similar manner to the

  6. (Vapor + liquid) equilibrium for the binary systems {l_brace}water + glycerol{r_brace} and {l_brace}ethanol + glycerol, ethyl stearate, and ethyl palmitate{r_brace} at low pressures

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, Renata; Santos, Priscilla G. dos; Mafra, Marcos R. [Department of Chemical Engineering, Federal University of Parana, CEP 81531-990, Curitiba, PR (Brazil); Cardozo-Filho, Lucio [Department of Chemical Engineering, Maringa State University (UEM), Av. Colombo 5790, 87020-900 Maringa, PR (Brazil); Corazza, Marcos L., E-mail: corazza@ufpr.br [Department of Chemical Engineering, Federal University of Parana, CEP 81531-990, Curitiba, PR (Brazil)

    2011-12-15

    Highlights: > We measured VLE for the binary system {l_brace}ethyl stearate and palmitate + ethanol{r_brace}. > The boiling temperatures were obtained using Othmer-type ebuliometer. > The experimental data were modeled using NRTL, UNIQUAC, and UNIFAC models. - Abstract: This work reports the experimental measurements {l_brace}(vapor + liquid) equilibrium{r_brace} for the systems {l_brace}water(1) + glycerol(2){r_brace}, {l_brace}ethanol(1) + glycerol(2){r_brace}, {l_brace}ethanol(1) + ethyl stearate(2){r_brace}, and {l_brace}ethanol(1) + ethyl palmitate(2){r_brace}. Boiling temperatures were measured using an Othmer-type ebulliometer over a pressure range of 14 kPa to 96 kPa. The experimental data were well correlated using the NRTL and UNIQUAC models. The performance of the UNIFAC-Dortmund model in relation to predicting the phase equilibrium of the systems was also studied.

  7. Characterisation of Fecal Soap Fatty Acids, Calcium Contents, Bacterial Community and Short-Chain Fatty Acids in Sprague Dawley Rats Fed with Different sn-2 Palmitic Triacylglycerols Diets.

    Science.gov (United States)

    Wan, Jianchun; Hu, Songyou; Ni, Kefeng; Chang, Guifang; Sun, Xiangjun; Yu, Liangli

    2016-01-01

    The structure of dietary triacylglycerols is thought to influence fatty acid and calcium absorption, as well as intestinal microbiota population of the host. In the present study, we investigated the impact of palmitic acid (PA) esterified at the sn-2 position on absorption of fatty acid and calcium and composition of intestinal microorganisms in rats fed high-fat diets containing either low sn-2 PA (12.1%), medium sn-2 PA (40.4%) or high sn-2 PA (56.3%), respectively. Fecal fatty acid profiles in the soaps were measured by gas chromatography (GC), while fecal calcium concentration was detected by ICP-MS. The fecal microbial composition was assessed using a 16S rRNA high-throughput sequencing technology and fecal short-chain fatty acids were detected by ion chromatograph. Dietary supplementation with a high sn-2 PA fat significantly reduced total fecal contents of fatty acids soap and calcium compared with the medium or low sn-2 PA fat groups. Diet supplementation with sn-2 PA fat did not change the entire profile of the gut microbiota community at phylum level and the difference at genera level also were minimal in the three treatment groups. However, high sn-2 PA fat diet could potentially improve total short-chain fatty acids content in the feces, suggesting that high dietary sn-2 PA fat might have a beneficial effect on host intestinal health.

  8. Synthesis, Structural Studies and Biological Evaluation of Connections of Thiosemicarbazide, 1,2,4-Triazole and 1,3,4-Thiadiazole with Palmitic Acid

    Directory of Open Access Journals (Sweden)

    Michał Jóźwiak

    2018-04-01

    Full Text Available Thirty new derivatives of palmitic acid were efficiently synthesized. All obtained compounds can be divided into three groups of derivatives: Thiosemicarbazides (compounds 1–10, 1,2,4-triazoles (compounds 1a–10a and 1,3,4-thiadiazoles (compounds 1b–10b moieties. 1H-NMR, 13C-NMR and MS methods were used to confirm the structure of derivatives. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans. Compounds 4, 5, 6, 8 showed significant inhibition against C. albicans. The range of MIC values was 50–1.56 μg/mL. The halogen atom, especially at the 3rd position of the phenyl group was significantly important for antifungal activity. The biological activity against Candida albicans and selected molecular descriptors were used as a basis for QSAR models, that have been determined by means of multiple linear regression. The models have been validated by means of the Leave-One-Out Cross Validation. The obtained QSAR models were characterized by high determination coefficients and good prediction power.

  9. Synthesis, Structural Studies and Biological Evaluation of Connections of Thiosemicarbazide, 1,2,4-Triazole and 1,3,4-Thiadiazole with Palmitic Acid.

    Science.gov (United States)

    Jóźwiak, Michał; Stępień, Karolina; Wrzosek, Małgorzata; Olejarz, Wioletta; Kubiak-Tomaszewska, Grażyna; Filipowska, Anna; Filipowski, Wojciech; Struga, Marta

    2018-04-03

    Thirty new derivatives of palmitic acid were efficiently synthesized. All obtained compounds can be divided into three groups of derivatives: Thiosemicarbazides (compounds 1 - 10 ), 1,2,4-triazoles (compounds 1a - 10a ) and 1,3,4-thiadiazoles (compounds 1b - 10b ) moieties. ¹H-NMR, 13 C-NMR and MS methods were used to confirm the structure of derivatives. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans . Compounds 4 , 5 , 6 , 8 showed significant inhibition against C. albicans . The range of MIC values was 50-1.56 μg/mL. The halogen atom, especially at the 3rd position of the phenyl group was significantly important for antifungal activity. The biological activity against Candida albicans and selected molecular descriptors were used as a basis for QSAR models, that have been determined by means of multiple linear regression. The models have been validated by means of the Leave-One-Out Cross Validation. The obtained QSAR models were characterized by high determination coefficients and good prediction power.

  10. Film fabrication of Fe or Fe3O4 nanoparticles mixed with palmitic acid for vertically aligned carbon nanotube growth using Langmuir-Blodgett technique

    Science.gov (United States)

    Nakamura, Kentaro; Kuriyama, Naoki; Takagiwa, Shota; Sato, Taiga; Kushida, Masahito

    2016-03-01

    Vertically aligned carbon nanotubes (VA-CNTs) were studied as a new catalyst support for polymer electrolyte fuel cells (PEFCs). Controlling the number density and the diameter of VA-CNTs may be necessary to optimize PEFC performance. As the catalyst for CNT growth, we fabricated Fe or Fe3O4 nanoparticle (NP) films by the Langmuir-Blodgett (LB) technique. The catalyst Fe or Fe3O4 NPs were widely separated by mixing with filler molecules [palmitic acid (C16)]. The number density of VA-CNTs was controlled by varying the ratio of catalyst NPs to C16 filler molecules. The VA-CNTs were synthesized from the catalyst NP-C16 LB films by thermal chemical vapor deposition (CVD) using acetylene gas as the carbon source. The developing solvents used in the LB technique and the hydrogen reduction conditions of CVD were optimized to improve the VA-CNT growth rate. We demonstrate that the proposed method can independently control both the density and the diameter of VA-CNTs.

  11. AICAR Protects against High Palmitate/High Insulin-Induced Intramyocellular Lipid Accumulation and Insulin Resistance in HL-1 Cardiac Cells by Inducing PPAR-Target Gene Expression

    Directory of Open Access Journals (Sweden)

    Ricardo Rodríguez-Calvo

    2015-01-01

    Full Text Available Here we studied the impact of 5-aminoimidazole-4-carboxamide riboside (AICAR, a well-known AMPK activator, on cardiac metabolic adaptation. AMPK activation by AICAR was confirmed by increased phospho-Thr172-AMPK and phospho-Ser79-ACC protein levels in HL-1 cardiomyocytes. Then, cells were exposed to AICAR stimulation for 24 h in the presence or absence of the AMPK inhibitor Compound C, and the mRNA levels of the three PPARs were analyzed by real-time RT-PCR. Treatment with AICAR induced gene expression of all three PPARs, but only the Ppara and Pparg regulation were dependent on AMPK. Next, we exposed HL-1 cells to high palmitate/high insulin (HP/HI conditions either in presence or in absence of AICAR, and we evaluated the expression of selected PPAR-targets genes. HP/HI induced insulin resistance and lipid storage was accompanied by increased Cd36, Acot1, and Ucp3 mRNA levels. AICAR treatment induced the expression of Acadvl and Glut4, which correlated to prevention of the HP/HI-induced intramyocellular lipid build-up, and attenuation of the HP/HI-induced impairment of glucose uptake. These data support the hypothesis that AICAR contributes to cardiac metabolic adaptation via regulation of transcriptional mechanisms.

  12. Vapour liquid equilibria of monocaprylin plus palmitic acid or methyl stearate at P = (1.20 and 2.50) kPa by using DSC technique

    International Nuclear Information System (INIS)

    Cunico, Larissa P.; Damaceno, Daniela S.; Matricarde Falleiro, Rafael M.; Sarup, Bent; Abildskov, Jens; Ceriani, Roberta; Gani, Rafiqul

    2015-01-01

    Highlights: • Novel VLE data for binary mixtures involving a partial acylglycerol (monocaprylin). • Use of a promising technique for measuring VLE/vapour pressure data (DSC technique). • The consistency of experimental data is analysed by a proposed methodology. • Regressed parameters are given for excess Gibbs thermodynamic models. • New regressed parameters are presented for UNIFAC to account for nonidealities. - Abstract: The Differential Scanning Calorimetry (DSC) technique is used for measuring isobaric (vapour + liquid) equilibria for two binary mixtures: {monocaprylin + palmitic acid (system 1) or methyl stearate (system 2)} at two different pressures P = (1.20 and 2.50) kPa. The obtained PTx data are correlated by Wilson, NRTL and UNIQUAC models. The original UNIFAC group contribution method is also considered and new binary interaction parameters for the main groups CH 2 , CCOO, OH and COOH are regressed, to account for the non-idealities found in these lipid systems. Established thermodynamic consistency tests are applied and attest the quality of the measured data. In terms of relevance of the selected components, system 1 can be found in the purification and deodorization steps during the production of edible oils, while, system 2 can be found in the purification steps of biodiesel. It should be noted that no such data could be found in the open literature, not only for the specific components selected but also for the combination of the classes of components considered; that is, acylglycerol plus fatty acid or fatty ester.

  13. Involvement of CD36 in Modulating the Decrease of NPY and AgRP Induced by Acute Palmitic Acid Stimulation in N1E-115 Cells

    Directory of Open Access Journals (Sweden)

    Yan Ma

    2017-06-01

    Full Text Available Central nervous system (CNS fatty acid sensing plays an important role in the regulation of food intake, and palmitic acid (PA is the most important long chain fatty acid (LCFA in the mammalian diet. To explore the effect of PA on central neuropeptide expression and the role of the cluster of the differentiation of 36 (CD36 in the process, N1E-115 cells were cultured with PA in the presence or absence of sulfosuccinimidyl-oleate (SSO, a CD36 inhibitor. Results showed that 10 μmol/L PA significantly reduced NPY and AgRP mRNA expression after 20 min of exposure, while the expression of CD36 was upregulated. The presence of SSO significantly attenuated the decrease of NPY and AgRP expression that was induced by PA alone, although no notable effect on PA- induced CD36 gene expression was observed. In conclusion, our study suggests the involvement of CD36 in the PA-induced decrease of NPY and AgRP in N1E-115 cells.

  14. Once-monthly injection of paliperidone palmitate in patients with recently diagnosed and chronic schizophrenia: a post-hoc comparison of efficacy and safety.

    Science.gov (United States)

    Si, Tianmei; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson; Feng, Yu

    2017-12-01

    The use of long-acting injectable antipsychotics in recently diagnosed schizophrenia remains less explored. We evaluated the efficacy and safety of paliperidone palmitate once-monthly (PP1M) treatment in adult patients with recently diagnosed vs. chronic schizophrenia. These post-hoc analyses included two multicenter studies. Study 1 (NCT01527305) enrolled recently diagnosed (≤5 years) and chronic (>5 years) patients; Study 2 (NCT01051531) enrolled recently diagnosed patients only. Recently diagnosed patients were further sub-grouped into ≤2 years or 2-5 years. The primary efficacy endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. In Study 1, 41.5% patients had recent diagnosis (≤2 years: 56.8%; 2-5 years: 43.2%); 58.5% had chronic schizophrenia. In Study 2, 52.8% and 47.2% patients were grouped into ≤2 years and 2-5 years, respectively. PANSS total score showed significantly greater improvement in patients with recently diagnosed vs. chronic schizophrenia. Similar results were obtained for PANSS responder rate, improvements in PANSS, and CGI-S scores. PP1M was efficacious in both recently diagnosed and chronic schizophrenia, with the benefits being more pronounced in patients with recently diagnosed schizophrenia. This adds to growing evidence recommending long-acting antipsychotic interventions at early stages of schizophrenia.

  15. Egr2 enhances insulin resistance via JAK2/STAT3/SOCS-1 pathway in HepG2 cells treated with palmitate.

    Science.gov (United States)

    Lu, Lin; Ye, Xinhua; Yao, Qing; Lu, Aijiao; Zhao, Zhen; Ding, Yang; Meng, Chuchen; Yu, Wenlong; Du, Yunfeng; Cheng, JinLuo

    2018-05-01

    Insulin resistance is generally responsible for the pathogenesis of type 2 diabetes mellitus (T2DM). Early growth response proteins-2 (Egr2) has been reported to be able to increase the expression of the suppressors of cytokine signaling-1 (SOCS-1), and impair insulin signaling pathway through suppression of insulin receptor substrates (IRS), including IRS-1 and IRS-2. However, whether Egr2 is directly involved in the development of insulin resistance, and how its potential contributions to insulin resistance still remain unknown. Here, our present investigation found that the expression levels of Egr2 were up-regulated when insulin resistance occurs, and knockdown of Egr2 abolished the effect of insulin resistance in HepG2 cells induced with palmitate (PA). Importantly, inhibition of Egr2 decreased the expression of SOCS-1 as well as reduced phosphorylation of JAK2 and STAT3. And, our data indicated that silencing of Egr2 accelerated hepatic glucose uptake and reversed the impaired lipid metabolism upon insulin resistance. In summary, the present study confirms that Egr2 could deteriorate insulin resistance via the pathway of JAK2/STAT3/SOCS-1 and may shed light on resolving insulin resistance and further the pathogenesis of T2DM. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Synthesis, characterization, and application of novel biodegradable self-assembled 2-(N-phthalimido) ethyl-palmitate nanoparticles for cancer therapy

    Science.gov (United States)

    Kasoju, Naresh; Bora, Debajeet K.; Bhonde, Ramesh R.; Bora, Utpal

    2010-03-01

    We report the synthesis of novel biodegradable nanoparticles (NPs) which can kill the cancer cells without any additional drug loading. The NP was a self-assembled form of a phthalimide based conjugate, in which the phthalimide moiety was responsible for the anticancer activity. We describe the synthesis of a novel 2-(N-phthalimido) ethyl palmitate (PHEP-Pal) conjugate and subsequent preparation of NPs by a simple self assembly process. The successful synthesis of conjugate was confirmed by various characterization studies including nuclear magnetic resonance spectroscope, Fourier transform infrared spectroscope, TOF-liquid chromatography mass spectroscope, differential scanning calorimetry, and X-ray diffraction unit. The synthesis, shape, size, and size distribution of PHEP-Pal NPs were determined by transmission electron microscope, atomic force microscope, and dynamic light scattering technique. Finally, cell culture studies using A549 and HeLa cells were done to evaluate the anticancer effect of PHEP-Pal NPs, which demonstrated the potency of these NPs for use in cancer chemotherapy.

  17. Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by palmitic acid; implications for a microbicide development.

    Directory of Open Access Journals (Sweden)

    Xudong Lin

    Full Text Available BACKGROUND: Approximately 80% of all new HIV-1 infections are acquired through sexual contact. Currently, there is no clinically approved microbicide, indicating a clear and urgent therapeutic need. We recently reported that palmitic acid (PA is a novel and specific inhibitor of HIV-1 fusion and entry. Mechanistically, PA inhibits HIV-1 infection by binding to a novel pocket on the CD4 receptor and blocks efficient gp120-to-CD4 attachment. Here, we wanted to assess the ability of PA to inhibit HIV-1 infection in cervical tissue ex vivo model of human vagina, and determine its effect on Lactobacillus (L species of probiotic vaginal flora. PRINCIPAL FINDINGS: Our results show that treatment with 100-200 µM PA inhibited HIV-1 infection in cervical tissue by up to 50%, and this treatment was not toxic to the tissue or to L. crispatus and jensenii species of vaginal flora. In vitro, in a cell free system that is independent of in vivo cell associated CD4 receptor; we determined inhibition constant (Ki to be ∼2.53 µM. SIGNIFICANCE: These results demonstrate utility of PA as a model molecule for further preclinical development of a safe and potent HIV-1 entry microbicide inhibitor.

  18. Topical Application of Trisodium Ascorbyl 6-Palmitate 2-Phosphate Actively Supplies Ascorbate to Skin Cells in an Ascorbate Transporter-Independent Manner

    Directory of Open Access Journals (Sweden)

    Shuichi Shibuya

    2017-06-01

    Full Text Available Ascorbic acid (AA possesses multiple beneficial functions, such as regulating collagen biosynthesis and redox balance in the skin. AA derivatives have been developed to overcome this compound’s high fragility and to assist with AA supplementation to the skin. However, how AA derivatives are transferred into cells and converted to AA in the skin remains unclear. In the present study, we showed that AA treatment failed to increase the cellular AA level in the presence of AA transporter inhibitors, indicating an AA transporter-dependent action. In contrast, torisodium ascorbyl 6-palmitate 2-phosphate (APPS treatment significantly enhanced the cellular AA level in skin cells despite the presence of inhibitors. In ex vivo experiments, APPS treatment also increased the AA content in a human epidermis model. Interestingly, APPS was readily metabolized and converted to AA in keratinocyte lysates via an intrinsic mechanism. Furthermore, APPS markedly repressed the intracellular superoxide generation and promoted viability associated with an enhanced AA level in Sod1-deficient skin cells. These findings indicate that APPS effectively restores the AA level and normalizes the redox balance in skin cells in an AA transporter-independent manner. Topical treatment of APPS is a beneficial strategy for supplying AA and improving the physiology of damaged skin.

  19. Cytoprotective effect of kaempferol against palmitic acid-induced pancreatic β-cell death through modulation of autophagy via AMPK/mTOR signaling pathway.

    Science.gov (United States)

    Varshney, Ritu; Gupta, Sumeet; Roy, Partha

    2017-06-15

    Lipotoxicity of pancreatic β-cells is the pathological manifestation of obesity-linked type II diabetes. We intended to determine the cytoprotective effect of kaempferol on pancreatic β-cells undergoing apoptosis in palmitic acid (PA)-stressed condition. The data showed that kaempferol treatment increased cell viability and anti-apoptotic activity in PA-stressed RIN-5F cells and murine pancreatic islets. Furthermore, kaempferol's ability to instigate autophagy was illustrated by MDC-LysoTracker red staining and TEM analysis which corroborated well with the observed increase in LC3 puncta and LC3-II protein expressions along with the concomitant decline in p62 expression. Apart from this, the data showed that kaempferol up/down-regulates AMPK/mTOR phosphorylation respectively. Subsequently, upon inhibition of AMPK phosphorylation by AMPK inhibitors, kaempferol-mediated autophagy was abolished which further led to the decline in β-cell survival. Such observations collectively lead to the conclusion that, kaempferol exerts its cytoprotective role against lipotoxicity by activation of autophagy via AMPK/mTOR pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Estradiol Uses Different Mechanisms in Astrocytes from the Hippocampus of Male and Female Rats to Protect against Damage Induced by Palmitic Acid

    Directory of Open Access Journals (Sweden)

    Laura M. Frago

    2017-10-01

    Full Text Available An excess of saturated fatty acids can be toxic for tissues, including the brain, and this has been associated with the progression of neurodegenerative diseases. Since palmitic acid (PA is a free fatty acid that is abundant in the diet and circulation and can be harmful, we have investigated the effects of this fatty acid on lipotoxicity in hippocampal astrocytes and the mechanism involved. Moreover, as males and females have different susceptibilities to some neurodegenerative diseases, we accessed the responses of astrocytes from both sexes, as well as the possible involvement of estrogens in the protection against fatty acid toxicity. PA increased endoplasmic reticulum stress leading to cell death in astrocytes from both males and females. Estradiol (E2 increased the levels of protective factors, such as Hsp70 and the anti-inflammatory cytokine interleukin-10, in astrocytes from both sexes. In male astrocytes, E2 decreased pJNK, TNFα, and caspase-3 activation. In contrast, in female astrocytes E2 did not affect the activation of JNK or TNFα levels, but decreased apoptotic cell death. Hence, although E2 exerted protective effects against the detrimental effects of PA, the mechanisms involved appear to be different between male and female astrocytes. This sexually dimorphic difference in the protective mechanisms induced by E2 could be involved in the different susceptibilities of males and females to some neurodegenerative processes.

  1. Influence of palmitic acid and hexadecanol on the phase transition temperature and molecular packing of dipalmitoylphosphatidyl-choline monolayers at the air-water interface

    Science.gov (United States)

    Lee, Ka Yee C.; Gopal, Ajaykumar; von Nahmen, Anja; Zasadzinski, Joseph A.; Majewski, Jaroslaw; Smith, Gregory S.; Howes, Paul B.; Kjaer, Kristian

    2002-01-01

    Palmitic acid (PA) and 1-hexadecanol (HD) strongly affect the phase transition temperature and molecular packing of dipalmitoylphosphatidylcholine (DPPC) monolayers at the air-water interface. The phase behavior and morphology of mixed DPPC/PA as well as DPPC/HD monolayers were determined by pressure-area-isotherms and fluorescence microscopy. The molecular organization was probed by synchrotron grazing incidence x-ray diffraction using a liquid surface diffractometer. Addition of PA or HD to DPPC monolayers increases the temperature of the liquid-expanded to condensed phase transition. X-ray diffraction shows that DPPC forms mixed crystals both with PA and HD over a wide range of mixing ratios. At a surface pressure (π) of 40 mN/m, increasing the amount of the single chain surfactant leads to a reduction in tilt angle of the aliphatic chains from nearly 30° for pure DPPC to almost 0° in a 1:1 molar ratio of DPPC and PA or HD. At this composition we also find closest packing of the aliphatic chains. Further increase of the amount of PA or HD does not change the lattice or the tilt.

  2. Targeted metabolomic analysis reveals the association between the postprandial change in palmitic acid, branched-chain amino acids and insulin resistance in young obese subjects.

    Science.gov (United States)

    Liu, Liyan; Feng, Rennan; Guo, Fuchuan; Li, Ying; Jiao, Jundong; Sun, Changhao

    2015-04-01

    Obesity is the result of a positive energy balance and often leads to difficulties in maintaining normal postprandial metabolism. The changes in postprandial metabolites after an oral glucose tolerance test (OGTT) in young obese Chinese men are unclear. In this work, the aim is to investigate the complex metabolic alterations in obesity provoked by an OGTT using targeted metabolomics. We used gas chromatography-mass spectrometry and ultra high performance liquid chromatography-triple quadrupole mass spectrometry to analyze serum fatty acids, amino acids and biogenic amines profiles from 15 control and 15 obese subjects at 0, 30, 60, 90 and 120 min during an OGTT. Metabolite profiles from 30 obese subjects as independent samples were detected in order to validate the change of metabolites. There were the decreased levels of fatty acid, amino acids and biogenic amines after OGTT in obesity. At 120 min, percent change of 20 metabolites in obesity has statistical significance when comparing with the controls. The obese parameters was positively associated with changes in arginine and histidine (Pchange in palmitic acid (PA), branched-chain amino acids (BCAAs) and phenylalanine between 1 and 120 min were positively associated with fasting insulin and HOMA-IR (all Presistance in obesity. Our findings offer new insights in the complex physiological regulation of the metabolism during an OGTT in obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Paliperidone palmitate once-monthly reduces risk of relapse of psychotic, depressive, and manic symptoms and maintains functioning in a double-blind, randomized study of schizoaffective disorder.

    Science.gov (United States)

    Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R Bruce; Walling, David P; Schooler, Nina R; Lindenmayer, Jean-Pierre; Canuso, Carla M; Alphs, Larry

    2015-03-01

    Schizoaffective disorder is a complex illness for which optimal treatment is not well established. Results of the first controlled, relapse-prevention study of paliperidone palmitate once-monthly injectable (paliperidone monthly) in schizoaffective disorder are presented. The study was conducted between September 20, 2010, and October 22, 2013. Patients with schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and randomly assigned (1:1) to paliperidone monthly or placebo in a 15-month, double-blind, relapse-prevention phase. Randomization was stratified by administration as monotherapy or adjunctive therapy and by study center. The primary endpoint was time to relapse. 334 patients were evaluated. Paliperidone monthly significantly delayed time to relapse for psychotic, depressive, and manic symptoms compared with placebo (P schizoaffective disorder (5.9%, 3.0%), headache (3.5%, 5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related adverse event was 7.1% for placebo and 8.5% for paliperidone monthly. Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic, depressive, and/or manic relapses; reduced their risk; and better maintained functioning in patients with schizoaffective disorder. Results support the value of maintenance treatment with paliperidone monthly in schizoaffective disorder. ClinicalTrials.gov identifier: NCT01193153. © Copyright 2015 Physicians Postgraduate Press, Inc.

  4. Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate.

    Science.gov (United States)

    Girardi, Paolo; Del Casale, Antonio; Rapinesi, Chiara; Kotzalidis, Georgios D; Splendori, Francesca; Verzura, Claudio; Trovini, Giada; Sorice, Serena; Carrus, Dario; Mancinelli, Iginia; Comparelli, Anna; De Filippis, Sergio; Francomano, Antonio; Ballerini, Andrea; Marcellusi, Andrea; Mennini, Francesco S; Ducci, Giuseppe; Sani, Gabriele; Pompili, Maurizio; Brugnoli, Roberto

    2018-05-01

    Long-acting injectable (LAI) antipsychotics can improve medication adherence and reduce hospitalisation rates compared with oral treatments. Paliperidone palmitate (PAL) and aripiprazole monohydrate (ARI) LAI treatments were associated with improvements in global functioning in patients with schizophrenia. The objective of this study was to assess the predictive factors of better overall functioning in patients with chronic schizophrenia and schizoaffective disorder treated with PAL and ARI. Enrolled were 143 (97 males, 46 females, mean age 38.24 years, SD = 12.65) patients with a diagnosis of schizophrenia or schizoaffective disorder, whom we allocated in two groups (PAL and ARI treatments). We assessed global functioning, amount of oral medications, adherence to oral treatment, and number of hospitalisations before LAI introduction and at assessment time point. Longer treatment time with LAIs (p schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations. Copyright © 2018 John Wiley & Sons, Ltd.

  5. Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats.

    Science.gov (United States)

    Yilmaz, Okkeş; Ozkan, Yusuf; Yildirim, Mehmet; Oztürk, A Ihsan; Erşan, Yasemin

    2002-01-01

    In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P cholesterol level was high in diabetes and D + ALA groups (P acid raised in diabetes group (P acid in D + FO, D + ALA, and diabetes groups was lower than control (P acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P acid (DHA) increased in D + AA6P and D + COM (P acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P acid level in D + ALA and D + FO groups was higher than control (P acid degree was raised by the effects of ALA and FO. Copyright 2002 Wiley-Liss, Inc.

  6. Prolonged Treatment with Free Fatty Acids has Post Receptor Effect in Hepatic Insulin Resistance: Evidence that Fatty Acids, Oleate and Palmitate have Insignificant Effect on the Insulin Receptor Beta In Vivo and Ex Vivo Primary Hepatocytes

    Directory of Open Access Journals (Sweden)

    Rafik Ragheb

    2009-01-01

    Full Text Available In the current study, we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor-beta subunit (IR-β, as well as the down stream target in PI3K pathway, total PKB/Akt as well as their phosphorylated forms. The assessment of FFAs treatment showed no direct and significant effect on the PI3K stimulation, specifically the IR-β in primary hepatic control cells treated with insulin. Cells treated with either oleate or palmitate (360 µM showed no statistically significant values following insulin stimulation (P > 0.05. To further investigate the effect of both FFAs and high insulin (1 µg, we examined the effects of oleate and palmitate at 360 µM concentration on IR-β as well as PKB. There was no significant difference in the total protein levels and their phosphorylated forms in cells treated with or without oleate or plamitate. Interestingly, IR-β tyrosine phosphorylation showed a similar insignificant effect in vivo and ex vivo hepatic cells treated with oleate or palmitate in comparison to their controls in the fructose fed hamsters.

  7. Catalytic oxidation using nitrous oxide

    Directory of Open Access Journals (Sweden)

    Juan Carlos Beltran-Prieto

    2017-01-01

    Full Text Available Nitrous oxide is a very inert gas used generally as oxidant as it offers some advantage compared with other oxidants such as O2 but a considerably higher temperature (> 526 °C is often required. For particular cases such as the oxidation of sugar alcohols, especially for the oxidation of primary alcohols to aldehydes, N2O has the advantage over O2 of a higher reaction selectivity. In the present paper we present the modelling of oxidation reaction of sugar alcohols using an oxidizing agent in low concentrations, which is important to suppress subsequent oxidation reactions due to the very low residual concentrations of the oxidizing agent. For orientation experiments we chose nitrous oxide generated by thermal decomposition of ammonium nitrate. Kinetic modeling of the reaction was performed after determination of the differential equations that describe the system under study.

  8. Safety and efficacy of paliperidone palmitate 1-month formulation in Chinese patients with schizophrenia: a 25-week, open-label, multicenter, Phase IV study

    Directory of Open Access Journals (Sweden)

    Zhao JP

    2017-08-01

    Full Text Available Jingping Zhao,1,* Lehua Li,1,* Jianguo Shi,2 Yi Li,3 Xiufeng Xu,4 Keqing Li,5 Lili Zhang,6 Shangli Cai,6 Yu Feng,6 Jianmin Zhuo,6 Weihong Liu,6 Huafei Lu6 1Department of Psychiatry, The Mental Health Institute, The Second Xiangya Hospital of Central South University, 2Department of Psychiatry, Mental Health Center of Xi’an City, 3Department of Psychiatry, Mental Health Center of Wuhan City, 4Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, 5Department of Psychiatry, The Sixth People’s Hospital of Hebei Province, 6Department of Medical Affairs, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China *These authors contributed equally to this work Rationale: Long-acting injectable (LAI paliperidone palmitate 1-month formulation (PP1M has demonstrated acceptable tolerability and favorable clinical outcomes in Western and Asian patients with schizophrenia. Hence, analysis of the outcomes of long-term PP1M treatment specifically in Chinese patients is of interest.Objective: The aim of this study is to evaluate the long-term safety and efficacy of PP1M treatment in Chinese patients with schizophrenia.Methods: In this 25-week, open-label, Phase IV study, patients (18–65 years diagnosed with schizophrenia and having a baseline Positive and Negative Syndrome Scale (PANSS total score of 60–120 (inclusive were enrolled. All patients received injections of PP1M 150 mg eq. (day 1 and 100 mg eq. (day 8, followed by a flexible once-monthly maintenance dosing (75, 100, or 150 mg eq..Results: Of the 353 patients, 234 (66.3% completed the study treatment (mean age, 31.1 years; 52.7% men. The PANSS total score (primary end point improved significantly over the 6-month treatment period (mean [standard deviation] change from baseline to end of treatment, -27.2 [18.30]; P<0.0001. The Clinical Global Impressions-Severity and Personal and Social Performance scores (secondary end points also improved

  9. Impact of Paliperidone Palmitate Versus Oral Atypical Antipsychotics on Health Care Resource Use and Costs in Veterans With Schizophrenia and Comorbid Substance Abuse.

    Science.gov (United States)

    Lefebvre, Patrick; Muser, Erik; Joshi, Kruti; DerSarkissian, Maral; Bhak, Rachel H; Duh, Mei Sheng; Shiner, Brian; Young-Xu, Yinong

    2017-07-01

    Almost half of all patients diagnosed with schizophrenia have a history of substance abuse (SA). However, data on treatment of schizophrenia with paliperidone palmitate (PP) among patients with comorbid SA are limited. The objective of this study was to compare all-cause and SA-related health care resource utilization and costs in veterans with schizophrenia and co-occurring SA who were treated with PP versus oral atypical antipsychotics (OAAs). Veterans Health Administration electronic health record data were used to conduct a retrospective longitudinal study in veterans with schizophrenia who initiated PP or OAA between January 1, 2010 and June 30, 2016, had ≥12 months of enrollment before treatment initiation (baseline), were diagnosed with SA, and had ≥1 Global Assessment of Functioning score during baseline. Differences in baseline characteristics were adjusted for using inverse probability of treatment weighting. Adjusted cost differences and incidence rate ratios (IRR) for the association between PP versus OAA and all-cause and SA-related health care costs and health care resource utilization in the 12 months after treatment initiation were estimated with corresponding 95% CIs using weighted linear and Poisson regression models, respectively. Of 6872 veterans in the study, 1684 (25%) and 5188 (75%) were treated with PP and OAA, respectively. After adjustment, PP was associated with fewer all-cause inpatient (IRR = 0.88; 95% CI, 0.85 to 0.90), mental health-related inpatient (IRR = 0.88; 95% CI, 0.85 to 0.91), and long-term care stays (IRR = 0.53; 95% CI, 0.44 to 0.64), but more frequent mental health intensive case management visits (IRR = 1.51; 95% CI, 1.49 to 1.53) compared with OAA (all P schizophrenia and comorbid SA. Thus, PP appears to be a valuable treatment option for patients in this subpopulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. 2-Dodecylcyclobutanone, a radiolytic product of palmitic acid, is genotoxic in primary human colon cells and in cells from preneoplastic lesions

    International Nuclear Information System (INIS)

    Knoll, Nadine; Weise, Anja; Claussen, Uwe; Sendt, Wolfgang; Marian, Brigitte; Glei, Michael; Pool-Zobel, Beatrice L.

    2006-01-01

    The irradiation of fat results in the formation of 2-alkylcyclobutanones, a new class of food contaminants. Results of previous in vitro studies with primary human colon cells and in vivo experiments with rats fed with 2-alkylcyclobutanones indicated that these radiolytic derivatives may be genotoxic and enhance the progression of colon tumors. The underlying mechanisms of these effects, however, are not clearly understood. Therefore we performed additional investigations to elucidate the genotoxic potential of 2-dodecylcyclobutanone (2dDCB) that is generated from palmitic acid. In particular, we explored the relative sensitivities of human colon cells, representing different stages of tumor development and healthy colon tissues, respectively. HT29clone19A cells, LT97 adenoma cells and primary human epithelial cells were exposed to 2dDCB (150-2097 μM). We determined cytotoxic effects using trypan blue exclusion. Genotoxicity, reflected as strand breaks, was assessed using the alkaline version of the comet assay and chromosomal abnormalities were investigated by 24-color fluorescence-in-situ-hybridization. 2dDCB was cytotoxic in a time- and dose-dependent manner in LT97 adenoma cells and in freshly isolated primary cells but not in the human colon tumor cell line. Associated with this was a marked induction of DNA damage by 2dDCB in LT97 adenoma cells and in freshly isolated colonocytes, whereas in the HT29clone19A cells no strand breaks were detectable. A long-term incubation of LT97 adenoma cells with lower concentrations of 2dDCB revealed cytogenetic effects. In summary, 2dDCB was clearly genotoxic in healthy human colon epithelial cells and in cells representing preneoplastic colon adenoma. These findings provide additional evidence that this compound may be regarded as a possible risk factor for processes in colon carcinogenesis related to initiation and progression

  11. Palmitic Acid Induces Osteoblastic Differentiation in Vascular Smooth Muscle Cells through ACSL3 and NF-κB, Novel Targets of Eicosapentaenoic Acid

    Science.gov (United States)

    Kageyama, Aiko; Matsui, Hiroki; Ohta, Masahiko; Sambuichi, Keisuke; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Yokoyama, Tomoyuki; Kurabayashi, Masahiko

    2013-01-01

    Free fatty acids (FFAs), elevated in metabolic syndrome and diabetes, play a crucial role in the development of atherosclerotic cardiovascular disease, and eicosapentaenoic acid (EPA) counteracts many aspects of FFA-induced vascular pathology. Although vascular calcification is invariably associated with atherosclerosis, the mechanisms involved are not completely elucidated. In this study, we tested the hypothesis that EPA prevents the osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC) induced by palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma. PA increased and EPA abolished the expression of the genes for bone-related proteins, including bone morphogenetic protein (BMP)-2, Msx2 and osteopontin in human aortic smooth muscle cells (HASMC). Among the long-chain acyl-CoA synthetase (ACSL) subfamily, ACSL3 expression was predominant in HASMC, and PA robustly increased and EPA efficiently inhibited ACSL3 expression. Importantly, PA-induced osteoblastic differentiation was mediated, at least in part, by ACSL3 activation because acyl-CoA synthetase (ACS) inhibitor or siRNA targeted to ACSL3 completely prevented the PA induction of both BMP-2 and Msx2. Conversely, adenovirus-mediated ACSL3 overexpression enhanced PA-induced BMP-2 and Msx2 expression. In addition, EPA, ACSL3 siRNA and ACS inhibitor attenuated calcium deposition and caspase activation induced by PA. Notably, PA induced activation of NF-κB, and NF-κB inhibitor prevented PA-induction of osteoblastic gene expression and calcium deposition. Immunohistochemistry revealed the prominent expression of ACSL3 in VSMC and macrophages in human non-calcifying and calcifying atherosclerotic plaques from the carotid arteries. These results identify ACSL3 and NF-κB as mediators of PA-induced osteoblastic differentiation and calcium deposition in VSMC and suggest that EPA prevents vascular calcification by inhibiting such a new molecular pathway elicited

  12. Osteotoxicity after chronic dietary administration of 13-CIS-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion

    International Nuclear Information System (INIS)

    Forsyth, K.S.; Gensler, H.L.; Watson, R.R.

    1989-01-01

    In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz[a]anthracene and promoted twice daily with 8 nmoles of 12-O-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU or retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP/g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion results in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased O-fold, 1.4-fold, and 3.6-fold. Bone deformities was augmented O-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium did not alter the bone toxicity of RP. 13-cis-retionic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidence by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osterotoxicities were similar in the mice fed diets supplemented with RP and CRA

  13. Relationship between response to aripiprazole once-monthly and paliperidone palmitate on work readiness and functioning in schizophrenia: A post-hoc analysis of the QUALIFY study.

    Directory of Open Access Journals (Sweden)

    Steven G Potkin

    Full Text Available Schizophrenia is a chronic disease with negative impact on patients' employment status and quality of life. This post-hoc analysis uses data from the QUALIFY study to elucidate the relationship between work readiness and health-related quality of life and functioning. QUALIFY was a 28-week, randomized study (NCT01795547 comparing the treatment effectiveness of aripiprazole once-monthly 400 mg and paliperidone palmitate once-monthly using the Heinrichs-Carpenter Quality-of-Life Scale as the primary endpoint. Also, patients' capacity to work and work readiness (Yes/No was assessed with the Work Readiness Questionnaire. We categorized patients, irrespective of treatment, by work readiness at baseline and week 28: No to Yes (n = 41, Yes to Yes (n = 49, or No at week 28 (n = 118. Quality-of-Life Scale total, domains, and item scores were assessed with a mixed model of repeated measures. Patients who shifted from No to Yes in work readiness showed robust improvements on Quality-of-Life Scale total scores, significantly greater than patients not ready to work at week 28 (least squares mean difference: 11.6±2.6, p<0.0001. Scores on Quality-of-Life Scale instrumental role domain and items therein-occupational role, work functioning, work levels, work satisfaction-significantly improved in patients shifting from No to Yes in work readiness (vs patients No at Week 28. Quality-of-Life Scale total scores also significantly predicted work readiness at week 28. Overall, these results highlight a strong association between improvements in health-related quality of life and work readiness, and suggest that increasing patients' capacity to work is an achievable and meaningful goal in the treatment of impaired functioning in schizophrenia.

  14. Long-acting injectable paliperidone palmitate versus oral paliperidone extended release: a comparative analysis from two placebo-controlled relapse prevention studies.

    Science.gov (United States)

    Markowitz, Michael; Fu, Dong-Jing; Levitan, Bennett; Gopal, Srihari; Turkoz, Ibrahim; Alphs, Larry

    2013-07-11

    Increasing availability and use of long-acting injectable antipsychotics have generated a need to compare these formulations with their oral equivalents; however, a paucity of relevant data is available. This post hoc comparison of the long-term efficacy, safety and tolerability of maintenance treatment with paliperidone palmitate (PP) versus oral paliperidone extended release (ER) used data from two similarly designed, randomised, double-blind (DB), placebo-controlled schizophrenia relapse prevention trials. Assessments included measures of time to relapse, symptom changes/functioning and treatment-emergent adverse events (TEAEs). Time to relapse between treatment groups was evaluated using a Cox proportional hazards model. Between-group differences for continuous variables for change scores during the DB phase were assessed using analysis of co-variance models. Categorical variables were evaluated using Chi-square and Fisher's exact tests. No adjustment was made for multiplicity. Approximately 45% of enrolled subjects in both trials were stabilised and randomised to the DB relapse prevention phase. Risk of relapse was higher in subjects treated with paliperidone ER than in those treated with PP [paliperidone ER/PP hazard ratio (HR), 2.52; 95% confidence interval (CI), 1.46-4.35; p 70, both approximately 58.5%; p = 1.000] compared with a 10.9% decrease for paliperidone ER (58.5% vs 47.6%, respectively; p = 0.048). The least squares mean change for Positive and Negative Syndrome Scale (PANSS) total score at DB end point in these previously stabilised subjects was 3.5 points in favour of PP (6.0 vs 2.5; p = 0.025). The rates of TEAEs and AEs of interest appeared similar. This analysis supports maintenance of effect with the injectable compared with the oral formulation of paliperidone in patients with schizophrenia. The safety profile of PP was similar to that of paliperidone ER. Future studies are needed to confirm these findings.

  15. Paliperidone palmitate once-monthly maintains improvement in functioning domains of the Personal and Social Performance scale compared with placebo in subjects with schizoaffective disorder.

    Science.gov (United States)

    Fu, Dong-Jing; Turkoz, Ibrahim; Walling, David; Lindenmayer, Jean-Pierre; Schooler, Nina R; Alphs, Larry

    2018-02-01

    Evaluate the effect of paliperidone palmitate once-monthly (PP1M) injectable on the specific functioning domains of the Personal and Social Performance (PSP) scale in patients with schizoaffective disorder (SCA) participating in a long-term study. This study (NCT01193153) included both in- and outpatient subjects with SCA experiencing an acute exacerbation of psychotic and mood symptoms. Subjects were treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers during a 25-week open-label (OL) phase. Stabilized subjects were randomly assigned 1:1 (PP1M or placebo) into a 15-month double-blind (DB) relapse-prevention period. Functioning of the randomized subjects during OL and DB phases was evaluated using the PSP scale (four domains: socially useful activities, personal/social relationships, self-care, and disturbing/aggressive behaviors). Three statistical approaches were utilized to analyze PSP scores to assess robustness and consistency of findings. No adjustments were made for multiplicity. 334 of 667 enrolled subjects were stabilized with PP1M, randomly assigned to PP1M (n=164) or placebo (n=170) in the DB phase, and included in this analysis. Improvements in all PSP domain scores were observed during the OL phase and were maintained during the DB phase with PP1M, but decreased with placebo. Differences compared to placebo were significant in all four PSP domains during the DB phase (P≤0.008). The analysis in this study showed that PP1M improves functioning, as measured by the four PSP domain scores, in symptomatic subjects with SCA. Functioning was maintained compared with placebo. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

    DEFF Research Database (Denmark)

    Wensaas, Andreas J; Rustan, Arild C; Just, Marlene

    2008-01-01

    Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence...... these processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA....... EPA markedly enhanced TAG accumulation in myotubes, more pronounced in T2D cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO(2) formation) was enhanced and lactate production decreased...

  17. Oxide ceramics

    International Nuclear Information System (INIS)

    Ryshkewitch, E.; Richerson, D.W.

    1985-01-01

    The book explores single-phase ceramic oxide systems from the standpoint of physical chemistry and technology. This second edition also focuses on advances in technology since publication of the original edition. These include improvements in raw materials and forming and sintering techniques, and the major role that oxide ceramics have had in development of advanced products and processes. The text is divided into five major sections: general fundamentals of oxide ceramics, advances in aluminum oxide technology, advances in zirconia technology, and advances in beryllium oxide technology

  18. Effect of impaired fatty acid oxidation on myocardial kinetics of 11C- and 123I-labelled fatty acids

    International Nuclear Information System (INIS)

    Lerch, R.

    1986-01-01

    Positron emission tomography with palmitate 11 C and single photon imaging with terminally radioiodinated fatty acid analogues (FFA 123 I) were evaluated for the noninvasive assessment of regional myocardial fatty acid metabolism during ischaemia. Decreased uptake of tracer and delayed clearance of activity in the ischaemic myocardium were reported for both 11 C- and 123 I-labelled compounds. However, since during ischaemia both myocardial blood flow and oxidative metabolism are reduced concomitantly, either factor can be responsible for the changes observed. Experimental preparations in which fatty acid metabolism can be modified independently of flow are helpful for the characterization of the relationship between metabolism and myocardial kinetics of labelled fatty acids. Results obtained during flow-independent inhibition of fatty acid oxidation include the following observations: - In dogs with controlled coronary perfusion the rate of clearance of palmitate 11 C-activity is decreased during diminished delivery of oxygen, regardless of whether myocardial perfusion is concomitantly reduced or not. - In isolated rabbit hearts perfused at normal flow, the extraction of FFA 123 I is decreased during hypoxia. - During pharmacological inhibition of fatty acid oxidation the deiodination of FFA 123 I is markedly reduced in rat hearts in vivo and in vitro. (orig.)

  19. When the kids conquered the kitchen

    DEFF Research Database (Denmark)

    Wistoft, Karen; Qvortrup, Lars

    2017-01-01

    Since the first Danish children's cookbook was published in 1847, cooking has been taught to Danish children. The objective of this article is to present a historical based analysis of Danish children's cookbooks from 1971-2016 with a perspective into the development of the New Nordic Kitchen. Al...

  20. Mobile and context: divide or conquer?

    CSIR Research Space (South Africa)

    Botha, Adèle

    2010-05-01

    Full Text Available The interdisciplinary field of Human Computer Interaction (HCI), having barely matured past its adolescent shoes, now faces the challenge of meaningfully integrating Mobile Human Computer Interaction (MHCI). MHCI however, when viewed as an emerging...

  1. Divide and conquer: enriching environmental sequencing data.

    Directory of Open Access Journals (Sweden)

    Anne Bergeron

    2007-09-01

    Full Text Available In environmental sequencing projects, a mix of DNA from a whole microbial community is fragmented and sequenced, with one of the possible goals being to reconstruct partial or complete genomes of members of the community. In communities with high diversity of species, a significant proportion of the sequences do not overlap any other fragment in the sample. This problem will arise not only in situations with a relatively even distribution of many species, but also when the community in a particular environment is routinely dominated by the same few species. In the former case, no genomes may be assembled at all, while in the latter case a few dominant species in an environment will always be sequenced at high coverage to the detriment of coverage of the greater number of sparse species.Here we show that, with the same global sequencing effort, separating the species into two or more sub-communities prior to sequencing can yield a much higher proportion of sequences that can be assembled. We first use the Lander-Waterman model to show that, if the expected percentage of singleton sequences is higher than 25%, then, under the uniform distribution hypothesis, splitting the community is always a wise choice. We then construct simulated microbial communities to show that the results hold for highly non-uniform distributions. We also show that, for the distributions considered in the experiments, it is possible to estimate quite accurately the relative diversity of the two sub-communities.Given the fact that several methods exist to split microbial communities based on physical properties such as size, density, surface biochemistry, or optical properties, we strongly suggest that groups involved in environmental sequencing, and expecting high diversity, consider splitting their communities in order to maximize the information content of their sequencing effort.

  2. Divide and conquer? Infection dynamics in metapopulations

    NARCIS (Netherlands)

    Jesse, M.

    2012-01-01

    Persistence of infectious agents in populations is an important issue in epidemiology. It is often assumed that spatial fragmentation of a population of hosts, in a so-called metapopulation, increases the probability of persistence of the infectious agents, and that increased movement of hosts

  3. Robots Conquering the Homeland of the Vikings

    DEFF Research Database (Denmark)

    Agger Nielsen, Jeppe; Sigh, Anne; Andersen, Kim Normann

    The movement of robots from the production line to the service sector provides a protein solution to innovate and transform public service delivery. However, although robots increasingly are adopted in public service delivery (e.g., in healthcare and eldercare) as an alternative to traditional...... labor intensive services, little is known about their impact on organizations work processes, and how key stakeholders react toward robots. On this backdrop, this single case study investigates implementation and use of robot vacuum cleaners in Danish eldercare at the local government level. Using...... an extended version of the technological frame concept, this paper illustrates how technologist, managers, frontline staff and clients have different perceptions towards robot vacuum cleaning. The technologist and managers praise the new innovation for facilitating savings on the current accounts. By contrast...

  4. Kubilius conquers America / Rokas M. Tracevskis

    Index Scriptorium Estoniae

    Tracevskis, Rokas M.

    2010-01-01

    5.- 9. maini kestnud Ameerika Ühendriikide visiidi ajal kohtus Leedu peaminister Andrius Kubilius riigisekretäri Hillary Rodham Clintoniga, kellega räägiti riikidevahelistest suhetest, CIA salavanglast ja Egle Kusaitest, kes väidetavalt plaanis Venemaa sõjalistel objektidel läbi viia terrorirünnakud. Andrius Kubilius kohtus ka IBMi esindajatega. IBM plaanib rajada Leetu uurimiskeskuse

  5. Conquering the Pumpkin Effect: A Lighting Alternative.

    Science.gov (United States)

    Stanley, Gary B.

    1993-01-01

    Turning off all the interior and exterior lighting when school buildings are closed saves money. In a small Illinois school district, nearly $14,000 were saved in electrical expenditures for six buildings. Another Illinois district currently has 19 of its 32 buildings blacked out at night and saves over $150,000 annually. Vandalism and loitering…

  6. Fascioliasis: can Cuba conquer this emerging parasitosis?

    Science.gov (United States)

    Rojas, Lázara; Vazquez, Antonio; Domenech, Ingrid; Robertson, Lucy J

    2010-01-01

    Fascioliasis, an emerging parasitic infection, impacts significantly on both veterinary and human health worldwide. Endemic foci are not limited only to areas of extensive livestock farming, but owing to the parasite's abilities to colonise new intermediate hosts and adapt to new environments, also occur in other places, including Cuba. In Cuba, despite a high prevalence of fascioliasis in livestock, and the widespread occurrence of two potential intermediate hosts, human infection has decreased steadily over the past 10 years. In other parts of the world, human fascioliasis is apparently becoming more frequent. Problems in counteracting the spread of fascioliasis, and approaches used in Cuba to limit zoonotic transmission are discussed, with emphasis on diagnostic and treatment problems, malacological initiatives, and the importance of an integrated control programme. Such programmes may be of benefit in other countries where the prevalence of human fascioliasis is increasing, and lessons may perhaps be learned from the Cuban approach. Copyright 2009 Elsevier Ltd. All rights reserved.

  7. Combine and conquer: Relating BIP and Reo

    NARCIS (Netherlands)

    K.P.C. Dokter (Kasper); S.-S.T.Q. Jongmans (Sung-Shik); F. Arbab (Farhad); S. Bliudze (Simon)

    2017-01-01

    textabstractCoordination languages simplify design and development of concurrent systems. Particularly, exogenous coordination languages, like BIP and Reo, enable system designers to express the interactions among components in a system explicitly. A formal relation between exogenous coordination

  8. Conquering fatigue: the battle for engagement

    NARCIS (Netherlands)

    J.F. Hopstaken (Jesper)

    2016-01-01

    markdownabstractThe central aim of this dissertation was to examine how motivation influences fatigue and through what psychophysiological mechanisms it influences cognition. With this aim in mind, task disengagement, which is defined as an affective, cognitive, and motivational state of commitment

  9. Angiopoietin-like 4 mediates PPAR delta effect on lipoprotein lipase-dependent fatty acid uptake but not on beta-oxidation in myotubes.

    Directory of Open Access Journals (Sweden)

    Marius R Robciuc

    Full Text Available Peroxisome proliferator-activated receptor (PPAR delta is an important regulator of fatty acid (FA metabolism. Angiopoietin-like 4 (Angptl4, a multifunctional protein, is one of the major targets of PPAR delta in skeletal muscle cells. Here we investigated the regulation of Angptl4 and its role in mediating PPAR delta functions using human, rat and mouse myotubes. Expression of Angptl4 was upregulated during myotubes differentiation and by oleic acid, insulin and PPAR delta agonist GW501516. Treatment with GW501516 or Angptl4 overexpression inhibited both lipoprotein lipase (LPL activity and LPL-dependent uptake of FAs whereas uptake of BSA-bound FAs was not affected by either treatment. Activation of retinoic X receptor (RXR, PPAR delta functional partner, using bexarotene upregulated Angptl4 expression and inhibited LPL activity in a PPAR delta dependent fashion. Silencing of Angptl4 blocked the effect of GW501516 and bexarotene on LPL activity. Treatment with GW501516 but not Angptl4 overexpression significantly increased palmitate oxidation. Furthermore, Angptl4 overexpression did not affect the capacity of GW501516 to increase palmitate oxidation. Basal and insulin stimulated glucose uptake, glycogen synthesis and glucose oxidation were not significantly modulated by Angptl4 overexpression. Our findings suggest that FAs-PPARdelta/RXR-Angptl4 axis controls the LPL-dependent uptake of FAs in myotubes, whereas the effect of PPAR delta activation on beta-oxidation is independent of Angptl4.

  10. HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in Type 2 diabetic mice and in palmitate-treated HepG2 cells.

    Science.gov (United States)

    Wei, Shengnan; Zhang, Ming; Yu, Yang; Xue, Huan; Lan, Xiaoxin; Liu, Shuping; Hatch, Grant; Chen, Li

    2016-11-15

    Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells. CPT-1 and phosphorylated ACCα expression were significantly decreased in livers of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. In contrast, expression of miR-122, HNF-4α, PEPCK, G6Pase, SREBP-1, FAS-1 and ACCα were significantly elevated in liver of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. Expression of HNF-4α increased whereas siRNA knockdown of HNF-4α decreased miR-122 levels in HepG2 cells compared to controls. In addition, expression of HNF-4α in HepG2 cells increased PEPCK, G6Pase, SREBP-1, FAS-1, ACCα mRNA and protein expression and decreased CPT-1 and p-ACCα mRNA and protein expression compared to controls. Addition of miR-122 inhibitors attenuated the HNF-4α mediated effect on expression of these gluconeogenic and lipid metabolism proteins. The results indicate that HNF-4α regulated miR-122 contributes to development of the gluconeogenic and lipid metabolism alterations observed in Type 2 diabetic mice and in palmitate-treated HepG2 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wanlu [Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Tang, Zhuqi; Zhu, Xiaohui [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China); Xia, Nana; Zhao, Yun; Wang, Suxin [Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Cui, Shiwei, E-mail: neifenmicui@163.com [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China); Wang, Cuifang, E-mail: binghuodinghuo@163.com [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China)

    2015-11-20

    High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion of TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway. - Highlights: • TRAF1 accelerated PA-induced IR in HepG2 cells mediated through NF-κB signaling. • Knockdown of TRAF1 alleviated PA-induced IR in HepG2 cells. • Knockdown of TRAF1 alleviated PA-induced lipid accumulation in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced suppression of glucose uptake in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced gluconeogenesis in HepG2 cells.

  12. TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway

    International Nuclear Information System (INIS)

    Zhang, Wanlu; Tang, Zhuqi; Zhu, Xiaohui; Xia, Nana; Zhao, Yun; Wang, Suxin; Cui, Shiwei; Wang, Cuifang

    2015-01-01

    High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion of TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway. - Highlights: • TRAF1 accelerated PA-induced IR in HepG2 cells mediated through NF-κB signaling. • Knockdown of TRAF1 alleviated PA-induced IR in HepG2 cells. • Knockdown of TRAF1 alleviated PA-induced lipid accumulation in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced suppression of glucose uptake in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced gluconeogenesis in HepG2 cells.

  13. Avaliação da estabilidade oxidativa do óleo bruto de açaí (Euterpe oleracea na presença de compostos fenólicos puros ou de extratos vegetais amazônicos Evaluation of oxidative stability of crude açai (Euterpe oleracea oil in the presence of pure phenolic compounds or Amazonian plant extracts

    Directory of Open Access Journals (Sweden)

    Jonas Joaquim Mangabeira da Silva

    2013-01-01

    Full Text Available A final 241 µM of ascorbyl palmitate and 555 µM of the following antioxidants separately: BHA, myricetin and quercetin standards, and extracts of Byrsonima crassifolia, Inga edulis or Euterpe oleracea, were added to crude açai oil and submitted to the oxidation process at 60 ºC for 11 days. Among the antioxidants used, only the myricetin standard showed the ability to defer the oxidation process until the third day of treatment. B. crassifolia, I. edulis and E. oleracea extracts showed no preventive capacity against the oxidation process, despite their high concentration phenolic compounds and antioxidant activities.

  14. Selective oxidation

    International Nuclear Information System (INIS)

    Cortes Henao, Luis F.; Castro F, Carlos A.

    2000-01-01

    It is presented a revision and discussion about the characteristics and factors that relate activity and selectivity in the catalytic and not catalytic partial oxidation of methane and the effect of variables as the temperature, pressure and others in the methane conversion to methanol. It thinks about the zeolites use modified for the catalytic oxidation of natural gas

  15. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to beta-palmitate and contribution to softening of stools pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    2014-01-01

    Following an application from Specialised Nutrition Europe (formerly IDACE), submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked...... to deliver an opinion on the scientific substantiation of a health claim related to beta-palmitate and contribution to softening of stools. The food constituent, beta-palmitate, that is the subject of the health claim, is sufficiently characterised. Contribution to softening of stools is a beneficial...... physiological effect for infants. In weighing the evidence the Panel took into account that, out of two human intervention studies with important methodological limitations, one suggested a stool-softening effect of beta-palmitate whereas the second did not, that one animal study did not support a stool...

  16. Efficacy and safety of paliperidone palmitate three-monthly formulation in East Asian patients with schizophrenia: subgroup analysis of a global, randomized, double-blind, Phase III, noninferiority study

    Directory of Open Access Journals (Sweden)

    Savitz AJ

    2017-08-01

    Full Text Available Adam J Savitz,1 Haiyan Xu,2 Srihari Gopal,1 Isaac Nuamah,2 Paulien Ravenstijn,3 David Hough,1 Maju Mathews,4 Yu Feng,5 Lu Yu,6 Masayoshi Takahashi,7 Dennis Liu,8 Gang Wang,9 Jin-Sang Yoon,10 Jiahn-Jyh Chen11 1Department of Central Nervous System, 2Department of Clinical Biostatistics, Janssen Research & Development, LLC, Titusville, NJ, USA; 3Department of Clinical Pharmacology, Janssen Research & Development, Beerse, Belgium; 4Global Medical Affairs, Neurosciences, Janssen Research & Development, NY, USA; 5Medical Affairs, Neurosciences, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 6Department of Clinical Development, Janssen Research & Development, Beijing, China; 7Department of Central Nervous System, Janssen Pharmaceutical KK, Tokyo, Japan; 8Playford Community Team, Northern Adelaide Local Health Network, Adelaide, SA, Australia; 9National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Affiliated Capital University of Medical Science, Beijing, China; 10Department of Psychiatry, Chonnam National University Hospital, Gwangju, South Korea; 11Department of Geriatric Psychiatry, Taoyuan Mental Hospital, Taoyuan, Taiwan Objective: To demonstrate the efficacy and safety of paliperidone palmitate three-monthly (PP3M formulation in an East Asian population with schizophrenia by subgroup analysis of a double-blind (DB, multicenter, noninferiority study. Patients and methods: Of 1,429 patients who entered the open-label (OL phase, 510 were East Asian (China: 296 [58%], Japan: 175 [34%], South Korea: 19 [4%] and Taiwan: 20 [4%]. In the 17-week OL phase, patients received paliperidone palmitate once-monthly (PP1M formulation on day 1 (150 mg eq., day 8 (100 mg eq. and once-monthly thereafter (50–150 mg eq., flexible. Following the OL phase, patients (n=344 East Asian entered DB phase and were randomized (1:1 to PP1M (n=174 or PP3M (n=170. Primary efficacy endpoint was the percentage of patients who

  17. A new method to determine oxidative stability of vegetable fats and oils at simulated frying temperature

    Directory of Open Access Journals (Sweden)

    Gertz Christian

    2001-01-01

    Full Text Available A new procedure at simulated frying conditions in our laboratory was developed to monitor frying stability of fats and oils. Water-conditioned silica was prepared and added to the fresh vegetable oil, which was heated for two hours at 170°C. The oil stability at frying temperature was then evaluated by determining the amount of formed dimeric triglycerides The results obtained showed that the stability of the vegetable oils at frying temperature could not be explained by the fatty acid composition alone. Corn oil was observed to be more stable than soybean oil, and rapeseed oil was better than olive oil. It was also observed that crude, non-refined oils were found to have a better heat stability than refin-ed oils. To estimate the effectiveness of synthetic and naturally occurring antioxidants, namely various tocopherols, tocopherol acetate and phytosterol fractions, phenolic compounds like quercetin, oryzanol, ferulic acid, gallates, BHT, BHA and other compounds like ascorbic acid 6-palmitate and squalene were added to refined sunflower and rape seed oil, and their oxidative stability at elevated temperature (OSET values determined. Both linoleic and oleic rich oils gave comparable results for the activity of the various compounds. alpha-tocopherol, tocopherol esters and BHA had low effects on oil stability at frying temperature, while ascorbyl palmitate and some phytosterol fractions were found to have the most stabilizing activity under frying conditions.

  18. Anodic oxidation

    CERN Document Server

    Ross, Sidney D; Rudd, Eric J; Blomquist, Alfred T; Wasserman, Harry H

    2013-01-01

    Anodic Oxidation covers the application of the concept, principles, and methods of electrochemistry to organic reactions. This book is composed of two parts encompassing 12 chapters that consider the mechanism of anodic oxidation. Part I surveys the theory and methods of electrochemistry as applied to organic reactions. These parts also present the mathematical equations to describe the kinetics of electrode reactions using both polarographic and steady-state conditions. Part II examines the anodic oxidation of organic substrates by the functional group initially attacked. This part particular

  19. Magnesium Oxide

    Science.gov (United States)

    Magnesium is an element your body needs to function normally. Magnesium oxide may be used for different reasons. Some people use it as ... one to four times daily depending on which brand is used and what condition you have. Follow ...

  20. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Osredkar Joško

    2012-05-01

    Full Text Available The human organism is exposed to the influence of various forms of stress, either physical, psychological or chemical, which all have in common that they may adversely affect our body. A certain amount of stress is always present and somehow directs, promotes or inhibits the functioning of the human body. Unfortunately, we are now too many and too often exposed to excessive stress, which certainly has adverse consequences. This is especially true for a particular type of stress, called oxidative stress. All aerobic organisms are exposed to this type of stress because they produce energy by using oxygen. For this type of stress you could say that it is rather imperceptibly involved in our lives, as it becomes apparent only at the outbreak of certain diseases. Today we are well aware of the adverse impact of radicals, whose surplus is the main cause of oxidative stress. However, the key problem remains the detection of oxidative stress, which would allow us to undertake timely action and prevent outbreak of many diseases of our time. There are many factors that promote oxidative stress, among them are certainly a fast lifestyle and environmental pollution. The increase in oxidative stress can also trigger intense physical activity that is directly associated with an increased oxygen consumption and the resulting formation of free radicals. Considering generally positive attitude to physical activity, this fact may seem at first glance contradictory, but the finding has been confimed by several studies in active athletes. Training of a top athlete daily demands great physical effort, which is also reflected in the oxidative state of the organism. However, it should be noted that the top athletes in comparison with normal individuals have a different defense system, which can counteract the negative effects of oxidative stress. Quite the opposite is true for irregular or excessive physical activity to which the body is not adapted.

  1. Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

    Science.gov (United States)

    Wang, Shudong; Gu, Junlian; Xu, Zheng; Zhang, Zhiguo; Bai, Tao; Xu, Jianxiang; Cai, Jun; Barnes, Gregory; Liu, Qiu-Ju; Freedman, Jonathan H; Wang, Yonggang; Liu, Quan; Zheng, Yang; Cai, Lu

    2017-06-01

    Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Oxidation catalyst

    Science.gov (United States)

    Ceyer, Sylvia T.; Lahr, David L.

    2010-11-09

    The present invention generally relates to catalyst systems and methods for oxidation of carbon monoxide. The invention involves catalyst compositions which may be advantageously altered by, for example, modification of the catalyst surface to enhance catalyst performance. Catalyst systems of the present invention may be capable of performing the oxidation of carbon monoxide at relatively lower temperatures (e.g., 200 K and below) and at relatively higher reaction rates than known catalysts. Additionally, catalyst systems disclosed herein may be substantially lower in cost than current commercial catalysts. Such catalyst systems may be useful in, for example, catalytic converters, fuel cells, sensors, and the like.

  3. Effect of C2 ceramide on the inositol phospholipid metabolism (uptake of 32P, 3H-serine and 3H-palmitic acid) and apoptosis-related morphological changes in Tetrahymena

    International Nuclear Information System (INIS)

    Kovacs, P.; Hegyesi, H.; Koehidai, L.; Nemes, P.; Csaba, G.

    1999-01-01

    Sphingomyelin metabolites have significant role in the regulation of many life processes of mammalian cells. In the present experiments the influence of phospholipid turnover and apoptosis related morphologic signs by one of this metabolite, C 2 ceramide was studied, and compared to the control, untreated cells, in the unicellular Tetrahymena. The incorporation of phospholipid head group components (serine, phosphorus) show a clear time-dependence; while the incorporation of fatty acid component (palmitic acid) is very fast: no significant alterations were found between 5- and 60-min incubations. C 2 ceramide treatment didn't alter 3 H-palmitic acid incorporation into phospholipids, however 3 H-serine incorporation was mainly inhibited. The amount of total incorporated 32 P was also decreased, on the other hand the lover concentration C 2 ceramide (10 μM) elevated the synthesis of inositol phospholipids. The higher concentration of C 2 ceramide (50 μM) had inhibitory effect on the synthesis of each phospholipids examined. This means that in the presence of the C 2 ceramide the synthesis, recovery and turnover of phospholipids, participating in signal transduction, are altered. However these observations were based the uptake of labeled phospholipid precursors, which gives information on the dynamics of the process, without using lipid mass measurements. C 2 ceramide also caused the rounding off the cells, DNA degradation and nuclear condensation. These latter observations point to morphological signs of apoptosis. The results call attention to the role of sphingomyelin metabolites on signalization of unicellulars, to the cross-talk between the inositol phospholipids and sphingomyelin metabolites, and the role of these molecules in the apoptotic processes at a low evolutionary level. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  4. Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2017-01-01

    Full Text Available Youwen Zhang, Deyin Tong, Daobiao Che, Bing Pei, Xiaodong Xia, Gaofeng Yuan, Xin Jin Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People’s Republic of China Abstract: The roles of ginsenoside compound K (CK in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 µg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects. Keywords: ginsenoside CK, ascorbyl palmitate, TPGS, mixed micelles, anti-tumor therapy

  5. Short-term starvation is a strategy to unravel the cellular capacity of oxidizing specific exogenous/endogenous substrates in mitochondria.

    Science.gov (United States)

    Zeidler, Julianna D; Fernandes-Siqueira, Lorena O; Carvalho, Ana S; Cararo-Lopes, Eduardo; Dias, Matheus H; Ketzer, Luisa A; Galina, Antonio; Da Poian, Andrea T

    2017-08-25

    Mitochondrial oxidation of nutrients is tightly regulated in response to the cellular environment and changes in energy demands. In vitro studies evaluating the mitochondrial capacity of oxidizing different substrates are important for understanding metabolic shifts in physiological adaptations and pathological conditions, but may be influenced by the nutrients present in the culture medium or by the utilization of endogenous stores. One such influence is exemplified by the Crabtree effect (the glucose-mediated inhibition of mitochondrial respiration) as most in vitro experiments are performed in glucose-containing media. Here, using high-resolution respirometry, we evaluated the oxidation of endogenous or exogenous substrates by cell lines harboring different metabolic profiles. We found that a 1-h deprivation of the main energetic nutrients is an appropriate strategy to abolish interference of endogenous or undesirable exogenous substrates with the cellular capacity of oxidizing specific substrates, namely glutamine, pyruvate, glucose, or palmitate, in mitochondria. This approach primed mitochondria to immediately increase their oxygen consumption after the addition of the exogenous nutrients. All starved cells could oxidize exogenous glutamine, whereas the capacity for oxidizing palmitate was limited to human hepatocarcinoma Huh7 cells and to C2C12 mouse myoblasts that differentiated into myotubes. In the presence of exogenous glucose, starvation decreased the Crabtree effect in Huh7 and C2C12 cells and abrogated it in mouse neuroblastoma N2A cells. Interestingly, the fact that the Crabtree effect was observed only for mitochondrial basal respiration but not for the maximum respiratory capacity suggests it is not caused by a direct effect on the electron transport system. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. RNA oxidation

    DEFF Research Database (Denmark)

    Kjaer, L. K.; Cejvanovic, V.; Henriken, T.

    2015-01-01

    .9 significant hazard ratio for death compared with the quartile with the lowest 8oxoGuo excretion when adjusted for age, sex, BMI, smoker status, s-HbA1c, urine protein excretion and s-cholesterol. We conclude that it is now established that RNA oxidation is an independent risk factor for death in type 2...

  7. Radiolytic oxidation

    International Nuclear Information System (INIS)

    Burns, W.G.; Ewart, F.T.; Hobley, J.; Smith, A.J.; Walters, W.S.; Williams, S.J.

    1991-01-01

    Work under the Radiolytic Oxidation Contract from 1986 until April 1989 is reported. The effects of alpha- and gamma-irradiation on the chemistries of plutonium, neptunium and technetium, under conditions representative of the near fields of intermediate and high level waste repositories, were investigated. Gamma-radiolysis of Np (IV) results in oxidation in solutions below pH 12. Solutions of Tc (VII) are reduced to Tc (IV) by gamma-irradiation in contact with blast furnace slag/ordinary Portland cement under an inert atmosphere but not when in contact with pulverized fuel ash/ordinary Portland cement. Tc (IV) is shown to be susceptible to oxidation by the products of the alpha-radiolysis of water. The results of 'overall effects' experiments, which combined representative components of typical ILW or HLW near fields, supported these observations and also showed enhanced plutonium concentrations in alpha-irradiated, HLW simulations. Mathematical models of the behaviour of plutonium and neptunium during gamma-radiolysis have been developed and indicate that oxidation to Pu (VI) is possible at dose rates typical of those expected for HLW. Simulations at ILW dose rates have indicated some effect upon the speciation of neptunium. Laboratory studies of the gamma-irradiation of Np (IV) in bentonite-equilibrated water have also been modelled. Computer code used: PHREEQE, 8 Figs.; 48 Tabs.; 38 refs

  8. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2012-01-01

    Full Text Available The unceasing need for oxygen is in contradiction to the fact that it is in fact toxic to mammals. Namely, its monovalent reduction can have as a consequence the production of short-living, chemically very active free radicals and certain non-radical agents (nitrogen-oxide, superoxide-anion-radicals, hydroxyl radicals, peroxyl radicals, singlet oxygen, peroxynitrite, hydrogen peroxide, hypochlorous acid, and others. There is no doubt that they have numerous positive roles, but when their production is stepped up to such an extent that the organism cannot eliminate them with its antioxidants (superoxide-dismutase, glutathione-peroxidase, catalase, transferrin, ceruloplasmin, reduced glutathion, and others, a series of disorders is developed that are jointly called „oxidative stress.“ The reactive oxygen species which characterize oxidative stress are capable of attacking all main classes of biological macromolecules, actually proteins, DNA and RNA molecules, and in particular lipids. The free radicals influence lipid peroxidation in cellular membranes, oxidative damage to DNA and RNA molecules, the development of genetic mutations, fragmentation, and the altered function of various protein molecules. All of this results in the following consequences: disrupted permeability of cellular membranes, disrupted cellular signalization and ion homeostasis, reduced or loss of function of damaged proteins, and similar. That is why the free radicals that are released during oxidative stress are considered pathogenic agents of numerous diseases and ageing. The type of damage that will occur, and when it will take place, depends on the nature of the free radicals, their site of action and their source. [Projekat Ministarstva nauke Republike Srbije, br. 173034, br. 175061 i br. 31085

  9. Control of lipid oxidation in extruded salmon jerky snacks.

    Science.gov (United States)

    Kong, Jian; Perkins, L Brian; Dougherty, Michael P; Camire, Mary Ellen

    2011-01-01

    A shelf-life study was conducted to evaluate the effect of antioxidants on oxidative stability of extruded jerky-style salmon snacks. Deterioration of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) due to lipid oxidation is a major concern for this healthy snack. A control jerky with no added antioxidants and 4 jerkies with antioxidants (rosemary, mixed tocopherols, tertiary butylhydroquinone, and ascorbyl palmitate) added as 0.02% of the lipid content were extruded in duplicate in a Coperion ZSK-25 twin screw extruder. Salmon jerkies from each formulation were placed in 3 mil barrier pouches, flushed with nitrogen, and stored at 35 °C and 75% relative humidity. Lipid oxidation was evaluated as by peroxide value and malonaldehyde content. Other chemical analyses included total fatty acid composition, lipid content, moisture, water activity, pH, and salt. Astaxanthin and CIE L*, a*, b* color were also analyzed at 4-wk intervals. Rosemary inhibited peroxide formation better than did other antioxidants at week 8; no treatment inhibited malonaldehyde levels. All jerkies had lower astaxanthin levels after 8 wk, but rosemary-treated jerky had higher pigment concentrations than did the control at weeks 4 and 8. Protection of omega-3 lipids in these extruded jerkies must be improved to offer consumers a convenient source of these healthful lipids. Practical Application: Salmon flesh can be extruded to produce a jerky that provides 410 mg of omega-3 lipids per serving. Natural antioxidants such as rosemary should be added at levels over 0.02% of the lipid content to help control lipid oxidation. Astaxanthin and CIE a* values correlated well with lipid stability and could be used to monitor quality during storage if initial values are known.

  10. Cluster Differentiating 36 (CD36) Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart.

    Science.gov (United States)

    Gharib, Mohamed; Tao, Huan; Fungwe, Thomas V; Hajri, Tahar

    2016-01-01

    Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS) leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36) protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear. The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity. Studies were conducted in control (Lean), obese leptin-deficient (Lepob/ob) and leptin-CD36 double null (Lepob/obCD36-/-) mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA) uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase-dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity. CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress.

  11. Medium chain acylcarnitines dominate the metabolite pattern in humans under moderate intensity exercise and support lipid oxidation.

    Directory of Open Access Journals (Sweden)

    Rainer Lehmann

    Full Text Available BACKGROUND: Exercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise. METHODOLOGY AND PRINCIPAL FINDINGS: First, we investigated plasma from healthy human subjects who completed two independent running studies under moderate, predominantly aerobic conditions. Samples obtained prior to and immediately after running and then 3 and 24 h into the recovery phase were analyzed by a non-targeted (NT- metabolomics approach applying liquid chromatography-qTOF-mass spectrometry. Under these conditions medium and long chain acylcarnitines were found to be the most discriminant plasma biomarkers of moderately intense exercise. Immediately after a 60 min (at 93% V(IAT or a 120 min run (at 70% V(IAT a pronounced, transient increase dominated by octanoyl-, decanoyl-, and dodecanoyl-carnitine was observed. The release of acylcarnitines as intermediates of partial beta-oxidation was verified in skeletal muscle cell culture experiments by probing (13C-palmitate metabolism. Further investigations in primary human myotubes and mouse muscle tissue revealed that octanoyl-, decanoyl-, and dodecanoyl-carnitine were able to support the oxidation of palmitate, proving more effective than L-carnitine. CONCLUSIONS: Medium chain acylcarnitines were identified and characterized by a functional metabolomics approach as the dominating biomarkers during a moderately intense exercise bout possessing the power to support fat oxidation. This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.

  12. AMPK activation through mitochondrial regulation results in increased substrate oxidation and improved metabolic parameters in models of diabetes.

    Directory of Open Access Journals (Sweden)

    Yonchu Jenkins

    Full Text Available Modulation of mitochondrial function through inhibiting respiratory complex I activates a key sensor of cellular energy status, the 5'-AMP-activated protein kinase (AMPK. Activation of AMPK results in the mobilization of nutrient uptake and catabolism for mitochondrial ATP generation to restore energy homeostasis. How these nutrient pathways are affected in the presence of a potent modulator of mitochondrial function and the role of AMPK activation in these effects remain unclear. We have identified a molecule, named R419, that activates AMPK in vitro via complex I inhibition at much lower concentrations than metformin (IC50 100 nM vs 27 mM, respectively. R419 potently increased myocyte glucose uptake that was dependent on AMPK activation, while its ability to suppress hepatic glucose production in vitro was not. In addition, R419 treatment of mouse primary hepatocytes increased fatty acid oxidation and inhibited lipogenesis in an AMPK-dependent fashion. We have performed an extensive metabolic characterization of its effects in the db/db mouse diabetes model. In vivo metabolite profiling of R419-treated db/db mice showed a clear upregulation of fatty acid oxidation and catabolism of branched chain amino acids. Additionally, analyses performed using both (13C-palmitate and (13C-glucose tracers revealed that R419 induces complete oxidation of both glucose and palmitate to CO2 in skeletal muscle, liver, and adipose tissue, confirming that the compound increases mitochondrial function in vivo. Taken together, our results show that R419 is a potent inhibitor of complex I and modulates mitochondrial function in vitro and in diabetic animals in vivo. R419 may serve as a valuable molecular tool for investigating the impact of modulating mitochondrial function on nutrient metabolism in multiple tissues and on glucose and lipid homeostasis in diabetic animal models.

  13. Mixed fuel strategy for carbon deposition mitigation in solid oxide fuel cells at intermediate temperatures.

    Science.gov (United States)

    Su, Chao; Chen, Yubo; Wang, Wei; Ran, Ran; Shao, Zongping; Diniz da Costa, João C; Liu, Shaomin

    2014-06-17

    In this study, we propose and experimentally verified that methane and formic acid mixed fuel can be employed to sustain solid oxide fuel cells (SOFCs) to deliver high power outputs at intermediate temperatures and simultaneously reduce the coke formation over the anode catalyst. In this SOFC system, methane itself was one part of the fuel, but it also played as the carrier gas to deliver the formic acid to reach the anode chamber. On the other hand, the products from the thermal decomposition of formic acid helped to reduce the carbon deposition from methane cracking. In order to clarify the reaction pathways for carbon formation and elimination occurring in the anode chamber during the SOFC operation, O2-TPO and SEM analysis were carried out together with the theoretical calculation. Electrochemical tests demonstrated that stable and high power output at an intermediate temperature range was well-maintained with a peak power density of 1061 mW cm(-2) at 750 °C. With the synergic functions provided by the mixed fuel, the SOFC was running for 3 days without any sign of cell performance decay. In sharp contrast, fuelled by pure methane and tested at similar conditions, the SOFC immediately failed after running for only 30 min due to significant carbon deposition. This work opens a new way for SOFC to conquer the annoying problem of carbon deposition just by properly selecting the fuel components to realize their synergic effects.

  14. Can microbial cells develop resistance to oxidative stress in antimicrobial photodynamic inactivation?

    Science.gov (United States)

    Kashef, Nasim; Hamblin, Michael R

    2017-03-01

    Infections have been a major cause of disease throughout the history of humans on earth. With the introduction of antibiotics, it was thought that infections had been conquered. However, bacteria have been able to develop resistance to antibiotics at an exponentially increasing rate. The growing threat from multi-drug resistant organisms calls for intensive action to prevent the emergence of totally resistant and untreatable infections. Novel, non-invasive, non-antibiotic strategies are needed that act more efficiently and faster than current antibiotics. One promising alternative is antimicrobial photodynamic inactivation (APDI), an approach that produces reactive oxygen species when dyes and light are combined. So far, it has been questionable if bacteria can develop resistance against APDI. This review paper gives an overview of recent studies concerning the susceptibility of bacteria towards oxidative stress, and suggests possible mechanisms of the development of APDI-resistance that should at least be addressed. Some ways to potentiate APDI and also to overcome future resistance are suggested. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Impacto da suplementação com retinil palmitato no pós-parto imediato sobre os níveis de retinol do colostro Impact on colostrum retinol levels of immediate postpartum supplementation with retinyl palmitate

    Directory of Open Access Journals (Sweden)

    Roberto Dimenstein

    2007-07-01

    Full Text Available OBJETIVO: Avaliar o efeito da suplementação com retinil palmitato sobre os níveis de retinol no colostro, investigando a influência de variáveis maternas (idade, tipo de parto e estado nutricional bioquímico sobre esses níveis. MÉTODO:Participaram do estudo 33 nutrizes atendidas na Maternidade Escola Januário Cicco, Estado do Rio Grande do Norte, Brasil. Foram coletadas, nas primeiras horas após o parto, uma amostra de sangue e uma de colostro. Uma nova amostra de colostro foi coletada 6 horas após suplementação materna com 200 000 UI de retinil palmitato. O retinol no sangue e colostro foi determinado por cromatografia líquida de alta eficiência. RESULTADOS: Os níveis médios de retinol no colostro antes da suplementação foram de 110,8 ± 82,3 µg/dL, tendo atingido 164,4 ± 106,5 µg/dL após a suplementação (P OBJECTIVE: To assess the effect of retinyl palmitate supplementation on colostrum retinol levels, investigating the influence of maternal variables (age, type of delivery, and biochemical nutritional status on these levels. METHOD: The study included 33 mothers receiving care at the Januário Cicco Maternity School, in the city of Natal, Rio Grande do Norte, Brazil. In the first hours after delivery, blood and colostrum samples were collected. Another colostrum sample was collected six hours after maternal supplementation with 200 000 IU of retinyl palmitate. Serum and colostrum retinol levels were determined by high-performance liquid chromatography. RESULTS: The mean retinol level in colostrum before the supplementation was 110.8 ± 82.3 µg/dL, and after supplementation it was 164.4 ± 106.5 µg/dL (P < 0.025. Of the 33 mothers, 12 of them either did not respond to supplementation or had an increase of less than 10% in colostrum retinol levels; serum retinol in these women was significantly lower as compared to the responders (P = 0.024. In comparison to women with a normal delivery, the mothers who underwent

  16. PREFACE: Semiconducting oxides Semiconducting oxides

    Science.gov (United States)

    Catlow, Richard; Walsh, Aron

    2011-08-01

    Semiconducting oxides are amongst the most widely studied and topical materials in contemporary condensed matter science, with interest being driven both by the fundamental challenges posed by their electronic and magnetic structures and properties, and by the wide range of applications, including those in catalysis and electronic devices. This special section aims to highlight recent developments in the physics of these materials, and to show the link between developing fundamental understanding and key application areas of oxide semiconductors. Several aspects of the physics of this wide and expanding range of materials are explored in this special section. Transparent semiconducting oxides have a growing role in several technologies, but challenges remain in understanding their electronic structure and the physics of charge carriers. A related problem concerns the nature of redox processes and the reactions which interconvert defects and charge carriers—a key issue which may limit the extent to which doping strategies may be used to alter electronic properties. The magnetic structures of the materials pose several challenges, while surface structures and properties are vital in controlling catalytic properties, including photochemical processes. The field profits from and exploits a wide range of contemporary physical techniques—both experimental and theoretical. Indeed, the interplay between experiment and computation is a key aspect of contemporary work. A number of articles describe applications of computational methods whose use, especially in modelling properties of defects in these materials, has a long and successful history. Several papers in this special section relate to work presented at a symposium within the European Materials Research Society (EMRS) meeting held in Warsaw in September 2010, and we are grateful to the EMRS for supporting this symposium. We would also like to thank the editorial staff of Journal of Physics: Condensed Matter for

  17. Radiometric studies on the oxidation of (I-14C) fatty acids by drug-susceptible and drug-resistant mycobacteria

    International Nuclear Information System (INIS)

    Camargo, E.E.; Kopajtic, T.M.; Hopkins, G.K.; Cannon, N.P.; Wagner Junior, H.N.

    1987-01-01

    A radiometric assay system has been used to study oxidation patterns of (l - 14 C) fatty acids by drug-susceptible and drug-resistant organisms of the genus Mycobacterium (M. tuberculosis - H 37 Rv and Erdman, M. bovis, M. avium, M. intracellulare, M.Kansasii and M. chelonei). The organisms were inoculated in sterile reaction vials containing liquid 7H9 medium, 10% ADC enrichment and 1.0 uli of one of the (l- 14 C) fatty acids (butyric, hexanoic, octanoic, decanoic, lauric, myristic, palmitic, stearic, oleic, linoleic, linolenic). Vials were incubated at 37 0 C and the 14 CO 2 envolved was measured daily for 3 days with a Bactec R-301 instrument. (M.A.C.) [pt

  18. Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids.

    Science.gov (United States)

    Phillips, Paul S; Ciaraldi, Theodore P; Kim, Dong-Lim; Verity, M Anthony; Wolfson, Tanya; Henry, Robert R

    2009-02-01

    Despite exceptional efficacy and safety, fear of muscle toxicity remains a major reason statins are underutilized. Evidence suggests that statin muscle toxicity may be mediated by abnormalities in lipid metabolism. To test the hypothesis that myotubes from patients intolerant of lipid-lowering therapies have abnormal fatty acid oxidation (FAO) responses we compared muscle from 11 subjects with statin intolerance (Intolerant) with muscle from seven statin-naive volunteers undergoing knee arthroplasty (Comparator). Gross muscle pathology was graded and skeletal muscle cell cultures were produced from each subject. FAO was assessed following treatment with increasing statin concentrations. There was no difference in muscle biopsy myopathy scores between the groups. Basal octanoate oxidation was greater in Intolerant than in Comparator subjects (P = 0.03). Lovastatin-stimulated palmitate oxidation tended to be greater for Intolerant compared to Control subjects' myotubes (P = 0.07 for 5 microM and P = 0.06 for 20 microM lovastatin). In conclusion abnormalities in FAO of Intolerant subjects appear to be an intrinsic characteristic of these subjects that can be measured in their cultured myotubes.

  19. Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Nataša Nikolić

    2012-01-01

    Full Text Available We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.

  20. The oxidation; Okislenie

    Energy Technology Data Exchange (ETDEWEB)

    Nikitin, V I

    1961-07-01

    In this chapter of book author determine that alkylene tetra hydro-{gamma}-piron, oxidated by potassium permanganate in all cases of passed oxidation gave oxidation products, confirmatory their structure.

  1. State-of-the-art Sn2+-based ternary oxides as photocatalysts for water splitting: electronic structures and optoelectronic properties

    KAUST Repository

    Noureldine, Dalal

    2016-09-19

    Developing visible light responsive metal oxide photocatalysts is a challenge that must be conquered to achieve high efficiency for water splitting or hydrogen evolution reactions. Valence band engineering is possible by forming ternary oxides using the combination of a metal cation with an s2d10 electronic configuration and a transition metal oxide with a d0 configuration. Many (Sn2+, Bi3+, Pb2+)-based ternary metal oxide photocatalysts have been reported for hydrogen and/or oxygen evolution under visible irradiation. Sn2+-based materials have attracted particular attention because tin is inexpensive, abundant and more environmentally friendly than lead or bismuth. In this review, we provide a fruitful library for Sn2+-based photocatalysts that have been reported to evolve hydrogen using sacrificial reagents, including SnNb2O6, Sn2Nb2O7, SnTaxNb2−xO6, SnTa2O6, Sn2Ta2O7, SnWO4 (α and β phases), SnSb2O6·nH2O, and Sn2TiO4. The synthesis method used in the literature and the resultant morphology and crystal structure of each compound are discussed. The density functional theory (DFT) calculations of the electronic structure and density of states are provided, and the consequent optoelectronic properties such as band gap, nature of the bandgap, dielectric constant, and effective masses are summarized. This review will help highlight the main challenges for Sn2+-based materials.

  2. State-of-the-art Sn2+-based ternary oxides as photocatalysts for water splitting: electronic structures and optoelectronic properties

    KAUST Repository

    Noureldine, Dalal; Takanabe, Kazuhiro

    2016-01-01

    Developing visible light responsive metal oxide photocatalysts is a challenge that must be conquered to achieve high efficiency for water splitting or hydrogen evolution reactions. Valence band engineering is possible by forming ternary oxides using the combination of a metal cation with an s2d10 electronic configuration and a transition metal oxide with a d0 configuration. Many (Sn2+, Bi3+, Pb2+)-based ternary metal oxide photocatalysts have been reported for hydrogen and/or oxygen evolution under visible irradiation. Sn2+-based materials have attracted particular attention because tin is inexpensive, abundant and more environmentally friendly than lead or bismuth. In this review, we provide a fruitful library for Sn2+-based photocatalysts that have been reported to evolve hydrogen using sacrificial reagents, including SnNb2O6, Sn2Nb2O7, SnTaxNb2−xO6, SnTa2O6, Sn2Ta2O7, SnWO4 (α and β phases), SnSb2O6·nH2O, and Sn2TiO4. The synthesis method used in the literature and the resultant morphology and crystal structure of each compound are discussed. The density functional theory (DFT) calculations of the electronic structure and density of states are provided, and the consequent optoelectronic properties such as band gap, nature of the bandgap, dielectric constant, and effective masses are summarized. This review will help highlight the main challenges for Sn2+-based materials.

  3. Jinlida granule inhibits palmitic acid induced-intracellular lipid accumulation and enhances autophagy in NIT-1 pancreatic β cells through AMPK activation.

    Science.gov (United States)

    Wang, Dingkun; Tian, Min; Qi, Yuan; Chen, Guang; Xu, Lijun; Zou, Xin; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2015-02-23

    Jinlida granule (JLDG), composed of seventeen Chinese medical herbs, is a widely used Chinese herbal prescription for treating diabetes mellitus. However, the mechanism underlying this effect remains unclear. To determine the main components in JLDG and to explore the effect of JLDG on autophagy and lipid accumulation in NIT-1 pancreatic β cells exposed to politic acid (PA) through AMP activated protein kinase (AMPK) signaling pathway. JLDG was prepared and the main components contained in the granules were identified by ultra performance liquid chromatography (UPLC) fingerprint. Intracellular lipid accumulation in NIT-1 cells was induced by culturing with medium containing PA. Intracellular lipid droplets were observed by Oil Red O staining and triglyceride (TG) content was measured by colorimetric assay. The formation of autophagosomes was observed under transmission electron microscope. The expression of AMPK and phospho-AMPK (pAMPK) proteins as well as its downstream fatty acid metabolism-related proteins (fatty acid synthase, FAS; acetyl-coA carboxylase, ACC; carnitine acyltransferase 1, CPT-1) and autophagy-related genes (mammal target of rapamycin, mTOR; tuberous sclerosis complex 1, TSC1; microtubule-associated protein 1 light chain 3, LC3-II) were determined by Western blot. The expression of sterol regulating element binding protein 1c (SREBP-1c) mRNA was examined by real time PCR (RT-PCR). Our data showed that JLDG could significantly reduce PA-induced intracellular lipid accumulation in NIT-1 pancreatic β cells. This effect was associated with increased protein expression of pAMPK and AMPK in NIT-1 cells. Treatment with JLDG also decreased the expression of AMPK downstream lipogenic genes (SREBP-1c mRNA, FAS and ACC proteins) whereas increased the expression of fatty acid oxidation gene (CPT-1 protein). Additionally, JLDG-treated cells displayed a markedly increase in the number of autophagosomes which was accompanied by the down-regulation of m

  4. Production and release of acylcarnitines by primary myotubes reflect the differences in fasting fat oxidation of the donors.

    Science.gov (United States)

    Wolf, Magnus; Chen, Shili; Zhao, Xinjie; Scheler, Mika; Irmler, Martin; Staiger, Harald; Beckers, Johannes; de Angelis, Martin Hrabé; Fritsche, Andreas; Häring, Hans-Ulrich; Schleicher, Erwin D; Xu, Guowang; Lehmann, Rainer; Weigert, Cora

    2013-06-01

    Acylcarnitines are biomarkers of incomplete β-oxidation and mitochondrial lipid overload but indicate also high rates of mitochondrial fatty acid oxidation. It is unknown whether the production of acylcarnitines in primary human myotubes obtained from lean, metabolically healthy subjects reflects the fat oxidation in vivo. Our objective was to quantify the acylcarnitine production in myotubes obtained from subjects with low and high fasting respiratory quotient (RQ). Fasting RQ was determined by indirect calorimetry. Muscle biopsies from the vastus lateralis muscle were taken from 6 subjects with low fasting RQ (mean 0.79 ± 0.03) and 6 with high fasting RQ (0.90 ± 0.03), and satellite cells were isolated, cultured, and differentiated to myotubes. Myotubes were cultivated with 125 μM (13)C-labeled palmitate for 30 minutes and 4 and 24 hours. Quantitative profiling of 42 intracellular and 31 extracellular acylcarnitines was performed by stable isotope dilution-based metabolomics analysis by liquid chromatography coupled to mass spectrometry. Myotubes from donors with high fasting RQ produced and released significant higher amounts of medium-chain acylcarnitines. High (13)C8 and (13)C10 acylcarnitine levels in the extracellular compartment correlated with high fasting RQ. The decreased expression of medium-chain acyl-coenzyme A dehydrogenase (MCAD) in these myotubes can explain the higher rate of incomplete fatty acid oxidation. A lower intracellular [(13)C]acetylcarnitine to carnitine and lower intracellular (13)C16/(13)C18 acylcarnitine to carnitine ratio indicate reduced fatty acid oxidation capacity in these myotubes. Mitochondrial DNA content was not different. Acylcarnitine production and release from primary human myotubes of donors with high fasting RQ indicate a reduced fatty acid oxidation capacity and a higher rate of incomplete fatty acid oxidation. Thus, quantitative profiling of acylcarnitine production in human myotubes can be a suitable tool to

  5. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Varma

    2015-06-01

    Full Text Available Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001. However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes.

  6. Thermally exfoliated graphite oxide

    Science.gov (United States)

    Prud'Homme, Robert K. (Inventor); Aksay, Ilhan A. (Inventor); Abdala, Ahmed (Inventor)

    2011-01-01

    A modified graphite oxide material contains a thermally exfoliated graphite oxide with a surface area of from about 300 sq m/g to 2600 sq m/g, wherein the thermally exfoliated graphite oxide displays no signature of the original graphite and/or graphite oxide, as determined by X-ray diffraction.

  7. Bitter melon extract ameliorates palmitate-induced apoptosis via inhibition of endoplasmic reticulum stress in HepG2 cells and high-fat/high-fructose-diet-induced fatty liver

    Directory of Open Access Journals (Sweden)

    Hwa Joung Lee

    2018-03-01

    Full Text Available Background: Bitter melon (BM improves glucose level, lipid homeostasis, and insulin resistance in vivo. However, the preventive mechanism of BM in nonalcoholic fatty liver disease (NAFLD has not been elucidated yet. Aim & Design: To determine the protective mechanism of bitter melon extract (BME, we performed experiments in vitro and in vivo. BME were treated palmitate (PA-administrated HepG2 cells. C57BL/6J mice were divided into two groups: high-fat/high-fructose (HF/HFr without or with BME supplementation (100 mg/kg body weight. Endoplasmic reticulum (ER stress, apoptosis, and biochemical markers were then examined by western blot and real-time PCR analyses. Results: BME significantly decreased expression levels of ER-stress markers (including phospho-eIF2α, CHOP, and phospho-JNK [Jun N-terminal kinases] in PA-treated HepG2 cells. BME also significantly decreased the activity of cleaved caspase-3 (a well known apoptotic-induced molecule and DNA fragmentation. The effect of BME on ER stress–mediated apoptosis in vitro was similarly observed in HF/HFr-fed mice in vivo. BME significantly reduced HF/HFr-induced hepatic triglyceride (TG and serum alanine aminotransferase (ALT as markers of hepatic damage in mice. In addition, BME ameliorated HF/HFr-induced serum TG and serum-free fatty acids. Conclusion: These data indicate that BME has protective effects against ER stress mediated apoptosis in HepG2 cells as well as in HF/HFr-induced fatty liver of mouse. Therefore, BME might be useful for preventing and treating NAFLD.

  8. Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults.

    Science.gov (United States)

    Voon, Phooi Tee; Ng, Tony Kock Wai; Lee, Verna Kar Mun; Nesaretnam, Kalanithi

    2011-12-01

    Dietary fat type is known to modulate the plasma lipid profile, but its effects on plasma homocysteine and inflammatory markers are unclear. We investigated the effects of high-protein Malaysian diets prepared with palm olein, coconut oil (CO), or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease (CVD) in healthy adults. A randomized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects. The 3 test fats, namely palmitic acid (16:0)-rich palm olein (PO), lauric and myristic acid (12:0 + 14:0)-rich CO, and oleic acid (18:1)-rich virgin olive oil (OO), were incorporated at two-thirds of 30% fat calories into high-protein Malaysian diets. No significant differences were observed in the effects of the 3 diets on plasma total homocysteine (tHcy) and the inflammatory markers TNF-α, IL-1β, IL-6, and IL-8, high-sensitivity C-reactive protein, and interferon-γ. Diets prepared with PO and OO had comparable nonhypercholesterolemic effects; the postprandial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower (P diet. Unlike the PO and OO diets, the CO diet was shown to decrease postprandial lipoprotein(a). Diets that were rich in saturated fatty acids prepared with either PO or CO, and an OO diet that was high in oleic acid, did not alter postprandial or fasting plasma concentrations of tHcy and selected inflammatory markers. This trial was registered at clinicaltrials.gov as NCT00941837.

  9. Sequence-specific {sup 1}H, {sup 13}C, and {sup 15}N resonance assignments for intestinal fatty-acid-binding protein complexed with palmitate (15.4 kDA)

    Energy Technology Data Exchange (ETDEWEB)

    Hodsdon, M.E.; Toner, J.J.; Cistola, D.P. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-12-01

    Intestinal fatty-acid-binding protein (I-FABP) belongs to a family of soluble, cytoplasmic proteins that are thought to function in the intracellular transport and trafficking of polar lipids. Individual members of this protein family have distinct specificities and affinities for fatty acids, cholesterol, bile salts, and retinoids. We are comparing several retinol- and fatty-acid-binding proteins from intestine in order to define the factors that control molecular recognition in this family of proteins. We have established sequential resonance assignments for uniformly {sup 13}C/{sup 15}N-enriched I-FABP complexed with perdeuterated palmitate at pH7.2 and 37{degrees}C. The assignment strategy was similar to that introduced for calmodulin. We employed seven three-dimensional NMR experiments to establish scalar couplings between backbone and sidechain atoms. Backbone atoms were correlated using triple-resonance HNCO, HNCA, TOCSY-HMQC, HCACO, and HCA(CO)N experiments. Sidechain atoms were correlated using CC-TOCSY, HCCH-TOCSY, and TOCSY-HMQC. The correlations of peaks between three-dimensional spectra were established in a computer-assisted manner using NMR COMPASS (Molecular Simulations, Inc.) Using this approach, {sup 1}H, {sup 13}C, and {sup 15}N resonance assignments have been established for 120 of the 131 residues of I-FABP. For 18 residues, amide {sup 1}H and {sup 15}N resonances were unobservable, apparently because of the rapid exchange of amide protons with bulk water at pH 7.2. The missing amide protons correspond to distinct amino acid patterns in the protein sequence, which will be discussed. During the assignment process, several sources of ambiguity in spin correlations were observed. To overcome this ambiguity, the additional inter-residue correlations often observed in the HNCA experiment were used as cross-checks for the sequential backbone assignments.

  10. The Enzymatic Oxidation of Graphene Oxide

    Science.gov (United States)

    Kotchey, Gregg P.; Allen, Brett L.; Vedala, Harindra; Yanamala, Naveena; Kapralov, Alexander A.; Tyurina, Yulia Y.; Klein-Seetharaman, Judith; Kagan, Valerian E.; Star, Alexander

    2011-01-01

    Two-dimensional graphitic carbon is a new material with many emerging applications, and studying its chemical properties is an important goal. Here, we reported a new phenomenon – the enzymatic oxidation of a single layer of graphitic carbon by horseradish peroxidase (HRP). In the presence of low concentrations of hydrogen peroxide (~40 µM), HRP catalyzed the oxidation of graphene oxide, which resulted in the formation of holes on its basal plane. During the same period of analysis, HRP failed to oxidize chemically reduced graphene oxide (RGO). The enzymatic oxidation was characterized by Raman, UV-Vis, EPR and FT-IR spectroscopy, TEM, AFM, SDS-PAGE, and GC-MS. Computational docking studies indicated that HRP was preferentially bound to the basal plane rather than the edge for both graphene oxide and RGO. Due to the more dynamic nature of HRP on graphene oxide, the heme active site of HRP was in closer proximity to graphene oxide compared to RGO, thereby facilitating the oxidation of the basal plane of graphene oxide. We also studied the electronic properties of the reduced intermediate product, holey reduced graphene oxide (hRGO), using field-effect transistor (FET) measurements. While RGO exhibited a V-shaped transfer characteristic similar to a single layer of graphene that was attributed to its zero band gap, hRGO demonstrated a p-type semiconducting behavior with a positive shift in the Dirac points. This p-type behavior rendered hRGO, which can be conceptualized as interconnected graphene nanoribbons, as a potentially attractive material for FET sensors. PMID:21344859

  11. Multimillion atom simulations of dynamics of oxidation of an aluminum nanoparticle and nanoindentation on ceramics.

    Science.gov (United States)

    Vashishta, Priya; Kalia, Rajiv K; Nakano, Aiichiro

    2006-03-02

    We have developed a first-principles-based hierarchical simulation framework, which seamlessly integrates (1) a quantum mechanical description based on the density functional theory (DFT), (2) multilevel molecular dynamics (MD) simulations based on a reactive force field (ReaxFF) that describes chemical reactions and polarization, a nonreactive force field that employs dynamic atomic charges, and an effective force field (EFF), and (3) an atomistically informed continuum model to reach macroscopic length scales. For scalable hierarchical simulations, we have developed parallel linear-scaling algorithms for (1) DFT calculation based on a divide-and-conquer algorithm on adaptive multigrids, (2) chemically reactive MD based on a fast ReaxFF (F-ReaxFF) algorithm, and (3) EFF-MD based on a space-time multiresolution MD (MRMD) algorithm. On 1920 Intel Itanium2 processors, we have demonstrated 1.4 million atom (0.12 trillion grid points) DFT, 0.56 billion atom F-ReaxFF, and 18.9 billion atom MRMD calculations, with parallel efficiency as high as 0.953. Through the use of these algorithms, multimillion atom MD simulations have been performed to study the oxidation of an aluminum nanoparticle. Structural and dynamic correlations in the oxide region are calculated as well as the evolution of charges, surface oxide thickness, diffusivities of atoms, and local stresses. In the microcanonical ensemble, the oxidizing reaction becomes explosive in both molecular and atomic oxygen environments, due to the enormous energy release associated with Al-O bonding. In the canonical ensemble, an amorphous oxide layer of a thickness of approximately 40 angstroms is formed after 466 ps, in good agreement with experiments. Simulations have been performed to study nanoindentation on crystalline, amorphous, and nanocrystalline silicon nitride and silicon carbide. Simulation on nanocrystalline silicon carbide reveals unusual deformation mechanisms in brittle nanophase materials, due to

  12. Tin-antimony oxide oxidation catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Frank J. [Open University, Department of Chemistry (United Kingdom)

    1998-12-15

    Tin-antimony oxide catalysts for the selective oxidation of hydrocarbons have been made by precipitation techniques. The dehydration of the amorphous dried precipitate by calcination at increasingly higher temperatures induces the crystallisation of a rutile-related tin dioxide-type phase and the segregation of antimony oxides which volatilise at elevated temperatures. The rutile-related tin dioxide-type phase contains antimony(V) in the bulk and antimony(III) in the surface. Specific catalytic activity for the oxidative dehydrogenation of butene to butadiene is associated with materials with large concentrations of antimony(III) in the surface.

  13. Cold acclimation increases mitochondrial oxidative capacity without inducing mitochondrial uncoupling in goldfish white skeletal muscle

    Directory of Open Access Journals (Sweden)

    Reinaldo Sousa Dos Santos

    2012-11-01

    Goldfish have been used for cold acclimation studies, which have focused on changes in glycolytic and oxidative enzymes or alterations in lipid composition in skeletal muscle. Here we examine the effects of cold acclimation on the functional properties of isolated mitochondria and permeabilized fibers from goldfish white skeletal muscle, focusing on understanding the types of changes that occur in the mitochondrial respiratory states. We observed that cold acclimation promoted a significant increase in the mitochondrial oxygen consumption rates. Western blot analysis showed that UCP3 was raised by ∼1.5-fold in cold-acclimated muscle mitochondria. Similarly, we also evidenced a rise in the adenine nucleotide translocase content in cold-acclimated muscle mitochondria compared to warm-acclimated mitochondria (0.96±0.05 vs 0.68±0.02 nmol carboxyatractyloside mg−1 protein. This was followed by a 2-fold increment in the citrate synthase activity, which suggests a higher mitochondrial content in cold-acclimated goldfish. Even with higher levels of UCP3 and ANT, the effects of activator (palmitate and inhibitors (carboxyatractyloside and GDP on mitochondrial parameters were similar in both warm- and cold-acclimated goldfish. Thus, we propose that cold acclimation in goldfish promotes an increase in functional oxidative capacity, with higher mitochondrial content without changes in the mitochondrial uncoupling pathways.

  14. Oxidation films morphology

    International Nuclear Information System (INIS)

    Paidassi, J.

    1960-01-01

    After studying the oxidation of several pure polyvalent metals (Fe, Cu, Mn, Ni, U) and of their oxides at high temperature and atmospheric pressure, the author suggests how to modify the usual representation of the oxide film (a piling of different oxide layers, homogeneous on a micrographic scale with a equi-axial crystallisation, free of mechanical tensions, with flat boundary surfaces) to have it nearer to reality. In this first part, the author exposes the study of the real micrographic structure of the oxidation film and gives examples of precipitation in the oxides during the cooling of the oxidised sample. (author) [fr

  15. Analysis of fatty acid methyl esters and oxidative stability of seed purpose watermelon (Citrullus lanatus) genotypes for edible oil.

    Science.gov (United States)

    Mahla, H R; Rathore, S S; Venkatesan, K; Sharma, R

    2018-04-01

    World's vegetable oil demand is increasing day by day and oil seed supply is limited to a dozen oil seed crops on commercial scale. Efforts were made to explore the potential of water melon a traditionally grown native crop of Indian arid zone having oil content over 30% and seed yield potential of 500-600 kg per hectare under rainfed conditions. An analysis was carried out to explore the suitability of watermelon [ Citrullus lanatus (Thunb.)] oil for human consumption on the basis of fatty acid (FA) composition in selected genotypes. Total oil content ranged between 10.0 and 31.0%. Eleven FA were identified in seed oil. Linoleic, stearic, palmitic and oleic acid were found as major FA while myristic, heptadecanoic, arachidic, 9-hexadecenoic and 14-eicosenoic acid was present in traces. Linoleic acid single polyunsaturated FA contributor found in the range of 43.95% (WM-44) to 55.29% (WM-18). Saturated FA content ranged between 32.24 and 37.61%. Significant genetic variation was observed for mono-unsaturated FA. Metabolic capacity to inter-conversion of FA and nutritive value of watermelon oil was described on the basis of ratio of FA group. Total phenolics, antioxidant activity, peroxide value and oxidizability were also estimated along with oxidative stability of oil. Multivariate analysis showed that, oil content has positive correlation with linoleic acid. The Euclidean based UPGMA clustering revealed that genotypes WM-18 is most suitable for trait specific breeding program for high linoleic acid ( n -6), desaturation ratio and oleic desaturation ratio with higher oil content and lowest palmitic acid.

  16. European Food Safety Authority; Response to comments on the Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the scientific substantiation of a health claim related to beta-palmitate and increased calcium absorption pursuant to Article 14 of Regulation (EC

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, EFSA was asked to review the scientific comments received on the Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the scientific substantiation of a health claim related to beta-palmitate and increased...... calcium absorption pursuant to Article 14 of Regulation (EC) No 1924/2006. Comments submitted to EFSA via the European Commission Services originated from the applicant (IDACE). EFSA has reviewed the comments and shared them with the chair of the NDA Panel, Prof. Albert Flynn, and the chair of the NDA...

  17. Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway.

    Science.gov (United States)

    Wei, Shengnan; Zhang, Ming; Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M

    2016-01-01

    Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122

  18. Internal fuel pin oxidizer

    International Nuclear Information System (INIS)

    Andrews, M.G.

    1978-01-01

    A nuclear fuel pin has positioned within it material which will decompose to release an oxidizing agent which will react with the cladding of the pin and form a protective oxide film on the internal surface of the cladding

  19. Oxidation-resistant cermet

    Science.gov (United States)

    Phillips, W. M.

    1977-01-01

    Chromium metal alloys and chromium oxide ceramic are combined to produce cermets with oxidation-resistant properties. Application of cermets includes use in hot corrosive environments requiring strong resistive materials.

  20. Bridged graphite oxide materials

    Science.gov (United States)

    Herrera-Alonso, Margarita (Inventor); McAllister, Michael J. (Inventor); Aksay, Ilhan A. (Inventor); Prud'homme, Robert K. (Inventor)

    2010-01-01

    Bridged graphite oxide material comprising graphite sheets bridged by at least one diamine bridging group. The bridged graphite oxide material may be incorporated in polymer composites or used in adsorption media.

  1. Oxidative phosphorylation revisited

    DEFF Research Database (Denmark)

    Nath, Sunil; Villadsen, John

    2015-01-01

    The fundamentals of oxidative phosphorylation and photophosphorylation are revisited. New experimental data on the involvement of succinate and malate anions respectively in oxidative phosphorylation and photophosphorylation are presented. These new data offer a novel molecular mechanistic...

  2. Oxidative Stress in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Varsha Shukla

    2011-01-01

    Full Text Available It has been demonstrated that oxidative stress has a ubiquitous role in neurodegenerative diseases. Major source of oxidative stress due to reactive oxygen species (ROS is related to mitochondria as an endogenous source. Although there is ample evidence from tissues of patients with neurodegenerative disorders of morphological, biochemical, and molecular abnormalities in mitochondria, it is still not very clear whether the oxidative stress itself contributes to the onset of neurodegeneration or it is part of the neurodegenerative process as secondary manifestation. This paper begins with an overview of how oxidative stress occurs, discussing various oxidants and antioxidants, and role of oxidative stress in diseases in general. It highlights the role of oxidative stress in neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis. The last part of the paper describes the role of oxidative stress causing deregulation of cyclin-dependent kinase 5 (Cdk5 hyperactivity associated with neurodegeneration.

  3. Zinc oxide overdose

    Science.gov (United States)

    Zinc oxide is an ingredient in many products. Some of these are certain creams and ointments used ... prevent or treat minor skin burns and irritation. Zinc oxide overdose occurs when someone eats one of ...

  4. Assessment of myocardial metabolism with iodine-123 heptadecanoic acid: effect of decreased fatty acid oxidation on deiodination

    International Nuclear Information System (INIS)

    Luethy, P.C.; Chatelain, P.; Papageorgiou, I.; Schubiger, A.; Lerch, R.A.

    1988-01-01

    Terminally radioiodinated fatty acid analogs are of potential use for the noninvasive delineation of regional alterations of fatty acid metabolism by gamma imaging. Since radioactivity from extracted iodine-123 heptadecanoic acid [( 123I]HDA) is released from the myocardium in form of free radioiodide (123I-) the present study was performed to determine whether deiodination of [123I]HDA is related to free fatty acid metabolism. Myocardial production of free radioiodide was measured in rat hearts in vitro and in vivo both under control conditions and after inhibition of fatty acid oxidation. In isolated rat hearts perfused at constant flow with a medium containing [123I]HDA, release of 123I- was markedly reduced during cardioplegia and pharmacologic inhibition of mitochondrial fatty acid transfer with POCA by 67% (p less than 0.005) and 72% (p less than 0.005), respectively. In fasted rats in vivo, 1 min after i.v. injection of [123I]HDA, 51 +/- 5% of myocardial radioactivity was recovered in the aqueous phase, containing free iodide, of myocardial lipid extracts. Aqueous activity was significantly decreased in fed (20 +/- 2%; p less than 0.002) and POCA pretreated (30 +/- 3.7%; p less than 0.05) animals exhibiting reduced oxidation of [14C]palmitate. Thus, deiodination of [123I]HDA was consistently reduced during inhibition of fatty acid oxidation in vitro and in vivo. The results apply to the interpretation of myocardial clearance curves of terminally radioiodinated fatty acid analogs

  5. Oxidative Stress in BPH

    Directory of Open Access Journals (Sweden)

    Murat Savas

    2009-01-01

    The present study has shown that there were not relationship between potency of oxidative stress and BPH. Further well designed studies should be planned to find out whether the oxidative stress-related parameters play role in BPH as an interesting pathology in regard of the etiopathogenesis. Keywords: benign prostatic hyperplasia, oxidative stress, prostate

  6. Sputtered indium oxide films

    International Nuclear Information System (INIS)

    Gillery, F.H.

    1986-01-01

    A method is described for depositing on a substrate multiple layer films comprising at least one primary layer of a metal oxide and at least one primary layer of a metal other than the metal of the oxide layer. The improvement described here comprises improving the adhesion between the metal oxide and metal layers by depositing between the layers an intermediate metal-containing layer having an affinity for both the metal and metal oxide layers. An article of manufacture is described comprising a nonmetallic substrate, and deposited thereon in any order: a. at least one coating layer of metal; b. at least one coating layer of an oxide of a metal other than the metal of the metal layer; and c. deposited between the metal and metal oxide layers an intermediate metal-containing layer having an affinity for both the metal and metal oxide layers

  7. Branched Chain Amino Acid Oxidation in Cultured Rat Skeletal Muscle Cells

    Science.gov (United States)

    Pardridge, William M.; Casanello-Ertl, Delia; Duducgian-Vartavarian, Luiza

    1980-01-01

    Leucine metabolism in skeletal muscle is linked to protein turnover. Since clofibrate is known both to cause myopathy and to decrease muscle protein content, the present investigations were designed to examine the effects of acute clofibrate treatment on leucine oxidation. Rat skeletal muscle cells in tissue culture were used in these studies because cultivated skeletal muscle cells, like muscle in vivo, have been shown to actively utilize branched chain amino acids and to produce alanine. The conversion of [1-14C]leucine to 14CO2 or to the [1-14C]keto-acid of leucine (α-keto-isocaproate) was linear for at least 2 h of incubation; the production of 14CO2 from [1-14C]leucine was saturable with a Km = 6.3 mM and a maximum oxidation rate (Vmax) = 31 nmol/mg protein per 120 min. Clofibric acid selectively inhibited the oxidation of [1-14C]leucine (Ki = 0.85 mM) and [U-14C]isoleucine, but had no effect on the oxidation of [U-14C]glutamate, -alanine, -lactate, or -palmitate. The inhibition of [1-14C]leucine oxidation by clofibrate was also observed in the rat quarter-diaphragm preparation. Clofibrate primarily inhibited the production of 14CO2 and had relatively little effect on the production of [1-14C]keto-acid of leucine. A physiological concentration—3.0 g/100 ml—of albumin, which actively binds clofibric acid, inhibited but did not abolish the effects of a 2-mM concentration of clofibric acid on leucine oxidation. Clofibrate treatment stimulated the net consumption of pyruvate, and inhibited the net production of alanine. The drug also increased the cytosolic NADH/NAD+ ratio as reflected by an increase in the lactate/pyruvate ratio, in association with a decrease in cell aspartate levels. The changes in pyruvate metabolism and cell redox state induced by the drug were delayed compared with the nearly immediate inhibition of leucine oxidation. These studies suggest that clofibric acid, in concentrations that approximate high therapeutic levels of the drug

  8. Hepatic beta-oxidation and carnitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides.

    Science.gov (United States)

    Peffer, Pasha Lyvers; Lin, Xi; Odle, Jack

    2005-06-01

    A suckling piglet model was used to study nutritional and pharmacologic means of stimulating hepatic fatty acid beta-oxidation. Newborn pigs were fed milk diets containing either long- or medium-chain triglycerides (LCT or MCT). The long-chain control diet was supplemented further with clofibric acid (0.5%) or isoproterenol (40 ppm), and growth was monitored for 10-12 days. Clofibrate increased rates of hepatic peroxisomal and mitochondrial beta-oxidation of [1-(14)C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive carnitine palmitoyltransferase (CPT I) activity increased 64% (P clofibrate. Increased CPT I activity was not congruent with changes in message, as elevated abundance of CPT I mRNA was not detected (P = 0.16) when assessed by qRT-PCR. Neither rates of beta-oxidation nor CPT activities were affected by dietary MCT or by isoproterenol treatment (P > 0.1). Collectively, these findings indicate that clofibrate effectively induced hepatic CPT activity concomitant with increased fatty acid beta-oxidation.

  9. Italmontaggi builds expertise Conquering monsoons, adverse conditions Bangladesh pipelines

    Energy Technology Data Exchange (ETDEWEB)

    1984-10-01

    Bangladesh natural gas pipeline projects have become a specialty for Italmontaggi Pte Ltd., Singapore-based gas pipeline contractor and engineering organization. The firm's latest project is a 35-mile, 24-in. gas pipeline, branching from the Bakhrabad-Chittagong main gas pipeline to the city gate station at Demra, near the capital city of Dacca. Gas is delivered to the Titas gas distribution system. The 35-mile turnkey project, valued at $25 million, included design, procurement, construction, and commissioning. A small pipeline was in existence from the Titas gas field to Dacca, but increased demand caused acute power shortages in the capital city's industrial areas. The new gas line will alleviate that problem. That project is a followup to Italmontaggi's successful completion of the major 108-mile, 24-in. main gas pipeline between the Bakhrabad gas fields, outside Dhaha, to the country's principal port and industrial center at Chittagong. Italmontaggi also installed 22 miles of ring main for the Chittagong gas distribution system. That included 12 miles of 24-in. and 10 miles of 16- and 20-in. to provide connections to industrial customers. Bangladesh lines difficult. The $45million contract for the Bakhrabad-toChittagong pipeline to Italmlontaggi, an autonomous offshoot of the Italian firm, resulted in a constant battle against hostile ground conditions, difficult access, and rapidly changing weather conditions. October-to- April is the dry season and Mayto-September is the wet season in this region. To keep the project moving, Italmontaggi developed two independent techniques for ground preparation during the wet season, and a pipelaying technique for the dry season. The new gas pipeline provides a major saving to the Bangladesh national economy as industries convert from oil to gas. Predicted savings are for more than $100 million in energy costs.

  10. PSA Duration: Conquering the Prepayment Risk of Mortgage Portfolios

    OpenAIRE

    Boleslav Gulko

    1996-01-01

    Money managers have little control over the values of their individual holdings, but they have considerable control over the risk exposure of their portfolios. This article introduces new tools for the risk management of mortgage portfolios. We extend the traditional duration analysis to two dimensions, interest rates and mortgage prepayments, and develop independent hedging rules for the interest rate risk and the prepayment risk. In particular, we define the PSA duration as a formal measure...

  11. The French nuclear team ready to conquer new market shares

    International Nuclear Information System (INIS)

    Levy, J.B.; Varin, P.; Verwaerde, D.

    2016-01-01

    In order to reinforce their partnership, EDF, CEA and AREVA have founded the France Nuclear Platform (FNP). FNP is a tripartite body that will allow EDF, CEA and AREVA to build a consistent common position to respond to the worldwide demand in terms of nuclear reactors, fuel cycle or spent fuel processing. Potential clients and particularly first-time buyers want to buy far more than nuclear reactors, they want to buy the whole experience of the most important nuclear operator in the world which is a guarantee of success, safety and security. In order to stay ahead of the competition, the French nuclear industry can rely on high quality standards, a policy of innovation and a well-developed safety culture. Today's promising markets for nuclear energy are concentrated in Asia: in China a growth rate of 60% over the next 15 years is expected for nuclear power, in India projects for the construction of several EPR are ongoing. (A.C.)

  12. How the machine learning conquers reconstruction in neutrino experiments

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    An evolution from the purely algorithmic approaches towards the machine learning solutions started a few years ago in the neutrino experiments. Now, this process turns into a true boom, especially in the experiments based on the imaging technologies, such as LArTPC’s used in MicroBooNE and DUNE experiments or liquid scintillator detector implemented by the NOvA Collaboration. High resolution, image-like projections of events obtained with these detectors proved to be hard pattern recognition problems for the conventional reconstruction techniques. In the seminar, I will present why the neutrino events are so challenging and how the essential difficulties are now being attacked with the machine learning.

  13. QUALIFICATIONS FRAMEWORKS FOR LIFELONG LEARNING CONQUERING THE WORLD?

    Directory of Open Access Journals (Sweden)

    Arjen Deij

    2014-01-01

    Full Text Available The paper reveals the international prospects of developing and spreading the qualifications frameworks across the globe. It introduces the key terms and concepts related to the given issue, and examines both the benefits and challenges of qualifications frameworks implementation. The author looks into the origins and causes of the worldwide interest in qualifications framework application, and gives the overview of related recent publications and their conclusions to reinforce the provided argumentation.

  14. How to conquer a tomato plant? Fusarium oxysporum effector targets

    NARCIS (Netherlands)

    de Sain, M.

    2016-01-01

    Pathogens secrete small proteins, called effectors, to alter the environment in their host to facilitate infection. The causal agent of Fusarium wilt on tomato, Fusarium oxysporum f. sp. lycopersici (Fol), secretes these proteins in the xylem sap of infected plants and hence they have been called

  15. To Conquer or Compel: War, Peace, and Economic Development

    OpenAIRE

    Gartzke, Erik; Rohner, Dominic

    2010-01-01

    Theories of economic development suggest variously that national income increases or decreases the propensity for states to fight, while systematic evidence of the impact of development on warfare is ambiguous or non-existent. The lack of empirical support for nominally opposing claims can be reconciled if elements of both perspectives are partially correct. We use a formal model to construct an explanation linking economic development with interstate conflict that resolves contradictory theo...

  16. May one conquer a radiation. Recommendations of experts

    International Nuclear Information System (INIS)

    Zhukovskaya, O.V.; Kovalev, S.D.; Stavrov, A.I.; Rolevich, I.V.; Antsipov, G.V.; Borovikov, A.N.; Baraboshkin, A.V.; Basalaeva, Z.N.

    1996-01-01

    The brief recommendations for the population living on radionuclides contaminated territories on prophylactic feed, agricultural work, keeping of the animals, preparation of food products to use, bee keeping, fishing and hunt, use of production of a forest, hygiene of labour and etc. The recommendations permit to ensure conditions of safe living and activity on contaminated territories. 4 refs., 8 tabs., 1 fig

  17. Generalized density-functional theory: Conquering the N ...

    Indian Academy of Sciences (India)

    Unknown

    mension – computational costs grow exponentially with increasing numbers of electrons. This motivates work that uses .... tional cost.7–10 In approaches based on Γ2, we trade the daunting problem of representing a high-dimen- .... mately accounting for N-representability. Moving forward another decade, Gilbert,13 Don-.

  18. International cooperation to conquer global inequities in reproductive health.

    Science.gov (United States)

    1992-01-01

    The effect of population growth is not limited to national boundaries. Indeed the inability of people in developing countries to control their own fertility has repercussions on global security and on the balance between population and environment as well a on their health and welfare. All nations need to take steps to slow down rapid population growth now, otherwise we will suffer serious consequences. The different between 2 UN projections of world population equals current world population size. Almost 90% of the increase of the larger projection would occur in developing countries, yet they are the least capable of managing big populations. Further major inequalities in reproductive health between developed and developing countries, as well as between men and women exist. The infant mortality rate in developed regions is around 6 times lower than it is in developing regions, child mortality is 7 times lower, and maternal mortality is 15 times lower. International collaboration to rid the world of these inequalities is need to improve reproductive health. Specifically, political and health leaders should mobilize necessary international and national resources. Even though there is more than US $50,000 million in official development assistance funds available annually, the level of population related funding has decreased to less than 1.1% of these funds for 1993-1994. Developed countries could reduce the debt burden to free funds for population activities and to reverse the flow from the poor countries in the Southern Hemisphere to the rich countries in the Northern Hemisphere. Besides developing countries spend much of their money on the military (e.g. sub-Saharan Africa spends US$ 10,000 million). International cooperation leading to peace would make significantly more money available for the social and health sectors, especially reproductive health care.

  19. Book Review MOBILITY CONQUERS: THE STORY OF 61 ...

    African Journals Online (AJOL)

    dkatz@icon.co.za

    officialdom cancelled the excellent series in 1961.2 In similar fashion, a strong combined team consisting of the Regimental Association of 61 Mechanised. Battalion ... The book proffers the influence of two famous inter-war British intellectual military commentators, JFC Fuller and BH Liddell Hart. These two gentlemen.

  20. Decomposed process mining with DivideAndConquer

    NARCIS (Netherlands)

    Verbeek, H.M.W.; Limonad, L.; Weber, B.

    2014-01-01

    Many known process mining techniques scale badly in the number of activities in an event log. Examples of such techniques include the ILP Miner and the standard replay, which also uses ILP techniques. To alleviate the problems these techniques face, we can decompose a large problem (with many

  1. Inland No. 2 plant conquers high ash. [USA

    Energy Technology Data Exchange (ETDEWEB)

    Brimm, B.; Lawton, J.T.

    1981-09-01

    The US preparation plant described cleans high volatile metallurgical coal. Yield of clean coal is lower than expected, because feed ash is higher than expected (37.5%), and size consist is different from that predicted.

  2. Conquering complexity - Dealing with uncertainty and ambiguity in water management

    NARCIS (Netherlands)

    Hommes, Saskia

    2008-01-01

    Water management problems are embedded in a natural and social system that is characterized by complexity. Knowledge uncertainty and the existence of divergent actors’ perceptions contribute to this complexity. Consequently, dealing with water management issues is not just a knowledge uncertainty

  3. Transport Methods Conquering the Seven-Dimensional Mountain

    International Nuclear Information System (INIS)

    Graziani, F; Olson, G

    2003-01-01

    In a wide variety of applications, a significant fraction of the momentum and energy present in a physical problem is carried by the transport of particles. Depending on the circumstances, the types of particles might involve some or all of photons, neutrinos, charged particles, or neutrons. In application areas that use transport, the computational time is usually dominated by the transport calculation. Therefore, there is a potential for great synergy; progress in transport algorithms could help quicken the time to solution for many applications. The complexity, and hence expense, involved in solving the transport problem can be understood by realizing that the general solution to the Boltzmann transport equation is seven dimensional: 3 spatial coordinates, 2 angles, 1 time, and 1 for speed or energy. Low-order approximations to the transport equation are frequently used due in part to physical justification but many times simply because a solution to the full transport problem is too computationally expensive. An example is the diffusion equation, which effectively drops the two angles in phase space by assuming that a linear representation in angle is adequate. Another approximation is the grey approximation, which drops the energy variable by averaging over it. If the grey approximation is applied to the diffusion equation, the expense of solving what amounts to the simplest possible description of transport is roughly equal to the cost of implicit computational fluid dynamics. It is clear therefore, that for those application areas needing some form of transport, fast, accurate and robust transport algorithms can lead to an increase in overall code performance and a decrease in time to solution. The seven-dimensional nature of transport means that factors of 100 or 1000 improvement in computer speed or memory are quickly absorbed in slightly higher resolution in space, angle, and energy. Therefore, the biggest advances in the last few years and in the next several years will be driven by algorithms. Because transport is an implicit problem requiring iteration, the biggest gains are to be made in finding faster techniques for acceleration to convergence. Some of these acceleration methods are very application specific because they are physics based; others are very general because they address the mathematics of the transport equation. Funding more research in the latter area could have a large impact on many physics applications. Usually it is a collaboration of someone with a tough problem to solve and someone with a new idea that makes the big advances. More heads are needed to continue the progress of the last few years. Unfortunately, transport as a discipline is not taught in many graduate schools. Students and researchers too often pick up transport theory in pieces on an ad hoc basis. Therefore, they don't know the published literature and existing techniques. Knowledge of advances in one application area often takes years to propagate to other application areas

  4. Oxidation Resistant Graphite Studies

    Energy Technology Data Exchange (ETDEWEB)

    W. Windes; R. Smith

    2014-07-01

    The Very High Temperature Reactor (VHTR) Graphite Research and Development Program is investigating doped nuclear graphite grades exhibiting oxidation resistance. During a oxygen ingress accident the oxidation rates of the high temperature graphite core region would be extremely high resulting in significant structural damage to the core. Reducing the oxidation rate of the graphite core material would reduce the structural effects and keep the core integrity intact during any air-ingress accident. Oxidation testing of graphite doped with oxidation resistant material is being conducted to determine the extent of oxidation rate reduction. Nuclear grade graphite doped with varying levels of Boron-Carbide (B4C) was oxidized in air at nominal 740°C at 10/90% (air/He) and 100% air. The oxidation rates of the boronated and unboronated graphite grade were compared. With increasing boron-carbide content (up to 6 vol%) the oxidation rate was observed to have a 20 fold reduction from unboronated graphite. Visual inspection and uniformity of oxidation across the surface of the specimens were conducted. Future work to determine the remaining mechanical strength as well as graphite grades with SiC doped material are discussed.

  5. Barium oxide, calcium oxide, magnesia, and alkali oxide free glass

    Science.gov (United States)

    Lu, Peizhen Kathy; Mahapatra, Manoj Kumar

    2013-09-24

    A glass composition consisting essentially of about 10-45 mole percent of SrO; about 35-75 mole percent SiO.sub.2; one or more compounds from the group of compounds consisting of La.sub.2O.sub.3, Al.sub.2O.sub.3, B.sub.2O.sub.3, and Ni; the La.sub.2O.sub.3 less than about 20 mole percent; the Al.sub.2O.sub.3 less than about 25 mole percent; the B.sub.2O.sub.3 less than about 15 mole percent; and the Ni less than about 5 mole percent. Preferably, the glass is substantially free of barium oxide, calcium oxide, magnesia, and alkali oxide. Preferably, the glass is used as a seal in a solid oxide fuel/electrolyzer cell (SOFC) stack. The SOFC stack comprises a plurality of SOFCs connected by one or more interconnect and manifold materials and sealed by the glass. Preferably, each SOFC comprises an anode, a cathode, and a solid electrolyte.

  6. Direct oxide reducing method

    International Nuclear Information System (INIS)

    Tokiwai, Moriyasu.

    1995-01-01

    Calcium oxides and magnetic oxides as wastes generated upon direct reduction are subjected to molten salt electrolysis, and reduced metallic calcium and magnesium are separated and recovered. Then calcium and magnesium are used recyclically as the reducing agent upon conducting direct oxide reduction. Even calcium oxides and magnesium oxides, which have high melting points and difficult to be melted usually, can be melted in molten salts of mixed fluorides or chlorides by molten-salt electrolysis. Oxides are decomposed by electrolysis, and oxygen is removed in the form of carbon monoxide, while the reduced metallic calcium and magnesium rise above the molten salts on the side of a cathode, and then separated. Since only carbon monoxide is generated as radioactive wastes upon molten salt electrolysis, the amount of radioactive wastes can be greatly reduced, and the amount of the reducing agent used can also be decreased remarkably. (N.H.)

  7. Oxidizer Scoping Studies

    Energy Technology Data Exchange (ETDEWEB)

    Chancellor, Christopher John [Los Alamos National Laboratory

    2016-11-07

    The purpose of this report is to present the results of the acceptable knowledge (AK) review of oxidizers present in active waste streams, provide a technical analysis of the oxidizers, and report the results of the scoping study testing. This report will determine the fastest burning oxidizer to be used in the development of a Test Plan for Preparation and Testing of Sorbents Mixed with Oxidizer found in Transuranic Waste (DWT-TP-001). The companion report, DWT-RPT-002, Sorbent Scoping Studies, contains similar information for sorbents identified during the AK review of TRU waste streams. The results of the oxidizer and sorbent scoping studies will be used to inform the QL1 test plan. The QL1 test results will support the development of a basis of knowledge document that will evaluate oxidizing chemicals and sorbents in TRU waste and provide guidance for treatment.

  8. Review of zircaloy oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, F.C. [Royal Military College of Canada, Kingston, Ontario (Canada); Lewis, B.J. [Univ. of Ontario Inst. of Technology, Faculty of Energy Systems and Nuclear Science, Oshawa, Ontario (Canada)

    2013-07-01

    This paper provides an overview of the kinetics for Zircaloy clad oxidation behaviour in steam and air during reactor accident conditions. The generation of chemical heat from metal/water reaction is considered. The effect of internal clad oxidation due to Zircaloy/UO{sub 2} interaction is also discussed. Low-temperature oxidation of Zircaloy due to water-side corrosion is further described. (author)

  9. OXIDATION OF TRANSURANIC ELEMENTS

    Science.gov (United States)

    Moore, R.L.

    1959-02-17

    A method is reported for oxidizing neptunium or plutonium in the presence of cerous values without also oxidizing the cerous values. The method consists in treating an aqueous 1N nitric acid solution, containing such cerous values together with the trivalent transuranic elements, with a quantity of hydrogen peroxide stoichiometrically sufficient to oxidize the transuranic values to the hexavalent state, and digesting the solution at room temperature.

  10. METAL OXIDE NANOPARTICLES

    Energy Technology Data Exchange (ETDEWEB)

    FERNANDEZ-GARCIA,M.; RODGRIGUEZ, J.A.

    2007-10-01

    This chapter covers the fundamental science, synthesis, characterization, physicochemical properties and applications of oxide nanomaterials. Explains fundamental aspects that determine the growth and behavior of these systems, briefly examines synthetic procedures using bottom-up and top-down fabrication technologies, discusses the sophisticated experimental techniques and state of the art theory results used to characterize the physico-chemical properties of oxide solids and describe the current knowledge concerning key oxide materials with important technological applications.

  11. Oxidation mechanisms occurring in wines

    OpenAIRE

    Oliveira, Carla Maria; Ferreira, António César Silva; Freitas, Victor De; Silva, Artur M. S.

    2011-01-01

    The present review aims to show the state of the art on the oxidation mechanisms occurring in wines, as well as the methods to monitor, classify and diagnose wine oxidation. Wine oxidation can be divided in enzymatic oxidation and non-enzymatic oxidation. Enzymatic oxidation almost entirely occurs in grape must and is largely correlated with the content of hydroxycinnamates, such as caffeoyltartaric acid and paracoumaroyltartaric acid, and flavan-3-ols. Non-enzymatic oxidation, al...

  12. Hepatic toxicity of dronedarone in mice: Role of mitochondrial β-oxidation

    International Nuclear Information System (INIS)

    Felser, Andrea; Stoller, Andrea; Morand, Réjane; Schnell, Dominik; Donzelli, Massimiliano; Terracciano, Luigi; Bouitbir, Jamal; Krähenbühl, Stephan

    2014-01-01

    Highlights: • Dronedarone is not hepatotoxic to mice up to 200 mg/kg/day. • At 400 mg/kg/day dronedarone decreases food intake and inhibits hepatic fatty acid metabolism. • Impaired hepatic fatty acid metabolism is associated with increased hepatocyte apoptosis and serum transaminases. • Mice with subclinical impairment of β-oxidation are slightly more susceptible to dronaderone than wild type mice. - Abstract: Dronedarone is an amiodarone-like antiarrhythmic drug associated with severe liver injury. Since dronedarone inhibits mitochondrial respiration and β-oxidation in vitro, mitochondrial toxicity may also explain dronedarone-associated hepatotoxicity in vivo. We therefore studied hepatotoxicity of dronedarone (200 mg/kg/day for 2 weeks or 400 mg/kg/day for 1 week by intragastric gavage) in heterozygous juvenile visceral steatosis (jvs +/− ) and wild-type mice. Jvs +/− mice have reduced carnitine stores and are sensitive for mitochondrial β-oxidation inhibitors. Treatment with dronedarone 200 mg/kg/day had no effect on body weight, serum transaminases and bilirubin, and hepatic mitochondrial function in both wild-type and jvs +/− mice. In contrast, dronedarone 400 mg/kg/day was associated with a 10–15% drop in body weight, and a 3–5-fold increase in transaminases and bilirubin in wild-type mice and, more accentuated, in jvs +/− mice. In vivo metabolism of intraperitoneal 14 C-palmitate was impaired in wild-type, and, more accentuated, in jvs +/− mice treated with 400 mg/kg/day dronedarone compared to vehicle-treated mice. Impaired β-oxidation was also found in isolated mitochondria ex vivo. A likely explanation for these findings was a reduced activity of carnitine palmitoyltransferase 1a in liver mitochondria from dronedarone-treated mice. In contrast, dronedarone did not affect the activity of the respiratory chain ex vivo. We conclude that dronedarone inhibits mitochondrial β-oxidation in and ex vivo, but not the respiratory chain

  13. Molecular water oxidation catalysis

    CERN Document Server

    Llobet, Antoni

    2014-01-01

    Photocatalytic water splitting is a promising strategy for capturing energy from the sun by coupling light harvesting and the oxidation of water, in order to create clean hydrogen fuel. Thus a deep knowledge of the water oxidation catalysis field is essential to be able to come up with useful energy conversion devices based on sunlight and water splitting. Molecular Water Oxidation Catalysis: A Key Topic for New Sustainable Energy Conversion Schemes presents a comprehensive and state-of-the-art overview of water oxidation catalysis in homogeneous phase, describing in detail the most importan

  14. Isotopes in oxidation reactions

    International Nuclear Information System (INIS)

    Stewart, R.

    1976-01-01

    The use of isotopes in the study of organic oxidation mechanisms is discussed. The help provided by tracer studies to demonstrate the two-equivalent path - hydride transfer, is illustrated by the examples of carbonium oxidants and the Wacker reaction. The role of kinetic isotope effects in the study of the scission of carbon-hydrogen bonds is illustrated by hydride abstraction, hydrogen atom abstraction, proton abstraction and quantum mechanical tunnelling. Isotopic studies on the oxidation of alcohols, carbonyl compounds, amines and hydrocarbons are discussed. The role of isotopes in the study of biochemical oxidation is illustrated with a discussion on nicotinamide and flavin coenzymes. (B.R.H.)

  15. Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress.

    Science.gov (United States)

    Sindhu, Sardar; Akhter, Nadeem; Kochumon, Shihab; Thomas, Reeby; Wilson, Ajit; Shenouda, Steve; Tuomilehto, Jaakko; Ahmad, Rasheed

    2018-01-01

    Metabolic diseases such as obesity and type-2 diabetes (T2D) are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC), or primary monocytes were treated with hydrogen peroxide (H2O2) for induction of reactive oxygen species (ROS)-mediated oxidative stress. Superoxide dismutase (SOD) activity was measured using a commercial kit. Data (mean±SEM) were compared using unpaired student's t-test and Pobesity as well as T2D which correlated with body mass index (BMI). ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB)/mitogen activated protein kinase (MAPK) signaling as well as endoplasmic reticulum (ER) stress. H2O2-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Oxidative stress induces the expression of TLR10 which may represent an immune marker for metabolic inflammation. © 2018 The Author(s). Published by S. Karger AG, Basel.

  16. Rare earth oxide doping in oxide cathodes

    International Nuclear Information System (INIS)

    Engelsen, Daniel den; Gaertner, Georg

    2006-01-01

    The effect on life performance and poisoning with O 2 by doping oxide cathodes with rare earth oxides and pseudo rare earth oxides, notably yttria, is qualitatively explained in terms of electrolysis of BaO during emission of electrons. Doped cathodes show less electrolysis and consume therefore less Ba during life: consequently, doped cathodes have a better life performance. However, the lower Ba-production makes doped cathodes more sensitive to oxygen poisoning. The experimentally found relation between conductivity and yttria concentration was the motive to propose a new model for the crystal imperfections in BaO. In this new imperfection model most Y 3+ -ions will combine with barium vacancies, therefore, the increase of the conductivity is modest and also the effect on the position of the Fermi level is modest. By assuming a combination of bulk and surface conductivity, the agreement between experiment and theory can be improved further

  17. Fatty Acid Mixtures from Nigella sativa Protects PC12 Cells from Oxidative Stress and Apoptosis Induced by Doxorubicin

    Directory of Open Access Journals (Sweden)

    Leila Hosseinzadeh

    2018-03-01

    Full Text Available Background: Fatty acids (FAs, the key structural elements of dietary lipids, are notable in the nutritional value of plants. Black cumin, a popular anti-inflammatory and antioxidant food seasoning, contains nonpolar constituents such as FAs. Methods: Seeds were extracted using hexane and their cytoprotective activity was assessed against doxorubicin (DOX-mediated oxidative stress and apoptosis in PC12 cell line. Results: In spite of the cellular death induced by DOX toward PC12 cells, bioassay-guided purification showed that pretreatment with FAs mixtures (24h attenuated DOX-mediated apoptosis, which could be attributed to the inhibited caspase 3 activity and enhanced mitochondrial membrane potential. Palmitic acid, caprylic acid and oleic acid each 1/3 in the mixture, also suppressed DOX-induced ROS generation. Conclusion: Our observation indicated that the subtoxic concentration of FAs from Nigella sativa could effectively protect the cells against oxidative stress, due to their antioxidant activity, and could be regarded as a dietary supplement.

  18. Consumption of NADPH for 2-HG Synthesis Increases Pentose Phosphate Pathway Flux and Sensitizes Cells to Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Susan J. Gelman

    2018-01-01

    Full Text Available Summary: Gain-of-function mutations in isocitrate dehydrogenase 1 (IDH1 occur in multiple types of human cancer. Here, we show that these mutations significantly disrupt NADPH homeostasis by consuming NADPH for 2-hydroxyglutarate (2-HG synthesis. Cells respond to 2-HG synthesis, but not exogenous administration of 2-HG, by increasing pentose phosphate pathway (PPP flux. We show that 2-HG production competes with reductive biosynthesis and the buffering of oxidative stress, processes that also require NADPH. IDH1 mutants have a decreased capacity to synthesize palmitate and an increased sensitivity to oxidative stress. Our results demonstrate that, even when NADPH is limiting, IDH1 mutants continue to synthesize 2-HG at the expense of other NADPH-requiring pathways that are essential for cell viability. Thus, rather than attempting to decrease 2-HG synthesis in the clinic, the consumption of NADPH by mutant IDH1 may be exploited as a metabolic weakness that sensitizes tumor cells to ionizing radiation, a commonly used anti-cancer therapy. : Using liquid chromatography/mass spectrometry (LC/MS and stable isotope tracing, Gelman et al. find that 2-HG production in cells with IDH1 mutations leads to increased pentose phosphate pathway activity to generate NADPH. Production of 2-HG competes with other NADPH-dependent pathways and sensitizes cells to redox stress. Keywords: 2-hydroxyglutarate, cancer metabolism, LC/MS, metabolomcis, pentose phosphate pathway, redox regulation

  19. Effects of thermal processing on physicochemical properties and oxidative stability of Balanities aegyptiaca kernels and extracted oil

    International Nuclear Information System (INIS)

    Elbadawi, S.M.A.; Ahmad, E.E.M.; Mariod, A.A.; Mathäus, B.

    2017-01-01

    In the present study, the effects of roasting and boiling on the proximate composition of the kernels as well as the physicochemical properties and oxidative stabilities of the extracted oils of Balanites aegyptiaca were investigated. Roasting was performed at 180 °C for 15 minutes, whereas boiling of the kernels was carried out in tap water for one hour. The oils from raw and thermally processed samples were extracted using n-hexane in a Soxhlet extraction apparatus and characterized. The roasting significantly (p < 0.05) influenced the peroxide value and the oxidative stability of the extracted oil in a positive way; whereas boiling had the opposite effect. The oils were composed of linoleic, oleic, stearic, and palmitic acids as the major fatty acids (96%) and contained predominantly α- and γ-tocopherols (ca. 400mg/kg). The study suggests that the oil from roasted kernels could be used as a natural antioxidant for enhancing the characteristics of other edible oils via blending. [es

  20. Stabilized chromium oxide film

    Science.gov (United States)

    Garwin, Edward L.; Nyaiesh, Ali R.

    1988-01-01

    Stabilized air-oxidized chromium films deposited on high-power klystron ceramic windows and sleeves having a thickness between 20 and 150.ANG. are useful in lowering secondary electron emission yield and in avoiding multipactoring and window failure due to overheating. The ceramic substrate for the film is chosen from alumina, sapphire or beryllium oxide.

  1. Catalyst for Ammonia Oxidation

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a bimetallic catalyst for ammonia oxidation, a method for producing a bimetallic catalyst for ammonia oxidation and a method for tuning the catalytic activity of a transition metal. By depositing an overlayer of less catalytic active metal onto a more catalytic...

  2. Reducible oxide based catalysts

    Science.gov (United States)

    Thompson, Levi T.; Kim, Chang Hwan; Bej, Shyamal K.

    2010-04-06

    A catalyst is disclosed herein. The catalyst includes a reducible oxide support and at least one noble metal fixed on the reducible oxide support. The noble metal(s) is loaded on the support at a substantially constant temperature and pH.

  3. Death from Nitrous Oxide.

    Science.gov (United States)

    Bäckström, Björn; Johansson, Bengt; Eriksson, Anders

    2015-11-01

    Nitrous oxide is an inflammable gas that gives no smell or taste. It has a history of abuse as long as its clinical use, and deaths, although rare, have been reported. We describe two cases of accidental deaths related to voluntary inhalation of nitrous oxide, both found dead with a gas mask covering the face. In an attempt to find an explanation to why the victims did not react properly to oncoming hypoxia, we performed experiments where a test person was allowed to breath in a closed system, with or without nitrous oxide added. Vital signs and gas concentrations as well as subjective symptoms were recorded. The experiments indicated that the explanation to the fact that neither of the descendents had reacted to oncoming hypoxia and hypercapnia was due to the inhalation of nitrous oxide. This study raises the question whether nitrous oxide really should be easily, commercially available. © 2015 American Academy of Forensic Sciences.

  4. RNA modifications by oxidation

    DEFF Research Database (Denmark)

    Poulsen, Henrik E; Specht, Elisabeth; Broedbaek, Kasper

    2012-01-01

    to encompass various classes of novel regulatory RNAs, including, e.g., microRNAs. It is well known that DNA is constantly oxidized and repaired by complex genome maintenance mechanisms. Analogously, RNA also undergoes significant oxidation, and there are now convincing data suggesting that oxidation......The past decade has provided exciting insights into a novel class of central (small) RNA molecules intimately involved in gene regulation. Only a small percentage of our DNA is translated into proteins by mRNA, yet 80% or more of the DNA is transcribed into RNA, and this RNA has been found......, and the consequent loss of integrity of RNA, is a mechanism for disease development. Oxidized RNA is found in a large variety of diseases, and interest has been especially devoted to degenerative brain diseases such as Alzheimer disease, in which up to 50-70% of specific mRNA molecules are reported oxidized, whereas...

  5. Engineering complex oxide interfaces for oxide electronics

    NARCIS (Netherlands)

    Roy, Saurabh

    2015-01-01

    A complex interplay of physics and chemistry in transition metal oxides determines their electronic, magnetic, and ferroic properties enabling a wide range of applications of these materials. BiFeO_3, a canonical multiferroic system exhibits the interesting feature of enhanced conductivity on

  6. Moderate Exercise Prevents Functional Remodeling of the Anterior Pituitary Gland in Diet-Induced Insulin Resistance in Rats: Role of Oxidative Stress and Autophagy.

    Science.gov (United States)

    Mercau, María E; Repetto, Esteban M; Perez, Matías N; Martinez Calejman, Camila; Sanchez Puch, Silvia; Finkielstein, Carla V; Cymeryng, Cora B

    2016-03-01

    A sustained elevation of glucocorticoid production, associated with the establishment of insulin resistance (IR) could add to the deleterious effects of the IR state. The aim of this study is to analyze the consequences of long-term feeding with a sucrose-rich diet (SRD) on Pomc/ACTH production, define the underlying cellular processes, and determine the effects of moderate exercise (ME) on these parameters. Animals fed a standard chow with or without 30% sucrose in the drinking water were subjected to ME. Circulating hormone levels were determined, and pituitary tissues were processed and analyzed by immunobloting and quantitative real-time PCR. Parameters of oxidative stress (OxS), endoplasmic reticulum stress, and autophagy were also determined. Rats fed SRD developed a decrease in pituitary Pomc/ACTH expression levels, increased expression of antioxidant enzymes, and induction of endoplasmic reticulum stress and autophagy. ME prevented pituitary dysfunction as well as induction of antioxidant enzymes and autophagy. Reporter assays were performed in AtT-20 corticotroph cells incubated in the presence of palmitic acid. Pomc transcription was inhibited by palmitic acid-dependent induction of OxS and autophagy, as judged by the effect of activators and inhibitors of both processes. Long-term feeding with SRD triggers the generation of OxS and autophagy in the pituitary gland, which could lead to a decline in Pomc/ACTH/glucocorticoid production. These effects could be attributed to an increase in fatty acids availability to the pituitary gland. ME was able to prevent these alterations, suggesting additional beneficial effects of ME as a therapeutic strategy in the management of IR.

  7. Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress.

    Science.gov (United States)

    Long, Yue; Dong, Xin; Yuan, Yawei; Huang, Jinqiang; Song, Jiangang; Sun, Yumin; Lu, Zhijie; Yang, Liqun; Yu, Weifeng

    2015-07-01

    The study examined the global metabolic and some biochemical changes in rats with cholestasis induced by bile duct ligation (BDL). Serum samples were collected in male Wistar rats with BDL (n = 8) and sham surgery (n = 8) at day 3 after surgery for metabolomics analysis using a combination of reversed phase chromatography and hydrophilic interaction chromatography (HILIC) and quadrupole-time-of-flight mass spectrometry (Q-TOF MS). The serum levels of malondialdehyde (MDA), total antioxidative capacity (T-AOC), glutathione (GSH) and glutathione disulfide (GSSG), the activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) were measured to estimate the oxidative stress state. Key changes after BDL included increased levels of l-phenylalanine, l-glutamate, l-tyrosine, kynurenine, l-lactic acid, LysoPC(c) (14:0), glycine and succinic acid and decreased levels of l-valine, PC(b) (19:0/0:0), taurine, palmitic acid, l-isoleucine and citric acid metabolism products. And treatment with BDL significantly decreased the levels of GSH, T-AOC as well as SOD, GSH-Px activities, and upregulated MDA levels. The changes could be mapped to metabolism of amino acids and lipids, Krebs cycle and glycolysis, as well as increased oxidative stress and decreased antioxidant capability. Our study indicated that BDL induces major changes in the metabolism of all 3 major energy substances, as well as oxidative stress.

  8. Protein oxidation in aquatic foods

    DEFF Research Database (Denmark)

    Baron, Caroline P.

    2014-01-01

    The chapter discusses general considerations about protein oxidation and reviews the mechanisms involved in protein oxidation and consequences of protein oxidation on fish proteins. It presents two case studies, the first deals with protein and lipid oxidation in frozen rainbow trout......, and the second with oxidation in salted herring. The mechanisms responsible for initiation of protein oxidation are unclear, but it is generally accepted that free radical species initiating lipid oxidation can also initiate protein oxidation. The chapter focuses on interaction between protein and lipid...... oxidation. The protein carbonyl group measurement is the widely used method for estimating protein oxidation in foods and has been used in fish muscle. The chapter also talks about the impact of protein oxidation on protein functionality, fish muscle texture, and food nutritional value. Protein oxidation...

  9. Oxidation of uraninite

    International Nuclear Information System (INIS)

    Janeczek, J.; Ewing, R.C.

    1993-06-01

    Samples of uraninite and pitchblende annealed at 1200 degrees C in H 2 , and untreated pitchblende were sequentially oxidized in air at 180-190 degrees C, 230 degrees C, and 300 degrees C. Uraninite and untreated pitchblende oxidized to the U 4 O 9 -type oxide, and their x-ray symmetry remained isometric up to 300 degrees C. Reduced pitchblende, after oxidation to UO 2+x and U 4 O 9 -type oxides, transformed into α-U 3 O 8 at 300 degrees C. Two major mechanisms control uraninite and untreated pitchblende stability during oxidation: 1. Th and/or lanthanide elements maintain charge balance and block oxygen interstitials near impurity cations; 2. the uraninite structure saturates with respect to excess and radiation-induced oxygen interstitials. Untreated pitchblende during oxidation behaved similarly to irradiated UO 2 in spent nuclear fuel; whereas, reduced pitchblende resembled non-irradiated UO 2 . An analysis of the data in the literature, as well as our own efforts (XRD, EMPA, SEM, AEM) to identify U 3 O 7 in samples form Cigar Lake, Canada, failed to provide conclusive evidence of the natural occurrence of tetragonal αU 3 O 7 . Most probably, reported occurrences of U 3 O 7 are mixtures of isometric uraninites of slightly different compositions, 45 refs

  10. Recovery of vanadium oxide

    International Nuclear Information System (INIS)

    Bates, C.P.; Clark, N.E.

    1985-01-01

    This invention relates to the recovery of vanadium oxide from molten metal. The invention provides a method for recovering vanadium oxide from molten metal, which includes passing oxygen and at least one coolant gas or shroud into the molten metal by way of at least one elongate lance. The invention also provides an arrangement for the recovery of vanadium oxide from molten metal, which includes at least one elongate lance extending into the molten metal. The lance is provided with at least one elongate bore extending therethrough. Means are provided to allow at least oxygen and at least one coolant gas to pass through the lance and into the molten metal

  11. Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Qiuqiao Xie

    2016-09-01

    Full Text Available Background/Aims: Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD, isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Methods: Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. Conclusions: DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway.

  12. Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway.

    Science.gov (United States)

    Xie, Qiuqiao; Zhang, Shijun; Chen, Chunxia; Li, Juman; Wei, Xiaojie; Xu, Xiaohui; Xuan, Feifei; Chen, Ning; Pham, Thithaihoa; Qin, Ni; He, Junhui; Ye, Fangxing; Huang, Wansu; Huang, Renbin; Wen, Qingwei

    2016-01-01

    Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD), isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA)-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway. © 2016 The Author(s) Published by S. Karger AG, Basel.

  13. High Current Oxide Cathodes

    National Research Council Canada - National Science Library

    Luhmann, N

    2000-01-01

    The aim of the AASERT supported research is to develop the plasma deposition/implantation process for coating barium, strontium and calcium oxides on nickel substrates and to perform detailed surface...

  14. Markers of protein oxidation

    DEFF Research Database (Denmark)

    Headlam, Henrietta A; Davies, Michael Jonathan

    2004-01-01

    Exposure of proteins to radicals in the presence of O2 gives both side-chain oxidation and backbone fragmentation. These processes can be interrelated, with initial side-chain oxidation giving rise to backbone damage via transfer reactions. We have shown previously that alkoxyl radicals formed...... of this process depends on the extent of oxidation at C-3 compared with other sites. HO*, generated by gamma radiolysis, gave the highest total carbonyl yield, with protein-bound carbonyls predominating over released. In contrast, metal ion/H2O2 systems, gave more released than bound carbonyls, with this ratio...... modulated by EDTA. This is ascribed to metal ion-protein interactions affecting the sites of initial oxidation. Hypochlorous acid gave low concentrations of released carbonyls, but high yields of protein-bound material. The peroxyl radical generator 2,2'-azobis(2-amidinopropane) hydrochloride...

  15. Oxidizer in phosphoric reactors

    International Nuclear Information System (INIS)

    Santos Benedetto, J. dos

    1985-01-01

    Oxidation during the manufacture of wet-process phosphoric acid affected the distribution of uranium and impurities between phosphoric acid and gypsum, by decreasing the uranium loss to gypsum and the impurities solubilization in phosphoric acid. (Author) [pt

  16. Single sheet iron oxides

    DEFF Research Database (Denmark)

    Yin, Zhou

    profile with reversible reduction and oxidation, suggesting the formation of FeII-OH/O-FeIII clusters as that in GRs were formed on the ITO electrode (trichloroethylene (TCE), tetrachloride (CT) and 4-chlorophenol are used to test...

  17. High Current Oxide Cathodes

    National Research Council Canada - National Science Library

    Luhmann, N

    2000-01-01

    .... The vacuum are plasma deposition gun developed at Lawrence Berkeley National Laboratory (LBNL) has been used to deposit oxides and nitrides with very precise control over deposition rate and composition.

  18. Titanium oxide fever

    International Nuclear Information System (INIS)

    De Jonge, D.; Visser, J.

    2012-01-01

    One measure to improve air quality is to apply photo-catalytic substances that capture NOx onto the road surface or onto baffle boards alongside the roads. The effect of titanium oxide containing clinkers with coating was discussed in the report 'Demonstration project of air-purifying pavement in Hengelo, The Netherlands' that was published in May 2011. This article examines the way in which the effectiveness of this study was determined. Can titanium oxide containing clinkers and coatings indeed capture NOx?. [nl

  19. Metal atom oxidation laser

    International Nuclear Information System (INIS)

    Jensen, R.J.; Rice, W.W.; Beattie, W.H.

    1975-01-01

    A chemical laser which operates by formation of metal or carbon atoms and reaction of such atoms with a gaseous oxidizer in an optical resonant cavity is described. The lasing species are diatomic or polyatomic in nature and are readily produced by exchange or other abstraction reactions between the metal or carbon atoms and the oxidizer. The lasing molecules may be metal or carbon monohalides or monoxides

  20. Chemistry of phospholipid oxidation.

    Science.gov (United States)

    Reis, Ana; Spickett, Corinne M

    2012-10-01

    The oxidation of lipids has long been a topic of interest in biological and food sciences, and the fundamental principles of non-enzymatic free radical attack on phospholipids are well established, although questions about detail of the mechanisms remain. The number of end products that are formed following the initiation of phospholipid peroxidation is large, and is continually growing as new structures of oxidized phospholipids are elucidated. Common products are phospholipids with esterified isoprostane-like structures and chain-shortened products containing hydroxy, carbonyl or carboxylic acid groups; the carbonyl-containing compounds are reactive and readily form adducts with proteins and other biomolecules. Phospholipids can also be attacked by reactive nitrogen and chlorine species, further expanding the range of products to nitrated and chlorinated phospholipids. Key to understanding the mechanisms of oxidation is the development of advanced and sensitive technologies that enable structural elucidation. Tandem mass spectrometry has proved invaluable in this respect and is generally the method of choice for structural work. A number of studies have investigated whether individual oxidized phospholipid products occur in vivo, and mass spectrometry techniques have been instrumental in detecting a variety of oxidation products in biological samples such as atherosclerotic plaque material, brain tissue, intestinal tissue and plasma, although relatively few have achieved an absolute quantitative analysis. The levels of oxidized phospholipids in vivo is a critical question, as there is now substantial evidence that many of these compounds are bioactive and could contribute to pathology. The challenges for the future will be to adopt lipidomic approaches to map the profile of oxidized phospholipid formation in different biological conditions, and relate this to their effects in vivo. This article is part of a Special Issue entitled: Oxidized phospholipids

  1. Thin zirconium oxides

    International Nuclear Information System (INIS)

    Oviedo, Cristina

    2000-01-01

    Polycrystalline Zr and two pure Zr single-crystal samples, one oriented with the normal to the surface parallel to the c-axis of the hcp structure (Z1) and the other with the normal perpendicular to c (Z2), were oxidised at 10 -8 , 10 -7 and 10 -6 Torr and room temperature. Oxidation kinetics, composition and thicknesses of the oxide films formed in each case were analyzed using XPS (X-ray Photoelectron Spectroscopy) as the main technique. The oxidation kinetics followed logarithmic laws in all cases. The deconvolution of XPS Zr3d peaks indicated the formation of two Zr-O compounds before the formation of ZrO 2 . Varying the photoelectrons take-off angle, the compound distribution inside the oxide films could be established. Thus, it was confirmed that the most external oxide, in contact with the gas, was ZrO 2 . The thickness of the films grown at the different pressures was determined. In the polycrystalline samples, thicknesses between 15 and 19 ± 2Angstroem were obtained for pressures between 10 -8 and 10 -6 Torr, in close coincidence with the determined ones for Z2. The thicknesses measured in Z1 were smaller, reaching 13 ± 2Angstroem for the oxidations performed at 10 -6 Torr. (author)

  2. Inhibition of NAPDH Oxidase 2 (NOX2 Prevents Oxidative Stress and Mitochondrial Abnormalities Caused by Saturated Fat in Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Leroy C Joseph

    Full Text Available Obesity and high saturated fat intake increase the risk of heart failure and arrhythmias. The molecular mechanisms are poorly understood. We hypothesized that physiologic levels of saturated fat could increase mitochondrial reactive oxygen species (ROS in cardiomyocytes, leading to abnormalities of calcium homeostasis and mitochondrial function. We investigated the effect of saturated fat on mitochondrial function and calcium homeostasis in isolated ventricular myocytes. The saturated fatty acid palmitate causes a decrease in mitochondrial respiration in cardiomyocytes. Palmitate, but not the monounsaturated fatty acid oleate, causes an increase in both total cellular ROS and mitochondrial ROS. Palmitate depolarizes the mitochondrial inner membrane and causes mitochondrial calcium overload by increasing sarcoplasmic reticulum calcium leak. Inhibitors of PKC or NOX2 prevent mitochondrial dysfunction and the increase in ROS, demonstrating that PKC-NOX2 activation is also required for amplification of palmitate induced-ROS. Cardiomyocytes from mice with genetic deletion of NOX2 do not have palmitate-induced ROS or mitochondrial dysfunction. We conclude that palmitate induces mitochondrial ROS that is amplified by NOX2, causing greater mitochondrial ROS generation and partial depolarization of the mitochondrial inner membrane. The abnormal sarcoplasmic reticulum calcium leak caused by palmitate could promote arrhythmia and heart failure. NOX2 inhibition is a potential therapy for heart disease caused by diabetes or obesity.

  3. Does oxidative stress shorten telomeres?

    NARCIS (Netherlands)

    Boonekamp, Jelle J.; Bauch, Christina; Mulder, Ellis; Verhulst, Simon

    Oxidative stress shortens telomeres in cell culture, but whether oxidative stress explains variation in telomere shortening in vivo at physiological oxidative stress levels is not well known. We therefore tested for correlations between six oxidative stress markers and telomere attrition in nestling

  4. Electrochemistry of hydrous oxide films

    International Nuclear Information System (INIS)

    Burke, L.D.; Lyons, M.E.G.

    1986-01-01

    The formation, acid-base properties, structural aspects, and transport processes of hydrous oxide films are discussed. Classical and nonclassical theoretical models of the oxide-solution interface are compared. Monolayer oxidation, behavior, and crystal growth of oxides on platinum, palladium, gold, iridium, rhodium, ruthenium, and some non-noble metals, including tungsten, are reviewed and compared

  5. Porous ceramics out of oxides

    International Nuclear Information System (INIS)

    Bakunov, V.S.; Balkevich, V.L.; Vlasov, A.S.; Guzman, I.Ya.; Lukin, E.S.; Poluboyarinov, D.N.; Poliskij, R.Ya.

    1977-01-01

    A review is made of manufacturing procedures and properties of oxide ceramics intended for high-temperature thermal insulation and thermal protection applications. Presented are structural characteristics of porous oxide refractories and their properties. Strength and thermal conductivity was shown to depend upon porosity. Described is a procedure for manufacturing porous ceramic materials from aluminium oxide, zirconium dioxide, magnesium oxide, beryllium oxide. The thermal resistance of porous ceramics from BeO is considerably greater than that of other high-refractoriness oxides. Listed are areas of application for porous materials based on oxides

  6. Staphylococcal response to oxidative stress

    Directory of Open Access Journals (Sweden)

    Rosmarie eGaupp

    2012-03-01

    Full Text Available Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous oxidative and nitrosative stress are often due to the bacteria’s interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, we summarize the cellular targets of oxidative stress, the mechanisms by which staphylococci sense oxidative stress and damage, oxidative stress protection and repair mechanisms, and regulation of the oxidative stress response. When possible, special attention is given to how the oxidative stress defense mechanisms help staphylococci control oxidative stress in the host.

  7. Effects of Eleutherococcus senticosus Cortex on Recovery from the Forced Swimming Test and Fatty Acid β-Oxidation in the Liver and Skeletal Muscle of mice.

    Science.gov (United States)

    Sumiyoshi, Maho; Kimura, Yoshiyuki

    2016-03-01

    The root and stem barks of Eleutherococcus senticosus have been used to treat emotional and physical fatigue in China, Russia, Korea, and Japan. The effects of E. senticosus on recovery from physical fatigue and the expenditure of energy currently remain unclear. We herein examined the effects of E. senticosus extract on recovery from physical fatigue after the forced swimming test as well as fatty acid β-oxidation in the liver and skeletal muscle of mice. 1) Physical fatigue; E. senticosus extract (500 and 1000 mg/kg, twice daily) was administered orally to ICR male mice for 7 consecutive days. After swimming had been performed for 15 min, each mouse was placed on the cover of a 100-mm culture plate, and the time for each mouse to move away from the cover was measured. 2) Fatty acid β-oxidation in the liver and skeletal muscle; E. senticosus extract (500 and 1000 mg/kg) was administered orally twice daily to C57BL/6J male mice for 21 consecutive days. The initial and final body and liver weight were measured, and then fatty acid β-oxidation activity in the liver and skeletal muscle was measured by methods using [1- 14 C] palmitic acid. Recovery times after forced swimming were shorter in E. senticosus extract (500 and 1000 mg/kg)-treated mice than in vehicle-treated mice. The body and liver weight had no effect by the oral administration of E. senticosus extract, vitamin mixture and L-carnitine. Fatty acid β-oxidation activity in skeletal muscle was increased by E. senticosus extract (500 and 1000 mg/kg). E. senticosus may enhance recovery from physical fatigue induced by forced swimming by accelerating energy changes through fatty acid β-oxidation in skeletal muscle.

  8. Inhibition of inflammation and oxidative stress by an imidazopyridine derivative X22 prevents heart injury from obesity.

    Science.gov (United States)

    Qian, Yuanyuan; Zhang, Yali; Zhong, Peng; Peng, Kesong; Xu, Zheng; Chen, Xuemei; Lu, Kongqin; Chen, Gaozhi; Li, Xiaokun; Liang, Guang

    2016-08-01

    Inflammation and oxidative stress plays an important role in the development of obesity-related complications and cardiovascular disease. Benzimidazole and imidazopyridine compounds are a class of compounds with a variety of activities, including anti-inflammatory, antioxidant and anti-cancer. X22 is an imidazopyridine derivative we synthesized and evaluated previously for anti-inflammatory activity in lipopolysaccharide-stimulated macrophages. However, its ability to alleviate obesity-induced heart injury via its anti-inflammatory actions was unclear. This study was designed to evaluate the cardioprotective effects of X22 using cell culture studies and a high-fat diet rat model. We observed that palmitic acid treatment in cardiac-derived H9c2 cells induced a significant increase in reactive oxygen species, inflammation, apoptosis, fibrosis and hypertrophy. All of these changes were inhibited by treatment with X22. Furthermore, oral administration of X22 suppressed high-fat diet-induced oxidative stress, inflammation, apoptosis, hypertrophy and fibrosis in rat heart tissues and decreased serum lipid concentration. We also found that the anti-inflammatory and anti-oxidative actions of X22 were associated with Nrf2 activation and nuclear factor-kappaB (NF-κB) inhibition, respectively, both in vitro and in vivo. The results of this study indicate that X22 may be a promising cardioprotective agent and that Nrf2 and NF-κB may be important therapeutic targets for obesity-related complications. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  9. Protein oxidation and peroxidation

    DEFF Research Database (Denmark)

    Davies, Michael Jonathan

    2016-01-01

    Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard...... to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners...... and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals...

  10. Bacterium oxidizing carbon monoxide

    Energy Technology Data Exchange (ETDEWEB)

    Kistner, A

    1953-01-01

    Present-day knowledge of the microbiological oxidation of carbon monoxide is based on doubtful observations and imperfect experimental procedures. By making use of shake cultures in contact with gas mixtures containing high concentrations of CO and by employing liquid enrichment media with a low content of organic matter and solid media of the same composition with not more than 1.2% agar, it proved possible to isolate a co-oxidizing bacterium of the genus hydrogenomonas from sewage sludge. For the first time irrefutable proof has been given of the oxidation of carbon monoxide by a pure culture of a bacterium, both in growing cultures and in resting cell suspensions. 12 references.

  11. Zircaloy oxidation studies

    International Nuclear Information System (INIS)

    Prater, J.T.; Beauchamp, R.H.; Saenz, N.T.

    1985-06-01

    The oxidation kinetics of Zircaloy-4 in steam have been determined at 1300-2400 0 C. Growth of the ZrO 2 and α-Zr layers display parabolic behavior over the entire temperature range studied. A discontinuity in the oxidation kinetics at 1510 0 C causes rates to increase above those previously established by the Baker-Just relationship. This increase coincides with the tetragonal-to-cubic phase transformation in ZrO/sub 2-x/. No discontinuity in the oxide growth rate is observed upon melting of Zr(0). The effects of temperature gradients have been taken into account and corrected values representative of near-isothermal conditions have been computed

  12. Oxidative Tritium Decontamination System

    International Nuclear Information System (INIS)

    Gentile, Charles A.; Parker, John J.; Guttadora, Gregory L.; Ciebiera, Lloyd P.

    2002-01-01

    The Princeton Plasma Physics Laboratory, Tritium Systems Group has developed and fabricated an Oxidative Tritium Decontamination System (OTDS), which is designed to reduce tritium surface contamination on various components and items. The system is configured to introduce gaseous ozone into a reaction chamber containing tritiated items that require a reduction in tritium surface contamination. Tritium surface contamination (on components and items in the reaction chamber) is removed by chemically reacting elemental tritium to tritium oxide via oxidation, while purging the reaction chamber effluent to a gas holding tank or negative pressure HVAC system. Implementing specific concentrations of ozone along with catalytic parameters, the system is able to significantly reduce surface tritium contamination on an assortment of expendable and non-expendable items. This paper will present the results of various experimentation involving employment of this system

  13. Krypton oxides under pressure.

    Science.gov (United States)

    Zaleski-Ejgierd, Patryk; Lata, Pawel M

    2016-02-02

    Under high pressure, krypton, one of the most inert elements is predicted to become sufficiently reactive to form a new class of krypton compounds; krypton oxides. Using modern ab-initio evolutionary algorithms in combination with Density Functional Theory, we predict the existence of several thermodynamically stable Kr/O species at elevated pressures. In particular, our calculations indicate that at approx. 300 GPa the monoxide, KrO, should form spontaneously and remain thermo- and dynamically stable with respect to constituent elements and higher oxides. The monoxide is predicted to form non-molecular crystals with short Kr-O contacts, typical for genuine chemical bonds.

  14. Sintering of beryllium oxide

    International Nuclear Information System (INIS)

    Caillat, R.; Pointud, R.

    1955-01-01

    This study had for origin to find a process permitting to manufacture bricks of beryllium oxide of pure nuclear grade, with a density as elevated as possible and with standardized shape. The sintering under load was the technique kept for the manufacture of the bricks. Because of the important toxicity of the beryllium oxide, the general features for the preliminary study of the sintering, have been determined while using alumina. The obtained results will be able to act as general indication for ulterior studies with sintering under load. (M.B.) [fr

  15. Thermal and oxidative stability of Atlantic salmon oil (Salmo salar L. and complexation with β-cyclodextrin

    Directory of Open Access Journals (Sweden)

    Daniel I. Hădărugă

    2016-02-01

    Full Text Available The thermal and oxidative stability of Atlantic salmon oil (Salmo salar L. as well as its β-cyclodextrin (β-CD complexation ability has been verified for the first time. The main omega-3 fatty acids, EPA and DHA, were significantly degraded, even at 50 °C. Their relative concentrations decrease from 6.1% for EPA and 4.1% for DHA to 1.7% and 1.5% after degradation at 150 °C, respectively. On the other hand, the relative concentrations of monounsaturated and saturated fatty acids remained constant or slightly increased by a few percent after degradation (e.g., from 10.7% to 12.9% for palmitic acid. Co-crystallization of ASO with β-CD at a host–guest ratio of 1:1 and 3:1 from an ethanol–water mixture and kneading methods has been used for the preparation of β-CD/ASO complexes. The analysis of the complexes by thermogravimetry, differential scanning calorimetry (DSC, and Karl Fischer titration (KFT as well as the decrease of the “strongly-retained” water content confirm the formation of the inclusion compound. Furthermore, the DSC parameters correlate well with the KFT kinetic data for β-CD/ASO complexes.

  16. Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation.

    Science.gov (United States)

    Nisr, Raid B; Affourtit, Charles

    2014-02-01

    Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. © 2013.

  17. Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation☆

    Science.gov (United States)

    Nisr, Raid B.; Affourtit, Charles

    2014-01-01

    Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. PMID:24212054

  18. Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to particles

    International Nuclear Information System (INIS)

    Vesterdal, Lise K.; Danielsen, Pernille H.; Folkmann, Janne K.; Jespersen, Line F.; Aguilar-Pelaez, Karin; Roursgaard, Martin; Loft, Steffen; Møller, Peter

    2014-01-01

    Exposure to particles has been suggested to generate hepatosteatosis by oxidative stress mechanisms. We investigated lipid accumulation in cultured human hepatocytes (HepG2) and rat liver after exposure to four different carbon-based particles. HepG2 cells were exposed to particles for 3 h and subsequently incubated for another 18 h to manifest lipid accumulation. In an animal model of metabolic syndrome we investigated the association between intake of carbon black (CB, 14 nm) particles and hepatic lipid accumulation, inflammation and gene expression of Srebp-1, Fasn and Scd-1 involved in lipid synthesis. There was a concentration-dependent increase in intracellular lipid content after exposure to CB in HepG2 cells, which was only observed after co-exposure to oleic/palmitic acid. Similar results were observed in HepG2 cells after exposure to diesel exhaust particles, fullerenes C 60 or pristine single-walled carbon nanotubes. All four types of particles also generated oxidatively damaged DNA, assessed as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after 3 h exposure. The animal model of metabolic syndrome showed increased lipid load in the liver after one oral exposure to 6.4 mg/kg of CB in lean Zucker rats. This was not associated with increased iNOS staining in the liver, indicating that the oral CB exposure was associated with hepatic steatosis rather than steatohepatitis. The lipid accumulation did not seem to be related to increased lipogenesis because there were unaltered gene expression levels in both the HepG2 cells and rat livers. Collectively, exposure to particles is associated with oxidative stress and steatosis in hepatocytes. - Highlights: • Oral exposure to nanosized carbon black was associated with hepatosteatosis in rats. • In vitro studies included carbon black, C 60 , diesel exhaust particles and SWCNTs. • Exposure to particles and free fatty acids increased lipid load in HepG2 cells. • Unaltered expression

  19. Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to particles

    Energy Technology Data Exchange (ETDEWEB)

    Vesterdal, Lise K.; Danielsen, Pernille H.; Folkmann, Janne K.; Jespersen, Line F.; Aguilar-Pelaez, Karin; Roursgaard, Martin; Loft, Steffen; Møller, Peter, E-mail: pemo@sund.ku.dk

    2014-01-15

    Exposure to particles has been suggested to generate hepatosteatosis by oxidative stress mechanisms. We investigated lipid accumulation in cultured human hepatocytes (HepG2) and rat liver after exposure to four different carbon-based particles. HepG2 cells were exposed to particles for 3 h and subsequently incubated for another 18 h to manifest lipid accumulation. In an animal model of metabolic syndrome we investigated the association between intake of carbon black (CB, 14 nm) particles and hepatic lipid accumulation, inflammation and gene expression of Srebp-1, Fasn and Scd-1 involved in lipid synthesis. There was a concentration-dependent increase in intracellular lipid content after exposure to CB in HepG2 cells, which was only observed after co-exposure to oleic/palmitic acid. Similar results were observed in HepG2 cells after exposure to diesel exhaust particles, fullerenes C{sub 60} or pristine single-walled carbon nanotubes. All four types of particles also generated oxidatively damaged DNA, assessed as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after 3 h exposure. The animal model of metabolic syndrome showed increased lipid load in the liver after one oral exposure to 6.4 mg/kg of CB in lean Zucker rats. This was not associated with increased iNOS staining in the liver, indicating that the oral CB exposure was associated with hepatic steatosis rather than steatohepatitis. The lipid accumulation did not seem to be related to increased lipogenesis because there were unaltered gene expression levels in both the HepG2 cells and rat livers. Collectively, exposure to particles is associated with oxidative stress and steatosis in hepatocytes. - Highlights: • Oral exposure to nanosized carbon black was associated with hepatosteatosis in rats. • In vitro studies included carbon black, C{sub 60}, diesel exhaust particles and SWCNTs. • Exposure to particles and free fatty acids increased lipid load in HepG2 cells. • Unaltered

  20. Catalytic Oxidation of Cyanogen Chloride over a Monolithic Oxidation Catalyst

    National Research Council Canada - National Science Library

    Campbell, Jeffrey

    1997-01-01

    The catalytic oxidation of cyanogen chloride was evaluated over a monolithic oxidation catalyst at temperatures between 200 and 300 deg C in air employing feed concentrations between 100 and 10,000 ppm...

  1. Uranium oxidation: characterization of oxides formed by reaction with water

    International Nuclear Information System (INIS)

    Fuller, E.L. Jr.; Smyrl, N.R.; Condon, J.B.; Eager, M.H.

    1983-01-01

    Three different uranium oxide samples have been characterized with respect to the different preparation techniques. Results show that the water reaction with uranium metal occurs cyclically forming laminar layers of oxide which spall off due to the strain at the oxide/metal interface. Single laminae are released if liquid water is present due to the prizing penetration at the reaction zone. The rate of reaction of water with uranium is directly proportional to the amount of adsorbed water on the oxide product. Rapid transport is effected through the open hydrous oxide product. Dehydration of the hydrous oxide irreversibly forms a more inert oxide which cannot be rehydrated to the degree that prevails in the original hydrous product of uranium oxidation with water. 27 figures

  2. Green oxidations: Titanium dioxide induced tandem oxidation coupling reactions

    OpenAIRE

    Jeena, Vineet; Robinson, Ross S

    2009-01-01

    Summary The application of titanium dioxide as an oxidant in tandem oxidation type processes is described. Under microwave irradiation, quinoxalines have been synthesized in good yields from the corresponding ?-hydroxyketones.

  3. Calculation procedure for formulating lauric and palmitic fat blends based on the grouping of triacylglycerol melting points; Procedimiento de cálculo para la formulación de mezclas de grasas lauricas y palmíticas basadas en el agrupamiento de puntos de fusión de triacilgliceroles

    Energy Technology Data Exchange (ETDEWEB)

    Nusantoro, B.P.; Yanty, N.A.M.; Van de Walle, D.; Hidayat, C.; Danthine, S.; Dewettinck, K.

    2017-07-01

    A calculation procedure for formulating lauric and palmitic fat blends has been developed based on grouping TAG melting points. This procedure offered more flexibility in choos