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Sample records for acid ffa level

  1. Selective Orthosteric Free Fatty Acid Receptor 2 (FFA2) Agonists

    PubMed Central

    Schmidt, Johannes; Smith, Nicola J.; Christiansen, Elisabeth; Tikhonova, Irina G.; Grundmann, Manuel; Hudson, Brian D.; Ward, Richard J.; Drewke, Christel; Milligan, Graeme; Kostenis, Evi; Ulven, Trond

    2011-01-01

    Free fatty acid receptor 2 (FFA2; GPR43) is a G protein-coupled seven-transmembrane receptor for short-chain fatty acids (SCFAs) that is implicated in inflammatory and metabolic disorders. The SCFA propionate has close to optimal ligand efficiency for FFA2 and can hence be considered as highly potent given its size. Propionate, however, does not discriminate between FFA2 and the closely related receptor FFA3 (GPR41). To identify FFA2-selective ligands and understand the molecular basis for FFA2 selectivity, a targeted library of small carboxylic acids was examined using holistic, label-free dynamic mass redistribution technology for primary screening and the receptor-proximal G protein [35S]guanosine 5′-(3-O-thio)triphosphate activation, inositol phosphate, and cAMP accumulation assays for hit confirmation. Structure-activity relationship analysis allowed formulation of a general rule to predict selectivity for small carboxylic acids at the orthosteric binding site where ligands with substituted sp3-hybridized α-carbons preferentially activate FFA3, whereas ligands with sp2- or sp-hybridized α-carbons prefer FFA2. The orthosteric binding mode was verified by site-directed mutagenesis: replacement of orthosteric site arginine residues by alanine in FFA2 prevented ligand binding, and molecular modeling predicted the detailed mode of binding. Based on this, selective mutation of three residues to their non-conserved counterparts in FFA3 was sufficient to transfer FFA3 selectivity to FFA2. Thus, selective activation of FFA2 via the orthosteric site is achievable with rather small ligands, a finding with significant implications for the rational design of therapeutic compounds selectively targeting the SCFA receptors. PMID:21220428

  2. Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120).

    PubMed

    Sparks, Steven M; Chen, Grace; Collins, Jon L; Danger, Dana; Dock, Steven T; Jayawickreme, Channa; Jenkinson, Stephen; Laudeman, Christopher; Leesnitzer, M Anthony; Liang, Xi; Maloney, Patrick; McCoy, David C; Moncol, David; Rash, Vincent; Rimele, Thomas; Vulimiri, Padmaja; Way, James M; Ross, Sean

    2014-07-15

    The exploration of a diarylsulfonamide series of free fatty acid receptor 4 (FFA4/GPR120) agonists is described. This work led to the identification of selective FFA4 agonist 8 (GSK137647A) and selective FFA4 antagonist 39. The in vitro profile of compounds 8 and 39 is presented herein.

  3. Extracellular Ionic Locks Determine Variation in Constitutive Activity and Ligand Potency between Species Orthologs of the Free Fatty Acid Receptors FFA2 and FFA3*

    PubMed Central

    Hudson, Brian D.; Tikhonova, Irina G.; Pandey, Sunil K.; Ulven, Trond; Milligan, Graeme

    2012-01-01

    Free fatty acid receptors 2 and 3 (FFA2 and FFA3) are G protein-coupled receptors for short chain free fatty acids (SCFAs). They respond to the same set of endogenous ligands but with distinct rank-order of potency such that acetate (C2) has been described as FFA2-selective, whereas propionate (C3) is non-selective. Although C2 was confirmed to be selective for human FFA2 over FFA3, this ligand was not selective between the mouse orthologs. Moreover, although C3 was indeed not selective between the human orthologs, it displayed clear selectivity for mouse FFA3 over mouse FFA2. This altered selectivity to C2 and C3 resulted from broad differences in SCFAs potency at the mouse orthologs. In studies to define the molecular basis for these observations, marked variation in ligand-independent constitutive activity was identified using a [35S]GTPγS assay. The orthologs with higher potency for the SCFAs, human FFA2 and mouse FFA3, displayed high constitutive activity in this assay, whereas the orthologs with lower potency for the agonist ligands, mouse FFA2 and human FFA3, did not. Sequence alignments of the second extracellular loop identified single negatively charged residues in FFA2 and FFA3 not conserved between species and predicted to form ionic lock interactions with arginine residues within the FFA2 or FFA3 agonist binding pocket to regulate constitutive activity and SCFA potency. Reciprocal mutation of these residues between species orthologs resulted in the induction (or repression) of constitutive activity and in most cases also yielded corresponding changes in SCFA potency. PMID:23066016

  4. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    PubMed Central

    Ulven, Trond

    2012-01-01

    The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD). Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and in regulation of appetite. More research is however required to clarify the potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets. PMID:23060857

  5. A New Pain Regulatory System via the Brain Long Chain Fatty Acid Receptor GPR40/FFA1 Signal.

    PubMed

    Nakamoto, Kazuo

    2017-01-01

     An increasingly large number of pharmacological and physiological works on fatty acids have shown that the functional properties of fatty acids are regulated by the amount of individual fatty acid intake and the distribution of fatty acids among organs. Recently, it has been determined that G-protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) is activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). GPR40/FFA1 is mainly expressed in the β cell of the pancreas, spinal cord and brain. It is reported that this receptor has a functional role in controlling blood glucose levels via the modulation of insulin secretion. However, its physiological function in the brain remains unknown. Our previous studies have shown that GPR40/FFA1 is expressed in pro-opiomelanocortin (POMC)-positive neurons of the arcuate nucleus, serotonergic neurons in the nucleus raphe magnus, and in noradrenergic neurons in the locus coeruleus. Furthermore, the intracerebroventricular injection of DHA or GW9508, which is a selective GPR40/FFA1 agonist, attenuates formalin-induced inflammatory pain behavior through increasing β-endorphin release in the hypothalamus. It also suppresses complete Freund's adjuvant-induced mechanical allodynia and thermal hyperalgesia. Our findings suggest that brain free long-chain fatty acids-GPR40/FFA1 signaling might have an important role in the modulation of endogenous pain control systems. In this review, I discuss the current status and our recent study regarding a new pain regulatory system via the brain long chain fatty acid receptor GPR40/FFA1 signal.

  6. Effects of arachidonic acid on FFA4 receptor: Signaling, phosphorylation and internalization.

    PubMed

    Villegas-Comonfort, S; Takei, Y; Tsujimoto, G; Hirasawa, A; García-Sáinz, J A

    2017-02-01

    Arachidonic acid increased intracellular calcium, in cells expressing green fluorescent protein-tagged human FFA4 receptors, with an EC50 of ~40µM. This action was not blocked by cyclooxygenase or lipoxigenase inhibitors but it was inhibited by AH7614, a FFA4 antagonist. Arachidonic acid induced ERK activation accompanied by EGF receptor transactivation. However, EGF transactivation was not the major mechanism through which the fatty acid induced ERK phosphorylation, as evidenced by the inability of AG1478 to block it. Arachidonic acid increased FFA4 receptor phosphorylation that reached its maximum within 15min with an EC50 of ~30µM; inhibitors of protein kinase C partially diminish this effect and AH7614 blocked it. Arachidonic acid induced rapid and sustained Akt/PKB phosphorylation and FFA4 - β-arrestin interaction. Confocal microscopy evidenced that FFA4 receptor activation and phosphorylation were associated to internalization. In conclusion, arachidonic acid is a bona fide FFA4 receptor agonist.

  7. Omega-3 polyunsaturated fatty acids accelerate airway repair by activating FFA4 in club cells.

    PubMed

    Lee, Kyoung-Pil; Park, Soo-Jin; Kang, Saeromi; Koh, Jung-Min; Sato, Koichi; Chung, Hae Young; Okajima, Fumikazu; Im, Dong-Soon

    2017-03-17

    A GPCR named FFA4 (also known as GPR120) was found to act as a GPCR for omega-3 polyunsaturated fatty acids. Its expression has been reported in lung epithelial club cells. The authors investigated whether supplementation of the omega-3 fatty acids benefits lung health. Omacor® (7.75 mg kg-1), clinically prescribed preparation of omega-3 fatty acids and FFA4-knockout mice were utilized in a naphthalene-induced mouse model of acute airway injury (one injection of 30 mg kg-1, i.p.). Naphthalene injection induced complete destruction of bronchiolar epithelial cells within a day. Appearance of bronchiolar epithelial cells was observed after 21 days in control mice. It was found, however, that supplementation of omacor accelerated the recovery. The appearance of bronchiolar epithelial cells was observed between 7 and 14 days after naphthalene injury in omacor-treated mice. In isolated club cells, omega-3 fatty acids were found to stimulate cell proliferation and migration but to inhibit cell differentiation. Using pharmacological tools and FFA4-knockout mice, FFA4 was found to be responsible for omega-3 fatty acids-induced proliferation in vitro in club cells. Furthermore, accelerated recovery from naphthalene-induced airway injury in omacor-treated mice was not observed in FFA4-knockout mice in vivo. Present findings indicate that omega-3 fatty acids-induced proliferation of bronchiole epithelial cells through FFA4 is responsible for omacor-induced accelerated recovery from airway injury. Therefore, intermittent administration of omacor needs to be tested for acute airway injury, because omega-3 fatty acids stimulate proliferation but inhibits differentiation of club cells.

  8. [Profile of free fatty acids (FFA) in serum of young Colombians with obesity and metabolic syndrome].

    PubMed

    Bermudez, J A; Velásquez, C M

    2014-12-01

    Obesity produces greater circulation of free fatty acids (FFA). In adults, the FFA composition changes in states of obesity; in adolescents, the results are contradictory. This study compare the FFA profile of obese youth with and without Metabolic Syndrome (MetS) and explore the association between FFA and metabolic alterations of obesity and MetS. A cross-sectional study with 96 young people between 10 and 18 years old was divided into three groups: 1) obese youth with MetS, 2) obese youth without MetS; and 3) adequate weight (AW), matched according to age, gender, pubertal maturation and socioeconomic stratum. The nutritional status was classified according to the body-mass index (BMI), according to the World Health Organization 2007 (WHO, 2007); the waist circumference (WC), adiposity, lipid profile, highly-sensitive reactive C protein (hsRCP), glucose, insulin and insulin resistance (IR), according to the homeostatic model assessment (HOMA Calculator Version 2.2.2). The FFA serum concentration was determined by gas chromatography. Both obese groups had higher adiposity, inflamation (hsRCP), FFA totals and frequency palmitoleic-16:Jn7, compared to AW. The obese with MetS presented more metabolic alterations, a greater amount of dihomo-γ-linolenic (DHGL-20:3n6) and a 20:3n6/18:2n6 relation, indicative of increased activity of A6 desaturase (D6D). The FFA totals, palmitoleic-l6:1n7, DHGL-20:3n6, D6D activity and hsRCP significantly correlated with variables of adiposity, IR and triglicerides. The results in obese with MetS corroborate the association among central obesity, inflammation and increased lipolysis in visceral adipose tissue and metabolic alterations.

  9. The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis.

    PubMed

    Fuller, Miles; Priyadarshini, Medha; Gibbons, Sean M; Angueira, Anthony R; Brodsky, Michael; Hayes, M Geoffrey; Kovatcheva-Datchary, Petia; Bäckhed, Fredrik; Gilbert, Jack A; Lowe, William L; Layden, Brian T

    2015-11-15

    The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene (Ffar2) expression is higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2-/- mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Together, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.

  10. The short chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis

    DOE PAGES

    Fuller, Miles; Priyadarshini, Medha; Gibbons, Sean M.; ...

    2015-09-22

    The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene (Ffar2) expression ismore » higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2-/- mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Altogether, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.« less

  11. The short chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis

    SciTech Connect

    Fuller, Miles; Priyadarshini, Medha; Gibbons, Sean M.; Angueira, Anthony R.; Brodsky, Michael; Hayes, M. Geoffrey; Kovatcheva-Datchary, Petia; Backhed, Fredrik; Gilbert, Jack A.; Lowe, Jr., William L.; Layden, Brian T.

    2015-09-22

    The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene (Ffar2) expression is higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2-/- mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Altogether, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.

  12. The Molecular Basis of Ligand Interaction at Free Fatty Acid Receptor 4 (FFA4/GPR120)*

    PubMed Central

    Hudson, Brian D.; Shimpukade, Bharat; Milligan, Graeme; Ulven, Trond

    2014-01-01

    The long-chain fatty acid receptor FFA4 (previously GPR120) is receiving substantial interest as a novel target for the treatment of metabolic and inflammatory disease. This study examines for the first time the detailed mode of binding of both long-chain fatty acid and synthetic agonist ligands at FFA4 by integrating molecular modeling, receptor mutagenesis, and ligand structure-activity relationship approaches in an iterative format. In doing so, residues required for binding of fatty acid and synthetic agonists to FFA4 have been identified. This has allowed for the refinement of a well validated model of the mode of ligand-FFA4 interaction that will be invaluable in the identification of novel ligands and the future development of this receptor as a therapeutic target. The model reliably predicted the effects of substituent variations on agonist potency, and it was also able to predict the qualitative effect of binding site mutations in the majority of cases. PMID:24860101

  13. Omega-3 fatty acids and other FFA4 agonists inhibit growth factor signaling in human prostate cancer cells.

    PubMed

    Liu, Ze; Hopkins, Mandi M; Zhang, Zhihong; Quisenberry, Chrystal B; Fix, Louise C; Galvan, Brianna M; Meier, Kathryn E

    2015-02-01

    Omega-3 fatty acids (n-3 FAs) are proposed to have many beneficial effects on human health. However, the mechanisms underlying their potential cancer preventative effects are unclear. G protein-coupled receptors (GPCRs) of the free fatty acid receptor (FFAR) family, FFA1/GPR40 and FFA4/GPR120, specifically bind n-3 FAs as agonist ligands. In this study, we examined the effects of n-3 FAs in human prostate cancer cell lines. Initial studies established that the long-chain n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid, inhibit proliferation of DU145 cells in response to lysophosphatidic acid (LPA), a mitogenic lipid mediator. When added alone to serum-starved DU145 cells, EPA transiently activates signaling events, including p70S6K phosphorylation. However, when added 15 minutes prior to LPA, EPA suppresses LPA-induced activating phosphorylations of ERK, FAK, and p70S6K, and expression of the matricellular protein CCN1. The rapid onset of the inhibitory action of EPA suggested involvement of a GPCR. Further studies showed that DU145 and PC-3 cells express mRNA and protein for both FFA4 and FFA1. TUG-891 (4-[(4-fluoro-4'-methyl[1,1'-biphenyl]-2-yl)methoxy]-benzenepropanoic acid), a selective agonist for FFA4, exerts inhibitory effects on LPA- and epidermal growth factor-induced proliferation and migration, similar to EPA, in DU145 and PC-3 cells. The effects of TUG-891 and EPA are readily reversible. The FFA1/FFA4 agonist GW9508 (4-[[(3-phenoxyphenyl)methyl]amino]-benzenepropranoic acid) likewise inhibits proliferation at doses that block FFA4. Knockdown of FFA4 expression prevents EPA- and TUG-891-induced inhibition of growth and migration. Together, these results indicate that activation of FFA4 initiates signaling events that can inhibit growth factor-induced signaling, providing a novel mechanism for suppression of cancer cell proliferation.

  14. Relationship of Length of Vocational Agriculture Teacher Contract to Supervised Occupational Experience Program Scope and FFA Chapter Activity Level.

    ERIC Educational Resources Information Center

    Arrington, Larry R.

    A study examined the relationship of length of vocational agriculture teacher contract to supervised occupational experience program scope and Future Farmers of America (FFA) chapter activity level. A questionnaire measuring the activity level of the FFA chapter and soliciting information on various extraneous variables was administered to the…

  15. Liver free fatty acid (FFA) accumulation as an indicator of ischemic injury during cold preservation

    SciTech Connect

    Nemoto, E.M.; Kang, Y.; DeWolf, A.M.; Lin, M.R.; Bleyaert, A.L.; Winter, P.M.

    1987-05-01

    Reliable assessment of hepatic viability prior to harvest and transplant could improve graft success and aid in evaluating the efficacy of liver preservation techniques. Hepatic tissue metabolites, protein (Pr) synthesis, and ATP have been studied, but none reliably correlate with hepatic viability. Therefore, they studied changes in liver FFA relative to changes in ATP and Pr synthesis during cold ischemic preservation. Rats mechanically ventilated on 0.5% isoflurane/70% N/sub 2/O/30% O/sub 2/ were heparinized and their livers perfused with air-equilibrated Euro-Collins solution (ECS) at 0-4/sup 0/C and kept on ice. A piece of the liver was removed after 0, 2, 6, 8, 12, 24, 36 and 48 h of preservation for ATP and FFA analysis. A portion of the liver was sliced (250 ..mu..m thick) and incubated in vitro for /sup 14/C-lysine incorporation in albumin. ATP, FFA and Pr synthesis were unchanged in the first 8 h, but markedly decreased between 8 and 12 h with little change thereafter. In contrast, between 8 and 48 h, arachidonic and stearic acids increased by 5 and 2-fold, respectively. Changes in ATP and Pr synthesis correlate with the empirically derived clinical maximum of 8 to 12 h preservation. FFA accumulation appears to reflect hepatic ischemic injury and may be a means of evaluating the quality of a donor liver.

  16. Dietary Fatty Acids and Their Potential for Controlling Metabolic Diseases Through Activation of FFA4/GPR120.

    PubMed

    Ulven, Trond; Christiansen, Elisabeth

    2015-01-01

    It is well known that the amount and type of ingested fat impacts the development of obesity and metabolic diseases, but the potential for beneficial effects from fat has received less attention. It is becoming clear that the composition of the individual fatty acids in diet is important. Besides acting as precursors of potent signaling molecules, dietary fatty acids act directly on intracellular and cell surface receptors. The free fatty acid receptor 4 (FFA4, previously GPR120) is linked to the regulation of body weight, inflammation, and insulin resistance and represents a potential target for the treatment of metabolic disorders, including type 2 diabetes and obesity. In this review, we discuss the various types of dietary fatty acids, the link between FFA4 and metabolic diseases, the potential effects of the individual fatty acids on health, and the ability of fatty acids to activate FFA4. We also discuss the possibility of dietary schemes that implement activation of FFA4.

  17. Structure−Activity Study of Dihydrocinnamic Acids and Discovery of the Potent FFA1 (GPR40) Agonist TUG-469

    PubMed Central

    2010-01-01

    The free fatty acid 1 receptor (FFA1 or GPR40), which is highly expressed on pancreatic β-cells and amplifies glucose-stimulated insulin secretion, has emerged as an attractive target for the treatment of type 2 diabetes. Several FFA1 agonists containing the para-substituted dihydrocinnamic acid moiety are known. We here present a structure−activity relationship study of this compound family suggesting that the central methyleneoxy linker is preferable for the smaller compounds, whereas the central methyleneamine linker gives higher potency to the larger compounds. The study resulted in the discovery of the potent and selective full FFA1 agonist TUG-469 (29). PMID:24900217

  18. Defining the Molecular Basis for the First Potent and Selective Orthosteric Agonists of the FFA2 Free Fatty Acid Receptor*

    PubMed Central

    Hudson, Brian D.; Due-Hansen, Maria E.; Christiansen, Elisabeth; Hansen, Anna Mette; Mackenzie, Amanda E.; Murdoch, Hannah; Pandey, Sunil K.; Ward, Richard J.; Marquez, Rudi; Tikhonova, Irina G.; Ulven, Trond; Milligan, Graeme

    2013-01-01

    FFA2 is a G protein-coupled receptor that responds to short chain fatty acids and has generated interest as a therapeutic target for metabolic and inflammatory conditions. However, definition of its functions has been slowed by a dearth of selective ligands that can distinguish it from the closely related FFA3. At present, the only selective ligands described for FFA2 suffer from poor potency, altered signaling due to allosteric modes of action, or a lack of function at non-human orthologs of the receptor. To address the need for novel selective ligands, we synthesized two compounds potentially having FFA2 activity and examined the molecular basis of their function. These compounds were confirmed to be potent and selective orthosteric FFA2 agonists. A combination of ligand structure-activity relationship, pharmacological analysis, homology modeling, species ortholog comparisons, and mutagenesis studies were then employed to define the molecular basis of selectivity and function of these ligands. From this, we identified key residues within both extracellular loop 2 and the transmembrane domain regions of FFA2 critical for ligand function. One of these ligands was active with reasonable potency at rodent orthologs of FFA2 and demonstrated the role of FFA2 in inhibition of lipolysis and glucagon-like peptide-1 secretion in murine-derived 3T3-L1 and STC-1 cell lines, respectively. Together, these findings describe the first potent and selective FFA2 orthosteric agonists and demonstrate key aspects of ligand interaction within the binding site of FFA2 that will be invaluable in future ligand development at this receptor. PMID:23589301

  19. Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40*

    PubMed Central

    Schmidt, Johannes; Liebscher, Kathrin; Merten, Nicole; Grundmann, Manuel; Mielenz, Manfred; Sauerwein, Helga; Christiansen, Elisabeth; Due-Hansen, Maria E.; Ulven, Trond; Ullrich, Susanne; Gomeza, Jesús; Drewke, Christel; Kostenis, Evi

    2011-01-01

    Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravation of insulin resistance and the risk of developing diabetes. However, the mechanisms accounting for the effects of CLAs on glucose homeostasis are incompletely understood. Herein we provide evidence that CLAs specifically activate the cell surface receptor FFA1, an emerging therapeutic target to treat type 2 diabetes. Using different recombinant cellular systems engineered to stably express FFA1 and a set of diverse functional assays including the novel, label-free non-invasive dynamic mass redistribution technology (Corning® Epic® biosensor), both CLA isomers cis-9, trans-11-CLA and trans-10, cis-12-CLA were found to activate FFA1 in vitro at concentrations sufficient to also account for FFA1 activation in vivo. Each CLA isomer markedly increased glucose-stimulated insulin secretion in insulin-producing INS-1E cells that endogenously express FFA1 and in primary pancreatic β-cells of wild type but not FFA1−/− knock-out mice. Our findings establish a clear mechanistic link between CLAs and insulin production and identify the cell surface receptor FFA1 as a molecular target for CLAs, explaining their acute stimulatory effects on insulin secretion in vivo. CLAs are also revealed as insulinotropic components in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes. PMID:21339298

  20. FFA Contests

    ERIC Educational Resources Information Center

    Schumann, Herbert

    1977-01-01

    A teacher educator gives reasons why the vocational agriculture teacher should become involved in preparing his students for Future Farmers of America (FFA) contests and some steps and precautions he should take to successfully integrate FFA contests into the instructional program. (MF)

  1. Concomitant Action of Structural Elements and Receptor Phosphorylation Determines Arrestin-3 Interaction with the Free Fatty Acid Receptor FFA4*

    PubMed Central

    Butcher, Adrian J.; Hudson, Brian D.; Shimpukade, Bharat; Alvarez-Curto, Elisa; Prihandoko, Rudi; Ulven, Trond; Milligan, Graeme; Tobin, Andrew B.

    2014-01-01

    In addition to being nutrients, free fatty acids act as signaling molecules by activating a family of G protein-coupled receptors. Among these is FFA4, previously called GPR120, which responds to medium and long chain fatty acids, including health-promoting ω-3 fatty acids, which have been implicated in the regulation of metabolic and inflammatory responses. Here we show, using mass spectrometry, mutagenesis, and phosphospecific antibodies, that agonist-regulated phosphorylation of the human FFA4 receptor occurred primarily at five residues (Thr347, Thr349, Ser350, Ser357, and Ser360) in the C-terminal tail. Mutation of these residues reduced both the efficacy and potency of ligand-mediated arrestin-3 recruitment as well as affecting recruitment kinetics. Combined mutagenesis of all five of these residues was insufficient to fully abrogate interaction with arrestin-3, but further mutagenesis of negatively charged residues revealed additional structural components for the interaction with arrestin-3 within the C-terminal tail of the receptor. These elements consist of the acidic residues Glu341, Asp348, and Asp355 located close to the phosphorylation sites. Receptor phosphorylation thus operates in concert with structural elements within the C-terminal tail of FFA4 to allow for the recruitment of arrestin-3. Importantly, these mechanisms of arrestin-3 recruitment operate independently from Gq/11 coupling, thereby offering the possibility that ligands showing stimulus bias could be developed that exploit these differential coupling mechanisms. Furthermore, this provides a strategy for the design of biased receptors to probe physiologically relevant signaling. PMID:24817122

  2. Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes

    PubMed Central

    2013-01-01

    Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing. PMID:23687558

  3. Prevocational Agribusiness and the FFA

    ERIC Educational Resources Information Center

    James, Kenneth A.

    1975-01-01

    The author discusses the development of the career education concept relating to agribusiness at the junior high and middle school level. In the prevocational agribusiness program, it is also effective to supplement the program with an FFA chapter. (JB)

  4. The Pharmacology of TUG-891, a Potent and Selective Agonist of the Free Fatty Acid Receptor 4 (FFA4/GPR120), Demonstrates Both Potential Opportunity and Possible Challenges to Therapeutic Agonism

    PubMed Central

    Hudson, Brian D.; Shimpukade, Bharat; Mackenzie, Amanda E.; Butcher, Adrian J.; Pediani, John D.; Christiansen, Elisabeth; Heathcote, Helen; Tobin, Andrew B.; Ulven, Trond

    2013-01-01

    TUG-891 [3-(4-((4-fluoro-4′-methyl-[1,1′-biphenyl]-2-yl)methoxy)phenyl)propanoic acid] was recently described as a potent and selective agonist for the long chain free fatty acid (LCFA) receptor 4 (FFA4; previously G protein–coupled receptor 120, or GPR120). Herein, we have used TUG-891 to further define the function of FFA4 and used this compound in proof of principle studies to indicate the therapeutic potential of this receptor. TUG-891 displayed similar signaling properties to the LCFA α-linolenic acid at human FFA4 across various assay end points, including stimulation of Ca2+ mobilization, β-arrestin-1 and β-arrestin-2 recruitment, and extracellular signal-regulated kinase phosphorylation. Activation of human FFA4 by TUG-891 also resulted in rapid phosphorylation and internalization of the receptor. While these latter events were associated with desensitization of the FFA4 signaling response, removal of TUG-891 allowed both rapid recycling of FFA4 back to the cell surface and resensitization of the FFA4 Ca2+ signaling response. TUG-891 was also a potent agonist of mouse FFA4, but it showed only limited selectivity over mouse FFA1, complicating its use in vivo in this species. Pharmacologic dissection of responses to TUG-891 in model murine cell systems indicated that activation of FFA4 was able to mimic many potentially beneficial therapeutic properties previously reported for LCFAs, including stimulating glucagon-like peptide-1 secretion from enteroendocrine cells, enhancing glucose uptake in 3T3-L1 adipocytes, and inhibiting release of proinflammatory mediators from RAW264.7 macrophages, which suggests promise for FFA4 as a therapeutic target for type 2 diabetes and obesity. Together, these results demonstrate both potential but also significant challenges that still need to be overcome to therapeutically target FFA4. PMID:23979972

  5. Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study

    PubMed Central

    Zhang, Juanwen; Zhao, Ying; Xu, Chengfu; Hong, Yani; Lu, Huanle; Wu, Jianping; Chen, Yu

    2014-01-01

    High serum free fatty acid (FFA) levels are associated with metabolic syndrome (MS). This study aimed to assess the association of fasting serum FFAs with nonalcoholic fatty liver disease (NAFLD) in a Chinese population. A total of 840 subjects fulfilled the diagnostic criteria of NAFLD and 331 healthy control participants were enrolled in this cross-sectional study. Fasting serum FFA levels and other clinical and laboratory parameters were measured. NAFLD patients had significantly higher serum FFA levels than controls (P < 0.001). Serum FFA levels were significantly and positively correlated with parameters of MS, inflammation indexes, and markers of hepatocellular damage. Elevated serum FFA levels were found in NAFLD subjects with individual components of MS (obesity, hypertriglyceridaemia, and hyperglycaemia). Stepwise regression showed that serum FFA levels were an independent factor predicting advanced fibrosis (FIB-4 ≥ 1.3) in NAFLD patients. Serum FFA levels correlated with NAFLD and could be used as an indicator for predicting advanced fibrosis in NAFLD patients. PMID:25060337

  6. State FFA Officers' Confidence and Trustworthiness of Biotechnology Information Sources

    ERIC Educational Resources Information Center

    Wingenbach, Gary J.; Rutherford, Tracy A.

    2007-01-01

    Are state FFA officers' awareness levels of agricultural topics reported in mass media superior to those who do not serve in leadership roles? The purpose of this study was to determine elected state FFA officers' awareness of biotechnology, and their confidence and trust of biotechnology information sources. Descriptive survey methods were used…

  7. An Examination of Middle School Agricultural Education and FFA Programs: Survey Results from State FFA Executive Secretaries.

    ERIC Educational Resources Information Center

    Rossetti, Rosemarie; McCaslin, N. L.

    A study collected information from 52 of the 53 state Future Farmers of America (FFA) executive secretaries who were sent questionnaires on middle school student enrollment in agricultural education and membership in the national FFA organization. Results showed that 30 states have agricultural education programs in the middle school level, with a…

  8. Effects of Increased Free Fatty Acid Availability on Adipose Tissue Fatty Acid Storage in Men

    PubMed Central

    Mundi, Manpreet S.; Koutsari, Chistina

    2014-01-01

    Context: A portion of free fatty acids (FFA) released from adipose tissue lipolysis are re-stored in adipocytes via direct uptake. Rates of direct adipose tissue FFA storage are much greater in women than men, but women also have greater systemic FFA flux and more body fat. Objective: We tested the hypotheses that experimental increases in FFA in men would equalize the rates of direct adipose tissue FFA storage in men and women. Design: We used a lipid emulsion infusion to raise FFA in men to levels seen in post-absorptive women. Direct FFA storage (μmol·kg fat−1·min−1) rates in abdominal and femoral fat was assessed using stable isotope tracer infusions to measure FFA disappearance rates and an iv FFA radiotracer bolus/timed biopsy. Setting: These studies were performed in a Clinical Research Center. Participants: Data from 13 non-obese women was compared with that from eight obese and eight non-obese men. Intervention: The men received a lipid emulsion infusion to raise FFA. Main Outcome Measures: We measured the rates of direct FFA storage in abdominal and femoral adipose tissue. Results: The three groups were similar in age and FFA flux by design; obese men had similar body fat percentage as non-obese women. Despite matching for FFA concentrations and flux, FFA storage per kg abdominal (P < .01) and femoral (P < .001) fat was less in both lean and obese men than in non-obese women. Abdominal FFA storage rates were correlated with proteins/enzymes in the FFA uptake/triglyceride synthesis pathway in men. Conclusion: The lesser rates of direct FFA adipose tissue in men compared with women cannot be explained by reduced FFA availability. PMID:25192251

  9. Advising an Urban FFA Chapter: A Narrative of Two Urban FFA Advisors

    ERIC Educational Resources Information Center

    Martin, Michael J.; Kitchel, Tracy

    2015-01-01

    Advising an urban FFA chapter can be a challenge for urban agriculture teachers. The contextual differences between the rural-oriented FFA and urban FFA members can make bridging the gap difficult. This narrative study sought to explore how the urban context shapes the work of an FFA chapter from the perspectives of two FFA advisors at the same…

  10. Regulation of prohormone convertase 2 protein expression via GPR40/FFA1 in the hypothalamus.

    PubMed

    Nakamoto, Kazuo; Aizawa, Fuka; Nishinaka, Takashi; Tokuyama, Shogo

    2015-09-05

    Previous studies have shown that the administration of docosahexaenoic acid (DHA) or GW9508, a GPR40/FFA1 (free fatty acid receptor) agonist, facilitates β-endorphin release in the arcuate nucleus of the hypothalamus in mice. However, the mechanisms mediating β-endorphin release induced by GPR40/FFA1 agonists remain unknown. In this study, we focused on the changes in expression of hypothalamic prohormone convertase (PC) 2, which is a calcium-dependent subtilisin-related proteolytic enzyme. The intracerebroventricular injection of DHA or GW9508 significantly increased PC2 protein expression in the hypothalamus. This increase in PC2 expression was inhibited by pretreatment with GW1100, a GPR40/FFA1 antagonist. Furthermore, PC2 protein expression gradually increased over time after complete Freund's adjuvant. These increase in PC2 expression were inhibited by pretreatment with GW1100. However, GW1100 by itself had no effect on PC2 levels. Taken together, our findings suggest that activation of the hypothalamic GPR40/FFA1 signaling pathway may regulate β-endorphin release via PC2, and regulate the endogenous pain control system.

  11. Effects of Acute Supramaximal Cycle Exercise on Plasma FFA Concentration in Obese Adolescent Boys

    PubMed Central

    Jabbour, Georges

    2015-01-01

    Aims The aims of the present study are 1) to evaluate the free fatty acid (FFA) profile and 2) to determine the relative anaerobic and aerobic contributions to total energy consumption during repeated supramaximal cycling bouts (SCE) in adolescent boys with different body weight statuses. Materials and Methods Normal-weight (NW), overweight (OW), and obese (OB) adolescent boys (n =15 per group) completed a SCE sessions consisted of 6 x 6s maximal sprints with 2 min of passive rest between each repetition. Plasma FFA levels were determined at rest, immediately after a 10 min warm-up, and immediately at the end of SCE. The anaerobic and aerobic contributions (%) were measured via repeated SCE bouts. Insulin resistance was calculated using the homoeostatic model assessment (HOMA-IR) index. Results The FFA concentrations measured immediately after SCE were higher in the OB group than in the OW and NW (p<0.01 and p<0.01, respectively) groups. Moreover, the anaerobic contributions to SCE were significantly lower in obese adolescents (p<0.01) and decreased significantly during the 2nd, 3rd and 4th repetitions. The FFA levels were significantly associated with the HOMA-IR index and aerobic contribution among adolescent boys (r=0.83 and r=0.91, respectively, p<0.01). Conclusion In contrast to the NW and OW groups, there is an increase in lipid mobilization and sift to aerobic energy metabolism during SCE in the OB group. PMID:26076464

  12. Adiponectin concentrations increase during acute FFA elevation in humans treated with rosiglitazone.

    PubMed

    Krzyzanowska, K; Mittermayer, F; Krugluger, W; Roden, M; Schernthaner, G; Wolzt, M

    2007-10-01

    The adipocytokine adiponectin is released by adipocytes upon activation of the peroxisome proliferator-activated receptor gamma (PPAR gamma). PPAR gamma has binding sites for thiazolidinediones and free fatty acids (FFAs). To evaluate if adiponectin serum concentrations are synergistically regulated by FFAs and thiazolidinediones IN VIVO plasma FFAs were acutely elevated in healthy subjects pre-treated with rosiglitazone or placebo. Sixteen healthy male subjects (23-37 years) were included in this double-blind, randomized, placebo-controlled parallel-group study. Rosiglitazone 8 mg or placebo was administered daily for 21 days. On the last day plasma FFA concentrations were increased by an intravenous triglyceride/heparin infusion. Blood for determination of adiponectin, C-reactive protein (CRP), leptin, resistin, FFAs, glucose, and insulin was drawn at baseline and on day 21 before and after 5 hours of triglyceride/heparin infusion. Adiponectin concentrations increased and FFA levels decreased in subjects receiving rosiglitazone (all p<0.05 VS. baseline). Lipid infusion significantly increased FFA plasma concentrations, with an attenuated elevation in rosiglitazone-treated subjects. However, adiponectin concentrations were only increased in subjects on rosiglitazone (p=0.018 VS. before lipid infusion), but not in controls. Leptin increased during lipid infusion in subjects receiving placebo but not in those on rosiglitazone. CRP and resistin were not affected by rosiglitazone or FFAs. The acute increase in circulating adiponectin concentrations during acutely elevated FFA depends on PPAR gamma activation in healthy subjects.

  13. Influence of FFA Activities on Critical Thinking Skills in Texas Three-Star FFA Chapters

    ERIC Educational Resources Information Center

    Latham, Lindsey; Rayfield, John; Moore, Lori L.

    2015-01-01

    The purpose of this study was to determine the relationship of FFA activities on critical thinking skills of Texas FFA members in three-star FFA chapters. This descriptive study was conducted in eight purposively selected three-star FFA chapters throughout Texas. Three-star chapters are those chapters who have emerged as outstanding programs…

  14. Serum free fatty acid levels in PCOS patients treated with glucophage, magnesium oxide and spironolactone.

    PubMed

    Muneyyirci-Delale, Ozgul; Kaplan, Julie; Joulak, Ibrahim; Yang, Lianfu; Von Gizycki, Hans; Nacharaju, Vijaya L

    2013-05-01

    To assess the effect of glucophage, magnesium oxide and spironolactone in altering free fatty acids (FFAs), 36 PCOS women were randomly divided into three groups. Group 1 (n = 14) was treated with 500 mg glucophage po bid, group 2 (n = 10) was treated with 400 mg magnesium oxide po bid and group 3 (n = 12) was treated with 50 mg spironolactone po bid for 12 weeks. A glucose tolerance test with 75 g glucose load was performed before and after treatment, collecting blood at 0, 1 and 2 h for insulin, glucose, FFA and aldosterone. Amount of FFA before and after treatment were compared by repeated measure ANOVA and represented as area under the curve. FFA levels before treatment were 0.83 ± 0.23, 0.77 ± 0.15 and 0.85 ± 0.28 and after treatment were 0.77 ± 0.48, 0.71 ± 0.18 and 0.66 ± 0.25 for glucophage, magnesium oxide and spironolactone-treated patients, respectively. The FFA levels were unchanged in the groups treated with glucophage and magnesium oxide but were significantly (p < 0.03) decreased in the group treated with spironolactone. Since FFAs are known to be involved in the development of insulin resistance, these results suggest that spironolactone may be useful for lowering insulin resistance in PCOS patients.

  15. A Status Report on Middle Grade Agricultural Education and FFA Programs in the United States.

    ERIC Educational Resources Information Center

    Rossetti, Rosemarie; McCaslin, N. L.

    1994-01-01

    Census of 52 Future Farmers of America (FFA) executive secretaries found the following: 30 states have middle-grade agricultural education; 19 have middle-grade FFA membership; 14 have a core agriculture curriculum; 17 have state-level competitions; most do not favor national middle-grade competitions; and few disadvantages apart from potential…

  16. Examining Camper Learning Outcomes and Knowledge Retention at Oklahoma FFA Leadership Camp

    ERIC Educational Resources Information Center

    Brown, Nicholas R.; Terry, Robert, Jr.; Kelsey, Kathleen D.

    2014-01-01

    The National FFA Organization is committed to providing non-formal learning activities focusing on leadership education. Summer camps are a major component of FFA activities and concentrate on personal growth, leadership development, and recreational activities for youth. This repeated measures study determined the level of cognitive gain and the…

  17. Barriers to Participation in the National FFA Organization According to Urban Agriculture Students

    ERIC Educational Resources Information Center

    Martin, Michael J.; Kitchel, Tracy

    2014-01-01

    Urban youth engaged in after-school organizations have more positive attributes compared to their unengaged contemporaries. The FFA is one particular intra-curricular organization with after-school components; yet, urban students do not participate in FFA at the same levels as rural students. The purpose of this descriptive study was to explore…

  18. The New FFA--Relevant, Flexible.

    ERIC Educational Resources Information Center

    Future Farmers of America, Washington, DC.

    To make education more relevant, the 1972 national seminar sought ways of integrating the Future Farmers of America (FFA) program with the broadened agricultural instruction program. Topics discussed included: (1) "Role of the FFA in the Changing Program of Agricultural Education" - William Gray (Moderator), (2) "But How Do We Get…

  19. Parliamentary Procedure for the FFA Member.

    ERIC Educational Resources Information Center

    Joestgen, John G.

    Information and examples concerning parliamentary procedures are presented in this instructional manual written for Wisconsin Future Farmers of America (FFA) members and FFA parliamentary procedure teams. Topics include the following: secretary minutes (bylaws, officers, quorum, order of business, meeting and session, introducing business,…

  20. Occupational Aspirations of State FFA Contest and Award Winners.

    ERIC Educational Resources Information Center

    Bowen, Blannie E.; Doerfert, David L.

    1989-01-01

    A study explored the occupational aspirations of 300 (of 503) students with high levels of participation in Future Farmers of America's (FFA) Computers in Agriculture (CIA), Proficiency Award (PA), and Prepared and Extemporaneous Speaking (PES) contests. CIA and PES winners aspired to professional occupations more than PA winners. PES winners…

  1. Effects of rice harvest moisture on kernel damage and milled rice surface free fatty acid levels.

    PubMed

    Parker, Amanda M; Proctor, Andrew; Eason, Robert L; Jain, Vishal

    2007-01-01

    Surface free fatty acid (FFA) on milled rice is a key factor in determining rice quality and acceptability to the brewing industry. Rice FFA oxidizes, causing off-flavors and odors to develop, compromising the brewing quality of milled rice. The effect of harvest moisture (13%, 16%, and 20%), harvester type (1688 Case and 9500 John Deere), and rice variety (Cocodrie and Bengal) on harvest damaged rough rice and milled rice surface FFA after drying to 12% moisture and 6 mo rough rice storage was examined. The Case harvester produced more damaged kernels than the John Deere harvester, but this was not reflected in surface FFA development. There were no significant FFA differences in variety or harvester type. Rice harvested at a higher moisture content (20%) produced significantly greater FFA values, with a peak near 0.1%, than rice harvested at lower moisture contents (13% and 16%), which had FFA values near 0.08%. Retention of bran by damaged kernels at high harvest moisture probably was responsible for promoting surface FFA development, but if bran was lost at lower harvest moistures, surface FFA, development was limited. Harvest moisture affected milled rice FFA, although rough rice was dried to 12% immediately after harvesting.

  2. Robust expertise effects in right FFA

    PubMed Central

    McGugin, Rankin Williams; Newton, Allen T; Gore, John C; Gauthier, Isabel

    2015-01-01

    The fusiform face area (FFA) is one of several areas in occipito-temporal cortex whose activity is correlated with perceptual expertise for objects. Here, we investigate the robustness of expertise effects in FFA and other areas to a strong task manipulation that increases both perceptual and attentional demands. With high-resolution fMRI at 7Telsa, we measured responses to images of cars, faces and a category globally visually similar to cars (sofas) in 26 subjects who varied in expertise with cars, in (a) a low load 1-back task with a single object category and (b) a high load task in which objects from two categories rapidly alternated and attention was required to both categories. The low load condition revealed several areas more active as a function of expertise, including both posterior and anterior portions of FFA bilaterally (FFA1/FFA2 respectively). Under high load, fewer areas were positively correlated with expertise and several areas were even negatively correlated, but the expertise effect in face-selective voxels in the anterior portion of FFA (FFA2) remained robust. Finally, we found that behavioral car expertise also predicted increased responses to sofa images but no behavioral advantages in sofa discrimination, suggesting that global shape similarity to a category of expertise is enough to elicit a response in FFA and other areas sensitive to experience, even when the category itself is not of special interest. The robustness of expertise effects in right FFA2 and the expertise effects driven by visual similarity both argue against attention being the sole determinant of expertise effects in extrastriate areas. PMID:25192631

  3. Robust expertise effects in right FFA.

    PubMed

    McGugin, Rankin Williams; Newton, Allen T; Gore, John C; Gauthier, Isabel

    2014-10-01

    The fusiform face area (FFA) is one of several areas in occipito-temporal cortex whose activity is correlated with perceptual expertise for objects. Here, we investigate the robustness of expertise effects in FFA and other areas to a strong task manipulation that increases both perceptual and attentional demands. With high-resolution fMRI at 7T, we measured responses to images of cars, faces and a category globally visually similar to cars (sofas) in 26 subjects who varied in expertise with cars, in (a) a low load 1-back task with a single object category and (b) a high load task in which objects from two categories were rapidly alternated and attention was required to both categories. The low load condition revealed several areas more active as a function of expertise, including both posterior and anterior portions of FFA bilaterally (FFA1/FFA2, respectively). Under high load, fewer areas were positively correlated with expertise and several areas were even negatively correlated, but the expertise effect in face-selective voxels in the anterior portion of FFA (FFA2) remained robust. Finally, we found that behavioral car expertise also predicted increased responses to sofa images but no behavioral advantages in sofa discrimination, suggesting that global shape similarity to a category of expertise is enough to elicit a response in FFA and other areas sensitive to experience, even when the category itself is not of special interest. The robustness of expertise effects in right FFA2 and the expertise effects driven by visual similarity both argue against attention being the sole determinant of expertise effects in extrastriate areas.

  4. Factors Impacting Members Decision to Continue FFA beyond High School

    ERIC Educational Resources Information Center

    Sanok, Danielle E.; Stripling, Christopher T.; Stephens, Carrie A.; Griffith, Andrew P.

    2015-01-01

    The purpose of this study was to determine the factors influencing FFA members to continue their FFA experience beyond high school. Two focus groups were conducted, one for collegiate FFA members and one for past/current state officers. Participants provided several areas of improvement for collegiate and alumni FFA membership. Participants noted…

  5. Critical Theory View of the National FFA Convention

    ERIC Educational Resources Information Center

    Martin, Michael J.; Kitchel, Tracy

    2015-01-01

    Urban FFA members face unique challenges if they want to become active members in the National FFA Organization. FFA leaders have realized that the FFA organization does not represent the evolving demographics of America and have made efforts to cater to urban and diverse high school audiences with some success. This study seeks to explore this…

  6. Urban FFA Members' Sense of the Organizational Culture of the FFA

    ERIC Educational Resources Information Center

    Martin, Michael J.; Kitchel, Tracy

    2014-01-01

    Organizational culture shapes how members of a group act. The culture has the power to exclude potential new members who do not fit into the culture of the organization. Research on urban school-based agriculture programs has indicated that urban agriculture students face barriers to their participation in the National FFA Organization (FFA).…

  7. Protective Effect of Unsaturated Fatty Acids on Palmitic Acid-Induced Toxicity in Skeletal Muscle Cells is not Mediated by PPARδ Activation.

    PubMed

    Tumova, Jana; Malisova, Lucia; Andel, Michal; Trnka, Jan

    2015-10-01

    Unsaturated free fatty acids (FFA) are able to prevent deleterious effects of saturated FFA in skeletal muscle cells although the mechanisms involved are still not completely understood. FFA act as endogenous ligands of peroxisome proliferator-activated receptors (PPAR), transcription factors regulating the expression of genes involved in lipid metabolism. The aim of this study was to determine whether activation of PPARδ, the most common PPAR subtype in skeletal muscle, plays a role in mediating the protective effect of unsaturated FFA on saturated FFA-induced damage in skeletal muscle cells and to examine an impact on mitochondrial respiration. Mouse C2C12 myotubes were treated for 24 h with different concentrations of saturated FFA (palmitic acid), unsaturated FFA (oleic, linoleic and α-linolenic acid), and their combinations. PPARδ agonist GW501516 and antagonist GSK0660 were also used. Both mono- and polyunsaturated FFA, but not GW501516, prevented palmitic acid-induced cell death. Mono- and polyunsaturated FFA proved to be effective activators of PPARδ compared to saturated palmitic acid; however, in combination with palmitic acid their effect on PPARδ activation was blocked and stayed at the levels observed for palmitic acid alone. Unsaturated FFA at moderate physiological concentrations as well as GW501516, but not palmitic acid, mildly uncoupled mitochondrial respiration. Our results indicate that although unsaturated FFA are effective activators of PPARδ, their protective effect on palmitic acid-induced toxicity is not mediated by PPARδ activation and subsequent induction of lipid regulatory genes in skeletal muscle cells. Other mechanisms, such as mitochondrial uncoupling, may underlie their effect.

  8. Intestinal Dysbiosis Is Associated with Altered Short-Chain Fatty Acids and Serum-Free Fatty Acids in Systemic Lupus Erythematosus

    PubMed Central

    Rodríguez-Carrio, Javier; López, Patricia; Sánchez, Borja; González, Sonia; Gueimonde, Miguel; Margolles, Abelardo; de los Reyes-Gavilán, Clara G.; Suárez, Ana

    2017-01-01

    Metabolic impairments are a frequent hallmark of systemic lupus erythematosus (SLE). Increased serum levels of free fatty acids (FFA) are commonly found in these patients, although the underlying causes remain elusive. Recently, it has been suggested that factors other than inflammation or clinical features may be involved. The gut microbiota is known to influence the host metabolism, the production of short-chain fatty acids (SCFA) playing a potential role. Taking into account that lupus patients exhibit an intestinal dysbiosis, we wondered whether altered FFA levels may be associated with the intestinal microbial composition in lupus patients. To this aim, total and specific serum FFA levels, fecal SCFA levels, and gut microbiota composition were determined in 21 SLE patients and 25 healthy individuals. The Firmicutes to Bacteroidetes (F/B) ratio was strongly associated with serum FFA levels in healthy controls (HC), even after controlling for confounders. However, this association was not found in lupus patients, where a decreased F/B ratio and increased FFA serum levels were noted. An altered production of SCFA was related to the intestinal dysbiosis in lupus, while SCFA levels paralleled those of serum FFA in HC. Although a different serum FFA profile was not found in SLE, specific FFA showed distinct patterns on a principal component analysis. Immunomodulatory omega-3 FFA were positively correlated to the F/B ratio in HC, but not in SLE. Furthermore, divergent associations were observed for pro- and anti-inflammatory FFA with endothelial activation biomarkers in lupus patients. Overall, these findings support a link between the gut microbial ecology and the host metabolism in the pathological framework of SLE. A potential link between intestinal dysbiosis and surrogate markers of endothelial activation in lupus patients is supported, FFA species having a pivotal role. PMID:28167944

  9. Intestinal Dysbiosis Is Associated with Altered Short-Chain Fatty Acids and Serum-Free Fatty Acids in Systemic Lupus Erythematosus.

    PubMed

    Rodríguez-Carrio, Javier; López, Patricia; Sánchez, Borja; González, Sonia; Gueimonde, Miguel; Margolles, Abelardo; de Los Reyes-Gavilán, Clara G; Suárez, Ana

    2017-01-01

    Metabolic impairments are a frequent hallmark of systemic lupus erythematosus (SLE). Increased serum levels of free fatty acids (FFA) are commonly found in these patients, although the underlying causes remain elusive. Recently, it has been suggested that factors other than inflammation or clinical features may be involved. The gut microbiota is known to influence the host metabolism, the production of short-chain fatty acids (SCFA) playing a potential role. Taking into account that lupus patients exhibit an intestinal dysbiosis, we wondered whether altered FFA levels may be associated with the intestinal microbial composition in lupus patients. To this aim, total and specific serum FFA levels, fecal SCFA levels, and gut microbiota composition were determined in 21 SLE patients and 25 healthy individuals. The Firmicutes to Bacteroidetes (F/B) ratio was strongly associated with serum FFA levels in healthy controls (HC), even after controlling for confounders. However, this association was not found in lupus patients, where a decreased F/B ratio and increased FFA serum levels were noted. An altered production of SCFA was related to the intestinal dysbiosis in lupus, while SCFA levels paralleled those of serum FFA in HC. Although a different serum FFA profile was not found in SLE, specific FFA showed distinct patterns on a principal component analysis. Immunomodulatory omega-3 FFA were positively correlated to the F/B ratio in HC, but not in SLE. Furthermore, divergent associations were observed for pro- and anti-inflammatory FFA with endothelial activation biomarkers in lupus patients. Overall, these findings support a link between the gut microbial ecology and the host metabolism in the pathological framework of SLE. A potential link between intestinal dysbiosis and surrogate markers of endothelial activation in lupus patients is supported, FFA species having a pivotal role.

  10. Functional genomics analysis of free fatty acid production under continuous phosphate limiting conditions.

    PubMed

    Youngquist, J Tyler; Korosh, Travis C; Pfleger, Brian F

    2016-10-13

    Free fatty acids (FFA) are an attractive platform chemical that serves as a functional intermediate in metabolic pathways for producing oleochemicals. Many groups have established strains of Escherichia coli capable of producing various chain-length mixtures of FFA by heterologous expression of acyl-ACP thioesterases. For example, high levels of dodecanoic acid are produced by an E. coli strain expressing the Umbellularia californica FatB2 thioesterase, BTE. Prior studies achieved high dodecanoic acid yields and productivities under phosphate-limiting media conditions. In an effort to understand the metabolic and physiological changes that led to increased FFA production, the transcriptome of this strain was assessed as a function of nutrient limitation and growth rate. FFA generation under phosphate limitation led to consistent changes in transporter expression, osmoregulation, and central metabolism. Guided by these results, targeted knockouts led to a further ~11 % in yield in FFA.

  11. FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics

    PubMed Central

    Li, Xiaoran; Fisch, Robert; Bughara, Moneb; Wicksteed, Barton; Kovatcheva-Datchary, Petia; Layden, Brian T.

    2016-01-01

    During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis. We found that maternal Ffar2 expression and impaired glucose tolerance during pregnancy had no effect on the growth rates, ad lib glucose and glucose tolerance in the offspring between 3 and 6 weeks of age. To disrupt short chain fatty acid production, we chronically treated WT mice and Ffar2-/- mice with broad range antibiotics and further compared their glucose tolerance prior to pregnancy and at gestational day 15, and also quantified cecum and plasma SCFAs. We found that during pregnancy antibiotic treatment reduced the levels of SCFAs in the cecum of the mice, but resulted in elevated levels of plasma SCFAs and altered concentrations of individual SCFAs. Along with these changes, gestational glucose tolerance in WT mice, but not Ffar2-/- mice improved while on antibiotics. Additional data showed that gestational glucose tolerance worsened in Ffar2-/- mice during a second pregnancy. Together, these results indicate that antibiotic treatment alone is inadequate to deplete plasma SCFA concentrations, and that modulation of gut microbiota by antibiotics does not disrupt the contribution of FFA2 to gestational glucose tolerance. PMID:27959892

  12. Modulating Membrane Composition Alters Free Fatty Acid Tolerance in Escherichia coli

    PubMed Central

    Lennen, Rebecca M.; Pfleger, Brian F.

    2013-01-01

    Microbial synthesis of free fatty acids (FFA) is a promising strategy for converting renewable sugars to advanced biofuels and oleochemicals. Unfortunately, FFA production negatively impacts membrane integrity and cell viability in Escherichia coli, the dominant host in which FFA production has been studied. These negative effects provide a selective pressure against FFA production that could lead to genetic instability at industrial scale. In prior work, an engineered E. coli strain harboring an expression plasmid for the Umbellularia californica acyl-acyl carrier protein (ACP) thioesterase was shown to have highly elevated levels of unsaturated fatty acids in the cell membrane. The change in membrane content was hypothesized to be one underlying cause of the negative physiological effects associated with FFA production. In this work, a connection between the regulator of unsaturated fatty acid biosynthesis in E. coli, FabR, thioesterase expression, and unsaturated membrane content was established. A strategy for restoring normal membrane saturation levels and increasing tolerance towards endogenous production of FFAs was implemented by modulating acyl-ACP pools with a second thioesterase (from Geobacillus sp. Y412MC10) that primarily targets medium chain length, unsaturated acyl-ACPs. The strategy succeeded in restoring membrane content and improving viability in FFA producing E. coli while maintaining FFA titers. However, the restored fitness did not increase FFA productivity, indicating the existence of additional metabolic or regulatory barriers. PMID:23349781

  13. Modulating membrane composition alters free fatty acid tolerance in Escherichia coli.

    PubMed

    Lennen, Rebecca M; Pfleger, Brian F

    2013-01-01

    Microbial synthesis of free fatty acids (FFA) is a promising strategy for converting renewable sugars to advanced biofuels and oleochemicals. Unfortunately, FFA production negatively impacts membrane integrity and cell viability in Escherichia coli, the dominant host in which FFA production has been studied. These negative effects provide a selective pressure against FFA production that could lead to genetic instability at industrial scale. In prior work, an engineered E. coli strain harboring an expression plasmid for the Umbellularia californica acyl-acyl carrier protein (ACP) thioesterase was shown to have highly elevated levels of unsaturated fatty acids in the cell membrane. The change in membrane content was hypothesized to be one underlying cause of the negative physiological effects associated with FFA production. In this work, a connection between the regulator of unsaturated fatty acid biosynthesis in E. coli, FabR, thioesterase expression, and unsaturated membrane content was established. A strategy for restoring normal membrane saturation levels and increasing tolerance towards endogenous production of FFAs was implemented by modulating acyl-ACP pools with a second thioesterase (from Geobacillus sp. Y412MC10) that primarily targets medium chain length, unsaturated acyl-ACPs. The strategy succeeded in restoring membrane content and improving viability in FFA producing E. coli while maintaining FFA titers. However, the restored fitness did not increase FFA productivity, indicating the existence of additional metabolic or regulatory barriers.

  14. FFA4/GPR120 agonists: a survey of the recent patent literature.

    PubMed

    Formicola, Rosa; Pevarello, Paolo; Kuhn, Christina; Liberati, Chiara; Piscitelli, Francesco; Sodano, Mariangela

    2015-01-01

    FFA4/GPR120, a member of the rhodopsin family of G-protein-coupled receptors (GPCRs), is becoming an important target for therapeutic intervention in several areas of disease, including metabolic diseases, inflammation and cancer. In the last few years several patents on original chemotypes have been generated by different companies. In this review an analysis of the patents in the FFA4 agonism field is presented, with an emphasis on the documents published between 2013 and mid-2015. A discussion of the biological methods used in the patents is included. The general interest in this area is growing fast as half of the existing patents on FFA4 agonists have been issued after 2013. There is, however, a need of further diversifying new chemical classes away form the current substrate-like, carboxylic acid-containing agonists.

  15. Depression of serum calcium by increased plasma free fatty acids in the rat: a mechanism for hypocalcemia in acute pancreatitis.

    PubMed

    Warshaw, A L; Lee, K H; Napier, T W; Fournier, P O; Duchainey, D; Axelrod, L

    1985-10-01

    Some patients with hypertriglyceridemia and acute pancreatitis have marked hypocalcemia and high levels of plasma free fatty acids (FFAs). This study tests the hypothesis that increased plasma FFAs can significantly reduce the calcium level in vivo, a phenomenon which is different from local formation of calcium soaps due to lipolysis of adipose tissue lipids. Free fatty acid elevation was induced in rats by the administration of heparin and by the infusion of triglycerides. The results show that, compared with controls, induction of elevated FFA (from 1.57 +/- 0.08 mEq/L to 5.64 +/- 0.35, mean +/- SEM) causes the concentration of calcium to fall rapidly (from 9.04 +/- 0.06 mg/dl to 8.42 +/- 0.10, p less than 0.001). There is a significant (p less than 0.001) positive correlation between spontaneous baseline concentration of FFA and the responsiveness of calcium concentration to FFA challenge. At near-normal levels of FFA there is a significant (p less than 0.001) correlation between the magnitude of increased FFA concentration and decreased calcium concentration. Additional studies in vivo and in vitro show that elevated plasma triglycerides per se did not interfere with measurement of calcium concentration; however, FFA-albumin complexes bind calcium and lower its measured value. These findings suggest that (a) changes in the concentration of FFA occurring spontaneously may affect measured serum calcium concentration; (b) the observed depression of serum calcium concentration may be due in part to intravascular sequestration of calcium by FFA, but increased flux of circulating calcium-FFA complexes into extravascular and intracellular sites may also be important; (c) the markedly increased FFA concentration in some patients with acute pancreatitis may contribute significantly to hypocalcemia and calcium flux in these patients. As parathyroid hormone secretion, function, or integrity may be impaired in pancreatitis, the depressant effect of FFA could be even

  16. Oleic acid exposure of cultured endothelial cells alters lipid mediator production

    EPA Science Inventory

    Diesel, biodiesel, and other combustion sources contain free fatty acid (FFA) components capable of entering the body through particulate inhalation. FFA can also be endogenously released into circulation in response to stress. When in circulation, bioactive FFA may interact with...

  17. Modeling of free fatty acid dynamics: insulin and nicotinic acid resistance under acute and chronic treatments.

    PubMed

    Andersson, Robert; Kroon, Tobias; Almquist, Joachim; Jirstrand, Mats; Oakes, Nicholas D; Evans, Neil D; Chappel, Michael J; Gabrielsson, Johan

    2017-02-21

    Nicotinic acid (NiAc) is a potent inhibitor of adipose tissue lipolysis. Acute administration results in a rapid reduction of plasma free fatty acid (FFA) concentrations. Sustained NiAc exposure is associated with tolerance development (drug resistance) and complete adaptation (FFA returning to pretreatment levels). We conducted a meta-analysis on a rich pre-clinical data set of the NiAc-FFA interaction to establish the acute and chronic exposure-response relations from a macro perspective. The data were analyzed using a nonlinear mixed-effects framework. We also developed a new turnover model that describes the adaptation seen in plasma FFA concentrations in lean Sprague-Dawley and obese Zucker rats following acute and chronic NiAc exposure. The adaptive mechanisms within the system were described using integral control systems and dynamic efficacies in the traditional [Formula: see text] model. Insulin was incorporated in parallel with NiAc as the main endogenous co-variate of FFA dynamics. The model captured profound insulin resistance and complete drug resistance in obese rats. The efficacy of NiAc as an inhibitor of FFA release went from 1 to approximately 0 during sustained exposure in obese rats. The potency of NiAc as an inhibitor of insulin and of FFA release was estimated to be 0.338 and 0.436 [Formula: see text], respectively, in obese rats. A range of dosing regimens was analyzed and predictions made for optimizing NiAc delivery to minimize FFA exposure. Given the exposure levels of the experiments, the importance of washout periods in-between NiAc infusions was illustrated. The washout periods should be [Formula: see text]2 h longer than the infusions in order to optimize 24 h lowering of FFA in rats. However, the predicted concentration-response relationships suggests that higher AUC reductions might be attained at lower NiAc exposures.

  18. Agrarianism: An Ideology of the National FFA Organization

    ERIC Educational Resources Information Center

    Martin, Michael J.; Kitchel, Tracy

    2013-01-01

    The traditions of the National FFA Organization (FFA) are grounded in agrarianism. This ideology focuses on the ability of farming and nature to develop citizens and integrity within people. Agrarianism has been an important thread of American rhetoric since the founding of country. The ideology has morphed over the last two centuries as the…

  19. Factors Influencing or Discouraging Secondary School Students' FFA Participation

    ERIC Educational Resources Information Center

    Phelps, Kirstin; Henry, Anna L.; Bird, William A.

    2012-01-01

    Modern adolescents are faced with a variety of choices regarding how to spend their free time. As recruitment and increased student participation continues to be a major priority of the National FFA Organization, it is essential to explore the reasons why students make the choice to become or not to become a member of FFA. This study was a part of…

  20. The Benefits of FFA Membership as Part of Agricultural Education

    ERIC Educational Resources Information Center

    Rose, Chelsea; Stephens, Carrie A.; Stripling, Christopher; Cross, Tim; Sanok, Danielle E.; Brawner, Shelby

    2016-01-01

    The study sought to identify the benefits of FFA membership based on the fulfillment of three basic human needs: love and belonging, self-esteem, and self-actualization. The study focused on the fulfillment of FFA members' basic human needs as defined by Abraham Maslow. The three needs on which this study focused are: love and belonging,…

  1. Treatment of Type 2 Diabetes by Free Fatty Acid Receptor Agonists

    PubMed Central

    Watterson, Kenneth R.; Hudson, Brian D.; Ulven, Trond; Milligan, Graeme

    2014-01-01

    Dietary free fatty acids (FFAs), such as ω-3 fatty acids, regulate metabolic and anti-inflammatory processes, with many of these effects attributed to FFAs interacting with a family of G protein-coupled receptors. Selective synthetic ligands for free fatty acid receptors (FFA1-4) have consequently been developed as potential treatments for type 2 diabetes (T2D). In particular, clinical studies show that Fasiglifam, an agonist of the long-chain FFA receptor, FFA1, improved glycemic control and reduced HbA1c levels in T2D patients, with a reduced risk of hypoglycemia. However, this ligand was removed from clinical trials due to potential liver toxicity and determining if this is a target or a ligand-specific feature is now of major importance. Pre-clinical studies also show that FFA4 agonism increases insulin sensitivity, induces weight loss, and reduces inflammation and the metabolic and anti-inflammatory effects of short chain fatty acids (SCFAs) are linked with FFA2 and FFA3 activation. In this review, we therefore show that FFA receptor agonism is a potential clinical target for T2D treatment and discuss ongoing drug development programs within industry and academia aimed at improving the safety and effectiveness of these potential treatments. PMID:25221541

  2. Flufenamic acid prevents behavioral manifestations of salicylate-induced tinnitus in the rat

    PubMed Central

    Ustundag, Yasemin; Bulut, Funda; Demir, Caner Feyzi; Bal, Ali

    2016-01-01

    Introduction Tinnitus is defined as a phantom auditory sensation, the perception of sound in the absence of external acoustic stimulation. Given that flufenamic acid (FFA) blocks TRPM2 cation channels, resulting in reduced neuronal excitability, we aimed to investigate whether FFA suppresses the behavioral manifestation of sodium salicylate (SSA)-induced tinnitus in rats. Material and methods Tinnitus was evaluated using a conditioned lick suppression model of behavioral testing. Thirty-one Wistar rats, randomly divided into four treatment groups, were trained and tested in the behavioral experiment: (1) control group: DMSO + saline (n = 6), (2) SSA group: DMSO + SSA (n = 6), (3) FFA group: FFA (66 mg/kg bw) + saline (n = 9), (4) FFA + SSA group: FFA (66 mg/kg bw) + SSA (400 mg/kg bw) (n = 10). Localization of TRPM2 to the plasma membrane of cochlear nucleus neurons was demonstrated by confocal microscopy. Results Pavlovian training resulted in strong suppression of licking, having a mean value of 0.05 ±0.03 on extinction day 1, which is below the suppression training criterion level of 0.20 in control tinnitus animals. The suppression rate for rats having both FFA (66 mg/kg bw) and SSA (400 mg/kg bw) injections was significantly lower than that for the rats having SSA injections (p < 0.01). Conclusions We suggest that SSA-induced tinnitus could possibly be prevented by administration of a TRPM2 ion channel antagonist, FFA at 66 mg/kg bw. PMID:26925138

  3. Insulin-Mediated FFA Suppression Is Associated with Triglyceridemia and Insulin Sensitivity Independent of Adiposity

    PubMed Central

    Bush, Nikki C.; Basu, Rita; Rizza, Robert A.; Nair, K. Sreekumaran; Khosla, Sundeep

    2012-01-01

    Context: A central/visceral fat distribution and excess free fatty acid (FFA) availability are associated with dyslipidemia and insulin resistance. However, these two characteristics often coexist, making it difficult to detect the independent contributions of each. Whether FFA suppression is more closely linked to metabolic abnormalities is not clear. Objective: The aim of the study was to examine the relationship between FFA suppression, body fat distribution, and fitness as contributors toward insulin resistance and hypertriglyceridemia. Design: We measured systemic palmitate turnover using an iv infusion of [9,10-3H]palmitate; upper body sc adipose tissue (UBSQ) and visceral adipose tissue (VAT) with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan; fitness with a graded exercise treadmill test; and insulin sensitivity with both the iv glucose tolerance test (IVGTT) (SIIVGTT) and mixed meal tolerance test (SIMeal). Setting: The study was conducted at a General Clinical Research Center. Participants: Baseline data were obtained from 140 elderly adults (age, 60–88 yr; 83 males) and 60 young adults (age, 18–31 yr; 31 males) who participated in a previously published trial assessing the effects of 2-yr supplementation of dehydroepiandrosterone or testosterone on body composition, glucose metabolism, and bone density. Interventions: There were no interventions. Main Outcome Measures: We measured fasting plasma triglyceride (TG) concentrations, SIIVGTT, and SIMeal. Results: Using multivariate regression analysis, the strongest combined predictors of TG concentrations were VAT, postmeal nadir FFA concentrations, sex, and age. The best predictors of SIIVGTT were IVGTT nadir palmitate concentration, VAT, UBSQ fat, fitness, and age, whereas the best predictors of SIMeal were meal nadir palmitate concentration, UBSQ fat, fitness, and sex. Conclusions: FFA suppression is associated with both fasting TG concentrations and insulin

  4. Omega-3 free fatty acids inhibit tamoxifen-induced cell apoptosis.

    PubMed

    Wu, Shufan; Guo, Yang; Wu, Yikuan; Zhu, Shenglong; He, Zhao; Chen, Yong Q

    2015-04-03

    Fish oil, which contains omega-3 fatty acids mainly in the form of triglycerides, has benefits for reducing breast cancer risk, similar to tamoxifen action. However, it remains to be elucidated whether the combination of omega-3 free fatty acid (ω-3FFA) with tamoxifen leads to improved treatment in breast cancer. In this study, we observed that ω-3FFA induces MCF-7 cell apoptosis to suppress cell growth. The treatment of breast cancer cells with ω-3FFA attenuated tamoxifen-induced cell apoptosis. ω-3FFA and tamoxifen significantly increased Erk1/2 and Akt phosphorylation levels in a dose and time dependent manner. Compared to ω-3FFA alone, the combination of tamoxifen with ω-3FFA significantly increased Erk1/2 and Akt phosphorylation levels. Because Erk1/2 and Akt activation has been linked to tamoxifen-related anti-estrogen resistance in breast cancer patients, these results indicate that ω-3FFA may interfere with the effects of tamoxifen in the prevention of breast cancer risk.

  5. Meeting record for FFA working meeting of November 15, 1991

    SciTech Connect

    Stejskal, G.F.

    1992-01-03

    This document provides a meeting record of the Federal Facility Agreement (FFA) working meeting to discuss progress on old issues and further required actions regarding environmental impacts of the Savannah River Facility. (FI)

  6. An Analysis of FFA Chapter Demographics as Compared to Schools and Communities

    ERIC Educational Resources Information Center

    Lawrence, Shannon; Rayfield, John; Moore, Lori L.; Outley, Corliss

    2013-01-01

    This descriptive study was a special project for the National FFA [Future Farmers of America] Organization to determine the demographic makeup of rural, suburban, urban, and randomly selected at-large FFA chapters from the four national FFA regions. Summary data for this study revealed that gender in selected FFA chapters was 55% male and 45%…

  7. Winning the War: A Historical Analysis of the FFA during World War II

    ERIC Educational Resources Information Center

    Wolf, Kattlyn J.; Connors, James J.

    2009-01-01

    The United States' participation in World War II affected millions of men, women, and children, both at home and around the world. The war effort also affected the Future Farmers of America (FFA). FFA members, agriculture teachers, and national FFA officers all volunteered to serve their country during the war. Local FFA chapters and individual…

  8. Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPARgamma in human colon cancer Caco-2 cells.

    PubMed

    Yasui, Yumiko; Hosokawa, Masashi; Sahara, Takehiko; Suzuki, Rikako; Ohgiya, Satoru; Kohno, Hiroyuki; Tanaka, Takuji; Miyashita, Kazuo

    2005-08-01

    Bitter gourd (Momordica charantia) seed oil (BGO) is a unique oil which contains 9cis, 11trans, 13trans-conjugated linolenic acid (9c,11t,13t-CLN) at a high level of more than 60%. In this study, we investigated the anti-proliferative and apoptosis-inducing effects of free fatty acids prepared from BGO (BGO-FFA) using colon cancer Caco-2 cells. BGO-FFA and purified 9c,11t,13t-CLN remarkably reduced the cell viability of Caco-2. In Caco-2 cells treated with BGO-FFA, DNA fragmentation of apoptosis indicators was observed in a dose-dependent manner. The expression level of apoptosis suppressor Bcl-2 protein was also decreased by BGO-FFA treatment. The GADD45 and p53, which play an important role in apoptosis-inducing pathways, were remarkably up-regulated by BGO-FFA treatment in Caco-2 cells. Up-regulation of PPARgamma mRNA and protein were also observed during apoptosis induced by BGO-FFA. These results suggest that BGO-FFA rich in 9c,11t,13t-CLN may induce apoptosis in Caco-2 cells through up-regulation of GADD45, p53 and PPARgamma.

  9. Effect of domoic acid on brain amino acid levels.

    PubMed

    Durán, R; Arufe, M C; Arias, B; Alfonso, M

    1995-03-01

    The administration of Domoic Acid (Dom) in a 0.2 mg/kg i.p. dose induces changes in the levels of amino acids of neurochemical interest (Asp, Glu, Gly, Tau, Ala, GABA) in different rat brain regions (hypothalamus, hippocampus, amygdala, striatum, cortex and midbrain). The most affected amino acid is the GABA, the main inhibitory amino acid neurotransmitter, whereas glutamate, the main excitatory amino acid, is not affected. The rat brain regions that seem to be the main target of the Dom action belong to the limbic system (hippocampus, amygdala). The possible implication of the amino acids in the actions of Dom is also discussed.

  10. Free fatty acids do not acutely increase asymmetrical dimethylarginine concentrations.

    PubMed

    Namiranian, K; Mittermayer, F; Artwohl, M; Pleiner, J; Schaller, G; Mayer, B X; Bayerle-Eder, M; Roden, M; Baumgartner-Parzer, S; Wolzt, M

    2005-12-01

    Concentrations of asymmetrical dimethylarginine (ADMA) and free fatty acids (FFAs) are elevated in insulin resistance which is associated with impaired vascular function. We hypothesized that FFAs could alter vascular tone by affecting ADMA concentrations. Plasma FFA levels were increased in seventeen healthy male volunteers by Intralipid/heparin infusion; hemodynamic and biochemical parameters were measured after 90 minutes. Plasma collected before and during Intralipid/heparin or equivalent synthetic FFAs was incubated with human umbilical vein endothelial cells (HUVECs) in vitro. Intralipid/heparin infusion resulted in an approximately seven-fold increase in plasma FFA levels to 1861 +/- 139 micromol/l, which was paralleled by increased systemic blood pressure and forearm blood flow. Intralipid/heparin did not affect ADMA (baseline mean 0.59 [95 % confidence interval [CI]: 0.54; 0.64] and 0.56 [CI: 0.51; 0.59] after 90 minutes), but slightly decreased SDMA (from 0.76, [CI: 0.70; 0.83] to 0.71 [CI: 0.64; 0.74], p < 0.05), and had no effect on ADMA/SDMA ratio. There was no correlation between ADMA and FFA concentrations or forearm blood flow. Incubation of HUVECs with FFA-rich plasma or synthetic FFAs induced an ADMA release after 24 hours, but not after 90 minutes. Acutely increased FFA levels caused hemodynamic effects but did not affect ADMA. Prolonged elevation of FFA levels might influence vascular function by increasing ADMA levels.

  11. Defense Priming and Jasmonates: A Role for Free Fatty Acids in Insect Elicitor-Induced Long Distance Signaling

    PubMed Central

    Li, Ting; Cofer, Tristan; Engelberth, Marie; Engelberth, Jurgen

    2016-01-01

    Green leaf volatiles (GLV) prime plants against insect herbivore attack resulting in stronger and faster signaling by jasmonic acid (JA). In maize this response is specifically linked to insect elicitor (IE)-induced signaling processes, which cause JA accumulation not only around the damage site, but also in distant tissues, presumably through the activation of electrical signals. Here, we present additional data further characterizing these distal signaling events in maize. Also, we describe how exposure to GLV increases free fatty acid (fFA) levels in maize seedlings, but also in other plants, and how increased fFA levels affect IE-induced JA accumulation. Increased fFA, in particular α-linolenic acid (LnA), caused a significant increase in JA accumulation after IE treatment, while JA induced by mechanical wounding (MW) alone was not affected. We also identified treatments that significantly decreased certain fFA level including simulated wind and rain. In such treated plants, IE-induced JA accumulation was significantly reduced when compared to un-moved control plants, while MW-induced JA accumulation was not significantly affected. Since only IE-induced JA accumulation was altered by changes in the fFA composition, we conclude that changing levels of fFA affect primarily IE-induced signaling processes rather than serving as a substrate for JA. PMID:27135225

  12. Infusion of long-chain fatty acid anions by continuous-flow centrifugation

    PubMed Central

    Greenough, William B.; Crespin, Stephen R.; Steinberg, Daniel

    1969-01-01

    We have developed a method for the rapid infusion into plasma of large amounts of long-chain free fatty acids (FFA). Unanesthetized dogs were connected by a peripheral artery to a closed, continuousflow centrifuge from which cells and plasma emerged in separate lines. Sodium oleate was infused directly into the plasma line before cells and plasma were recombined and returned to the animal through a peripheral vein. The centrifugation procedure itself produced only small changes in circulating levels of glucose, FFA, and electrolytes. Plasma flow rates as high as 100 ml/min could be maintained, and centrifugations of 12 hr were accomplished without complications. During centrifugation, sodium oleate was infused at rates up to 80 μEq/kg per min for 2.5 hr; the maximum molar ratio of FFA to albumin without hemolysis was 10:1. Plasma FFA levels rose rapidly after infusions were started and reached constant elevated levels within 15-20 min. Oleate infusion at 10-50 μEq/kg per min produced a rise in plasma FFA proportional to the infusion rate. The maximum increment in plasma FFA above control values was 1.66 μEq/ml. When infusions ended, plasma FFA declined rapidly to control levels. Oleate infusion at rates below 30 μEq/kg per min did not reduce levels of other plasma FFA. Infusion at high rates was accompanied by a marked fall in blood glucose. This method permits adminsitration of long-chain fatty acids in sufficient quantities to study their individual metabolic effects, and provides a new way to supply lipid calories parenterally. PMID:5822596

  13. Factors Related to the Success of New Mexico Vocational Agriculture Teachers as FFA Advisors. Summary of Research.

    ERIC Educational Resources Information Center

    Vaughan, Paul R.; Bender, Ralph E.

    This study was designed to (1) identify competencies in which a New Mexico vocational agriculture teacher's perceived level of proficiency was related to the degree of success of his Future Farmers of America (FFA) chapter, (2) identify characteristics possessed by New Mexico vocational agriculture teachers which showed a significant relationship…

  14. Identifying Quality Indicators of SAE and FFA: A Delphi Approach

    ERIC Educational Resources Information Center

    Jenkins, Charles Cordell, III; Kitchel, Tracy

    2009-01-01

    The purpose of this study was to determine quality indicators for SAE and FFA according to 36 experts across the United States. This is a part of a larger study looking at all components of the traditional three-circle model. The study utilized the Delphi technique to garner expert opinion about quality indicators in Agricultural Education. For…

  15. Examining Year-Long Leadership Gains in FFA Members by Prior FFA Involvement, Class Year, and Gender

    ERIC Educational Resources Information Center

    Rosch, David; Simonsen, Jon C.; Velez, Jonathan J.

    2015-01-01

    Students (N = 160) in three diverse FFA chapters were surveyed in early fall, midwinter, and late spring in regard to their leadership skills, confidence in leading, and motivation to engage in leadership-oriented behaviors. The results indicated small-to-moderate gains in transformational leadership skill and a marginally significant…

  16. Factors Related to the Success of New Mexico Vocational Agriculture Teachers as FFA Advisors

    ERIC Educational Resources Information Center

    Vaughn, Paul R.

    1976-01-01

    A study to identify characteristics which are related to the degree of success of an FFA advisor, and to identify competencies in which a teacher's perceived proficiency are related to his success as an FFA advisor. (HD)

  17. The Impact of Learning Styles on Learning Outcomes at FFA Camp: What Campers Retain over Time

    ERIC Educational Resources Information Center

    Brown, Nicholas R.; Terry, Robert, Jr.; Kelsey, Kathleen D.

    2013-01-01

    Twenty-four states host FFA summer camps to support adolescent maturation along with indoctrination into the culture and values of the FFA. Camps typically include a variety of activities designed to engage members in social activities and non-formal academic content. More than 1500 campers attend the Oklahoma FFA Alumni Leadership Camp annually…

  18. Student Self-Perceptions of Leadership in Two Missouri FFA Chapters: A Collective Case Study

    ERIC Educational Resources Information Center

    Kagay, Rachel Bartholomew; Marx, Adam A.; Simonsen, Jon C.

    2015-01-01

    The focus of this study is the self-perceptions of leadership engagement of FFA members in two FFA chapters in Missouri. This multiple case study used documentation of student self-perceptions, researcher observations, and focus groups. The two cases included 24 high school students comprised of FFA officers and members, who provided their…

  19. Self-Perceived Youth Leadership and Life Skills of Iowa FFA Members.

    ERIC Educational Resources Information Center

    Wingenbach, Gary J.; Kahler, Alan A.

    1997-01-01

    The Youth Leadership and Life Skills Development Scale was completed by 282 of 316 Iowa Future Farmers of America (FFA) members. The strongest relationship appeared between their scores and FFA leadership activities. Other factors affecting life/leadership skills development included after-school jobs, years in FFA, grades, and gender. (SK)

  20. ADAPTING THE FFA TO A CHANGING PROGRAM OF VOCATIONAL AGRICULTURE. RESEARCH SERIES IN AGRICULTURAL EDUCATION.

    ERIC Educational Resources Information Center

    KANTER, EARL F.; BENDER, RALPH E.

    THE PURPOSE OF THIS NATIONAL STUDY WAS TO SUGGEST WAYS OF ADAPTING THE FUTURE FARMERS OF AMERICA (FFA) TO A CHANGING PROGRAM OF VOCATIONAL AGRICULTURE THROUGH IDENTIFYING NEW PURPOSES OF THE FFA AND EVALUATING SELECTED OPERATIONAL GUIDELINES AND NATIONAL AND STATE FFA ACTIVITIES. MEMBERS OF THE UNITED STATES OFFICE OF EDUCATION, HEAD STATE…

  1. The effects of forskolin and rolipram on cAMP, cGMP and free fatty acid levels in diet induced obesity.

    PubMed

    Doseyici, S; Mehmetoglu, I; Toker, A; Yerlikaya, F H; Erbay, E

    2014-07-01

    Obesity is a major health problem. We investigated the effects of forskolin and rolipram in the diet of animals in which obesity had been induced. We used 50 female albino Wistar rats that were assigned randomly into five groups as follows: group 1, control; group 2, high fat diet; group 3, high fat diet + forskolin; group 4, high fat diet + rolipram; and group 5, high fat diet + rolipram + forskolin. The rats were fed for 10 weeks and rolipram and forskolin were administered during last two weeks. The animals were sacrificed and blood samples were obtained. Serum cAMP, cGMP and free fatty acids (FFA) levels were measured using ELISA assays. We also measured weight gain during the 10 week period. cAMP and FFA levels of groups 3, 4 and 5 were significantly higher than those of groups 1 and 2. We found no significant differences in serum cGMP levels among the groups. The weight gain in groups 3, 4 and 5 was significantly less than for group 2. We also found that the weight gain in group 5 was significantly less than in groups 3 and 4. We found that both forskolin and rolipram stimulated lipolysis and inhibited body weight increase by increasing cAMP levels. Also, combination therapy using the two agents may be more effective in preventing diet induced obesity than either agent alone. We found also that these agents did not effect cellular cGMP levels in diet induced obesity.

  2. Identification of Transport Proteins Involved in Free Fatty Acid Efflux in Escherichia coli

    PubMed Central

    Lennen, Rebecca M.; Politz, Mark G.; Kruziki, Max A.

    2013-01-01

    Escherichia coli has been used as a platform host for studying the production of free fatty acids (FFA) and other energy-dense compounds useful in biofuel applications. Most of the FFA produced by E. coli are found extracellularly. This finding suggests that a mechanism for transport across the cell envelope exists, yet knowledge of proteins that may be responsible for export remains incomplete. Production of FFA has been shown to cause cell lysis, induce stress responses, and impair basic physiological processes. These phenotypes could potentially be diminished if efflux rates were increased. Here, a total of 15 genes and operons were deleted and screened for their impact on cell viability and titer in FFA-producing E. coli. Deletions of acrAB and rob and, to a lower degree of statistical confidence, emrAB, mdtEF, and mdtABCD reduced multiple measures of viability, while deletion of tolC nearly abolished FFA production. An acrAB emrAB deletion strain exhibited greatly reduced FFA titers approaching the tolC deletion phenotype. Expression of efflux pumps on multicopy plasmids did not improve endogenous FFA production in an acrAB+ strain, but plasmid-based expression of acrAB, mdtEF, and an mdtEF-tolC artificial operon improved the MIC of exogenously added decanoate for an acrAB mutant strain. The findings suggest that AcrAB-TolC is responsible for most of the FFA efflux in E. coli, with residual activity provided by other resistance-nodulation-cell division superfamily-type efflux pumps, including EmrAB-TolC and MdtEF-TolC. While the expression of these proteins on multicopy plasmids did not improve production over the basal level, their identification enables future engineering efforts. PMID:23104810

  3. Defective liver disposal of free fatty acids in patients with impaired glucose tolerance.

    PubMed

    Iozzo, Patricia; Turpeinen, Anu K; Takala, Teemu; Oikonen, Vesa; Bergman, Jörgen; Grönroos, Tove; Ferrannini, Ele; Nuutila, Pirjo; Knuuti, Juhani

    2004-07-01

    The liver exchanges high fluxes of glucose and free fatty acids (FFA) and is one main site of their reciprocal regulation. Acute exposure to hyperglycemia and hyperinsulinemia has been shown to reduce splanchnic beta-oxidation in healthy humans. We investigated whether a spontaneous condition of chronic mild hyperglycemia and hyperinsulinemia affects liver FFA uptake. Hepatic FFA influx rate constant (LKi) was measured after a 12-15-h fast in 10 patients with impaired glucose tolerance (IGT) and eight control subjects using positron emission tomography in combination with the long-chain FFA analog 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Compared with controls, IGT patients had higher serum insulin, glucose, and triglyceride levels (1.71 +/- 0.24 vs. 0.59 +/- 0.06 mmol/liter, P < 0.001), lower high-density lipoprotein (1.04 +/- 0.11 vs. 1.42 +/- 0.13 mmol/liter, P < 0.05), and similar FFA levels (0.59 +/- 0.06 vs. 0.56 +/- 0.05 mmol/liter(-1), P = not significant). LKi was significantly reduced in IGT (0.288 +/- 0.014 min(-1)) compared with control subjects (0.341 +/- 0.014 min(-1), P < 0.02). LKi was negatively correlated with plasma glucose (r = 0.51, P < 0.03), glycosylated hemoglobin (r = 0.55, P < 0.02), and blood lactate levels (r = 0.52, P < 0.03). We conclude that, in IGT patients, the ability of the liver to extract FFA from the circulation appears to be impaired. The reciprocal relationship between hepatic FFA extraction and glucose/lactate flux may derive from intrahepatic substrate competition.

  4. The Quest for the FFA and Where It Led.

    PubMed

    Kanwisher, Nancy

    2017-02-01

    This article tells the story behind our first paper on the fusiform face area (FFA): how we chose the question, developed the methods, and followed the data to find the FFA and subsequently many other functionally specialized cortical regions. The paper's impact had less to do with the particular findings in the paper itself and more to do with the method that it promoted and the picture of the human mind and brain that it led to. The use of a functional localizer to define a candidate region in each subject individually enabled us not just to make pictures of brain activation, but also to ask principled, hypothesis-driven questions about a thing in nature. This method enabled stronger and more extensive tests of the function of each cortical region than had been possible before in humans and, as a result, has produced a large body of evidence that the human cortex contains numerous regions that are specifically engaged in particular mental processes. The growing inventory of cortical regions with distinctive and often very specific functions can be seen as an initial sketch of the basic components of the human mind. This sketch also serves as a roadmap into the vast and exciting new landscape of questions about the computations, structural connections, time course, development, plasticity, and evolution of each of these regions, as well as the hardest question of all: how do these regions work together to produce human intelligence?

  5. Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40.

    PubMed

    Hidalgo, Jorge; Teuber, Stefanie; Morera, Francisco J; Ojeda, Camila; Flores, Carlos A; Hidalgo, María A; Núñez, Lucía; Villalobos, Carlos; Burgos, Rafael A

    2017-04-05

    Anthocyanins are pigments with antihyperglycemic properties, and they are potential candidates for developing functional foods for the therapy or prevention of Diabetes mellitus type 2 (DM2). The mechanism of these beneficial effects of anthocyanins are, however, hard to explain, given their very low bioavailability due to poor intestinal absorption. We propose that free fatty acid receptor 1 (FFA1, also named GPR40), is involved in an inhibitory effect of the anthocyanidin delphinidin over intestinal glucose absorption. We show the direct effects of delphinidin on the intestine using jejunum samples from RF/J mice, and the human intestinal cell lines HT-29, Caco-2, and NCM460. By the use of specific pharmacological antagonists, we determined that delphinidin inhibits glucose absorption in both mouse jejunum and a human enterocytic cell line in a FFA1-dependent manner. Delphinidin also affects the function of sodium-glucose cotransporter 1 (SGLT1). Intracellular signaling after FFA1 activation involved cAMP increase and cytosolic Ca(2+) oscillations originated from intracellular Ca(2+) stores and were followed by store-operated Ca(2+) entry. Taken together, our results suggest a new GPR-40 mediated local mechanism of action for delphinidin over intestinal cells that may in part explain its antidiabetic effect. These findings are promising for the search for new prevention and pharmacological treatment strategies for DM2 management.

  6. FFA-induced hepatic insulin resistance in vivo is mediated by PKCδ, NADPH oxidase, and oxidative stress.

    PubMed

    Pereira, Sandra; Park, Edward; Mori, Yusaku; Haber, C Andrew; Han, Ping; Uchida, Toyoyoshi; Stavar, Laura; Oprescu, Andrei I; Koulajian, Khajag; Ivovic, Alexander; Yu, Zhiwen; Li, Deling; Bowman, Thomas A; Dewald, Jay; El-Benna, Jamel; Brindley, David N; Gutierrez-Juarez, Roger; Lam, Tony K T; Najjar, Sonia M; McKay, Robert A; Bhanot, Sanjay; Fantus, I George; Giacca, Adria

    2014-07-01

    Fat-induced hepatic insulin resistance plays a key role in the pathogenesis of type 2 diabetes in obese individuals. Although PKC and inflammatory pathways have been implicated in fat-induced hepatic insulin resistance, the sequence of events leading to impaired insulin signaling is unknown. We used Wistar rats to investigate whether PKCδ and oxidative stress play causal roles in this process and whether this occurs via IKKβ- and JNK-dependent pathways. Rats received a 7-h infusion of Intralipid plus heparin (IH) to elevate circulating free fatty acids (FFA). During the last 2 h of the infusion, a hyperinsulinemic-euglycemic clamp with tracer was performed to assess hepatic and peripheral insulin sensitivity. An antioxidant, N-acetyl-L-cysteine (NAC), prevented IH-induced hepatic insulin resistance in parallel with prevention of decreased IκBα content, increased JNK phosphorylation (markers of IKKβ and JNK activation, respectively), increased serine phosphorylation of IRS-1 and IRS-2, and impaired insulin signaling in the liver without affecting IH-induced hepatic PKCδ activation. Furthermore, an antisense oligonucleotide against PKCδ prevented IH-induced phosphorylation of p47(phox) (marker of NADPH oxidase activation) and hepatic insulin resistance. Apocynin, an NADPH oxidase inhibitor, prevented IH-induced hepatic and peripheral insulin resistance similarly to NAC. These results demonstrate that PKCδ, NADPH oxidase, and oxidative stress play a causal role in FFA-induced hepatic insulin resistance in vivo and suggest that the pathway of FFA-induced hepatic insulin resistance is FFA → PKCδ → NADPH oxidase and oxidative stress → IKKβ/JNK → impaired hepatic insulin signaling.

  7. Comparison and validation of 2 analytical methods for the determination of free fatty acids in dairy products by gas chromatography with flame ionization detection.

    PubMed

    Mannion, David T; Furey, Ambrose; Kilcawley, Kieran N

    2016-07-01

    Accurate quantification of free fatty acids (FFA) in dairy products is important for quality control, nutritional, antimicrobial, authenticity, legislative, and flavor purposes. In this study, the performance of 2 widely used gas chromatographic flame ionization detection methods for determination of FFA in dairy products differing in lipid content and degree of lipolysis were evaluated. We used a direct on-column approach where the isolated FFA extract was injected directly and a derivatization approach where the FFA were esterified in the injector to methyl esters using tetramethylammonium hydroxide as a catalyst. A comprehensive validation was undertaken to establish method linearity, limits of detection, limits of quantification, accuracy, and precision. Linear calibrations of 3 to 700mg/L (R(2)>0.999) and 20 to 700mg/L (R(2)>0.997), and limits of detection and limits of quantification of 0.7 and 3mg/L and 5 and 20mg/L were obtained for the direct injection on-column and the derivatization method, respectively. Intraday precision of 1.5 to 7.2% was obtained for both methods. The direct injection on-column method had the lower levels of limits of detection and quantification, because FFA are directly injected onto the GC as opposed to the split injection used in the derivatization method. However, the direct injection on-column method experienced accumulative column phase deterioration and irreversible FFA absorption because of the acidic nature of the injection extract, which adversely affected method robustness and the quantification of some longer chain FFA. The derivatization method experienced issues with quantification of butyric acid at low concentrations because of coelution with the injection solvent peak, loss of polyunsaturated FFA due to degradation by tetramethylammonium hydroxide, and the periodic emergence of by-product peaks of the tetramethylammonium hydroxide reaction that interfered with the quantification of some short-chain FFA. The

  8. TCF2 attenuates FFA-induced damage in islet β-cells by regulating production of insulin and ROS.

    PubMed

    Quan, Xiaojuan; Zhang, Lin; Li, Yingna; Liang, Chunlian

    2014-07-30

    Free fatty acids (FFAs) are cytotoxic to pancreatic islet β-cells and play a crucial role in the diabetes disease process. A recent study revealed a down-regulation of transcription factor 2 (TCF2) levels during FFA-mediated cytotoxicity in pancreatic β-cells. However, its function during this process and the underlying mechanism remains unclear. In this study, treatment with palmitic acid (PA) at high levels (400 and 800 μM) decreased β-cell viability and TCF2 protein expression, along with the glucose-stimulated insulin secretion (GSIS). Western and RT-PCR analysis confirmed the positive regulatory effect of TCF2 on GSIS through promotion of the key regulators pancreatic duodenal homeobox-1 (PDX1) and glucose transporter 2 (GLUT2) in β-cells. In addition, both PI3K/AKT and MEK/ERK showed decreased expression in PA (800 μM)-treated β-cells. Overexpression of TCF2 could effectively restore the inhibitory effect of PA on the activation of PI3K/AKT and MEK/ERK as well as β-cell viability, simultaneously, inhibited PA-induced reactive oxygen species (ROS) generation. After blocking the PI3K/AKT and MAPK/ERK signals with their specific inhibitor, the effect of overexpressed TCF2 on β-cell viability and ROS production was obviously attenuated. Furthermore, a protective effect of TCF2 on GSIS by positive modulation of JNK-PDX1/GLUT2 signaling was also confirmed. Accordingly, our study has confirmed that TCF2 positively modulates insulin secretion and further inhibits ROS generation via the PI3K/AKT and MEK/ERK signaling pathways. Our work may provide a new therapeutic target to achieve prevention and treatment of diabetes.

  9. GPR40/FFA1 and Neutral Sphingomyelinase Are Involved in Palmitate-Boosted Inflammatory Response of Microvascular Endothelial Cells to LPS

    PubMed Central

    Lu, Zhongyang; Li, Yanchun; Jin, Junfei; Zhang, Xiaoming; Hannun, Yusuf A.; Huang, Yan

    2015-01-01

    Objectives Increased levels of both saturated fatty acids (SFAs) and lipopolysaccharide (LPS) are associated with type 2 diabetes. However, it remains largely unknown how SFAs interact with LPS to regulate inflammatory responses in microvascular endothelial cells (MIC ECs) that are critically involved in atherosclerosis as a diabetic complication. In this study, we compared the effects of LPS, palmitic acid (PA), the most abundant saturated fatty acid, or the combination of LPS and PA on interleukin (IL)-6 expression by MIC ECs and explored the underlying mechanisms. Methods Human cardiac MIC ECs were treated with LPS, PA and LPS plus PA and the regulatory pathways including receptors, signal transduction, transcription and post-transcription, and sphingolipid metabolism for IL-6 expression were investigated. Results G protein-coupled receptor (GPR)40 or free fatty acid receptor 1 (FFA1), but not toll-like receptor 4, was involved in PA-stimulated IL-6 expression. PA not only stimulated IL-6 expression by itself, but also remarkably enhanced LPS-stimulated IL-6 expression via a cooperative stimulation on mitogen-activated protein kinase and nuclear factor kappa B signaling pathways, and both transcriptional and post-transcriptional activation. Furthermore, PA induced a robust neutral sphingomyelinase (nSMase)-mediated sphingomyelin hydrolysis that was involved in PA-augmented IL-6 upregulation. Conclusion PA boosted inflammatory response of microvascular endothelial cells to LPS via GPR40 and nSMase. PMID:25795558

  10. The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment

    PubMed Central

    Björkman, Lena; Mårtensson, Jonas; Winther, Malene; Gabl, Michael; Holdfeldt, André; Uhrbom, Martin; Bylund, Johan; Højgaard Hansen, Anders; Pandey, Sunil K.; Ulven, Trond; Forsman, Huamei

    2016-01-01

    Ligands with improved potency and selectivity for free fatty acid receptor 2 (FFA2R) have become available, and we here characterize the neutrophil responses induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an increase in the cytosolic concentration of Ca2+, and the neutrophils were then desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The activated FFA2R induced superoxide anion secretion at a low level in naive blood neutrophils. This response was largely increased by tumor necrosis factor alpha (TNF-α) in a process associated with a recruitment of easily mobilizable granules, but neutrophils recruited to an aseptic inflammation in vivo were nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin A-treated neutrophils, but no reactivation of desensitized FFA2R was induced by this drug, suggesting that the cytoskeleton is not directly involved in terminating the response. The functional and regulatory differences between the receptors that recognize short-chain fatty acids and formylated peptides, respectively, imply different roles of these receptors in the orchestration of inflammation and confirm the usefulness of a selective FFA2R agonist and antagonist as tools for the exploration of the precise role of the FFA2R. PMID:27503855

  11. Bridging Horizons. An Advisor's Guide to FFA Involvement for Members with Disabilities.

    ERIC Educational Resources Information Center

    Ploss, Adrienne J.; Field, William E.; Frick, Martin J.

    This guide is designed to provide Future Farmers of America (FFA) advisors with information to assist them in their efforts to include all youth in FFA, including those with disabilities. It addresses benefits of involving youth with disabilities and federal, state, and local legislation and regulations concerning people with disabilities.…

  12. Fitting Vo-Ag and FFA Together Best for Students and Teachers.

    ERIC Educational Resources Information Center

    Snyder, H. Leon

    1979-01-01

    The Future Farmers of America (FFA) is more than a leadership development organization and when used as an intracurricular activity, it can serve as a teaching tool. The FFA adds advantages to the program in areas such as supervised experience, award motivation, providing real world experience, public relations, travel, and competition. (LRA)

  13. The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice

    PubMed Central

    Moon, Morgan L.; Joesting, Jennifer J.; Lawson, Marcus A.; Chiu, Gabriel S.; Blevins, Neil A.; Kwakwa, Kristin A.; Freund, Gregory G.

    2014-01-01

    Objectives Excess fat in the diet can impact neuropsychiatric functions by negatively affecting cognition, mood and anxiety. We sought to show that the free fatty acid (FFA), palmitic acid, can cause adverse biobehaviors in mice that lasts beyond an acute elevation in plasma FFAs. Methods Mice were administered palmitic acid or vehicle as a single intraperitoneal (IP) injection. Biobehaviors were profiled 2 and 24 hrs after palmitic acid treatment. Quantification of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their major metabolites was performed in cortex, hippocampus and amygdala. FFA concentration was determined in plasma. Relative fold change in mRNA expression of unfolded protein response (UPR)-associated genes was determined in brain regions. Results In a dose-dependent fashion, palmitic acid rapidly reduced mouse locomotor activity by a mechanism that did not rely on TLR4, MyD88, IL-1, IL-6 or TNFα but was dependent on fatty acid chain length. Twenty-four hrs after palmitic acid administration mice exhibited anxiety-like behavior without impairment in locomotion, food intake, depressive-like behavior or spatial memory. Additionally, the serotonin metabolite 5-HIAA was increased by 33% in the amygdala 24 hrs after palmitic acid treatment. Conclusions Palmitic acid induces anxiety-like behavior in mice while increasing amygdala-based serotonin metabolism. These effects occur at a time point when plasma FFA levels are no longer elevated. PMID:25016520

  14. The In vitro Effects of Nano-encapsulated Conjugated Linoleic Acid on Stability of Conjugated Linoleic Acid and Fermentation Profiles in the Rumen.

    PubMed

    Heo, Wan; Kim, Eun Tae; Cho, Sung Do; Kim, Jun Ho; Kwon, Seong Min; Jeong, Ha Yeon; Ki, Kwang Seok; Yoon, Ho Baek; Ahn, Young Dae; Lee, Sung Sill; Kim, Young Jun

    2016-03-01

    This study was aimed to evaluate the stability of conjugated linoleic acids (CLAs) by nano-encapsulation against in vitro ruminal biohydrogenation by microbial enzymatic conversion. CLAs (free fatty acid form of CLA [CLA-FFA], nano-encapsulated CLA-FFA, triglyceride form of CLA [CLA-TG], and nano-encapsulated CLA-TG) were used in the in vitro fermentation experiments. When Butyrivibrio fibrisolvens (B. fibrisolvens) was incubated with CLA-FFAs, the concentrations of cis-9, trans-11 CLA and vaccenic acid (VA) slightly was decreased and increased by nano-encapsulation, respectively. When B. fibrisolvens was incubated with CLA-TG, the concentrations of cis-9, trans-11 CLA and VA decreased, but these were increased when B. fibrisolvens was incubated with nano-encapsulated CLA-TG. The nano-encapsulation was more effective against the in vitro biohydrogenation activity of B.fibrisolvens incubated with CLA-FFA than with CLA-TG. In the in vitro ruminal incubation test, the total gas production and concentration of total volatile fatty acids incubated with nano-encapsulated CLA-FFA and CLA-TG were increased significantly after 24 h incubation (p<0.05). Nano-encapsulated CLA-FFA might, thus, improve the ruminal fermentation characteristics without adverse effects on the incubation process. In addition, nano-encapsulated CLA-FFA increased the population of Fibrobacter succinogenes and decreased the population of B. fibrisolvens population. These results indicate that nano-encapsulation could be applied to enhance CLA levels in ruminants by increasing the stability of CLA without causing adverse effects on ruminal fermentation.

  15. The In vitro Effects of Nano-encapsulated Conjugated Linoleic Acid on Stability of Conjugated Linoleic Acid and Fermentation Profiles in the Rumen

    PubMed Central

    Heo, Wan; Kim, Eun Tae; Cho, Sung Do; Kim, Jun Ho; Kwon, Seong Min; Jeong, Ha Yeon; Ki, Kwang Seok; Yoon, Ho Baek; Ahn, Young Dae; Lee, Sung Sill; Kim, Young Jun

    2016-01-01

    This study was aimed to evaluate the stability of conjugated linoleic acids (CLAs) by nano-encapsulation against in vitro ruminal biohydrogenation by microbial enzymatic conversion. CLAs (free fatty acid form of CLA [CLA-FFA], nano-encapsulated CLA-FFA, triglyceride form of CLA [CLA-TG], and nano-encapsulated CLA-TG) were used in the in vitro fermentation experiments. When Butyrivibrio fibrisolvens (B. fibrisolvens) was incubated with CLA-FFAs, the concentrations of cis-9, trans-11 CLA and vaccenic acid (VA) slightly was decreased and increased by nano-encapsulation, respectively. When B. fibrisolvens was incubated with CLA-TG, the concentrations of cis-9, trans-11 CLA and VA decreased, but these were increased when B. fibrisolvens was incubated with nano-encapsulated CLA-TG. The nano-encapsulation was more effective against the in vitro biohydrogenation activity of B.fibrisolvens incubated with CLA-FFA than with CLA-TG. In the in vitro ruminal incubation test, the total gas production and concentration of total volatile fatty acids incubated with nano-encapsulated CLA-FFA and CLA-TG were increased significantly after 24 h incubation (p<0.05). Nano-encapsulated CLA-FFA might, thus, improve the ruminal fermentation characteristics without adverse effects on the incubation process. In addition, nano-encapsulated CLA-FFA increased the population of Fibrobacter succinogenes and decreased the population of B. fibrisolvens population. These results indicate that nano-encapsulation could be applied to enhance CLA levels in ruminants by increasing the stability of CLA without causing adverse effects on ruminal fermentation. PMID:26950867

  16. Beyond the FFA: The Role of the Ventral Anterior Temporal Lobes in Face Processing

    PubMed Central

    Collins, Jessica A.; Olson, Ingrid R.

    2014-01-01

    Extensive research has supported the existence of a specialized face-processing network that is distinct from the visual processing areas used for general object recognition. The majority of this work has been aimed at characterizing the response properties of the fusiform face area (FFA) and the occipital face area (OFA), which together are thought to constitute the core network of brain areas responsible for facial identification. Although accruing evidence has shown that face-selective patches in the ventral anterior temporal lobes (vATLs) are interconnected with the FFA and OFA, and that they play a role in facial identification, the relative contribution of these brain areas to the core face-processing network has remained unarticulated. Here we review recent research critically implicating the vATLs in face perception and memory. We propose that current models of face processing should be revised such that the ventral anterior temporal lobes serve a centralized role in the visual face-processing network. We speculate that a hierarchically organized system of face processing areas extends bilaterally from the inferior occipital gyri to the vATLs, with facial representations becoming increasingly complex and abstracted from low-level perceptual features as they move forward along this network. The anterior temporal face areas may serve as the apex of this hierarchy, instantiating the final stages of face recognition. We further argue that the anterior temporal face areas are ideally suited to serve as an interface between face perception and face memory, linking perceptual representations of individual identity with person-specific semantic knowledge. PMID:24937188

  17. Degree of free fatty acid saturation influences chocolate rejection in human assessors.

    PubMed

    Running, Cordelia A; Hayes, John E; Ziegler, Gregory R

    2017-02-01

    In foods, free fatty acids (FFAs) traditionally have been viewed as contributing an odor, yet evidence has accumulated that FFAs also contribute a unique taste ("oleogustus"). However, minimal work has been conducted using actual foods to test the contribution of FFA to taste preferences. Here, we investigate flavor, taste, and aroma contributions of added FFA in chocolate, as some commercial manufacturers already use lipolysis of triglycerides to generate unique profiles. We hypothesized that small added concentrations of FFAs would increase preferences for chocolate, whereas higher added concentrations would decrease preferences. We also hypothesized a saturated fatty acid (stearic C18) would have a lesser effect than a monounsaturated (oleic C18:1), which would have a lesser effect than a polyunsaturated (linoleic C18:2) fatty acid. For each, paired preference tests were conducted for 10 concentrations (0.04% to 2.25%) of added FFAs compared with the control chocolate without added FFAs. Stearic acid was tested for flavor (tasting and nares open), whereas the unsaturated fatty acids were tested for both aroma (orthonasal only and no tasting) and taste (tasting with nares blocked to eliminate retronasal odor). We found no preference for any added FFA chocolate; however, rejection was observed independently for both taste and aroma of unsaturated fatty acids, with linoleic acid reaching rejection at lower concentrations than oleic acid. These data indicate that degree of unsaturation influences rejection of both FFA aroma and taste in chocolate. Thus, alterations of FFA profiles in foods should be approached cautiously to avoid shifting concentrations of unsaturated fatty acids to hedonically unacceptable levels.

  18. Association of free fatty acids with the insulin-resistant state but not with central obesity in individuals from Venezuela.

    PubMed

    Campos, Gilberto; Fernández, Virginia; Fernández, Erika; Molero, Emperatriz; Morales, Luz Marina; Raleigh, Xiomara; Connell, Lissette; Ryder, Elena

    2010-03-01

    Individuals with insulin resistance (IR) usually have upper body obesity phenotype, often accompanied by an increase in plasma free fatty acids (FFA). Since the Venezuelan population has a high frequency of IR and central obesity, the purpose of this work was to determine FFA levels in 47 Venezuelan individuals, men and women, 24-58 years old, and analyze their relationship with central obesity and parameters of carbohydrate and lipid metabolism. Basal concentrations of TG, total cholesterol, LDL-C, and HDL-C were measured, and FFA, glucose and insulin, at basal state and at different times after a glucose load. Eighteen individuals presented insulin resistance (HOMA-IR > 2.7) and 29 were non-insulin resistant (non-IR). Insulin resistant individuals (IR) had higher waist circumference, BMI and basal concentrations of FFA than the non-IR. No differences were observed in skin folds and other basal lipids studied. The increased FFA seemed to be related to the IR associated to BMI and not to central obesity, since the difference between IR and non-IR disappeared when they were matched for waist circumference. After a glucose load, FFA decreased in both groups, but remained significantly elevated in IR subjects. This effect disappeared after matching for BMI or waist circumference, inferring that it was independent of anthropometries. FFA were positively associated with HOMA-IR, glucose and TG levels; however, there was.no association with BMI or waist circumference. These findings, and the lack of elements to support the presence of hepatic IR, common to increased visceral lipolysis, might suggest that the IR present in the obese individuals studied, might be due to an increase in subcutaneous fat.

  19. Free fatty acids and oxidative changes of a raw goat milk cheese through maturation.

    PubMed

    Delgado, Francisco J; González-Crespo, José; Cava, Ramón; Ramírez, Rosario

    2011-05-01

    Free fatty acids (FFA) and lipid and protein oxidation changes were studied throughout maturation process of a raw goat milk cheese with protected designation of origin. Cheeses were analyzed at 4 different times of maturation, at 1, 30, 60, and 90 d. All FFA significantly increased during maturation and the relative increase was higher for long-chain than medium- or short-chain FFA. At the end of maturation, oleic (C18:1 n9), butyric (C4:0), and palmitic (C16:0) acids were the most abundant. The higher levels of short-chain fatty acids (SCFA) regarding total FFA obtained at the end of Ibores cheese ripening compared with other raw goat milk cheeses, highlight the notable role of SCFA on the flavor of this cheese owing to their low-odor thresholds. Lipid oxidation values significantly increased during maturation process but low levels of malondialdehyde were reported; however, protein oxidation did not significantly change during ripening.

  20. Synovial fluid lactic acid levels in septic arthritis.

    PubMed

    Riley, T V

    1981-01-01

    Synovial fluid lactic acid estimations were carried out on 50 samples by gas liquid chromatography. Specimens from 4 patients with bacteria arthritis, other than gonococcal, had a mean lactic acid concentration of 215 mg/dl. One patient with gonococcal arthritis had a synovial fluid lactic acid of 30 mg/dl. Forty-one patients with inflammatory arthritis and 4 patients with degenerative arthritis had mean synovial fluid lactic acid levels of 27 and 23 mg/dl respectively. The estimation of synovial fluid lactic acid is reliable in differentiating septic arthritis from inflammatory and degenerative arthritis except when the infecting organism is NEisseria gonorrhoeae.

  1. Cerebrospinal fluid ascorbic acid levels in neurological disorders.

    PubMed

    Brau, R H; García-Castiñeiras, S; Rifkinson, N

    1984-02-01

    The ascorbic acid/dehydroascorbic acid system was analyzed in the cerebrospinal fluid (CSF) of 41 patients with different neurological disorders. The chi-square test of covariance analysis revealed in this sample significant differences in the CSF levels of total ascorbic acid when patients were classified by diagnostic categories. The population analyzed contained a group of 18 patients (back pain/sciatica group) in whom no overt neurological abnormalities were disclosed upon evaluation. Taking the CSF levels of total ascorbic acid and dehydroascorbic acid in these patients as the reference (3.57 +/- 0.87 (SD)/100 ml and 0.53 +/- 0.19 mg/100 ml, respectively), it was found that head-traumatized patients showed a significant reduction in the concentration of total ascorbic acid in the CSF. CSF ascorbic acid levels were also significantly lower in patients with increased intracranial pressure (noninfected hydrocephalus group) and in patients with cerebral tumors. Although the CSF concentration of dehydroascorbic acid did not correspondingly increase over the reference values in these three groups of patients, the tendency existed for dehydroascorbic acid to represent in them a higher percentage of total ascorbic acid. After examining different alternatives, it is concluded that the hypothesis of free radical damage to the central nervous system after certain types of injury (trauma, ischemia, and tumors) may provide a satisfactory explanation of our findings. A rationale for the use of vitamin C in the management of some neurological patients is also derived from this work.

  2. A hybrid SVM-FFA method for prediction of monthly mean global solar radiation

    NASA Astrophysics Data System (ADS)

    Shamshirband, Shahaboddin; Mohammadi, Kasra; Tong, Chong Wen; Zamani, Mazdak; Motamedi, Shervin; Ch, Sudheer

    2016-07-01

    In this study, a hybrid support vector machine-firefly optimization algorithm (SVM-FFA) model is proposed to estimate monthly mean horizontal global solar radiation (HGSR). The merit of SVM-FFA is assessed statistically by comparing its performance with three previously used approaches. Using each approach and long-term measured HGSR, three models are calibrated by considering different sets of meteorological parameters measured for Bandar Abbass situated in Iran. It is found that the model (3) utilizing the combination of relative sunshine duration, difference between maximum and minimum temperatures, relative humidity, water vapor pressure, average temperature, and extraterrestrial solar radiation shows superior performance based upon all approaches. Moreover, the extraterrestrial radiation is introduced as a significant parameter to accurately estimate the global solar radiation. The survey results reveal that the developed SVM-FFA approach is greatly capable to provide favorable predictions with significantly higher precision than other examined techniques. For the SVM-FFA (3), the statistical indicators of mean absolute percentage error (MAPE), root mean square error (RMSE), relative root mean square error (RRMSE), and coefficient of determination ( R 2) are 3.3252 %, 0.1859 kWh/m2, 3.7350 %, and 0.9737, respectively which according to the RRMSE has an excellent performance. As a more evaluation of SVM-FFA (3), the ratio of estimated to measured values is computed and found that 47 out of 48 months considered as testing data fall between 0.90 and 1.10. Also, by performing a further verification, it is concluded that SVM-FFA (3) offers absolute superiority over the empirical models using relatively similar input parameters. In a nutshell, the hybrid SVM-FFA approach would be considered highly efficient to estimate the HGSR.

  3. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

  4. Uric Acid Levels in Normotensive Children of Hypertensive Parents

    PubMed Central

    Yildirim, Ali; Keles, Fatma; Kosger, Pelin; Ozdemir, Gokmen; Ucar, Birsen; Kilic, Zubeyir

    2015-01-01

    This study evaluated uric acid concentrations in normotensive children of parents with hypertension. Eighty normotensive children from families with and without a history of essential hypertension were included. Concentrations of lipid parameters and uric acid were compared. Demographic and anthropometric characteristics were similar in the groups. Systolic and diastolic blood pressure were higher in the normotensive children of parents with hypertension without statistically significant difference (P > 0.05). Uric acid concentrations were higher in the normotensive children of parents with hypertension (4.61 versus 3.57 mg/dL, P < 0.01). Total cholesterol and triglyceride concentrations were similar in the two groups. Systolic and diastolic blood pressure were significantly higher in control children aged >10 years (P < 0.01). Uric acid levels were significantly higher in all children with more pronounced difference after age 10 of years (P < 0.001). Positive correlations were found between the level of serum uric acid and age, body weight, body mass index, and systolic and diastolic blood pressure in the normotensive children of parents. The higher uric acid levels in the normotensive children of hypertensive parents suggest that uric acid may be a predeterminant of hypertension. Monitoring of uric acid levels in these children may allow for prevention or earlier treatment of future hypertension. PMID:26464873

  5. [Hydroxycinnamic acid levels of various batches from mugwort flowering tops].

    PubMed

    Fraisse, D; Carnat, A; Carnat, A-P; Guédon, D; Lamaison, J-L

    2003-07-01

    Dried flowering tops of 24 harvested batches (Artemisia vulgaris: 13; Artemisia verlotiorum: 11) and 12 batches of mugwort from commercial origin were examined. The levels of principal compounds averaged respectively: total hydroxycinnamic acids 6.09; 10.29 and 9.13%, chlorogenic acid 0.79; 2.05 and 1.35%, 1,5-dicaffeoylquinic acid 0.51; 4.01 and 1.25%, 3,5-dicaffeoylquinic acid 2.21; 1.25 and 2.60%. Specifications were discussed for an European Pharmacopoeial monography.

  6. Serum uric acid levels and cardiovascular disease: the Gordian knot

    PubMed Central

    Tugores, Antonio; Rodríguez-González, Fayna

    2016-01-01

    Hyperuricemia is defined as serum uric acid level of more than 7 mg/dL and blood levels of uric acid are causally associated with gout, as implicated by evidence from randomized clinical trials using urate lowering therapies. Uric acid as a cardiovascular risk factor often accompanies metabolic syndrome, hypertension, diabetes, dyslipidemia, chronic renal disease, and obesity. Despite the association of hyperuricemia with cardiovascular risk factors, it has remained controversial as to whether uric acid is an independent predictor of cardiovascular disease. To settle this issue, and in the absence of large randomized controlled trials, Mendelian randomization analysis in which the exposure is defined based on the presence or absence of a specific allele that influences a risk factor of interest have tried to shed light on this. PMID:28066631

  7. Characterization of the esterification reaction in high free fatty acid oils

    NASA Astrophysics Data System (ADS)

    Altic, Lucas Eli Porter

    Energy and vegetable oil prices have caused many biodiesel producers to turn to waste cooking oils as feedstocks. These oils contain high levels of free fatty acids (FFAs) which make them difficult or impossible to convert to biodiesel by conventional production methods. Esterification is required for ultra-high FFA feedstocks such as Brown Grease. In addition, ultrasonic irradiation has the potential to improve the kinetics of the esterification reaction. 2-level, multi-factor DOE experiments were conducted to characterize the esterification reaction in ultra-high FFA oils as well as determine whether ultrasonic irradiation gives any benefit besides energy input. The study determined that sulfuric acid content had the greatest effect followed by temperature and water content (inhibited reaction). Methanol content had no effect in the range studied. A small interaction term existed between sulfuric acid and temperature. The study also concluded that sonication did not give any additional benefit over energy input.

  8. Independence of sialic acid levels in normal and malignant growth.

    PubMed

    Khadapkar, S V; Sheth, N A; Bhide, S V

    1975-06-01

    Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue.

  9. Plasma amino acid response to graded levels of escape protein.

    PubMed

    Gibb, D J; Klopfenstein, T J; Britton, R A; Lewis, A J

    1992-09-01

    A trial was conducted to examine the potential of using plasma amino acid responses to graded levels of escape protein to determine limiting amino acids in cattle. Growing calves (n = 120; mean BW = 220 +/- 21 kg) were fed a basal diet of corncob:sorghum silage (61:39) and were individually supplemented with distillers' dried grains (DDG), heat-damaged DDG (H-DDG), feather meal (FTH), or urea. The urea supplement was mixed with DDG and H-DDG to allow 0, 20, 35, 50, 65, or 80% of the supplemental CP to come from distillers' protein and maintain an 11.5% CP diet. Urea supplement was mixed with FTH to allow 0, 22, 39, 56, 73, or 90% of the supplemental CP to come from FTH. Dietary CP ranged from 11.5% at the 0% level to 17.3% at the 90% level. Plasma concentration of most essential plasma amino acids responded (P less than .10) linearly and(or) quadratically to increased escape protein. The broken-line response of plasma methionine at low DDG intake suggested that methionine was limiting at low levels of escape protein. An initial decrease followed by a plateau fit by a broken line indicated that histidine became limiting in FTH diets, and lysine eventually became limiting for DDG, H-DDG, and FTH diets before maximum BW gain was reached. Results indicate that plasma amino acid responses may identify amino acids that become limiting with increasing escape protein.

  10. A Nationwide Examination of Middle School Enrollment in Agricultural Education and Membership in the National FFA Organization.

    ERIC Educational Resources Information Center

    Rossetti, Rosemarie; And Others

    The purpose of this study was to determine the status of middle and junior high school agricultural education and FFA (Future Farmers of America) programs. In spring 1991. questionnaires were sent to all state FFA Executive Secretaries (n=53); 52 returned questionnaires. Three teachers in each of 9 states identified as having middle or junior high…

  11. Career Development, Supervised Agricultural Experience, and FFA. The Connecticut Vocational Agriculture Education Curriculum.

    ERIC Educational Resources Information Center

    Mannebach, Alfred J.; And Others

    This curriculum guide was developed to help teachers and administrators in Connecticut Regional Vocational Agriculture Centers to update and upgrade their vocational agriculture curriculum in the areas of career development, supervised agricultural experience (SAE), and Future Farmers of America (FFA). The curriculum incorporates the competencies…

  12. Needed: Educational Objectives and Administrative Criteria for the National FFA Contests.

    ERIC Educational Resources Information Center

    Smith, Mack W.; Kahler, Alan A.

    1987-01-01

    The purpose of the study was to establish overall educational objectives and administrative criteria for the national Future Farmers of America (FFA) contests. Through a series of three questionnaires, input was received from a Delphi panel of 33 members that generated and identified objectives and criteria. (CH)

  13. A Historical Review of Leadership Development in the FFA and 4-H

    ERIC Educational Resources Information Center

    Hoover, Tracy S.; Scholl, Jan F.; Dunigan, Anne H.; Mamontova, Nadezhda

    2007-01-01

    FFA and 4-H are two youth-based organizations that cite leadership development as a key foundational component. The purpose of this study was to review and document the historical development of leadership events and activities in both programs. Evidence can be found of leadership development in schools, conferences, and camps. Leadership-related…

  14. Association of Renal Manifestations with Serum Uric Acid in Korean Adults with Normal Uric Acid Levels

    PubMed Central

    Jung, Dong-Hyuk; Lee, Yong-Jae; Lee, Hye-Ree; Lee, Jung-Hyun

    2010-01-01

    Several studies have reported that hyperuricemia is associated with the development of hypertension and cardiovascular disease. Increasing evidences also suggest that hyperuricemia may have a pathogenic role in the progression of renal disease. Paradoxically, uric acid is also widely accepted to have antioxidant activity in experimental studies. We aimed to investigate the association between glomerular filtration rate (GFR) and uric acid in healthy individuals with a normal serum level of uric acid. We examined renal function determined by GFR and uric acid in 3,376 subjects (1,896 men; 1,480 women; aged 20-80 yr) who underwent medical examinations at Gangnam Severance Hospital from November 2006 to June 2007. Determinants for renal function and uric acid levels were also investigated. In both men and women, GFR was negatively correlated with systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, uric acid, log transformed C reactive protein, and log transformed triglycerides. In multivariate regression analysis, total uric acid was found to be an independent factor associated with estimated GFR in both men and women. This result suggests that uric acid appears to contribute to renal impairment in subjects with normal serum level of uric acid. PMID:21165292

  15. [8-hydroxy-dihydroberberine ameliorated insulin resistance induced by high FFA and high glucose in 3T3-L1 adipocytes].

    PubMed

    Xu, Li-jun; Lu, Fu-er; Yi, Ping; Wang, Zeng-si; Wei, Shi-chao; Chen, Guang; Dong, Hui; Zou, Xin

    2009-11-01

    The purpose of the study is to investigate the effect of 8-hydroxy-dihydroberberine on insulin resistance induced by high free fatty acid (FFA) and high glucose in 3T3-L1 adipocytes and its possible molecular mechanism. Palmic acid or glucose in combination with insulin was used to induce insulin resistance in 3T3-L1 adipocytes. 8-Hydroxy-dihydroberberine and berberine were added to the cultured medium separately, which were considered as treated group and positive control group. The rate of glucose uptake was determined by 2-deoxy-[3H]-D-glucose method. The amount of glucose consumption in the medium was measured by glucose oxidase method. Cell growth and proliferation of 3T3-L1 adipocytes were detected with Cell Counting Kit-8 (CCK-8) assay. After incubated with palmic acid for 24 hours or glucose with insulin for 18 hours, the rate of glucose transport in 3T3-L1 adipocytes was inhibited by 67% and 58%, respectively. The amount of glucose consumption in 3T3-L1 adipose cells was decreased by 41% after cells were incubated with palmic acid for 24 h. However, the above changes were reversed by pretreatment with 8-hydroxy-dihydroberberine for 24 and 48 h. Significant difference existed between groups. Insulin resistance in 3T3-L1 adipocytes, which is induced by high FFA and high glucose, could be ameliorated by 8-hydroxy-dihydroberberine.

  16. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  17. Relationship between Uric Acid Level and Achievement Motivation. Final Report.

    ERIC Educational Resources Information Center

    Mueller, Ernst F.; French, John R. P., Jr.

    In an investigation of the relationship of uric acid (a metabolic end product) to achievement, this study hypothesized that a person's serum urate level (a factor often associated with gout) is positively related to achievement need as well as indicators of actual achievement. (Speed of promotion and number of yearly publications were chosen as…

  18. Puget Sound acidity levels drop after ASARCO shutdown

    SciTech Connect

    Not Available

    1987-07-01

    The levels of acidity in Puget Sound region rainfall have decreased significantly since the shutdown of the ASARCO copper smelter in Tacoma, Washington, according to a study funded by the US Environmental Protection Agency. Results indicate that sulfate and hydrogen ion concentrations obtained from samples taken before the closure were significantly different than those collected after the shutdown. Rainwater samples collected downwind during smelter operation were also significantly different from those collected upwind. Sulfur dioxide is considered to be one of the principal contributors to acid rain. The smelter was a major source of sulfur dioxide emissions in the Puget Sound region before it shut down in March 1985.

  19. High Level Waste System Impacts from Acid Dissolution of Sludge

    SciTech Connect

    KETUSKY, EDWARD

    2006-04-20

    This research evaluates the ability of OLI{copyright} equilibrium based software to forecast Savannah River Site High Level Waste system impacts from oxalic acid dissolution of Tank 1-15 sludge heels. Without further laboratory and field testing, only the use of oxalic acid can be considered plausible to support sludge heel dissolution on multiple tanks. Using OLI{copyright} and available test results, a dissolution model is constructed and validated. Material and energy balances, coupled with the model, identify potential safety concerns. Overpressurization and overheating are shown to be unlikely. Corrosion induced hydrogen could, however, overwhelm the tank ventilation. While pH adjustment can restore the minimal hydrogen generation, resultant precipitates will notably increase the sludge volume. OLI{copyright} is used to develop a flowsheet such that additional sludge vitrification canisters and other negative system impacts are minimized. Sensitivity analyses are used to assess the processability impacts from variations in the sludge/quantities of acids.

  20. Altered Serum Uric Acid Level in Lichen Planus Patients

    PubMed Central

    Chakraborti, Goutam; Biswas, Rabindranath; Chakraborti, Sandip; Sen, Pradyot Kumar

    2014-01-01

    Background: Lichen planus (LP) is a common disorder whose etiopathogenesis is not clear. Recently, it has been suggested that increased reactive oxygen species (ROS) play important roles in the underlying mechanism of LP. Objectives: The principal aim of this study was to evaluate serum uric acid (UA) levels as a measure of the antioxidant defense status in LP patients. Methods: Serum UA levels were determined in 58 LP patients and 61 controls. Results: Serum UA levels were significantly decreased in patients with respect to controls. Moreover, serum UA level was decreased according to increasing duration of disease. Conclusions: The results of our study suggest that LP is associated with decrease of UA levels in serum. UA may be a potential, useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring. PMID:25484383

  1. A Mutant of Arabidopsis with Increased Levels of Stearic Acid.

    PubMed Central

    Lightner, J.; Wu, J.; Browse, J.

    1994-01-01

    A mutation at the fab2 locus of Arabidopsis caused increased levels of stearate in leaves. The increase in leaf stearate in fab2 varied developmentally, and the largest increase occurred in young leaves, where stearate accounted for almost 20% of total leaf fatty acids. The fatty acid composition of leaf lipids isolated from the fab2 mutant showed increased stearate in all the major glycerolipids of both the chloroplast and extrachloroplast membranes. Although the stearate content was increased, the fab2 mutant still contained abundant amounts of 18:1, 18:2, and 18:3 fatty acids. These results are consistent with the expectations for a mutation partially affecting the action of the stromal stearoyl-acyl carrier protein desaturase. Positional analysis indicated that the extra 18:0 is excluded with high specificity from the sn-2 position of both chloroplast and extrachloroplast glycerolipids. Although stearate content was increased in all the major leaf membrane lipids, the amount of increase varied considerably among the different lipids, from a high of 25% of fatty acids in phosphatidylcholine to a low of 2.9% of fatty acids in monogalactosyldiacylglycerol. PMID:12232421

  2. Physiological Effects of Free Fatty Acid Production in Genetically Engineered Synechococcus elongatus PCC 7942

    PubMed Central

    Ruffing, Anne M.; Jones, Howland D.T.

    2012-01-01

    The direct conversion of carbon dioxide into biofuels by photosynthetic microorganisms is a promising alternative energy solution. In this study, a model cyanobacterium, Synechococcus elongatus PCC 7942, is engineered to produce free fatty acids (FFA), potential biodiesel precursors, via gene knockout of the FFA-recycling acyl-ACP synthetase and expression of a thioesterase for release of the FFA. Similar to previous efforts, the engineered strains produce and excrete FFA, but the yields are too low for large-scale production. While other efforts have applied additional metabolic engineering strategies in an attempt to boost FFA production, we focus on characterizing the engineered strains to identify the physiological effects that limit cell growth and FFA synthesis. The strains engineered for FFA-production show reduced photosynthetic yields, chlorophyll-a degradation, and changes in the cellular localization of the light-harvesting pigments, phycocyanin and allophycocyanin. Possible causes of these physiological effects are also identified. The addition of exogenous linolenic acid, a polyunsaturated FFA, to cultures of S. elongatus 7942 yielded a physiological response similar to that observed in the FFA-producing strains with only one notable difference. In addition, the lipid constituents of the cell and thylakoid membranes in the FFA-producing strains show changes in both the relative amounts of lipid components and the degree of saturation of the fatty acid side chains. These changes in lipid composition may affect membrane integrity and structure, the binding and diffusion of phycobilisomes, and the activity of membrane-bound enzymes including those involved in photosynthesis. Thus, the toxicity of unsaturated FFA and changes in membrane composition may be responsible for the physiological effects observed in FFA-producing S. elongatus 7942. These issues must be addressed to enable the high yields of FFA synthesis necessary for large-scale biofuel

  3. Activation of β3-adrenoceptors increases in vivo free fatty acid uptake and utilization in brown but not white fat depots in high-fat-fed rats

    PubMed Central

    Warner, Amy; Kjellstedt, Ann; Carreras, Alba; Böttcher, Gerhard; Peng, Xiao-Rong; Seale, Patrick; Oakes, Nicholas

    2016-01-01

    Activation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) present potential new therapies for obesity and type 2 diabetes. Here, we examined the effects of β3-adrenergic stimulation on tissue-specific uptake and storage of free fatty acids (FFA) and its implications for whole body FFA metabolism in diet-induced obese rats using a multi-radiotracer technique. Male Wistar rats were high fat-fed for 12 wk and administered β3-agonist CL316,243 (CL, 1 mg·kg−1·day−1) or saline via osmotic minipumps during the last 3 wk. The rats were then fasted and acutely infused with a tracer mixture ([14C]palmitate and the partially metabolized R-[3H]bromopalmitate) under anesthesia. CL infusion decreased body weight gain and fasting plasma glucose levels. While core body temperature was unaffected, infrared thermography showed an increase in tail heat dissipation following CL infusion. Interestingly, CL markedly increased both FFA storage and utilization in interscapular and perirenal BAT, whereas the flux of FFA to skeletal muscle was decreased. In this rat model of obesity, only sporadic populations of beige adipocytes were detected in the epididymal WAT depot of CL-infused rats, and there was no change in FFA uptake or utilization in WAT following CL infusion. In summary, β3-agonism robustly increased FFA flux to BAT coupled with enhanced utilization. Increased BAT activation most likely drove the increased tail heat dissipation to maintain thermostasis. Our results emphasize the quantitative role of brown fat as the functional target of β3-agonism in obesity. PMID:27780820

  4. Kinetic study of free fatty acid esterification reaction catalyzed by recoverable and reusable hydrochloric acid.

    PubMed

    Su, Chia-Hung

    2013-02-01

    The catalytic performance and recoverability of several homogeneous acid catalysts (hydrochloric, sulfuric, and nitric acids) for the esterification of enzyme-hydrolyzed free fatty acid (FFA) and methanol were studied. Although all tested catalysts drove the reaction to a high yield, hydrochloric acid was the only catalyst that could be considerably recovered and reused. The kinetics of the esterification reaction catalyzed by hydrochloric acid was investigated under varying catalyst loading (0.1-1M), reaction temperature (303-343K), and methanol/FFA molar ratio (1:1-20:1). In addition, a pseudo-homogeneous kinetic model incorporating the above factors was developed. A good agreement (r(2)=0.98) between the experimental and calculated data was obtained, thus proving the reliability of the model. Furthermore, the reusability of hydrochloric acid in FFA esterification can be predicted by the developed model. The recoverable hydrochloric acid achieved high yields of FFA esterification within five times of reuse.

  5. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

    SciTech Connect

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert J.

    2014-09-05

    Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.

  6. Membrane Stresses Induced by Overproduction of Free Fatty Acids in Escherichia coli.

    SciTech Connect

    Lennen, Rebecca M.; Kruziki, Max A.; Kumar, Kritika; Zinkel, Robert A.; Burnum, Kristin E.; Lipton, Mary S.; Hoover, Spencer W.; Ranatunga, Don Ruwan; Wittkopp, Tyler M.; Marner II, Wesley D.; Pfleger, Brian F.

    2011-11-01

    Microbially produced fatty acids are potential precursors to high energy density biofuels, including alkanes and alkyl ethyl esters by either catalytic conversion of free fatty acids (FFAs) or enzymatic conversions of acyl-acyl carrier protein or acyl-coenzyme A intermediates. Metabolic engineering efforts aimed at overproducing FFAs in Escherichia coli have achieved less than 30% of the maximum theoretical yield on the supplied carbon source. In this work, the viability, morphology, transcript levels, and protein levels of a strain of E. coli that overproduces medium chain length FFAs was compared to an engineered control strain. By early stationary phase, an 85% reduction in viable cell counts and exacerbated loss of inner membrane integrity were observed in the FFA overproducing strain. These effects were enhanced in strains endogenously producing FFAs compared to strains exposed to exogenously fed FFAs. Under two sets of cultivation conditions, long chain unsaturated fatty acid content greatly increased and the expression of genes and proteins required for unsaturated fatty acid biosynthesis were significantly decreased. Membrane stresses were further implicated by increased expression of genes and proteins of the phage shock response, the MarA/Rob/SoxS regulon, and the nuo and cyo operons of aerobic respiration. Gene deletion studies confirmed the importance of the phage shock proteins and Rob for maintaining cell viability, however little to no change in FFA titers was observed after 24 h cultivation. The results of this study serve as a baseline for future targeted attempts to improve FFA yields and titers in E. coli.

  7. Does high serum uric acid level cause aspirin resistance?

    PubMed

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage.

  8. Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

    1997-01-01

    The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in

  9. Improved Free Fatty Acid Production in Cyanobacteria with Synechococcus sp. PCC 7002 as Host

    PubMed Central

    Ruffing, Anne M.

    2014-01-01

    Microbial free fatty acids (FFAs) have been proposed as a potential feedstock for renewable energy. The ability to directly convert carbon dioxide into FFAs makes cyanobacteria ideal hosts for renewable FFA production. Previous metabolic engineering efforts using the cyanobacterial hosts Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 have demonstrated this direct conversion of carbon dioxide into FFAs; however, FFA yields in these hosts are limited by the negative impact of FFA production on the host cell physiology. This work investigates the use of Synechococcus sp. PCC 7002 as a cyanobacterial host for FFA production. In comparison to S. elongatus PCC 7942, Synechococcus sp. PCC 7002 strains produced and excreted FFAs at similar concentrations but without the detrimental effects on host physiology. The enhanced tolerance to FFA production with Synechococcus sp. PCC 7002 was found to be temperature-dependent, with physiological effects such as reduced photosynthetic yield and decreased photosynthetic pigments observed at higher temperatures. Additional genetic manipulations were targeted for increased FFA production, including thioesterases and ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). Overexpression of non-native RuBisCO subunits (rbcLS) from a psbAI promoter resulted in more than a threefold increase in FFA production, with excreted FFA concentrations reaching >130 mg/L. This work illustrates the importance of host strain selection for cyanobacterial biofuel production and demonstrates that the FFA tolerance of Synechococcus sp. PCC 7002 can allow for high yields of excreted FFA. PMID:25152890

  10. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs.

  11. Ocean acidification increases fatty acids levels of larval fish

    PubMed Central

    Díaz-Gil, Carlos; Catalán, Ignacio A.; Palmer, Miquel; Faulk, Cynthia K.; Fuiman, Lee A.

    2015-01-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  12. Association between serum folic acid level and erectile dysfunction.

    PubMed

    Karabakan, M; Erkmen, A E; Guzel, O; Aktas, B K; Bozkurt, A; Akdemir, S

    2016-06-01

    This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml(-1) in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED.

  13. Cytokine levels affected by gamma-linolenic acid.

    PubMed

    Dirks, J; van Aswegen, C H; du Plessis, D J

    1998-10-01

    This study was undertaken to assess whether gamma-linolenic acid (GLA) in the form of evening primrose oil (EPO) could affect rat serum cytokines, interferon-gamma (IFN-gamma), monocyte chemotactic protein-1 (MCP-1) and tumour necrosis factor-alpha (TNF-alpha). The following diets were administered: control, glucan, Freund's adjuvant and glucan plus Freund's adjuvant with and without GLA. In the presence of GLA, the IFN-gamma and MCP-1 levels were significantly decreased in contrast to the control group of TNF-alpha, which was significantly stimulated. On account of interaction between diets and GLA, the remaining diet groups of TNF-alpha were either not affected or were inhibited in the presence of GLA. The observations indicate that GLA may modulate the level of serum IFN-gamma, MCP-1 and TNF-alpha, which may be a worthwhile line of treatment in certain human diseases.

  14. A rotamer energy level study of sulfuric acid.

    PubMed

    Partanen, Lauri; Pesonen, Janne; Sjöholm, Elina; Halonen, Lauri

    2013-10-14

    It is a common approach in quantum chemical calculations for polyatomic molecules to rigidly constrain some of the degrees of freedom in order to make the calculations computationally feasible. However, the presence of the rigid constraints also affects the kinetic energy operator resulting in the frozen mode correction, originally derived by Pesonen [J. Chem. Phys. 139, 144310 (2013)]. In this study, we compare the effects of this correction to several different approximations to the kinetic energy operator used in the literature, in the specific case of the rotamer energy levels of sulfuric acid. The two stable conformers of sulfuric acid are connected by the rotations of the O-S-O-H dihedral angles and possess C2 and Cs symmetry in the order of increasing energy. Our results show that of the models tested, the largest differences with the frozen mode corrected values were obtained by simply omitting the passive degrees of freedom. For the lowest 17 excited states, this inappropriate treatment introduces an increase of 9.6 cm(-1) on average, with an increase of 8.7 cm(-1) in the zero-point energies. With our two-dimensional potential energy surface calculated at the CCSD(T)-F12a/VDZ-F12 level, we observe a radical shift in the density of states compared to the harmonic picture, combined with an increase in zero point energy. Thus, we conclude that the quantum mechanical inclusion of the different conformers of sulfuric acid have a significant effect on its vibrational partition function, suggesting that it will also have an impact on the computational values of the thermodynamic properties of any reactions where sulfuric acid plays a role. Finally, we also considered the effect of the anharmonicities for the other vibrational degrees of freedom with a VSCF-calculation at the DF-MP2-F12/VTZ-F12 level of theory but found that the inclusion of the other conformer had the more important effect on the vibrational partition function.

  15. Serum hyaluronic acid levels in patients with ankylosing spondylitis.

    PubMed

    Duruöz, Mehmet Tuncay; Turan, Yasemin; Cerrahoglu, Lale; Isbilen, Banu

    2008-05-01

    Our aim in this study was to investigate serum hyaluronic acid (HA) levels and the relationship between clinical parameters in ankylosing spondylitis (AS). Approximately 30 patients with AS and 30 healthy individuals were recruited in this study consecutively. Cross-sectional study was planned, and demographic, clinical, functional, radiological, and laboratory data of patients were evaluated. Disease activity, functional status, and quality of life were assessed, respectively, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Short-Form 36 (SF-36). Mander Enthesis Index (MEI) was used for evaluation of enthesis involvement. We examined serum concentrations of HA (ng/ml) in patients with AS and controls. The mean ages of patients and control group were 38.3 (SD=10.8) and 42.7 (SD=10.6) years, respectively. The mean of serum HA levels in AS patients was 40.4 (SD=34.8) ng/ml and in controls was 24.9 (SD=20.2). There was significant difference of HA levels between two groups (p=0.04). Furthermore, there was a significant correlation between HA level and distance of hand-floor (r=0.444, p=0.014), modified lumbar Schober's (r= -0.413, p=0.023), distance of chin to chest (r=0.436, p=0.016), right sacroiliit grade (r=0.601, p<0.001), left sacroiliit grade (r=0.610, p<0.001), C reactive protein level (r=0.404, p=0.027), albumin (r= -0.464, p=0.010), C3 (p=0.449, p=0.013), and IgA levels (r=0.369, p=0.045). However, there was no significant correlation between HA levels with MEI, BASFI, BASDAI, and SF-36 (p >or= 0.05). Serum HA level was significantly higher in AS patients than controls. However, there was no significant correlation between serum HA level and disease-specific measures as BASFI and BASDAI; it had significant relation with spinal mobility limitation, sacroiliitis, and laboratory parameters related with acute inflammation. The serum HA level may be a potential biomarker of axial

  16. Evaluation of feeding glycerol on free-fatty acid production and fermentation kinetics of mixed ruminal microbes in vitro.

    PubMed

    Krueger, N A; Anderson, R C; Tedeschi, L O; Callaway, T R; Edrington, T S; Nisbet, D J

    2010-11-01

    Ruminant-derived foods contain high proportions of saturated fats as a result of ruminal biohydrogenation that rapidly saturates and thus limits the availability of free unsaturated fatty acids for assimilation. The objective of this study was to evaluate the effects of glycerol on ruminal free-fatty acid (FFA) production rates and in vitro fermentation kinetics of alfalfa hay. In vitro incubations demonstrated 48% and 77% reductions in rates of FFA accumulation in incubations supplemented with 2% and 20% glycerol as compared to controls. In vitro incubations with alfalfa hay demonstrated that increasing levels of glycerol did not affect NDF digestibility of the hay. Additionally, increasing amounts of glycerol decreased the acetate to propionate ratio in the rumen. These results suggest that inhibiting bacterial fat degradation may promote ruminal passage of total lipid, thereby providing greater proportions of beneficial unsaturated fat for incorporation into beef products.

  17. Disruption of glucose homeostasis and induction of insulin resistance by elevated free fatty acids in human L02 hepatocytes.

    PubMed

    Wan, X-D; Yang, W-B; Xia, Y-Z; Wang, J-F; Lu, T; Wang, X-M

    2009-05-01

    Free fatty acids (FFA) have been implicated as an important causative link between obesity, insulin resistance, and Type 2 diabetes. However, the underlying mechanisms especially for FFA-mediated hepatic insulin resistance are not fully elucidated. Here, we investigated the impaired sites in insulin signaling pathways and mechanisms of insulin resistance induced by elevated FFA in L02 hepatocytes. L02 cells were cultured in Dulbecco's modified eagle medium containing various concentrations of palmitic acid (PA) for 24 h followed by 10(-7) mol/l insulin stimulation. In some experiments, cells were pre-treated with enzymatic inhibitor Wortmannin (10(-6) mol/l). Glucose levels in medium, cytosolic glycogen contents, and phosphoenolpyruvate carboxykinase (PEPCK) activity were measured. Protein level of insulin receptor substrate (IRS)-2 and phosphorylated Akt were detected by Western blot analysis. L02 cells treated with high levels of PA exhibited increased glucose levels, whereas hepatic glycogen contents were decreased in a dose-dependent manner as compared to the control cells. There was a significant attenuation of IRS- 2 protein expression in the cells cultured with PA, and Wortmannin intervention exhibited different IRS-2 protein level with or without PA treatment. In accordance with the reduced IRS-2 level, the insulin-stimulated phosphorylation of Akt was diminished in the PA-treated cells. Basal PEPCK activity and insulin- regulated PEPCK activity were overstimulated in the cells incubated with PA. These data indicate high levels of FFA can disrupt glucose homeostasis, inflict some defects in insulin signaling, and induce insulin resistance in L02 cells.

  18. Endogenous Levels of Abscisic Acid and Decanoic Acid in Dutch Iris Bulbs and the Influence of Abscisic Acid and Decanoic Acid on Iris Meristems Cultured In Vitro1

    PubMed Central

    Doss, Robert P.; Kimura, Yosh; Christian, James K.

    1983-01-01

    Abscisic acid (ABA) and decanoic acid inhibited shoot elongation and floral development of Dutch iris (Iris hollandica Hoog. cv Ideal) meristems cultured in vitro. No synergism with respect to inhibition of leaf growth between ABA and decanoic acid was observed. With monthly harvest dates, from July 10, 1981 to October 10, 1981, there was a progressive decrease in endogenous level of free ABA in `Ideal' iris bulbs. Bulbs subjected to a full set of the usual preplanting storage conditions flowered, on average, 46 days after planting versus 194 days after planting for bulbs planted directly after harvest. ABA levels at harvest were 4- to 5-fold those after the preplanting storage treatment. In general, ABA levels did not correlate well with the length of time from planting until flowering of iris bulbs. Endogenous decanoic acid levels did not follow any pattern with respect to harvest date or postharvest treatment. After the postharvest high temperature treatment, there was about a 3-fold increase in nonscale decanoic acid concentration. Decanoic acid levels, in nonscale tissue, remained high after each of the other postharvest treatments. It is concluded that there is no good evidence to support the contention that either ABA or decanoic acid is directly involved in iris bulb dormancy. PMID:16663072

  19. A study of the relationship between bile salts, bile salt-stimulated lipase, and free fatty acids in breast milk: normal infants and those with breast milk jaundice.

    PubMed

    Forsyth, J S; Donnet, L; Ross, P E

    1990-08-01

    Breast milk jaundice has been reported to be associated with increased lipase activity and elevated free fatty acid (FFA) concentrations within breast milk. We have previously shown that bile salts are present in small concentrations in breast milk and the aim of this study was to examine the relationship of bile salt-stimulated lipase (BSSL) activity, FFA concentration, and bile salt concentration in milks of normal infants and the milk of infants with breast milk jaundice. Mothers of healthy newborn infants were recruited in the early newborn period and 42 provided breast milk samples at 2 weeks, 30 at 6 weeks, 16 at 10 weeks, and 13 at 14 weeks postnatally. We initially studied the effect of lactation on bile salts and found there was a significant decline in both cholate and chenodeoxycholate levels with duration of lactation (p less than 0.05). There was also a significant fall in BSSL activity with duration of lactation (p less than 0.05), but no correlation was found between BSSL activity and bile salt concentration. FFA concentrations were similar throughout lactation and were not related to either BSSL activity or bile salt concentration. There was a significant increase in the concentration of cholate and the cholate-to-chenodeoxycholate ratio in the milks of 12 infants with breast milk jaundice compared with normal milks, the BSSL activity was similar and contrary to previous reports, the FFA concentration was not increased in the milks of infants with breast milk jaundice.

  20. Low irradiances affect abscisic acid, indole-3-acidic acid, and cytokinin levels of wheat (Triticum aestivum L.) tissues

    NASA Technical Reports Server (NTRS)

    Nan, R.; Carman, J. G.; Salisbury, F. B.

    1999-01-01

    Wheat (Triticum aestivum L.) plants were grown under four irradiance levels: 1,400, 400, 200, and 100 micromol m-2 s-1. Leaves and roots were sampled before, during, and after the boot stage, and levels of abscisic acid (ABA), indole-3-acetic acid (IAA), zeatin, zeatin riboside, dihydrozeatin, dihydrozeatin riboside, isopentenyl adenine, and isopentenyl adenosine were quantified using noncompetitive indirect ELISA systems. Levels of IAA in leaves and roots of plants exposed to 100 micromol m-2 s-1 of irradiance were 0.7 and 2.9 micromol kg-1 dry mass (DM), respectively. These levels were 0.2 and 1.0 micromol kg-1 DM, respectively, when plants were exposed to 1,400 micromol m-2 s-1. Levels of ABA in leaves and roots of plants exposed to 100 micromol m-2 s-1 were 0.65 and 0.55 micromol kg-1 DM, respectively. They were 0.24 micromol kg-1 DM (both leaves and roots) when plants were exposed to 1,400 micromol m-2 s-1. Levels of isopentenyl adenosine in leaves (24.3 nmol kg-1 DM) and roots (29.9 nmol kg-1 DM) were not affected by differences in the irradiance regime. Similar values were obtained in a second experiment. Other cytokinins could not be detected (<10 nmol kg 1 DM) in either experiment with the sample sizes used (150-600 mg DM for roots and shoots, respectively).

  1. Alterations of amino Acid level in depressed rat brain.

    PubMed

    Yang, Pei; Li, Xuechun; Ni, Jian; Tian, Jingchen; Jing, Fu; Qu, Changhai; Lin, Longfei; Zhang, Hui

    2014-10-01

    Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and γ-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-α-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, γ-amino-n-butyric acid and L-α-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant.

  2. A Novel RSSI Prediction Using Imperialist Competition Algorithm (ICA), Radial Basis Function (RBF) and Firefly Algorithm (FFA) in Wireless Networks

    PubMed Central

    Goudarzi, Shidrokh; Haslina Hassan, Wan; Abdalla Hashim, Aisha-Hassan; Soleymani, Seyed Ahmad; Anisi, Mohammad Hossein; Zakaria, Omar M.

    2016-01-01

    This study aims to design a vertical handover prediction method to minimize unnecessary handovers for a mobile node (MN) during the vertical handover process. This relies on a novel method for the prediction of a received signal strength indicator (RSSI) referred to as IRBF-FFA, which is designed by utilizing the imperialist competition algorithm (ICA) to train the radial basis function (RBF), and by hybridizing with the firefly algorithm (FFA) to predict the optimal solution. The prediction accuracy of the proposed IRBF–FFA model was validated by comparing it to support vector machines (SVMs) and multilayer perceptron (MLP) models. In order to assess the model’s performance, we measured the coefficient of determination (R2), correlation coefficient (r), root mean square error (RMSE) and mean absolute percentage error (MAPE). The achieved results indicate that the IRBF–FFA model provides more precise predictions compared to different ANNs, namely, support vector machines (SVMs) and multilayer perceptron (MLP). The performance of the proposed model is analyzed through simulated and real-time RSSI measurements. The results also suggest that the IRBF–FFA model can be applied as an efficient technique for the accurate prediction of vertical handover. PMID:27438600

  3. Elevation of serum levels of beta-aminoisobutyric acid in uremic patients and the toxicity of the amino acid.

    PubMed

    Gejyo, F; Kinoshita, Y; Ikenaka, T

    1977-12-01

    A reliable method for the determination of beta-aminoisobutyric acid in serum was developed utilizing an automated amino acid analyzer. The serum concentrations of beta-aminoisobutyric acid were determined in 20 normal subjects and in 71 uremic patients. The mean serum level of beta-aminoisobutyric acid was markedly increased in the uremic patients to 0.856 +/- 0.910 (mean +/- SD) mg/100 ml as compared with a normal value of 0.026 +/- 0.027 mg/100 ml. The distribution of serum beta-aminoisobutyric acid level in uremic patients was wide-spread, and there was no correlation between the serum levels of the amino acid and those of urea nitrogen, creatinine and uric acid. The toxicity of beta-aminoisobutyric acid on mice with acute renal failure induced by uranyl acetate was investigated and compared with that of alpha-amino-n-butyric acid and gamma-amino-n-butyric acid. All mice given more than 4 g/kg body wt of beta-aminoisobutyric acid showed twitching and cramps, and some of them died. However, the control mice given an equivalent dose of alpha-amino-n-butyric acid or gamma-amino-n-butyric acid showed no change. These results suggest that beta-aminoisobutyric acid might be a factor influencing the development and progression of uremic toxemia.

  4. Serum uric acid levels during leprosy reaction episodes

    PubMed Central

    Alves-Junior, Eduardo R.; Arruda, Talita A.; Lopes, Jose C.; Fontes, Cor J.F.

    2016-01-01

    Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18–69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with

  5. Nonoxidative Free Fatty Acid Disposal Is Greater in Young Women than Men

    PubMed Central

    Koutsari, Christina; Basu, Rita; Rizza, Robert A.; Nair, K. Sreekumaran; Khosla, Sundeep

    2011-01-01

    Context: Large increases in systemic free fatty acid (FFA) availability in the absence of a corresponding increase in fatty acid oxidation can create a host of metabolic abnormalities. These adverse responses are thought to be the result of fatty acids being shunted into hepatic very low-density lipoprotein-triglyceride production and/or intracellular lipid storage and signaling pathways because tissues are forced to increase nonoxidative FFA disposal. Objective: The objective of the study was to examine whether variations in postabsorptive nonoxidative FFA disposal within the usual range predict insulin resistance and hypertriglyceridemia. Design: We measured: systemic FFA turnover using a continuous iv infusion of [9–10, 3H]palmitate; substrate oxidation with indirect calorimetry combined with urinary nitrogen excretion; whole-body and peripheral insulin sensitivity with the labeled iv glucose tolerance test minimal model. Setting: the study was conducted at the Mayo Clinic General Clinical Research Center. Participants: Participants included healthy, postabsorptive, nonobese adults (21 women and 21 men). Interventions: There were no interventions. Main Outcome Measures: Nonoxidative FFA disposal (micromoles per minute), defined as the FFA disappearance rate minus fatty acid oxidation. Results: Women had 64% greater nonoxidative FFA disposal rate than men but a better lipid profile and similar insulin sensitivity. There was no significant correlation between nonoxidative FFA disposal and whole-body sensitivity, peripheral insulin sensitivity, or fasting serum triglyceride concentrations in men or women. Conclusions: Healthy nonobese women have greater rates of nonoxidative FFA disposal than men, but this does not appear to relate to adverse health consequences. Understanding the sex-specific interaction between adipose tissue lipolysis and peripheral FFA removal will help to discover new approaches to treat FFA-induced abnormalities. PMID:21123445

  6. Acetic acid vapor levels associated with facial prosthetics

    SciTech Connect

    McElroy, T.H.; Guerra, O.N.; Lee, S.A.

    1985-01-01

    The use of Silastic Medical Adhesive Type A in the fabrication of facial prostheses may cause health hazards to the patient and the operator because of acetic acid emissions. Caution must be exercised to remove acetic acid vapors from the air and unliberated acetic acid from material applied directly to the skin.

  7. Lower serum uric acid level predicts mortality in dialysis patients

    PubMed Central

    Bae, Eunjin; Cho, Hyun-Jeong; Shin, Nara; Kim, Sun Moon; Yang, Seung Hee; Kim, Dong Ki; Kim, Yong-Lim; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam Ho; Kim, Yon Su; Lee, Hajeong

    2016-01-01

    Abstract We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007–2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis. PMID:27310949

  8. Probiotic in lamb rennet paste enhances rennet lipolytic activity, and conjugated linoleic acid and linoleic acid content in Pecorino cheese.

    PubMed

    Santillo, A; Albenzio, M; Quinto, M; Caroprese, M; Marino, R; Sevi, A

    2009-04-01

    Cheeses manufactured using traditional lamb rennet paste, lamb rennet paste containing Lactobacillus acidophilus, and lamb rennet paste containing a mix of Bifidobacterium lactis and Bifidobacterium longum were characterized for the lipolytic pattern during ripening. Lipase activity of lamb rennet paste, lamb rennet containing Lb. acidophilus, and lamb rennet containing a mix of bifidobacteria was measured in sheep milk cream substrate. Rennet paste containing probiotics showed a lipase activity 2-fold greater than that displayed by traditional rennet. Total free fatty acid (FFA) in sheep milk cream was lower in lamb rennet paste (981 microg/g of milk cream) than in lamb rennet containing Lb. acidophilus (1,382.4 microg/g of milk cream) and in lamb rennet containing a mix of bifidobacteria (1,227.5 microg/g of milk cream) according to lipase activity of lamb rennet paste. The major increase of FFA in all cheeses occurred during the first 30 d of ripening with the greatest values being observed for C16:0, C18:0 C18:1. At 60 d of ripening all cheeses showed a reduction in the amount of free fatty acids; in particular, total free fatty acids underwent a decrease of more than 30% from 30 to 60 d in cheeses manufactured using traditional lamb rennet paste, whereas the same parameter decreased 10% in cheeses manufactured using lamb rennet paste containing Lb. acidophilus and cheeses manufactured using lamb rennet paste containing a mix of B. lactis and B. longum. Cheese containing Lb. acidophilus was characterized by the greatest levels of total conjugated linoleic acids (CLA) 9-cis, 11-trans CLA and 9-trans, 11-trans CLA, whereas cheese containing bifidobacteria displayed the greatest levels of free linoleic acid. Rennet pastes containing viable cells of Lb. acidophilus and a mix of B. lactis and B. longum were able to influence the amount of FFA and CLA in Pecorino cheese during ripening.

  9. Higher transcription levels in ascorbic acid biosynthetic and recycling genes were associated with higher ascorbic acid accumulation in blueberry.

    PubMed

    Liu, Fenghong; Wang, Lei; Gu, Liang; Zhao, Wei; Su, Hongyan; Cheng, Xianhao

    2015-12-01

    In our preliminary study, the ripe fruits of two highbush blueberry (Vaccinium corymbosum L.) cultivars, cv 'Berkeley' and cv 'Bluecrop', were found to contain different levels of ascorbic acid. However, factors responsible for these differences are still unknown. In the present study, ascorbic acid content in fruits was compared with expression profiles of ascorbic acid biosynthetic and recycling genes between 'Bluecrop' and 'Berkeley' cultivars. The results indicated that the l-galactose pathway was the predominant route of ascorbic acid biosynthesis in blueberry fruits. Moreover, higher expression levels of the ascorbic acid biosynthetic genes GME, GGP, and GLDH, as well as the recycling genes MDHAR and DHAR, were associated with higher ascorbic acid content in 'Bluecrop' compared with 'Berkeley', which indicated that a higher efficiency ascorbic acid biosynthesis and regeneration was likely to be responsible for the higher ascorbic acid accumulation in 'Bluecrop'.

  10. Catalytic synthesis of biodiesel from high free fatty acid-containing feedstocks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recyclable and reusable heterogeneous diarylammonium catalysts are highly effective in catalyzing the esterification of the free fatty acid (FFA) present in greases to methyl esters to reduce the FFA content from 12-40 wt% to 0.5 – 1 wt%. The resulting ester-glyceride mixture (pretreated grease) co...

  11. Dependence of intestinal amino acid uptake on dietary protein or amino acid levels

    SciTech Connect

    Karasov, W.H.; Solberg, D.H.; Diamond, J.M.

    1987-05-01

    To understand how intestinal amino acid (AA) transport is regulated by dietary substrate levels, the authors measured uptake of seven radioactively-labelled AAs and glucose across the jejunal brush-border membrane of mice kept on one of three isocaloric rations differing in nitrogen content. In the high-protein ration, uptake increased by 77-81% for the nonessential, less toxic AAs, proline, and aspartate but only by 32-61% for the more toxic essential AAs tested. In the nitrogen-deficient ration, uptake decreased for the nonessential aspartate and proline but stayed constant or increased for essential AAs and for the nonessential alanine. These patterns imply independent regulation of the intestine's various AA transporters. With decreasing dietary AA (or protein), the imino acid and acidic AA private transporters are repressed, while activities of the basic AA transporter and the neutral AA public transporter decrease to an asymptote or else go through a minimum. These regulatory patterns can be understood as a compromise among conflicting constraints imposed by protein's multiple roles as a source of calories, nitrogen, and essential AAs and by the toxicity of essential AAs at high concentrations.

  12. Interaction of aminooxyacetic acid and ethacrynic acid with intense sound at the level of the cochlea.

    PubMed

    Kisiel, D L; Bobbin, R P

    1982-02-01

    Results of previous investigation of the interaction of intense sound and drugs have, in general, failed to show a protective effect mediated by pre-administration with a drug having transient ototoxic effects. The present investigation was designed to further evaluate a protective effect found previously at the anatomical level and explained with an electrochemical theory of noise damage. The alternating current (a.c) potential and compound eighth nerve action potential (CAP) amplitude were monitored in aminooxyacetic acid (AOAA)- or ethacrynic acid (EA)-treated guinea pigs exposed to either moderate or high levels of intense sound and compared to changes observed in the same potentials in animals exposed to the intense sounds alone. Results showed protective effects only in the moderate--intense sound-exposure groups, with changes in sensitivity and voltage on the linear part of the input--output curve of the a.c cochlear potential found to be the only conditions where differences occurred. These results were difficult to interpret in terms of a protective effect and point to the need for obtaining additional data before an electrochemical mechanism is shown to play a role in the effect of intense sound on the cochlea.

  13. Accumulating Evidence Supports a Taste Component for Free Fatty Acids in Humans

    PubMed Central

    Mattes, Richard D.

    2011-01-01

    The requisite criteria for what constitutes a taste primary have not been established. Recent advances in understanding of the mechanisms and functions of taste have prompted suggestions for an expanded list of unique taste sensations, including fat, or more specifically, free fatty acids (FFA). A set of criteria are proposed here and the data related to FFA are reviewed on each point. It is concluded that the data are moderate to strong that there are: A) adaptive advantages to FFA detection in the oral cavity; B) adequate concentrations of FFA to serve as taste stimuli; C) multiple complimentary putative FFA receptors on taste cells; D) signals generated by FFA that are conveyed by gustatory nerves; E) sensations generated by FFA that can be detected and scaled by psychophysical methods in humans when non-gustatory cues are masked; and F) physiological responses to oral fat/FFA exposure. On no point is there strong evidence challenging these observations. The reviewed findings are suggestive, albeit not definitive, that there is a taste component for FFA. PMID:21557960

  14. Changes in the serum composition of free-fatty acids during an intravenous glucose tolerance test.

    PubMed

    Soriguer, Federico; García-Serrano, Sara; García-Almeida, Jose M; Garrido-Sánchez, Lourdes; García-Arnés, Juan; Tinahones, Francisco J; Cardona, Isabel; Rivas-Marín, Jose; Gallego-Perales, Jose L; García-Fuentes, Eduardo

    2009-01-01

    Recent studies suggest that measuring the free-fatty acids (FFA) during an intravenous glucose tolerance test (IVGTT) may provide information about the metabolic associations between serum FFA and carbohydrate and insulin metabolism. We evaluated the FFA profile during an IVGTT and determined whether this test changes the composition and concentration of FFA. An IVGTT was given to 38 severely obese persons before and 7 months after undergoing bariatric surgery and also to 12 healthy, nonobese persons. The concentration and composition of the FFA were studied at different times during the test. The concentration of FFA fell significantly faster during the IVGTT in the controls and in the severely obese persons with normal-fasting glucose (NFG) than in the severely obese persons with impaired-fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) (P < 0.05). Significant differences were found in the time to minimum serum concentrations of FFA (control = NFG < IFG < T2DM) (P < 0.001). These variables improved after bariatric surgery in the three groups. The percentage of monounsaturated and n-6 polyunsaturated FFA in the control subjects and in the obese persons, both before and after surgery, decreased significantly during the IVGTT. In conclusion, during an IVGTT, severely obese persons with IFG or T2DM experienced a lower fall in the FFA than the severely obese persons with NFG and the controls, becoming normal after bariatric surgery.

  15. Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy.

    PubMed

    Zhang, Fuyang; Zhao, Shihao; Yan, Wenjun; Xia, Yunlong; Chen, Xiyao; Wang, Wei; Zhang, Jinglong; Gao, Chao; Peng, Cheng; Yan, Feng; Zhao, Huishou; Lian, Kun; Lee, Yan; Zhang, Ling; Lau, Wayne Bond; Ma, Xinliang; Tao, Ling

    2016-11-01

    The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD+BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR), inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA) in the HFD+BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte.

  16. Free Fatty Acid Receptors and Cancer: From Nutrition to Pharmacology.

    PubMed

    Hopkins, Mandi M; Meier, Kathryn E

    2017-01-01

    The effects of fatty acids on cancer cells have been studied for decades. The roles of dietary long-chain n-3 polyunsaturated fatty acids, and of microbiome-generated short-chain butyric acid, have been of particular interest over the years. However, the roles of free fatty acid receptors (FFARs) in mediating effects of fatty acids in tumor cells have only recently been examined. In reviewing the literature, the data obtained to date indicate that the long-chain FFARs (FFA1 and FFA4) play different roles than the short-chain FFARs (FFA2 and FFA3). Moreover, FFA1 and FFA4 can in some cases mediate opposing actions in the same cell type. Another conclusion is that different types of cancer cells respond differently to FFAR activation. Currently, the best-studied models are prostate, breast, and colon cancer. FFA1 and FFA4 agonists can inhibit proliferation and migration of prostate and breast cancer cells, but enhance growth of colon cancer cells. In contrast, FFA2 activation can in some cases inhibit proliferation of colon cancer cells. Although the available data are sometimes contradictory, there are several examples in which FFAR agonists inhibit proliferation of cancer cells. This is a unique response to GPCR activation that will benefit from a mechanistic explanation as the field progresses. The development of more selective FFAR agonists and antagonists, combined with gene knockout approaches, will be important for unraveling FFAR-mediated inhibitory effects. These inhibitory actions, mediated by druggable GPCRs, hold promise for cancer prevention and/or therapy.

  17. Chronic exposure to free fatty acid reduces pancreatic beta cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation.

    PubMed Central

    Bollheimer, L C; Skelly, R H; Chester, M W; McGarry, J D; Rhodes, C J

    1998-01-01

    The pancreatic beta cell normally maintains a stable balance among insulin secretion, insulin production, and insulin degradation to keep optimal intracellular stores of the hormone. Elevated levels of FFA markedly enhance insulin secretion; however, the effects of FFA on insulin production and intracellular stores remain unclear. In this study, twofold elevation in total circulating FFA effected by infusion of lard oil and heparin into rats for 6 h under normoglycemic conditions resulted in a marked elevation of circulating insulin levels evident after 4 h, and a 30% decrease in pancreatic insulin content after a 6-h infusion in vivo. Adding 125 muM oleate to isolated rat pancreatic islets cultured with 5.6 mM glucose caused a 50% fall in their insulin content over 24 h, coupled with a marked enhancement of basal insulin secretion. Both effects of fatty acid were blocked by somatostatin. In contrast to the stimulatory effects of oleate on insulin secretion, glucose-induced proinsulin biosynthesis was inhibited by oleate up to 24 h, but was unaffected thereafter. This result was in spite of a two- to threefold oleate-induced increase in preproinsulin mRNA levels, underscoring the importance of translational regulation of proinsulin biosynthesis in maintaining beta cell insulin stores. Collectively, these results suggest that chronically elevated FFA contribute to beta cell dysfunction in the pathogenesis of NIDDM by significantly increasing the basal rate of insulin secretion. This increase in turn results in a decrease in the beta cell's intracellular stores that cannot be offset by commensurate FFA induction of proinsulin biosynthesis. PMID:9486980

  18. Chicoric Acid Levels in Basil (Ocimum basilicum L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, we reported the presence of chicoric acid in basil leaves (confirmed by co-chromatography with purchased standard). Chicoric acid being the chief phenolic of the Echinacea purpurea plant which is popularly consumed as a dietary supplement. For this study, basil products commonly purchased ...

  19. Circulating Levels of Uric Acid and Risk for Metabolic Syndrome.

    PubMed

    Rubio-Guerra, Alberto F; Morales-López, Herlinda; Garro-Almendaro, Ana K; Vargas-Ayala, German; Durán-Salgado, Montserrat B; Huerta-Ramírez, Saul; Lozano-Nuevo, Jose J

    2017-01-01

    Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia.

  20. Fatty Acid Saturation of Albumin Used in Resuscitation Fluids Modulates Cell Damage in Shock: In Vitro Results Using a Novel Technique to Measure Fatty Acid Binding Capacity.

    PubMed

    Penn, Alexander H; Dubick, Michael A; Torres Filho, Ivo P

    2017-03-21

    The use of albumin for resuscitation has not proven as beneficial in human trials as expected from numerous animal studies. One explanation could be the practice of adding fatty acid (FA) during manufacture of pharmaceutical albumin. During ischemia, unbound free FAs (FFA) in the circulation could potentially induce cellular damage. We hypothesized that albumins with higher available binding capacities (ABC) for FFAs may prevent that damage. Therefore, we developed a technique to measure ABC, determined if pharmaceutical human serum albumin (HSA) has decreased ABC compared to FA-free bovine serum albumin (BSA), and if binding capacity would affect hemolysis when blood is mixed with exogenous FFA at levels similar to those observed in shock. The new assay used exogenous oleic acid (OA), glass fiber filtration, and a FFA assay kit. RBC hemolysis was determined by mixing 0-5 mM OA with PBS, HSA, FA-free BSA, or FA-saturated BSA and measuring plasma hemoglobin after incubation with human blood. 5% HSA contained 4.7±0.2 mM FFA, leaving an ABC of 5.0 ± 0.6 mM, compared to FA-free BSA's ABC of 7.0 ± 1.3 mM (P < 0.024). Hemolysis after OA was reduced with FA-free BSA but increased with FA-saturated BSA. HSA provided intermediate results. 25% solutions of FA-free BSA and HSA were more protective, while 25% FA-saturated BSA was more damaging than 5% solutions. These findings suggest that increased FA saturation may reverse albumin's potential benefit to lessen cellular damage and may explain, at least in part, its failure in human trauma studies.

  1. An Examination of Middle School Enrollment in Agricultural Education and Membership in the National FFA Organization in the United States. Summary of Research 73.

    ERIC Educational Resources Information Center

    Rossetti, Rosemarie; And Others

    The status of middle and junior high school agricultural education and Future Farmers of America (FFA) programs in the United States was the focus of a study. Data were collected through a census of the FFA executive secretaries and a survey of a purposive sample of 27 successful middle or junior high school agricultural education programs in 9…

  2. Relationship between body fat mass and free fatty acid kinetics in men and women.

    PubMed

    Mittendorfer, Bettina; Magkos, Faidon; Fabbrini, Elisa; Mohammed, B Selma; Klein, Samuel

    2009-10-01

    An increased release of free fatty acids (FFAs) into plasma likely contributes to the metabolic complications associated with obesity. However, the relationship between body fat and FFA metabolism is unclear because of conflicting results from different studies. The goal of our study was to determine the inter-relationships between body fat, sex, and plasma FFA kinetics. We determined FFA rate of appearance (Ra) in plasma, by using stable isotopically labeled tracer techniques, during basal conditions in 106 lean, overweight, and obese, nondiabetic subjects (43 men and 63 women who had 7.0-56.0% body fat). Correlation analyses demonstrated: (i) no differences between men and women in the relationship between fat mass (FM) and total FFA Ra (micromol/min); (ii) total FFA Ra increased linearly with increasing FM (r=0.652, P<0.001); (iii) FFA Ra per kg FM decreased in a curvilinear fashion with increasing FM (r=-0.806; P<0.001); (iv) FFA Ra in relationship to fat-free mass (FFM) was greater in obese than lean subjects and greater in women than in men; and (v) abdominal fat itself was not an important determinant of total FFA Ra. We conclude that total body fat, not regional fat distribution or sex, is an important modulator of the rate of FFA release into plasma. Although increased adiposity is associated with a decrease in fatty acid release in relationship to FM, this downregulation is unable to completely compensate for the increase in FM, so total FFA Ra and FFA Ra with respect to FFM are greater in women than in men and in obese than in lean subjects.

  3. Salivary Sialic Acid Levels in Smokeless Tobacco Users

    PubMed Central

    Farhad Mollashahi, Leila; Honarmand, Marieh; Nakhaee, Alireza; Mollashahi, Ghasem

    2016-01-01

    Background Smokeless tobacco chewing is one of the known risk factors for oral cancer. It is consumed widely by residents of southeastern Iran. Objectives In this study, salivary free and total sialic acid, and total protein were compared in paan consumers and non-consumers. Patients and Methods In this cross-sectional study, unstimulated saliva of 94 subjects (44 paan consumers and 50 non-consumers) who were referred to the oral medicine department of the dentistry school of Zahedan were collected. Salivary free and total sialic acid, and total protein concentration were measured by standard biochemical methods, and the obtained data were analyzed using SPSS 20 through the non-parametric Mann-Whitney test. Results The concentration of salivary free sialic acid (23.21 ± 18.98 mg/L) was significantly increased in paan consumers. The concentration of salivary Total sialic acid (TSA) (39.57 ± 26.58 mg/L) and total protein (0.77 ± 0.81 mg/mL) showed increases in paan consumers, however, the results were not statistically significant. Conclusions Salivary free and total sialic acid, and total protein were higher in the paan consumers compared to non-consumers. Due to the carcinogenic effect of smokeless tobacco, measurement of these parameters in saliva may be useful in early detection of oral cancer. PMID:27622172

  4. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine.

    PubMed

    Naithani, Manisha; Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus.

  5. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine

    PubMed Central

    Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus. PMID:27064332

  6. Effect of somatic cell count in goat milk on yield, sensory quality, and fatty acid profile of semisoft cheese.

    PubMed

    Chen, S X; Wang, J Z; Van Kessel, J S; Ren, F Z; Zeng, S S

    2010-04-01

    This study investigated the effect of somatic cell count (SCC) in goat milk on yield, free fatty acid (FFA) profile, and sensory quality of semisoft cheese. Sixty Alpine goats without evidence of clinical mastitis were assigned to 3 groups with milk SCC level of <500,000 (low), 500,000 to 1,000,000 (medium), and 1,000,000 to 1,500,000 (high) cells/mL. Thirty kilograms of goat milk with mean SCC levels of 410,000 (low), 770,000 (medium), and 1,250,000 (high) cells/mL was obtained for the manufacture of semisoft cheese for 2 consecutive weeks in 3 lactation stages. The composition of milk was analyzed and cheese yield was recorded on d 1. Cheese samples on d 1, 60, and 120 were analyzed for total sensory scores, flavor, and body and texture by a panel of 3 expert judges and were also analyzed for FFA. Results indicated that milk composition did not change when milk SCC varied from 214,000 to 1,450,000 cells/mL. Milk with higher SCC had a lower standard plate count, whereas coliform count and psychrotrophic bacteria count were not affected. However, milk components (fat, protein, lactose, casein, and total solids) among the 3 groups were similar. As a result, no significant differences in the yield of semisoft goat cheeses were detected. However, total sensory scores and body and texture scores for cheeses made from the high SCC milk were lower than those for cheeses made from the low and medium SCC milks. The difference in milk SCC levels also resulted in diverse changes in cheese texture (hardness, springiness, and so on) and FFA profiles. Individual and total FFA increased significantly during ripening, regardless the SCC levels. It is concluded that SCC in goat milk did not affect the yield of semisoft cheese but did result in inferior sensory quality of aged cheeses.

  7. d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.

    PubMed

    Weatherly, Choyce A; Du, Siqi; Parpia, Curran; Santos, Polan T; Hartman, Adam L; Armstrong, Daniel W

    2017-02-16

    The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (l- plus d-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured d-amino acid levels in brain tissue are typically ∼10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured d-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its d-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its d-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this d-amino acid is yet unknown. However, results suggest that d-glutamate metabolism is likely a unidirectional process and not a cycle, as per the l-glutamate/glutamine cycle. The results suggest that there might be unreported d-amino acid racemases in mammalian brains. The regulation and function of specific other d-amino acids are discussed.

  8. Acyl Ghrelin Induces Insulin Resistance Independently of GH, Cortisol, and Free Fatty Acids

    PubMed Central

    Vestergaard, Esben T.; Jessen, Niels; Møller, Niels; Jørgensen, Jens Otto Lunde

    2017-01-01

    Ghrelin produced in the gut stimulates GH and ACTH secretion from the pituitary and also stimulates appetite and gastric emptying. We have shown that ghrelin also induces insulin resistance via GH-independent mechanisms, but it is unknown if this effect depends on ambient fatty acid (FFA) levels. We investigated the impact of ghrelin and pharmacological antilipolysis (acipimox) on insulin sensitivity and substrate metabolism in 8 adult hypopituitary patients on stable replacement with GH and hydrocortisone using a 2 × 2 factorial design: Ghrelin infusion, saline infusion, ghrelin plus short-term acipimox, and acipimox alone. Peripheral and hepatic insulin sensitivity was determined with a hyperinsulinemic euglycemic clamp in combination with a glucose tracer infusion. Insulin signaling was assayed in muscle biopsies. Peripheral insulin sensitivity was reduced by ghrelin independently of ambient FFA concentrations and was increased by acipimox independently of ghrelin. Hepatic insulin sensitivity was increased by acipimox. Insulin signaling pathways in skeletal muscle were not consistently regulated by ghrelin. Our data demonstrate that ghrelin induces peripheral insulin resistance independently of GH, cortisol, and FFA. The molecular mechanisms remain elusive, but we speculate that ghrelin is a hitherto unrecognized direct regulator of substrate metabolism. We also suggest that acipimox per se improves hepatic insulin sensitivity. PMID:28198428

  9. Lipotoxic effect of p21 on free fatty acid-induced steatosis in L02 cells.

    PubMed

    Wang, Jie-wei; Wan, Xing-yong; Zhu, Hua-tuo; Lu, Chao; Yu, Wei-lai; Yu, Chao-hui; Shen, Zhe; Li, You-ming

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is increasingly regarded as a hepatic manifestation of metabolic syndrome. Though with high prevalence, the mechanism is poorly understood. This study aimed to investigate the effects of p21 on free fatty acid (FFA)-induced steatosis in L02 cells. We therefore analyzed the L02 cells with MG132 and siRNA treatment for different expression of p21 related to lipid accumulation and lipotoxicity. Cellular total lipid was stained by Oil Red O, while triglyceride content, cytotoxicity assays, lipid peroxidation markers and anti-oxidation levels were measured by enzymatic kits. Treatment with 1 mM FFA for 48 hr induced magnificent intracellular lipid accumulation and increased oxidative stress in p21 overload L02 cells compared to that in p21 knockdown L02 cells. By increasing oxidative stress and peroxidation, p21 accelerates FFA-induced lipotoxic effect in L02 cells and might provide information about potentially new targets for drug development and treatments of NAFLD.

  10. RNA-Seq analysis and targeted mutagenesis for improved free fatty acid production in an engineered cyanobacterium

    PubMed Central

    2013-01-01

    Background High-energy-density biofuels are typically derived from the fatty acid pathway, thus establishing free fatty acids (FFAs) as important fuel precursors. FFA production using photosynthetic microorganisms like cyanobacteria allows for direct conversion of carbon dioxide into fuel precursors. Recent studies investigating cyanobacterial FFA production have demonstrated the potential of this process, yet FFA production was also shown to have negative physiological effects on the cyanobacterial host, ultimately limiting high yields of FFAs. Results Cyanobacterial FFA production was shown to generate reactive oxygen species (ROS) and lead to increased cell membrane permeability. To identify genetic targets that may mitigate these toxic effects, RNA-seq analysis was used to investigate the host response of Synechococcus elongatus PCC 7942. Stress response, nitrogen metabolism, photosynthesis, and protein folding genes were up-regulated during FFA production while genes involved in carbon and hydrogen metabolisms were down-regulated. Select genes were targeted for mutagenesis to confirm their role in mitigating FFA toxicity. Gene knockout of two porins and the overexpression of ROS-degrading proteins and hypothetical proteins reduced the toxic effects of FFA production, allowing for improved growth, physiology, and FFA yields. Comparative transcriptomics, analyzing gene expression changes associated with FFA production and other stress conditions, identified additional key genes involved in cyanobacterial stress response. Conclusions A total of 15 gene targets were identified to reduce the toxic effects of FFA production. While single-gene targeted mutagenesis led to minor increases in FFA production, the combination of these targeted mutations may yield additional improvement, advancing the development of high-energy-density fuels derived from cyanobacteria. PMID:23919451

  11. New alleles of FATB-1A to reduce palmitic acid levels in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In wild-type soybeans, palmitic acid typically constitutes 10% of the total seed oil. Palmitic acid is a saturated fat linked to increased cholesterol levels, and reducing levels of saturated fats in soybean oil has been a breeding target. To identify novel and useful variation that could help in re...

  12. Plasma Amino Acid Levels in Children with Autism and Their Families.

    ERIC Educational Resources Information Center

    Aldred, Sarah; Moore, Kieran M.; Fitzgerald, Michael; Waring, Rosemary H.

    2003-01-01

    Plasma amino acid levels were measured in autistic (n=12), Asperger syndrome (n=11) patients, their parents and siblings. Patients with autism or Asperger syndrome and their siblings and parents all had raised glutamic acid, phenyalanine, asparagine, tyrosine, alanine, and lysine levels than age-matched controls. Results suggest dysregulated amino…

  13. The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

    PubMed Central

    Jenssen, Trond; Hartmann, Anders; Diep, Lien M.; Dahle, Dag O.; Reisæter, Anna V.; Bjerve, Kristian S.; Christensen, Jeppe H.; Schmidt, Erik B.; Svensson, My

    2015-01-01

    Background and objectives Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants. Design, setting, participants, & measurements In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation. Results There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with low levels (<7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality. Conclusions Higher plasma phospholipid marine n-3

  14. Plasma ω-3 fatty acid levels negatively and ω-6 fatty acid levels positively associated with other cardiovascular risk factors including homocysteine in severe obese subjects.

    PubMed

    Mehmetoglu, Idris; Yerlikaya, F Hümeyra; Kurban, Sevil; Polat, Hakkı

    2012-01-01

    Obesity and homocysteine (tHcy) are important risk factors for cardiovascular diseases (CVD). Plasma omega-3 fatty acids (ω-3 FAs) and omega-6 fatty acids (ω-6 FAs) are essential fatty acids with diverse biological effects in human health and disease. We have investigated the relation of plasma ω-3 FAs and ω-6 FAs levels with other cardiovascular risk factors including tHcy in severe obese subjects. This study was performed on 96 severe obese and 65 normal weight subjects. Plasma fatty acid composition was measured by GC/MS and serum tHcy level was measured by HPLC methods. There were no differences between groups in terms of concentrations of serum tHcy, plasma ω-3 FAs, ω-6 FAs and ω-3/ω-6 ratio, whereas serum vitamin B-12 (p<0.01) and folic acid (p<0.05) levels were lower than those of the normal weight subjects. Homocysteine positively correlated with ω-6 FAs and negatively correlated with ω-3 FAs in severe obese and normal weight subjects. Serum vitamin B-12 positively correlated with ω-3 FAs (p<0.01) and ω-3/ω-6 ratio (p<0.01) and negatively correlated with ω-6 FAs (p<0.05) in severe obese subjects. Serum folic acid positively correlated with ω-3 FAs (p<0.01) in severe obese subjects. Our results suggest an association between the plasma ω-3 FAs and ω-6 FAs and serum tHcy concentrations in severe obese and normal weight subjects. Low levels vitamin B-12 and folic acid may have been responsible for the elevated tHcy levels in severe obese subjects, increasing the risk for future development of cardiovascular diseases.

  15. Mitochondrial free fatty acid β-oxidation supports oxidative phosphorylation and proliferation in cancer cells.

    PubMed

    Rodríguez-Enríquez, Sara; Hernández-Esquivel, Luz; Marín-Hernández, Alvaro; El Hafidi, Mohammed; Gallardo-Pérez, Juan Carlos; Hernández-Reséndiz, Ileana; Rodríguez-Zavala, José S; Pacheco-Velázquez, Silvia C; Moreno-Sánchez, Rafael

    2015-08-01

    Oxidative phosphorylation (OxPhos) is functional and sustains tumor proliferation in several cancer cell types. To establish whether mitochondrial β-oxidation of free fatty acids (FFAs) contributes to cancer OxPhos functioning, its protein contents and enzyme activities, as well as respiratory rates and electrical membrane potential (ΔΨm) driven by FFA oxidation were assessed in rat AS-30D hepatoma and liver (RLM) mitochondria. Higher protein contents (1.4-3 times) of β-oxidation (CPT1, SCAD) as well as proteins and enzyme activities (1.7-13-times) of Krebs cycle (KC: ICD, 2OGDH, PDH, ME, GA), and respiratory chain (RC: COX) were determined in hepatoma mitochondria vs. RLM. Although increased cholesterol content (9-times vs. RLM) was determined in the hepatoma mitochondrial membranes, FFAs and other NAD-linked substrates were oxidized faster (1.6-6.6 times) by hepatoma mitochondria than RLM, maintaining similar ΔΨm values. The contents of β-oxidation, KC and RC enzymes were also assessed in cells. The mitochondrial enzyme levels in human cervix cancer HeLa and AS-30D cells were higher than those observed in rat hepatocytes whereas in human breast cancer biopsies, CPT1 and SCAD contents were lower than in human breast normal tissue. The presence of CPT1 and SCAD in AS-30D mitochondria and HeLa cells correlated with an active FFA utilization in HeLa cells. Furthermore, the β-oxidation inhibitor perhexiline blocked FFA utilization, OxPhos and proliferation in HeLa and other cancer cells. In conclusion, functional mitochondria supported by FFA β-oxidation are essential for the accelerated cancer cell proliferation and hence anti-β-oxidation therapeutics appears as an alternative promising approach to deter malignant tumor growth.

  16. The Effects of Lowering Uric Acid Levels Using Allopurinol on Components of Metabolic Syndrome

    PubMed Central

    Heimbach, Esther J.; Bowden, Rodney G.; Griggs, Jackson O.; Beaujean, A. Alexander; Doyle, Eva I.; Doyle, Robert D.

    2012-01-01

    Background Researchers have reported an independent direct relationship between lipid levels and hyperuricemia with MetS. The purpose of this study was to determine the relationship between serum uric acid levels and lipids among patients on allopurinol. Methods A retrospective secondary data analysis was conducted on 66 adult patients from a family health clinic in Central Texas. Medical records used were recorded during a nine year period (2002 - 2010) ascertaining the relationship between uric acid and lipids. Results Spearman correlations revealed a weak correlation between uric acid and total cholesterol, a weak correlation between uric acid and triglycerides and LDL-C. A weak inverse correlation was discovered between uric acid and HDL-C. A moderate correlation was discovered when all lipid variables combined were compared to uric acid. Conclusions We discovered LDL-C and triglycerides to be significant predictors of uric acid with weak correlations. Additionally, weak correlations existed between uric acid and total cholesterol and HDL-C with an inverse relationship discovered with HDL-C. These findings support the literature suggesting that uric acid is more likely to be associated with total cholesterol and triglycerides. In addition, new discoveries serve as an indication that LDL-C may also be associated with uric acids levels. The mechanism by which uric acid may regulate lipids is elusive but suggestions have included suppression of lipid peroxidase and decreases in critical lipase activity.

  17. Associations of free fatty acids with insulin secretion and action among African-American and European-American girls and women.

    PubMed

    Goree, Laura Lee T; Darnell, Betty E; Oster, Robert A; Brown, Marian A; Gower, Barbara A

    2010-02-01

    Ethnic differences in insulin secretion and action between African Americans (AAs) and European Americans (EAs) may influence mobilization of free fatty acids (FFAs). We tested the hypotheses that FFA concentrations would be associated with measures of insulin secretion and action before and during a glucose challenge test. Subjects were 48 prepubertal girls, 60 premenopausal women, and 46 postmenopausal women. Fasting insulin (insulin(0)), the acute insulin response to glucose (AIR(g)), the insulin sensitivity index (S(I)), basal and nadir FFA (FFA(0), FFA(nadir)), and nadir time (TIME(nadir)) were determined during an intravenous glucose tolerance test (IVGTT). Stepwise multiple linear regression (MLR) analysis was conducted to identify associations of FFA(0), FFA(nadir), and TIME(nadir) with ethnicity, age group, insulin measures, indexes of body composition from dual-energy X-ray absorptiometry, and measures of fat distribution from computed tomography scan. In this population, insulin(0) and AIR(g) were higher among AAs vs. EAs, whereas S(I) was lower, independent of age group. MLR analyses indicated that FFA(0) was best predicted by lean tissue mass (LTM), leg fat mass, ethnicity (lower in AAs), S(I), and insulin(0). FFA(nadir) was best predicted by FFA(0), age group, and intra-abdominal adipose tissue (IAAT). TIME(nadir) was best predicted by leg fat mass, AIR(g), and S(I). In conclusion, indexes of insulin secretion and action were associated with FFA dynamics in healthy girls and women. Lower FFA(0) among AAs was independent of insulin(0) and S(I). Whether lower FFA(0) is associated with substrate oxidation or risk for obesity remains to be determined.

  18. In vitro analysis of flufenamic acid activity against Candida albicans biofilms.

    PubMed

    Chavez-Dozal, Alba A; Jahng, Maximillian; Rane, Hallie S; Asare, Kingsley; Kulkarny, Vibhati V; Bernardo, Stella M; Lee, Samuel A

    2014-01-01

    In a recent high-throughput screen against specific Candida albicans drug targets, several compounds that exhibited non-specific antifungal activity were identified, including the non-steroidal anti-inflammatory drug flufenamic acid (FFA). This study sought to determine the effect of different doses of FFA, alone or in combination with fixed concentrations of the standard antifungal agents amphotericin B (AmB), caspofungin (CAS) or fluconazole (FLU), for the prevention and treatment of C. albicans biofilms. Biofilms were formed in a 96-well microplate followed by evaluation of antifungal activity using the XTT assay. FFA concentrations of ≥512mg/L demonstrated >80% prevention of biofilm formation. FFA concentrations of 1024mg/L demonstrated >85% reduction of mature biofilms. When FFA (≥8mg/L) was used in combination with FLU (32mg/L), antifungal activity increased to 99% for the prevention of biofilm formation. Similarly, when a FFA concentration of ≥8mg/L was used in combination with either AmB (0.25mg/L) or CAS (0.125mg/L), antifungal activity also increased up to 99% for the prevention of biofilm formation. The inhibitory effect of FFA on C. albicans biofilms has not been reported previously, therefore these findings suggest that FFA in combination with traditional antifungals might be useful for the treatment and prevention of C. albicans biofilms.

  19. Hippuric Acid Levels in Paint Workers at Steel Furniture Manufacturers in Thailand

    PubMed Central

    Decharat, Somsiri

    2014-01-01

    Background The aims of this study were to determine hippuric acid levels in urine samples, airborne toluene levels, acute and chronic neurological symptoms, and to describe any correlation between urinary hippuric acid and airborne toluene. Methods The hippuric acid concentration in the urine of 87 paint workers exposed to toluene at work (exposed group), and 87 nonexposed people (control group) was studied. Study participants were selected from similar factories in the same region. Urine samples were collected at the end of a shift and analyzed for hippuric acid by high performance liquid chromatography. Air samples for the estimation of toluene exposure were collected with diffusive personal samplers and the toluene quantified using gas–liquid chromatography. The two groups were also interviewed and observed about their work practices and health. Results The median of the 87 airborne toluene levels was 55 ppm (range, 12–198 ppm). The median urinary hippuric acid level was 800 mg/g creatinine (range, 90–2547 mg/g creatinine). A statistically significant positive correlation was found between airborne toluene exposure and urine hippuric acid levels (r = 0.548, p < 0.01). Workers with acute symptoms had significantly higher hippuric acid levels than those who did not (p < 0.05). It was concluded that there was a significant correlation between toluene exposure, hippuric acid levels, and health (p < 0.001). Conclusion There appears to be a significant correlation between workers exposure to toluene at work, their urine hippuric acid levels, and resulting symptoms of poor health. Improvements in working conditions and occupational health education are required at these workplaces. There was good correlation between urinary hippuric acid and airborne toluene levels. PMID:25516817

  20. Messenger ribonucleic acid levels in disrupted human anterior cruciate ligaments.

    PubMed

    Lo, Ian K Y; Marchuk, Linda; Hart, David A; Frank, Cyril B

    2003-02-01

    Thirty patients had anterior cruciate ligament reconstruction for ongoing instability. Two groups were defined according to gross morphologic features identified during reconstruction: anterior cruciate ligament disruptions with scars attached to a structure in the joint and disruptions without reattachments. Reverse transcription polymerase chain reaction for a subset of extracellular matrix molecules, proteinases, and proteinase inhibitors was done on samples of scarred anterior cruciate ligament tissue removed during reconstructive surgery. Results of the nonattached scar group showed significantly increased mRNA levels for Type I collagen, and an increased Type I to Type III collagen ratio compared with that for the attached scar group. In the first year after injury, decorin mRNA levels in the nonattached scar group also were significantly higher than in the attached scar group. Biglycan mRNA levels in the nonattached scar group correlated closely with Type I collagen mRNA levels. These results suggest differences in cellular expression in torn anterior cruciate ligaments that attach to structures in the joint versus those which do not. Although the molecular mechanisms responsible for these differences have not been delineated, different molecular signals may influence the gross morphologic features of anterior cruciate ligament disruptions or alternatively, differing gross morphologic features may be subject to different mechanical loads leading to altered molecular expression. However, the finding of endogenous cellular activity in injured anterior cruciate ligaments raises the possibility that this activity may be enhanced to improve outcomes.

  1. Plasma D-lactic acid level: a useful marker to distinguish perforated from acute simple appendicitis.

    PubMed

    Demircan, Mehmet; Cetin, Selma; Uguralp, Sema; Sezgin, Nurzen; Karaman, Abdurrahman; Gozukara, Engin M

    2004-10-01

    Early diagnosis of perforated appendicitis is important for reducing morbidity rates. The aim of this study was to determine the value and utility of plasma D-lactic acid levels in identifying the type of appendicitis. In this clinical study, plasma D-lactic acid levels were assessed in 44 consecutive paediatric patients (23 with acute appendicitis, 21 with perforated appendicitis) before laparotomy. D-lactic acid levels were determined by an enzymatic spectrophotometric technique using a D-lactic acid dehydrogenase kit. Patients with perforated appendicitis had higher D-lactic acid levels (3.970 +/- 0.687 mg/dL) than patients in the control group (0.478 +/- 0.149 mg/dL) and patients with acute appendicitis (1.409 +/- 0.324 mg/dL; p < 0.05). For a plasma D-lactic acid level greater than 2.5 mg/dL, the sensitivity and specificity of the D-lactic acid assay were 96% and 87%, respectively. The positive predictive value was 87%, the negative predictive value was 96%, and the diagnostic value was 91%. These results suggest that the measurement of plasma D-lactic acid levels may be a useful adjunct to clinical and radiological findings in distinguishing perforated from acute non-perforated appendicitis in children.

  2. An oleaginous bacterium that intrinsically accumulates long-chain free Fatty acids in its cytoplasm.

    PubMed

    Katayama, Taiki; Kanno, Manabu; Morita, Naoki; Hori, Tomoyuki; Narihiro, Takashi; Mitani, Yasuo; Kamagata, Yoichi

    2014-02-01

    Medium- and long-chain fatty acids are present in organisms in esterified forms that serve as cell membrane constituents and storage compounds. A large number of organisms are known to accumulate lipophilic materials as a source of energy and carbon. We found a bacterium, designated GK12, that intrinsically accumulates free fatty acids (FFAs) as intracellular droplets without exhibiting cytotoxicity. GK12 is an obligatory anaerobic, mesophilic lactic acid bacterium that was isolated from a methanogenic reactor. Phylogenetic analysis based on 16S rRNA gene sequences showed that GK12 is affiliated with the family Erysipelotrichaceae in the phylum Firmicutes but is distantly related to type species in this family (less than 92% similarity in 16S rRNA gene sequence). Saturated fatty acids with carbon chain lengths of 14, 16, 18, and 20 were produced from glucose under stress conditions, including higher-than-optimum temperatures and the presence of organic solvents that affect cell membrane integrity. FFAs were produced at levels corresponding to up to 25% (wt/wt) of the dry cell mass. Our data suggest that FFA accumulation is a result of an imbalance between excess membrane fatty acid biosynthesis due to homeoviscous adaptation and limited β-oxidation activity due to anaerobic growth involving lactic acid fermentation. FFA droplets were not further utilized as an energy and carbon source, even under conditions of starvation. A naturally occurring bacterium that accumulates significant amounts of long-chain FFAs with noncytotoxicity would provide useful strategies for microbial biodiesel production.

  3. Serum fatty acid binding protein 4, free fatty acids and metabolic risk markers

    PubMed Central

    Karakas, Sidika E.; Almario, Rogelio U.; Kim, Kyoungmi

    2009-01-01

    Fatty acid binding protein (FABP) 4 chaperones free fatty acids (FFA) in the adipocytes during lipolysis. Serum FFA relates to Metabolic Syndrome (METS) and serum FABP4 is emerging as a novel risk marker. In 36 overweight/obese women, serum FABP4 and FFA were measured hourly during 5-hour oral glucose tolerance test (OGTT). Insulin resistance was determined using frequently sampled intravenous GTT (FS-IVGTT). Serum lipids and inflammation markers were measured at fasting. During OGTT, serum FABP4 decreased by 40%, reaching its nadir at 3h (from 45.3±3.1 to 31.9±1.6 ng/mL) and stayed below the baseline at 5 h (35.9±2.2 ng/mL) (p < 0.0001 for both, compared to the baseline). Serum FFA decreased by 10 fold, reaching a nadir at 2h (from 0.611±0.033 to 0.067±0.004 mmol/L), then rebounded to 0.816±0.035 mmol/ L at 5h (p < 0.001 for both, compared to baseline). Both fasting-FABP4 and nadir-FABP4 correlated with obesity. Nadir-FABP4 correlated also with insulin resistance parameters from FS-IVGTT and with inflammation. Nadir-FFA, but not fasting-FFA, correlated with the METS-parameters. In conclusion, fasting-FABP4 related to metabolic risk markers more strongly than fasting-FFA. Nadir-FABP4 and nadir-FFA measured after glucose loading may provide better risk assessment than the fasting values. PMID:19394980

  4. Genome level analysis of bacteriocins of lactic acid bacteria.

    PubMed

    Singh, Neetigyata Pratap; Tiwari, Abhay; Bansal, Ankiti; Thakur, Shruti; Sharma, Garima; Gabrani, Reema

    2015-06-01

    Bacteriocins are antimicrobial peptides which are ribosomally synthesized by mainly all bacterial species. LABs (lactic acid bacteria) are a diverse group of bacteria that include around 20 genera of various species. Though LABs have a tremendous potential for production of anti-microbial peptides, this group of bacteria is still underexplored for bacteriocins. To study the diversity among bacteriocin encoding clusters and the putative bacteriocin precursors, genome mining was performed on 20 different species of LAB not reported to be bacteriocin producers. The phylogenetic tree of gyrB, rpoB, and 16S rRNA were constructed using MEGA6 software to analyze the diversity among strains. Putative bacteriocins operons identified were found to be diverse and were further characterized on the basis of physiochemical properties and the secondary structure. The presence of at least two cysteine residues in most of the observed putative bacteriocins leads to disulphide bond formation and provide stability. Our data suggests that LABs are prolific source of low molecular weight non modified peptides.

  5. Membrane Stresses Induced by Overproduction of Free Fatty Acids in Escherichia coli▿†

    PubMed Central

    Lennen, Rebecca M.; Kruziki, Max A.; Kumar, Kritika; Zinkel, Robert A.; Burnum, Kristin E.; Lipton, Mary S.; Hoover, Spencer W.; Ranatunga, Don R.; Wittkopp, Tyler M.; Marner, Wesley D.; Pfleger, Brian F.

    2011-01-01

    Microbially produced fatty acids are potential precursors to high-energy-density biofuels, including alkanes and alkyl ethyl esters, by either catalytic conversion of free fatty acids (FFAs) or enzymatic conversion of acyl-acyl carrier protein or acyl-coenzyme A intermediates. Metabolic engineering efforts aimed at overproducing FFAs in Escherichia coli have achieved less than 30% of the maximum theoretical yield on the supplied carbon source. In this work, the viability, morphology, transcript levels, and protein levels of a strain of E. coli that overproduces medium-chain-length FFAs was compared to an engineered control strain. By early stationary phase, an 85% reduction in viable cell counts and exacerbated loss of inner membrane integrity were observed in the FFA-overproducing strain. These effects were enhanced in strains endogenously producing FFAs compared to strains exposed to exogenously fed FFAs. Under two sets of cultivation conditions, long-chain unsaturated fatty acid content greatly increased, and the expression of genes and proteins required for unsaturated fatty acid biosynthesis were significantly decreased. Membrane stresses were further implicated by increased expression of genes and proteins of the phage shock response, the MarA/Rob/SoxS regulon, and the nuo and cyo operons of aerobic respiration. Gene deletion studies confirmed the importance of the phage shock proteins and Rob for maintaining cell viability; however, little to no change in FFA titer was observed after 24 h of cultivation. The results of this study serve as a baseline for future targeted attempts to improve FFA yields and titers in E. coli. PMID:21948837

  6. delta-Aminolevulinic acid dehydratase activity, urinary delta-aminolevulinic acid concentration and zinc protoporphyrin level among people with low level of lead exposure.

    PubMed

    Wang, Qi; Zhao, Huan-hu; Chen, Jian-wei; Hao, Qiao-ling; Gu, Kang-ding; Zhu, Ye-xiang; Zhou, Yi-kai; Ye, Lin-xiang

    2010-01-01

    To evaluate the relationship of delta-aminolevulinic acid dehydratase (ALAD) activity, urinary delta-aminolevulinic acid (ALAU) level and blood zinc protoporphyrin (ZPP) concentration to low blood lead (PbB) levels, these biomarkers were determined for all subjects enrolled from a rural area of southeast China where people had low levels of exposure to lead. The mean values of PbB, ALAD, ALAU and ZPP were 67.11 microg/L (SD: 1.654, range: 10.90-514.04), 339.66 nmol ml(-1)h(-1) (1.419, 78.33-793.13), 20.64 microg/L (1.603, 2.00-326.00), and 0.14 micromol/L (3.437, 0.01-2.26), respectively. ALAD was inversely associated with low levels of PbB. ZPP was inversely related to low levels of PbB but positively related to relatively higher levels of PbB. Alcohol drinking contributed to low ALAD in men. Women had higher ZPP than men. ALAU had no significant association with PbB. In conclusion, ALAD possibly has a non-linear relation with low to moderate levels of PbB. At moderate levels of PbB, ZPP increases with increasing levels of PbB. ALAU is not suitable as an indicator for low levels of lead exposure.

  7. Limiting amino acids in bengal gram (Cicer arietinum) as determined from blood amino acid levels and amino acid supplementation studies in the rat.

    PubMed

    Khader, V; Rao, S V

    1982-01-01

    The limiting amino acids of Bengal gram (Cicer arietinum) were determined from plasma amino acid score and ratio and growth response of weanling rats to supplements of amino acids. The results indicated that methionine, threonine and tryptophan are the most limiting amino acids. Protein efficiency ratio of raw and cooked Bengal gram fed at a dietary level of 10% protein increased from 2.7 to 3.7 and 2.4 to 3.4, respectively, on supplementing the diets with methionine, threonine and tryptophan. Plasma levels of lysine, methionine, threonine and tryptophan were similar in rats fed raw or cooked Bengal gram, indicating that the trypsin or other inhibitors that may be present in the raw gram do not affect the biological availability of these amino acids.

  8. Molecular characterization of the level of sialic acids N-acetylneuraminic acid, N-glycolylneuraminic acid, and ketodeoxynonulosonic acid in porcine milk during lactation.

    PubMed

    Jahan, M; Wynn, P C; Wang, B

    2016-10-01

    Sialic acids (Sia) are key monosaccharide constituents of sialylated glycoproteins (Sia-GP), human sialylated milk oligosaccharide (Sia-MOS), and gangliosides. Human milk sialylated glycoconjugates (Sia-GC) are bioactive compounds known to act as prebiotics and promote neurodevelopment, immune function, and gut maturation in newborns. Only limited data are available on the Sia content of porcine milk. The objective of this study was to quantitatively determine the total level of Sia N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), and ketodeoxynonulosonic acid (KDN) in porcine milk and to compare these levels in gilt and sow milk during lactation. Milk from 8 gilts and 22 sows was collected at 3 stages of lactation (colostrum, transition, and mature milk). Standard and experimental samples were derivatized using 1,2-diamino-4,5-methylenedioxy-benzene and analyzed by ultra-high-performance liquid chromatography using a fluorescence detector. The following new findings are reported: (1) Gilt and sow milk contained significant levels of total Sia, with the highest concentration in colostrum (1,238.5 mg/L), followed by transition milk (778.3 mg/L) and mature milk (347.2 mg/L); (2) during lactation, the majority of Sia was conjugated to Sia-GP (41-46%), followed by Sia-MOS (31-42%) and a smaller proportion in gangliosides (12-28%); (3) Neu5Ac was the major form of Sia (93-96%), followed by Neu5Gc (3-6%) and then KDN (1-2%), irrespective of milk fraction or stage of lactation; (4) the concentration of Sia in Sia-GP and Sia-MOS showed a significant decline during lactation, but the level of ganglioside Sia remained relatively constant; (5) mature gilt milk contained a significantly higher concentration of Sia-GP than sow milk. The high concentration of total Sia in porcine milk suggests that Sia-GC are important nutrients that contribute to the optimization of neurodevelopment, immune function, and growth and development in piglets. These findings

  9. Blood folic acid, vitamin B12, and homocysteine levels in pregnant women with fetal growth restriction.

    PubMed

    Jiang, H L; Cao, L Q; Chen, H Y

    2016-12-19

    Deficiencies in nutrients such as folic acid and vitamin B12 may play a role in fetal growth restriction (FGR). However, whether folic acid, vitamin B12, or homocysteine is associated with FGR in Chinese populations remains unclear. This study investigated the relationship between these nutrient deficiencies and FGR in pregnant Chinese women. We selected 116 mother and infant pairs, and categorized the neonates into the FGR, appropriate for gestational age, and large for gestational age groups. Birth weight, body length, head circumference, body mass index (BMI), and Rohrer's body index of the newborns were measured. Serum folic acid, vitamin B12, and homocysteine levels were measured in mothers during the first three days of their hospital stay. Results showed that the FGR group exhibited reduced folic acid and vitamin B12 levels and elevated homocysteine levels than those in the other two groups. Folic acid and vitamin B12 levels were positively correlated with birth weight, head circumference, and BMI, whereas homocysteine level was negatively correlated with these variables. The FGR ratio in the folic acid and vitamin B12 deficiency group was higher than that in the sufficiency group (χ(2) = 4.717 and 4.437, P = 0.029 and 0.035, respectively). In addition, elevated homocysteine was associated with FGR (χ(2) = 5.366, P = 0.021). In conclusion, we found that folic acid and vitamin B12 deficiency was associated with elevated homocysteine levels, which may increase susceptibility to FGR.

  10. A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study

    PubMed Central

    2011-01-01

    Background Neuropeptide Y (NPY) is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue (AT). Acipimox (Aci) inhibits lipolysis in AT and reduces plasma glycerol and free fatty acid (FFA) levels. Exercise and Aci are enhancers of growth hormone (GH) and NPY secretion and exercise may alter leptin levels. We expect to find abnormal neuropeptidergic response in plasma and AT in patients with bulimia nervosa (BN). We hypothesize that Aci influences these peptides via a FFA-independent mechanism and that Aci inhibits lipolysis through a cyclic adenosine monophosphate (cAMP)-dependent pathway. Dysregulations of the AT-brain axis peptides might be involved in binge eating as is the case in BN. Methods The objective of this study was to determine the responses of plasma NPY, GH, leptin, FFA and glycerol levels to exercise in BN patients and healthy women (C) given the anti-lipolytic drug Aci or placebo. The secondary objective of this study was to compare the responses of extracellular glycerol levels and plasma glycerol levels to exercise alone or together with Aci administration in BN patients and C women. Extracellular glycerol was measured in vivo in subcutaneous (sc) abdominal AT using microdialysis. Eight BN and eight C women were recruited for this single-blind, randomized study. Aci or placebo was given 1 hour before the exercise (45 min, 2 W/kg of lean body mass [LBM]). NPY, GH, leptin, FFA, glycerol plasma and AT glycerol levels were measured using commercial kits. Results The primary outcome of this study was that the exercise with Aci administration resulted in plasma NPY and GH increase (after a 45-minute exercise) and leptin (after a 90-minute post-exercise recovering phase) increased more in BN patients. The secondary outcomes of this study were that the exercise with Aci administration induced a higher decrease of extracellular glycerol in BN patients compared to the C group

  11. In vivo blockade of thalamic GABA(B) receptors increases excitatory amino-acid levels.

    PubMed

    Nyitrai, G; Emri, Z; Crunelli, V; Kékesi, K A; Dobolyi, A; Juhász, G

    1996-12-30

    The effect of intrathalamic application of GABA(B) receptor antagonists on the basal excitatory amino-acid levels was studied using microdialysis probes implanted in the dorsal lateral geniculate nucleus and in the ventrobasal complex. In both nuclei, continuous perfusion of the GABA(B) receptor antagonist 3-aminopropyl-(diethoxymethyl)-phosphinic acid (CGP 35348) produced an increase in the extracellular concentration of aspartate and (to a lesser extent) glutamate, but no change was observed in the level of taurine, the main amino acid involved in the regulation of brain osmolarity processes. In contrast, 3-amino-2-hydroxy-2-(4-chlorophenyl)-propanesulphonic acid (2-hydroxy-saclofen), another GABA(B) receptor antagonist, failed to affect the extracellular concentration of aspartate, glutamate and taurine. Thus, the basal level of excitatory amino acids in the thalamus in vivo is under the control of CGP 35348-sensitive GABA(B) receptors.

  12. Unusually high levels of n-6 polyunsaturated fatty acids in whale sharks and reef manta rays.

    PubMed

    Couturier, L I E; Rohner, C A; Richardson, A J; Pierce, S J; Marshall, A D; Jaine, F R A; Townsend, K A; Bennett, M B; Weeks, S J; Nichols, P D

    2013-10-01

    Fatty acid (FA) signature analysis has been increasingly used to assess dietary preferences and trophodynamics in marine animals. We investigated FA signatures of connective tissue of the whale shark Rhincodon typus and muscle tissue of the reef manta ray Manta alfredi. We found high levels of n-6 polyunsaturated fatty acids (PUFA), dominated by arachidonic acid (20:4n-6; 12-17 % of total FA), and comparatively lower levels of the essential n-3 PUFA-eicosapentaenoic acid (20:5n-3; ~1 %) and docosahexaenoic acid (22:6n-3; 3-10 %). Whale sharks and reef manta rays are regularly observed feeding on surface aggregations of coastal crustacean zooplankton during the day, which generally have FA profiles dominated by n-3 PUFA. The high levels of n-6 PUFA in both giant elasmobranchs raise new questions about the origin of their main food source.

  13. Effects of toxic work environments on sperm quality and ascorbic acid levels

    SciTech Connect

    Dawson, E.B.; Harris, W.A.; Powell, L.C. )

    1990-02-26

    Surveys have shown that toxic work environments lower sperm quality, and controlled studies indicate that ascorbic acid supplementation improves sperm viability and agglutination. The sperm quality of 50 subjects each from: (1) office workers, (2) a lead smelter, (3) petroleum refineries, and (4) a herbicide plant were compared with serum and semen ascorbic acid levels. The sperm characteristics studied were: count as million/ml and as percent; viability, motility, clumping, and abnormal morphology. The serum ascorbic acid levels were directly proportional to sperm viability and inversely correlated to clumping of all groups. Moreover, serum ascorbic acid levels were also inversely correlated to twin tail and amorphous forms of abnormal sperm morphology. The results of the study indicate that toxic environments depress sperm quality and suggest that ascorbic acid supplementation will improve sperm quality and fertility.

  14. Eicosopentaneoic Acid and Other Free Fatty Acid Receptor Agonists Inhibit Lysophosphatidic Acid- and Epidermal Growth Factor-Induced Proliferation of Human Breast Cancer Cells

    PubMed Central

    Hopkins, Mandi M.; Zhang, Zhihong; Liu, Ze; Meier, Kathryn E.

    2016-01-01

    Many key actions of ω-3 (n-3) fatty acids have recently been shown to be mediated by two G protein-coupled receptors (GPCRs) in the free fatty acid receptor (FFAR) family, FFA1 (GPR40) and FFA4 (GPR120). n-3 Fatty acids inhibit proliferation of human breast cancer cells in culture and in animals. In the current study, the roles of FFA1 and FFA4 were investigated. In addition, the role of cross-talk between GPCRs activated by lysophosphatidic acid (LPA), and the tyrosine kinase receptor activated by epidermal growth factor (EGF), was examined. In MCF-7 and MDA-MB-231 human breast cancer cell lines, both LPA and EGF stimulated proliferation, Erk activation, Akt activation, and CCN1 induction. LPA antagonists blocked effects of LPA and EGF on proliferation in MCF-7 and MDA-MB-231, and on cell migration in MCF-7. The n-3 fatty acid eicosopentaneoic acid inhibited LPA- and EGF-induced proliferation in both cell lines. Two synthetic FFAR agonists, GW9508 and TUG-891, likewise inhibited LPA- and EGF-induced proliferation. The data suggest a major role for FFA1, which was expressed by both cell lines. The results indicate that n-3 fatty acids inhibit breast cancer cell proliferation via FFARs, and suggest a mechanism involving negative cross-talk between FFARS, LPA receptors, and EGF receptor. PMID:26821052

  15. Eicosopentaneoic Acid and Other Free Fatty Acid Receptor Agonists Inhibit Lysophosphatidic Acid- and Epidermal Growth Factor-Induced Proliferation of Human Breast Cancer Cells.

    PubMed

    Hopkins, Mandi M; Zhang, Zhihong; Liu, Ze; Meier, Kathryn E

    2016-01-26

    Many key actions of ω-3 (n-3) fatty acids have recently been shown to be mediated by two G protein-coupled receptors (GPCRs) in the free fatty acid receptor (FFAR) family, FFA1 (GPR40) and FFA4 (GPR120). n-3 Fatty acids inhibit proliferation of human breast cancer cells in culture and in animals. In the current study, the roles of FFA1 and FFA4 were investigated. In addition, the role of cross-talk between GPCRs activated by lysophosphatidic acid (LPA), and the tyrosine kinase receptor activated by epidermal growth factor (EGF), was examined. In MCF-7 and MDA-MB-231 human breast cancer cell lines, both LPA and EGF stimulated proliferation, Erk activation, Akt activation, and CCN1 induction. LPA antagonists blocked effects of LPA and EGF on proliferation in MCF-7 and MDA-MB-231, and on cell migration in MCF-7. The n-3 fatty acid eicosopentaneoic acid inhibited LPA- and EGF-induced proliferation in both cell lines. Two synthetic FFAR agonists, GW9508 and TUG-891, likewise inhibited LPA- and EGF-induced proliferation. The data suggest a major role for FFA1, which was expressed by both cell lines. The results indicate that n-3 fatty acids inhibit breast cancer cell proliferation via FFARs, and suggest a mechanism involving negative cross-talk between FFARS, LPA receptors, and EGF receptor.

  16. Pyrazinoic acid decreases the proton motive force, respiratory ATP synthesis activity, and cellular ATP levels.

    PubMed

    Lu, Ping; Haagsma, Anna C; Pham, Hoang; Maaskant, Janneke J; Mol, Selena; Lill, Holger; Bald, Dirk

    2011-11-01

    Pyrazinoic acid, the active form of the first-line antituberculosis drug pyrazinamide, decreased the proton motive force and respiratory ATP synthesis rates in subcellular mycobacterial membrane assays. Pyrazinoic acid also significantly lowered cellular ATP levels in Mycobacterium bovis BCG. These results indicate that the predominant mechanism of killing by this drug may operate by depletion of cellular ATP reserves.

  17. Implications of dietary fatty acids during pregnancy on placental, fetal and postnatal development--a review.

    PubMed

    Herrera, Emilio

    2002-04-01

    During pregnancy, the mother adapts her metabolism to support the continuous draining of substrates by the fetus. Her increase in net body weight (free of the conceptus) corresponds to the accumulation of fat depots during the first two-thirds of gestation, switching to an accelerated breakdown of these during the last trimester. Under fasting conditions, adipose tissue lipolytic activity is highly enhanced, and its products, free fatty acids (FFA) and glycerol, are mainly driven to maternal liver, where FFA are converted to ketone bodies and glycerol to glucose, which easily cross the placenta and sustain fetal metabolism. Lipolytic products reaching maternal liver are also used for triglyceride synthesis that are released in turn to the circulation, where together with an enhanced transfer of triglycerides among the different lipoprotein fractions, and a decrease in extrahepatic lipoprotein lipase activity, increase the content of triglycerides in all the lipoprotein fractions. Long chain polyunsaturated fatty acids (LCPUFA) circulate in maternal plasma associated to lipoprotein triglycerides, and in a minor proportion in the form of FFA. Despite the lack of a direct placental transfer of triglycerides, diffusion of their fatty acids to the fetus is ensured by means of lipoprotein receptors, lipoprotein lipase activity and intracellular lipase activities in the placenta. Maternal plasma FFA are also an important source of LCPUFA to the fetus, and their placental uptake occurs via a selective process of facilitated membrane translocation involving a plasma membrane fatty acid-binding protein. This mechanism together with a selective cellular metabolism determine the actual rate of placental transfer and its selectivity, resulting even in an enrichment of certain LCPUFA in fetal circulation as compared to maternal. The degree to which the fetus is capable of fatty acid desaturation and elongation is not clear, although both term and preterm infants can synthesize

  18. [A retrospective study analysis of urinary hippuric acid levels in occupational toxicology exams].

    PubMed

    Gonzalez, Kelly Cristina; Sagebin, Fernando Rodrigues; Oliveira, Paola Garcia; Glock, Luiz; Thiesen, Flavia Valladão

    2010-06-01

    Hippuric acid is the primary metabolite of toluene, a solvent widely used in industrial processes with considerable toxic effects, a fact which justifies regularly monitoring individuals with occupational exposure to this solvent. This work aims at evaluating urinary hippuric acid levels found in workers subject to biological monitoring. A retrospective study was carried out with data referring from 2002 to 2005, in which exams results and employment status were analyzed (periodic, post-employment, and pre-employment exams). Results indicate a significant reduction in hippuric acid levels for 2005. Periodic exams presented higher results than pre-employment and post-employment exams. No significant difference was found in individuals grouped according to their status in each of the established intervals, their reference numbers, and maximum biological levels allowed. Hippuric acid levels detected indicate low risk of toluene exposure for the population under evaluation, probably due to a growing concern with the deployment of measures regarding occupational hygiene.

  19. Coumarin effects on amino acid levels in mice prefrontal cortex and hippocampus.

    PubMed

    Pereira, Elaine Cristina; Lucetti, Daniel Luna; Barbosa-Filho, José Maria; de Brito, Eliane Magalhães; Monteiro, Valdécio Silvano; Patrocínio, Manoel Cláudio Azevedo; de Moura, Rebeca Ribeiro; Leal, Luzia Kalyne Almeida Moreira; Macedo, Danielle Silveira; de Sousa, Francisca Cléa Florenço; de Barros Viana, Glauce Socorro; Vasconcelos, Silvânia Maria Mendes

    2009-04-24

    Coumarin is a compound known to be present in a wide variety of plants, microorganisms and animal species. Most of its effects were studied in organs and systems other than the central nervous system. The present work evaluated the effect of coumarin administration on the levels of gamma-aminobutyric acid (GABA), glutamate (GLU), glycine (GLY) and taurine (TAU) in the prefrontal cortex and hippocampus of mice. Male Swiss mice were treated with distilled water (controls), coumarin (20 or 40 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Results showed that in the prefrontal cortex, coumarin at the lowest dose increased the levels of GLU and TAU, while GABA increased with both doses studied and GLY had its levels increased only at the dose of 40 mg/kg. Diazepam (DZP) increased the levels of GABA and TAU and decreased the levels of GLU and GLY in this area. In the hippocampus, only glutamate had its levels decreased after coumarin treatment, while diazepam increased the levels of GABA and TAU and decreased the levels of GLU in this brain region. We concluded that coumarin stimulates the release of endogenous amino acids, increasing the levels of inhibitory and excitatory amino acids in the prefrontal cortex, and decreasing glutamate levels in the hippocampus. Together, these results are of interest, considering that some neurodegenerative diseases and seizures are related to the imbalance of the amino acid levels in the CNS suggesting a perspective of a therapeutic use of coumarins in these disorders.

  20. Analysis of methylphosphonic acid, ethyl methylphosphonic acid and isopropyl methylphosphonic acid at low microgram per liter levels in groundwater.

    PubMed

    Sega, G A; Tomkins, B A; Griest, W H

    1997-11-28

    A method is described for determining methylphosphonic acid, ethyl methylphosphonic acid and isopropyl methylphosphonic acid, which are hydrolysis products of the nerve agents VX (S-2-diisopropylaminoethyl O-ethyl methylphosphonothiolate) and GB (sarin, isopropylmethyl phosphonofluoridate). The analytes are extracted from 50 ml groundwater using a solid-phase extraction column packed with 500 mg of silica with a bonded quaternary amine phase, and are eluted and derivatized with methanolic trimethylphenylammonium hydroxide. Separation and quantitation are achieved using a capillary column gas chromatograph equipped with a flame photometric detector operated in its phosphorus-selective mode. Two independent statistically-unbiased procedures were employed to determine the detection limits, which ranged between 3 and 9 micrograms/l, for the three analytes.

  1. High-level exogenous glutamic acid-independent production of poly-(γ-glutamic acid) with organic acid addition in a new isolated Bacillus subtilis C10.

    PubMed

    Zhang, Huili; Zhu, Jianzhong; Zhu, Xiangcheng; Cai, Jin; Zhang, Anyi; Hong, Yizhi; Huang, Jin; Huang, Lei; Xu, Zhinan

    2012-07-01

    A new exogenous glutamic acid-independent γ-PGA producing strain was isolated and characterized as Bacillus subtilis C10. The factors influencing the endogenous glutamic acid supply and the biosynthesis of γ-PGA in this strain were investigated. The results indicated that citric acid and oxalic acid showed the significant capability to support the overproduction of γ-PGA. This stimulated increase of γ-PGA biosynthesis by citric acid or oxalic acid was further proved in the 10 L fermentor. To understand the possible mechanism contributing to the improved γ-PGA production, the activities of four key intracellular enzymes were measured, and the possible carbon fluxes were proposed. The result indicated that the enhanced level of pyruvate dehydrogenase (PDH) activity caused by oxalic acid was important for glutamic acid synthesized de novo from glucose. Moreover, isocitrate dehydrogenase (ICDH) and glutamate dehydrogenase (GDH) were the positive regulators of glutamic acid biosynthesis, while 2-oxoglutarate dehydrogenase complex (ODHC) was the negative one.

  2. Amino acid limitation induces down-regulation of WNT5a at transcriptional level

    SciTech Connect

    Wang Zuguang; Chen Hong

    2009-01-23

    An aberrant WNT signaling contributes to the development and progression of multiple cancers. WNT5a is one of the WNT signaling molecules. This study was designed to test the hypothesis that amino acid deprivation induces changes in the WNT signaling pathway in colon cancer cells. Results showed that targets of the amino acid response pathway, ATF3 and p21, were induced in the human colon cancer cell line SW480 during amino acid limitation. There was a significant decrease in the WNT5a mRNA level following amino acid deprivation. The down-regulation of WNT5a mRNA by amino acid deprivation is not due to mRNA destabilization. There is a reduction of nuclear {beta}-catenin protein level by amino acid limitation. Under amino acid limitation, phosphorylation of ERK1/2 was increased and the blockage of ERK1/2 by the inhibitor U0126 partially restored WNT5a mRNA level. In conclusion, amino acid limitation in colon cancer cells induces phosphorylation of ERK1/2, which then down-regulates WNT5a expression.

  3. Solvent extraction in the treatment of acidic high-level liquid waste : where do we stand?

    SciTech Connect

    Horwitz, E. P.; Schulz, W. W.

    1998-06-18

    During the last 15 years, a number of solvent extraction/recovery processes have been developed for the removal of the transuranic elements, {sup 90}Sr and {sup 137}Cs from acidic high-level liquid waste. These processes are based on the use of a variety of both acidic and neutral extractants. This chapter will present an overview and analysis of the various extractants and flowsheets developed to treat acidic high-level liquid waste streams. The advantages and disadvantages of each extractant along with comparisons of the individual systems are discussed.

  4. Simultaneous conversion of free fatty acids and triglycerides to biodiesel by immobilized Aspergillus oryzae expressing Fusarium heterosporum lipase.

    PubMed

    Amoah, Jerome; Quayson, Emmanuel; Hama, Shinji; Yoshida, Ayumi; Hasunuma, Tomohisa; Ogino, Chiaki; Kondo, Akihiko

    2017-03-01

    The presence of high levels of free fatty acids (FFA) in oil is a barrier to one-step biodiesel production. Undesirable soaps are formed during conventional chemical methods, and enzyme deactivation occurs when enzymatic methods are used. This work investigates an efficient technique to simultaneously convert a mixture of free fatty acids and triglycerides (TAG). A partial soybean hydrolysate containing 73.04% free fatty acids and 24.81% triglycerides was used as a substrate for the enzymatic production of fatty acid methyl ester (FAME). Whole-cell Candida antarctica lipase B-expressing Aspergillus oryzae, and Novozym 435 produced only 75.2 and 73.5% FAME, respectively. Fusarium heterosporum lipase-expressing A. oryzae produced more than 93% FAME in 72 h using three molar equivalents of methanol. FFA and TAG were converted simultaneously in the presence of increasing water content that resulted from esterification. Therefore, F. heterosporum lipase with a noted high level of tolerance of water could be useful in the industrial production of biodiesel from feedstock that has high proportion of free fatty acids.

  5. Extracellular Loop 2 of the Free Fatty Acid Receptor 2 Mediates Allosterism of a Phenylacetamide Ago-Allosteric ModulatorS⃞

    PubMed Central

    Smith, Nicola J.; Ward, Richard J.; Stoddart, Leigh A.; Hudson, Brian D.; Kostenis, Evi; Ulven, Trond; Morris, Joanne C.; Tränkle, Christian; Tikhonova, Irina G.; Adams, David R.

    2011-01-01

    Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molecular mechanisms mediating the activity of 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide (4-CMTB), a recently described phenylacetamide allosteric agonist and allosteric modulator of endogenous ligand function at human FFA2, by combining our previous knowledge of the orthosteric binding site with targeted examination of 4-CMTB structure-activity relationships and mutagenesis and chimeric receptor generation. Here we show that 4-CMTB is a selective agonist for FFA2 that binds to a site distinct from the orthosteric site of the receptor. Ligand structure-activity relationship studies indicated that the N-thiazolyl amide is likely to provide hydrogen bond donor/acceptor interactions with the receptor. Substitution at Leu173 or the exchange of the entire extracellular loop 2 of FFA2 with that of FFA3 was sufficient to reduce or ablate, respectively, allosteric communication between the endogenous and allosteric agonists. Thus, we conclude that extracellular loop 2 of human FFA2 is required for transduction of cooperative signaling between the orthosteric and an as-yet-undefined allosteric binding site of the FFA2 receptor that is occupied by 4-CMTB. PMID:21498659

  6. Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

    PubMed

    Faggiano, A; Pivonello, R; Melis, D; Alfieri, R; Filippella, M; Spagnuolo, G; Salvatore, F; Lombardi, G; Colao, A

    2002-02-01

    Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0

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

    PubMed

    Luo, Yi; 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.

  8. Genetic loci associated with circulating levels of very long-chain saturated fatty acids[S

    PubMed Central

    Lemaitre, Rozenn N.; King, Irena B.; Kabagambe, Edmond K.; Wu, Jason H. Y.; McKnight, Barbara; Manichaikul, Ani; Guan, Weihua; Sun, Qi; Chasman, Daniel I.; Foy, Millennia; Wang, Lu; Zhu, Jingwen; Siscovick, David S.; Tsai, Michael Y.; Arnett, Donna K.; Psaty, Bruce M.; Djousse, Luc; Chen, Yii-Der I.; Tang, Weihong; Weng, Lu-Chen; Wu, Hongyu; Jensen, Majken K.; Chu, Audrey Y.; Jacobs, David R.; Rich, Stephen S.; Mozaffarian, Dariush; Steffen, Lyn; Rimm, Eric B.; Hu, Frank B.; Ridker, Paul M.; Fornage, Myriam; Friedlander, Yechiel

    2015-01-01

    Very long-chain saturated fatty acids (VLSFAs) are saturated fatty acids with 20 or more carbons. In contrast to the more abundant saturated fatty acids, such as palmitic acid, there is growing evidence that circulating VLSFAs may have beneficial biological properties. Whether genetic factors influence circulating levels of VLSFAs is not known. We investigated the association of common genetic variation with plasma phospholipid/erythrocyte levels of three VLSFAs by performing genome-wide association studies in seven population-based cohorts comprising 10,129 subjects of European ancestry. We observed associations of circulating VLSFA concentrations with common variants in two genes, serine palmitoyl-transferase long-chain base subunit 3 (SPTLC3), a gene involved in the rate-limiting step of de novo sphingolipid synthesis, and ceramide synthase 4 (CERS4). The SPTLC3 variant at rs680379 was associated with higher arachidic acid (20:0 , P = 5.81 × 10−13). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (P = 2.65 × 10−40) and in analyses that adjusted for 20:0, with lower levels of behenic acid (P = 4.22 × 10−26) and lignoceric acid (P = 3.20 × 10−21). These novel associations suggest an inter-relationship of circulating VLSFAs and sphingolipid synthesis. PMID:25378659

  9. Metformin impairs systemic bile acid homeostasis through regulating SIRT1 protein levels.

    PubMed

    Chen, Qi; Yang, Xiaoying; Zhang, Huabing; Kong, Xingxing; Yao, Lu; Cui, Xiaona; Zou, Yongkang; Fang, Fude; Yang, Jichun; Chang, Yongsheng

    2017-01-01

    Metformin is widely used to treat hyperglycemia. However, metformin treatment may induce intrahepatic cholestasis and liver injury in a few patients with type II diabetes through an unknown mechanism. Here we show that metformin decreases SIRT1 protein levels in primary hepatocytes and liver. Both metformin-treated wild-type C57 mice and hepatic SIRT1-mutant mice had increased hepatic and serum bile acid levels. However, metformin failed to change systemic bile acid levels in hepatic SIRT1-mutant mice. Molecular mechanism study indicates that SIRT1 directly interacts with and deacetylates Foxa2 to inhibit its transcriptional activity on expression of genes involved in bile acids synthesis and transport. Hepatic SIRT1 mutation elevates Foxa2 acetylation levels, which promotes Foxa2 binding to and activating genes involved in bile acids metabolism, impairing hepatic and systemic bile acid homeostasis. Our data clearly suggest that hepatic SIRT1 mediates metformin effects on systemic bile acid metabolism and modulation of SIRT1 activity in liver may be an attractive approach for treatment of bile acid-related diseases such as cholestasis.

  10. Genetic loci associated with circulating levels of very long-chain saturated fatty acids.

    PubMed

    Lemaitre, Rozenn N; King, Irena B; Kabagambe, Edmond K; Wu, Jason H Y; McKnight, Barbara; Manichaikul, Ani; Guan, Weihua; Sun, Qi; Chasman, Daniel I; Foy, Millennia; Wang, Lu; Zhu, Jingwen; Siscovick, David S; Tsai, Michael Y; Arnett, Donna K; Psaty, Bruce M; Djousse, Luc; Chen, Yii-Der I; Tang, Weihong; Weng, Lu-Chen; Wu, Hongyu; Jensen, Majken K; Chu, Audrey Y; Jacobs, David R; Rich, Stephen S; Mozaffarian, Dariush; Steffen, Lyn; Rimm, Eric B; Hu, Frank B; Ridker, Paul M; Fornage, Myriam; Friedlander, Yechiel

    2015-01-01

    Very long-chain saturated fatty acids (VLSFAs) are saturated fatty acids with 20 or more carbons. In contrast to the more abundant saturated fatty acids, such as palmitic acid, there is growing evidence that circulating VLSFAs may have beneficial biological properties. Whether genetic factors influence circulating levels of VLSFAs is not known. We investigated the association of common genetic variation with plasma phospholipid/erythrocyte levels of three VLSFAs by performing genome-wide association studies in seven population-based cohorts comprising 10,129 subjects of European ancestry. We observed associations of circulating VLSFA concentrations with common variants in two genes, serine palmitoyl-transferase long-chain base subunit 3 (SPTLC3), a gene involved in the rate-limiting step of de novo sphingolipid synthesis, and ceramide synthase 4 (CERS4). The SPTLC3 variant at rs680379 was associated with higher arachidic acid (20:0 , P = 5.81 × 10(-13)). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (P = 2.65 × 10(-40)) and in analyses that adjusted for 20:0, with lower levels of behenic acid (P = 4.22 × 10(-26)) and lignoceric acid (P = 3.20 × 10(-21)). These novel associations suggest an inter-relationship of circulating VLSFAs and sphingolipid synthesis.

  11. Nonsteroidal anti-inflammatory drug flufenamic acid is a potent activator of AMP-activated protein kinase.

    PubMed

    Chi, Yuan; Li, Kai; Yan, Qiaojing; Koizumi, Schuichi; Shi, Liye; Takahashi, Shuhei; Zhu, Ying; Matsue, Hiroyuki; Takeda, Masayuki; Kitamura, Masanori; Yao, Jian

    2011-10-01

    Flufenamic acid (FFA) is a nonsteroidal anti-inflammatory drug (NSAID). It has anti-inflammatory and antipyretic properties. In addition, it modulates multiple channel activities. The mechanisms underlying the pharmacological actions of FFA are presently unclear. Given that AMP-activated protein kinase (AMPK) has both anti-inflammatory and channel-regulating functions, we examined whether FFA induces AMPK activation. 1) Exposure of several different types of cells to FFA resulted in an elevation of AMPKα phosphorylation at Thr172. This effect of FFA was reproduced by functionally and structurally similar mefenamic acid, tolfenamic acid, niflumic acid, and meclofenamic acid. 2) FFA-induced activation of AMPK was largely abolished by the treatment of cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (an intracellular Ca(2+) chelator) or depletion of extracellular Ca(2+), whereas it was mimicked by stimulation of cells with the Ca(2+) ionophore 5-(methylamino)-2-({(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl}methyl)-1,3-benzoxazole-4-carboxylic acid (A23187) or ionomycin. 3) FFA triggered a rise in intracellular Ca(2+), which was abolished by cyclosporine, a blocker of mitochondrial permeability transition pore. Cyclosporine also abolished FFA-induced activation of AMPK. 4) Inhibition of Ca(2+)/calmodulin-dependent kinase kinase β (CaMKKβ) with 7-oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic acid acetate (STO-609) or down-regulation of CaMKKβ with short interfering RNA largely abrogated FFA-induced activation of AMPK. 5) FFA significantly suppressed nuclear factor-κB activity and inducible nitric-oxide synthase expression triggered by interleukin-1β and tumor necrosis factor α. This suppression was also largely abrogated by STO-609. Taken together, we conclude that FFA induces AMPK activation through the Ca(2+)-CaMKKβ pathway

  12. Flufenamic acid decreases neuronal excitability through modulation of voltage-gated sodium channel gating.

    PubMed

    Yau, Hau-Jie; Baranauskas, Gytis; Martina, Marco

    2010-10-15

    The electrophysiological phenotype of individual neurons critically depends on the biophysical properties of the voltage-gated channels they express. Differences in sodium channel gating are instrumental in determining the different firing phenotypes of pyramidal cells and interneurons; moreover, sodium channel modulation represents an important mechanism of action for many widely used CNS drugs. Flufenamic acid (FFA) is a non-steroidal anti-inflammatory drug that has been long used as a blocker of calcium-dependent cationic conductances. Here we show that FFA inhibits voltage-gated sodium currents in hippocampal pyramidal neurons; this effect is dose-dependent with IC(50) = 189 μm. We used whole-cell and nucleated patch recordings to investigate the mechanisms of FFA modulation of TTX-sensitive voltage-gated sodium current. Our data show that flufenamic acid slows down the inactivation process of the sodium current, while shifting the inactivation curve ~10 mV toward more hyperpolarized potentials. The recovery from inactivation is also affected in a voltage-dependent way, resulting in slower recovery at hyperpolarized potentials. Recordings from acute slices demonstrate that FFA reduces repetitive- and abolishes burst-firing in CA1 pyramidal neurons. A computational model based on our data was employed to better understand the mechanisms of FFA action. Simulation data support the idea that FFA acts via a novel mechanism by reducing the voltage dependence of the sodium channel fast inactivation rates. These effects of FFA suggest that it may be an effective anti-epileptic drug.

  13. Chronic Depression of Serum Sialic Acid Levels in Alloxan-Induced Diabetes

    DTIC Science & Technology

    1974-10-01

    Serum L- Fucose , Protein-Bound Hexose, and Total Protein Levels in Alloxan Diabetic and Control Rats at Various Time Intervals After Treatment 5...ABSTRACT This study was performed to determine whether alloxan treatment of rats alters levels of the terminal carbohydrate residues L- fucose and...occurs with no apparent alteration in the level of L- fucose . The depression in sialic acid level may be attributed in part to decreased activities of

  14. Serum nitrite and nitrate levels in epileptic children using valproic acid or carbamazepine.

    PubMed

    Karabiber, Hamza; Yakinci, Cengiz; Durmaz, Yasar; Temel, Ismail; Mehmet, Nihayet

    2004-01-01

    In experimental epilepsy studies, nitric oxide was found to act as both proconvulsant and anticonvulsant. The objective of this study was to investigate the effects of valproic acid and carbamazepine on serum levels of nitrite and nitrate, which are the metabolites of nitric oxide. To achieve this goal, serum nitrite and nitrate levels were determined in active epileptic 34 children using valproic acid and 23 children using carbamazepine and in non-active epileptic 38 children (control group) not using any antiepileptic drug. In the valproic acid group serum nitrite and nitrate levels were 2.66 +/- 2.11 micromol/l and 69.35 +/- 23.20 micromol/l, 1.89 +/- 1.01 micromol/l and 49.39 +/- 10.61 micromol/l in the carbamazepine group, and 1.22 +/- 0.55 micromol/l, 29.53 +/- 10.05 micromol in the control group, respectively. Nitrite and nitrate levels were significantly high in both valproic acid and carbamazepine groups compared to the control group (P < 0.01). When valproic acid and carbamazepine groups were compared to each other, level of nitrate was found statistically higher in the valproic acid group in relation to the carbamazepine group (P < 0.01), however, there was no statistically significant difference in the levels of nitrite (P > 0.05). No relation could be found between serum drug levels and nitrite and nitrate levels. According to these results, it can be suggested that valproic acid and carbamazepine might have antiepileptic effects through nitric oxide.

  15. Comparative Indole-3-Acetic Acid Levels in the Slender Pea and Other Pea Phenotypes 1

    PubMed Central

    Law, David M.; Davies, Peter J.

    1990-01-01

    Free indole-3-acetic acid levels were measured by gas chromatography-mass spectrometry in three ultra-tall `slender' Pisum sativum L. lines differing in gibberellin content. Measurements were made for apices and stem elongation zones of light-grown plants and values were compared with wild-type, dwarf, and nana phenotypes in which internode length is genetically regulated, purportedly via the gibberellin level. Indole-3-acetic acid levels of growing stems paralleled growth rates in all lines, and were high in all three slender genotypes. Growth was inhibited by p-chlorophenoxyisobutyric acid, demonstrating the requirement of auxin activity for stem elongation, and also by the ethylene precursor 1-aminocyclopropane-1-carboxylic acid. It is concluded that the slender phenotype may arise from constant activation of a gibberellin receptor or transduction chain event leading directly or indirectly to elevated levels of indole-3-acetic acid, and that increased indole-3-acetic acid levels are a significant factor in the promotion of stem elongation. PMID:16667653

  16. Uric Acid Level and Erectile Dysfunction In Patients With Coronary Artery Disease

    PubMed Central

    Solak, Yalcin; Akilli, Hakan; Kayrak, Mehmet; Aribas, Alpay; Gaipov, Abduzhappar; Turk, Suleyman; Perez-Pozo, Santos E.; Covic, Adrian; McFann, Kim; Johnson, Richard J.; Kanbay, Mehmet

    2013-01-01

    Introduction Erectile dysfunction (ED) is a frequent complaint of elderly subjects, and is closely associated with endothelial dysfunction and cardiovascular disease. Uric acid is also associated with endothelial dysfunction, oxidative stress and cardiovascular disease, raising the hypothesis that an increased serum uric acid might predict erectile dysfunction in patients who are at risk for coronary artery disease. Aim To evaluate the association of serum uric acid levels with presence and severity of ED in patients presenting with chest pain of presumed cardiac origin. Methods This is a cross-sectional study of 312 adult male patients with suspected coronary artery disease who underwent exercise stress test (EST) for workup of chest pain and completed a sexual health inventory for men (SHIM) survey form to determine the presence and severity of ED. Routine serum biochemistry (and uric acid levels) were measured. Logistic regression analysis was used to assess risk factors for ED. Main Outcome Measures The short version of the international index of erectile function (IIEF-5) questionnaire diagnosed ED (cutoff score ≤21). Serum Uric acid levels were determined. Patients with chest pain of suspected cardiac origin underwent an exercise stress test. Results 149 of 312 (47.7%) male subjects had ED by survey criteria. Patients with ED were older and had more frequent CAD, hypertension, diabetes, and impaired renal function, and also had significantly higher levels of uric acid, fibrinogen, glucose, CRP, triglycerides compared with patients without ED. Uric acid levels were associated with ED by univariate analysis (OR = 1.36, p = 0.002); however, this association was not observed in multivariate analysis adjusted for eGFR. Conclusion Subjects presenting with chest pain of presumed cardiac origin are more likely to have ED if they have elevated uric acid levels. PMID:24433559

  17. Polyunsaturated Fatty Acid Levels in Maternal Erythrocytes of Japanese Women during Pregnancy and after Childbirth

    PubMed Central

    Kawabata, Terue; Kagawa, Yasuo; Kimura, Fumiko; Miyazawa, Teruo; Saito, Shoji; Arima, Takahiro; Nakai, Kunihiko; Yaegashi, Nobuo

    2017-01-01

    Background: The transport of polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), to the fetus from maternal stores increases depending on the fetal requirements for PUFA during the last trimester of pregnancy. Therefore, maternal blood PUFA changes physiologically with gestational age. However, the changes in PUFA levels in maternal blood erythrocytes during pregnancy and after childbirth have not been fully investigated in a fish-eating population. Objective: To examine the changes of ARA and DHA levels in maternal erythrocytes with the progress of pregnancy and the relationship between maternal and umbilical cord erythrocyte PUFA levels in pregnant Japanese women who habitually eat fish and shellfish. Design: This study was performed as a part of the adjunct study of the Japan Environment and Children’s Study (JECS). The participants were 74 pregnant women. The maternal blood samples were collected at 27, 30, and 36 weeks of pregnancy, and 2 days and 1 month after delivery, and umbilical cord blood was collected at delivery. The fatty acid levels of erythrocytes in these blood samples were determined. Results: ARA and DHA levels in maternal erythrocytes tended to decrease with the progress of pregnancy. While the DHA level decreased further after delivery, the ARA level returned to the value at 27 weeks of pregnancy within 1 month after delivery. The n-3 and n-6 PUFA levels in maternal erythrocytes at 27, 30, and 36 weeks of pregnancy were significantly positively correlated with the corresponding fatty acid levels in umbilical cord erythrocytes. Conclusion: The present findings showed a significant change in erythrocyte PUFA levels during pregnancy and after childbirth in a fish-eating population. The PUFA levels of maternal blood after the second trimester may be a reliable marker for predicting PUFA levels in infants’ circulating blood. PMID:28272345

  18. Cerebral lateralization of face-sensitive areas in left-handers: only the FFA does not get it right.

    PubMed

    Bukowski, Henryk; Dricot, Laurence; Hanseeuw, Bernard; Rossion, Bruno

    2013-10-01

    Face perception is highly lateralized to the right hemisphere (RH) in humans, as supported originally by observations of face recognition impairment (prosopagnosia) following brain damage. Divided visual field presentations, neuroimaging and event-related potential studies have supported this view. While the latter studies are typically performed in right-handers, the few reported cases of prosopagnosia with unilateral left damage were left-handers, suggesting that handedness may shift or qualify the lateralization of face perception. We tested this hypothesis by recording the whole set of face-sensitive areas in 11 left-handers, using a face-localizer paradigm in functional magnetic resonance imaging (fMRI) (faces, cars, and their phase-scrambled versions). All face-sensitive areas identified (superior temporal sulcus, inferior occipital cortex, anterior infero-temporal cortex, amygdala) were strongly right-lateralized in left-handers, this right lateralization bias being as large as in a population of right-handers (40) tested with the same paradigm (Rossion et al., 2012). The notable exception was the so-called 'Fusiform face area' (FFA), an area that was slightly left lateralized in the population of left-handers. Since the left FFA is localized closely to an area sensitive to word form in the human brain ('Visual Word Form Area' - VWFA), the enhanced left lateralization of the FFA in left-handers may be due to a decreased competition with the representation of words. The implications for the neural basis of face perception, aetiology of brain lateralization in general, and prosopagnosia are also discussed.

  19. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

  20. Plasma HDL reduces nonesterified fatty acid hydroperoxides originating from oxidized LDL: a mechanism for its antioxidant ability.

    PubMed

    Kotosai, Mari; Shimada, Sachiko; Kanda, Mai; Matsuda, Namiko; Sekido, Keiko; Shimizu, Yoshibumi; Tokumura, Akira; Nakamura, Toshiyuki; Murota, Kaeko; Kawai, Yoshichika; Terao, Junji

    2013-06-01

    The antioxidant property of plasma high-density lipoprotein (HDL) is thought to be involved in potential anti-atherogenic effects but the exact mechanism is not known. We aimed to reveal the contribution of HDL on the elimination of lipid hydroperoxides (LOOH) derived from oxidized low-density lipoprotein (LDL). Oxidized LDL prepared by copper ion-induced oxidation contained nonesterified fatty acid hydroperoxides (FFA-OOH) and lysophosphatidylcholine (lysoPtdCho), in addition to cholesteryl ester hydroperoxides (CE-OOH) and phosphatidylcholine hydroperoxides (PtdCho-OOH). A platelet-activating factor-acetylhydrolase (PAF-AH) inhibitor suppressed formation of FFA-OOH and lysoPtdCho in oxidized LDL. Among LOOH species, FFA-OOH was preferentially reduced by incubating oxidized LDL with HDL. HDL exhibited selective FFA-OOH reducing ability if it was mixed with a liposomal solution containing FFA-OOH, CE-OOH and PtdCho-OOH. Two-electron reduction of the hydroperoxy group to the hydroxy group was confirmed by the formation of 13-hydroxyoctadecadienoic acid from 13-hydroperoxyoctadecadienoic acid in HPLC analyses. This reducing effect was also found in apolipoprotein A-1 (apoA-1). FFA-OOH released from PtdCho-OOH due to PAF-AH activity in oxidized LDL undergo two-electron reduction by the reducing ability of apoA1 in HDL. This preferential reduction of FFA-OOH may participate in the mechanism of the antioxidant property of HDL.

  1. Screening and identification of differentially expressed genes in goose hepatocytes exposed to free fatty acid.

    PubMed

    Pan, Zhixiong; Wang, Jiwen; Kang, Bo; Lu, Lizhi; Han, Chunchun; Tang, Hui; Li, Liang; Xu, Feng; Zhou, Zehui; Lv, Jia

    2010-12-15

    The overaccumulation of triglycerides in hepatocytes induces hepatic steatosis; however, little is known about the mechanism of goose hepatic steatosis. The aim of this study was to define an experimental model of hepatocellular steatosis with TG overaccumulation and minimal cytotoxicity, using a mixture of various proportions of oleate and palmitate free fatty acids (FFAs) to induce fat-overloading, then using suppressive subtractive hybridization and a quantitative PCR approach to identify genes with higher or lower expression levels after the treatment of cells with FFA mixtures. Overall, 502 differentially expressed clones, representing 21 novel genes and 87 known genes, were detected by SSH. Based on functional clustering, up- and down-regulated genes were mostly related to carbohydrate and lipid metabolism, enzyme activity and signal transduction. The expression of 20 selected clones involved with carbohydrate and lipid metabolism pathways was further studied by quantitative PCR. The data indicated that six clones similar to the genes ChREBP, FoxO1, apoB, IHPK2, KIF1B, and FSP27, which participate in de novo synthesis of fatty acid and secretion of very low density lipoproteins, had significantly lower expression levels in the hepatocytes treated with FFA mixtures. Meanwhile, 13 clones similar to the genes DGAT-1, ACSL1, DHRS7, PPARα, L-FABP, DGAT-2, PCK, ACSL3, CPT-1, A-FABP, PPARβ, MAT, and ALDOB had significantly higher expression levels in the hepatocytes treated with FFA mixtures. These results suggest that several metabolic pathways are altered in goose hepatocytes, which may be useful for further research into the molecular mechanism of goose hepatic steatosis.

  2. Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo.

    PubMed

    Yasar, Ali; Gunduz, Kamer; Onur, Ece; Calkan, Mehmet

    2012-01-01

    The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.

  3. Two Levels of Caffeine Ingestion on Blood Lactate and Free Fatty Acid Responses during Incremental Exercise.

    ERIC Educational Resources Information Center

    McNaughton, Lars

    1987-01-01

    Research was conducted to determine the effects of two doses of caffeine on the lactate threshold and also to examine the effects on substrate utilization during incremental cycle ergometry. Results found that caffeine increased heart rates and free fatty acid levels for all workloads and decreased blood lactate levels at some of the workloads.…

  4. Accurate calculation of the p Ka of trifluoroacetic acid using high-level ab initio calculations

    NASA Astrophysics Data System (ADS)

    Namazian, Mansoor; Zakery, Maryam; Noorbala, Mohammad R.; Coote, Michelle L.

    2008-01-01

    The p Ka value of trifluoroacetic acid has been successfully calculated using high-level ab initio methods such as G3 and CBS-QB3. Solvation energies have been calculated using CPCM continuum model of solvation at the HF and B3-LYP levels of theory with various basis sets. Excellent agreement with experiment (to within 0.4 p Ka units) was obtained using CPCM solvation energies at the B3-LYP/6-31+G(d) level (or larger) in conjunction with CBS-QB3 or G3 gas-phase energies of trifluoroacetic acid and its anion.

  5. Fasting levels of monoketonic bile acids in human peripheral and portal circulation.

    PubMed

    Björkhem, I; Angelin, B; Einarsson, K; Ewerth, S

    1982-09-01

    . Einarsson, and S. Ewerth. Fasting levels of monoketonic bile acids in human peripheral and portal circulation.

  6. Evaluation of serum sialic acid, fucose levels and their ratio in oral squamous cell carcinoma

    PubMed Central

    Chinnannavar, Sangamesh Ningappa; Ashok, Lingappa; Vidya, Kodige Chandrashekhar; Setty, Sunil Mysore Kantharaja; Narasimha, Guru Eraiah; Garg, Ranjana

    2015-01-01

    Background: Detection of cancer at the early stage is of utmost importance to decrease the morbidity and mortality of the disease. Apart from the conventional biopsy, minimally invasive methods like serum evaluation are used for screening large populations. Thus, this study aimed to estimate serum levels of sialic acid and fucose and their ratio in oral cancer patients and in healthy control group to evaluate their role in diagnosis. Materials and Methods: Serum samples were collected from 52 healthy controls (group I) and 52 squamous cell carcinoma patients (group II). Estimation of serum levels of sialic acid and fucose and their ratio was performed. This was correlated histopathologically with the grades of carcinoma. Statistical analysis was done by using analysis of variance (ANOVA) test and unpaired “t” test. Results: Results showed that serum levels of sialic acid and fucose were significantly higher in oral cancer patients compared to normal healthy controls (P < 0.001). The sialic acid to fucose ratio was significantly lower in cancer patients than in normal controls (P < 0.01). However, comparison with histological grading, habits, gender, and age group did not show any significant result. Conclusion: The mean serum sialic acid and fucose levels showed an increasing trend from controls to malignant group and their corresponding ratio showed decreasing trend from controls to malignant group. The ratio of sialic acid to fucose can be a useful diagnostic aid for oral cancer patients. PMID:26759796

  7. Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter α protein.

    PubMed

    Miyata, Masaaki; Hayashi, Kenjiro; Yamakawa, Hiroki; Yamazoe, Yasushi; Yoshinari, Kouichi

    2015-01-01

    Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.

  8. Decreased eicosapentaenoic acid levels in acne vulgaris reveals the presence of a proinflammatory state.

    PubMed

    Aslan, İbrahim; Özcan, Filiz; Karaarslan, Taner; Kıraç, Ebru; Aslan, Mutay

    2017-01-01

    This study aimed to determine circulating levels of polyunsaturated fatty acids (PUFAs), secretory phospholipase A2 (sPLA2), lipoprotein lipase (LPL) and measure circulating protein levels of angiopoietin-like protein 3 (ANGPTL3), ANGPTL4, cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in patients with acne vulgaris. Serum from 21 control subjects and 31 acne vulgaris patients were evaluated for levels of arachidonic acid (AA, C20:4n- 6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3). PUFA levels were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Lipid profile, routine biochemical and hormone parameters were assayed by standard kit methods Serum EPA levels were significantly decreased while AA/EPA and DGLA/EPA ratio were significantly increased in acne vulgaris patients compared to controls. Serum levels of AA, DGLA and DHA showed no significant difference while activity of sPLA2 and LPL were significantly increased in acne vulgaris compared to controls. Results of this study reveal the presence of a proinflammatory state in acne vulgaris as shown by significantly decreased serum EPA levels and increased activity of sPLA2, AA/EPA and DGLA/EPA ratio. Increased LPL activity in the serum of acne vulgaris patients can be protective through its anti-dyslipidemic actions. This is the first study reporting altered EPA levels and increased sPLA2 activity in acne vulgaris and supports the use of omega-3 fatty acids as adjuvant treatment for acne patients.

  9. Childrens' learning and behaviour and the association with cheek cell polyunsaturated fatty acid levels.

    PubMed

    Kirby, A; Woodward, A; Jackson, S; Wang, Y; Crawford, M A

    2010-01-01

    Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs), particularly omega-3, in their red blood cells and plasma, and that supplementation with omega-3 fatty acids may alleviate behavioural symptoms in this population. However, in order to compare levels it seems appropriate to establish fatty acid levels in a mainstream school aged population and if levels relate to learning and behaviour. To date no study has established this. For this study, cheek cell samples from 411 typically developing school children were collected and analysed for PUFA content, in order to establish the range in this population. In addition, measures of general classroom attention and behaviour were assessed in these children by teachers and parents. Cognitive performance tests were also administered in order to explore whether an association between behaviour and/or cognitive performance and PUFA levels exists. Relationships between PUFA levels and socio-economic status were also explored. Measures of reading, spelling and intelligence did not show any association with PUFA levels, but some associations were noted with the level of omega-3 fatty acids and teacher and parental reports of behaviour, with some evidence that higher omega-3 levels were associated with decreased levels of inattention, hyperactivity, emotional and conduct difficulties and increased levels of prosocial behaviour. These findings are discussed in relation to previous findings from omega-3 supplementation studies with children.

  10. Inverse Association Between Serum Uric Acid Levels and Alzheimer's Disease Risk.

    PubMed

    Du, Na; Xu, Donghua; Hou, Xu; Song, Xuejia; Liu, Cancan; Chen, Ying; Wang, Yangang; Li, Xin

    2016-05-01

    The association between Alzheimer's disease and uric acid levels had gained great interest in recent years, but there was still lack of definite evidence. A systematic review and meta-analysis of relevant studies was performed to comprehensively estimate the association. Relevant studies published before October 26, 2014, were searched in PubMed, Embase, and China Biology Medicine (CBM) databases. Study-specific data were combined using random-effects or fixed-effects models of meta-analysis according to between-study heterogeneity. Twenty-four studies (21 case-control and 3 cohort studies) were finally included into the meta-analysis. Those 21 case-control studies included a total of 1128 cases of Alzheimer's disease and 2498 controls without Alzheimer's disease. Those 3 cohort studies included a total of 7327 participants. Meta-analysis showed that patients with Alzheimer's disease had lower levels of uric acid than healthy controls (weighted mean difference (WMD) = -0.77 mg/dl, 95% CI -2.28 to -0.36, P = 0.0002). High serum uric acid levels were significantly associated with decreased risk of Alzheimer's disease (risk ratio (RR) = 0.66, 95% CI 0.52-0.85, P = 0.001). There was low risk of publication bias in the meta-analysis. There is an inverse association between serum uric acid levels and Alzheimer's disease. High serum uric acid level is a protective factor of Alzheimer's disease.

  11. Serum sialic acid and glycoprotein levels in some Libyan cancer patients.

    PubMed

    Balo, N N; Ishaq, M

    1991-01-01

    Sialic acid is a common conjugate of some serum glycoproteins and glycolipids. Elevated levels of serum sialic acid and alterations in serum glycoproteins have been observed in certain types of cancer. In this study sialic acid concentration in the sera of patients with various types of cancer was determined. In addition to this, serum glycoproteins were also analysed by electrophoretic method. Our results indicate that serum sialic acid levels are generally raised in all types of cancer studied. This increase was more pronounced in case of lung, bronchogenic, intestinal and breast cancer. Some alterations in the serum glycoprotein profiles were also observed, particularly in bronchogenic and gall bladder cancer where an additional band in the low molecular weight region was present and in lung, breast and lymphoma where a band in the middle molecular weight region was found missing when compared with normals.

  12. Ascorbic acid inhibits PMP22 expression by reducing cAMP levels.

    PubMed

    Kaya, Ferdinand; Belin, Sophie; Bourgeois, Patrice; Micaleff, Joelle; Blin, Olivier; Fontés, Michel

    2007-03-01

    Charcot-Marie-Tooth [CMT] syndrome is the most common hereditary peripheral neuropathy. CMT1A, which accounts for 50% of all CMT cases, usually results from triploidy of the PMP22 gene. Preclinical trials using an animal model show that disabled mice force-fed with high doses of ascorbic acid partially recover muscular strength after a few months of treatment, and suggest that high doses of ascorbic acid repress PMP22 expression. In this study, we demonstrated that ascorbic acid represses PMP22 gene expression by acting on intracellular cAMP levels and adenylate cyclase activity. This action is dose dependent and specific to ascorbic acid, since repression is not observed after treatment with other antioxidants. The new properties of ascorbic acid are discussed, along with the implications of these findings for CMT disease treatment.

  13. New insights into fatty acid modulation of pancreatic beta-cell function.

    PubMed

    Haber, Esther P; Procópio, Joaquim; Carvalho, Carla R O; Carpinelli, Angelo R; Newsholme, Philip; Curi, Rui

    2006-01-01

    Insulin resistance states as found in type 2 diabetes and obesity are frequently associated with hyperlipidemia. Both stimulatory and detrimental effects of free fatty acids (FFA) on pancreatic beta cells have long been recognized. Acute exposure of the pancreatic beta cell to both high glucose concentrations and saturated FFA results in a substantial increase of insulin release, whereas a chronic exposure results in desensitization and suppression of secretion. Reduction of plasma FFA levels in fasted rats or humans severely impairs glucose-induced insulin release but palmitate can augment insulin release in the presence of nonstimulatory concentrations of glucose. These results imply that changes in physiological plasma levels of FFA are important for regulation of beta-cell function. Although it is widely accepted that fatty acid (FA) metabolism (notably FA synthesis and/or formation of LC-acyl-CoA) is necessary for stimulation of insulin secretion, the key regulatory molecular mechanisms controlling the interplay between glucose and fatty acid metabolism and thus insulin secretion are not well understood but are now described in detail in this review. Indeed the correct control of switching between FA synthesis or oxidation may have critical implications for beta-cell function and integrity both in vivo and in vitro. LC-acyl-CoA (formed from either endogenously synthesized or exogenous FA) controls several aspects of beta-cell function including activation of certain types of PKC, modulation of ion channels, protein acylation, ceramide- and/or NO-mediated apoptosis, and binding to and activating nuclear transcriptional factors. The present review also describes the possible effects of FAs on insulin signaling. We have previously reported that acute exposure of islets to palmitate up-regulates some key components of the intracellular insulin signaling pathway in pancreatic islets. Another aspect considered in this review is the potential source of fatty acids

  14. Beta-alanine and beta-aminoisobutyric acid levels in two siblings with dihydropyrimidinase deficiency.

    PubMed

    van Kuilenburg, A B P; Stroomer, A E M; Bosch, A M; Duran, M

    2008-06-01

    Dihydropyrimidinase (DHP) deficiency is an inborn error of the pyrimidine degradation pathway, affecting the hydrolytic ring opening of the dihydropyrimidines. In two siblings with a complete DHP deficiency and a variable clinical presentation, a normal concentration of beta-alanine and strongly decreased levels of beta-aminoisobutyric acid were observed in plasma, urine and CSF. No major differences were observed for the concentrations of the beta-amino acids in plasma and urine between the symptomatic and asymptomatic sibling. Thus, the relevance of the shortage of beta-aminoisobutyric acid for the onset of a clinical phenotype in patients with DHP deficiency remains to be established.

  15. Spectra, energy levels, and energy transition of lanthanide complexes with cinnamic acid and its derivatives

    NASA Astrophysics Data System (ADS)

    Zhou, Kaining; Feng, Zhongshan; Shen, Jun; Wu, Bing; Luo, Xiaobing; Jiang, Sha; Li, Li; Zhou, Xianju

    2016-04-01

    High resolution spectra and luminescent lifetimes of 6 europium(III)-cinnamic acid complex {[Eu2L6(DMF)(H2O)]·nDMF·H2O}m (L = cinnamic acid I, 4-methyl-cinnamic acid II, 4-chloro-cinnamic acid III, 4-methoxy-cinnamic acid IV, 4-hydroxy-cinnamic acid V, 4-nitro-cinnamic acid VI; DMF = N, N-dimethylformamide, C3H7NO) were recorded from 8 K to room temperature. The energy levels of Eu3 + in these 6 complexes are obtained from the spectra analysis. It is found that the energy levels of the central Eu3 + ions are influenced by the nephelauxetic effect, while the triplet state of ligand is lowered by the p-π conjugation effect of the para-substituted functional groups. The best energy matching between the ligand triplet state and the central ion excited state is found in complex I. While the other complexes show poorer matching because the gap of 5D0 and triplet state contracts.

  16. Spectra, energy levels, and energy transition of lanthanide complexes with cinnamic acid and its derivatives.

    PubMed

    Zhou, Kaining; Feng, Zhongshan; Shen, Jun; Wu, Bing; Luo, Xiaobing; Jiang, Sha; Li, Li; Zhou, Xianju

    2016-04-05

    High resolution spectra and luminescent lifetimes of 6 europium(III)-cinnamic acid complex {[Eu2L6(DMF)(H2O)]·nDMF·H2O}m (L=cinnamic acid I, 4-methyl-cinnamic acid II, 4-chloro-cinnamic acid III, 4-methoxy-cinnamic acid IV, 4-hydroxy-cinnamic acid V, 4-nitro-cinnamic acid VI; DMF=N, N-dimethylformamide, C3H7NO) were recorded from 8 K to room temperature. The energy levels of Eu(3+) in these 6 complexes are obtained from the spectra analysis. It is found that the energy levels of the central Eu(3+) ions are influenced by the nephelauxetic effect, while the triplet state of ligand is lowered by the p-π conjugation effect of the para-substituted functional groups. The best energy matching between the ligand triplet state and the central ion excited state is found in complex I. While the other complexes show poorer matching because the gap of (5)D0 and triplet state contracts.

  17. Serum iron, vitamin B12 and folic acid levels in Parkinson's disease.

    PubMed

    Madenci, Gulizar; Bilen, Sule; Arli, Berna; Saka, Mustafa; Ak, Fikri

    2012-07-01

    We aimed to investigate possible associations between systemic iron metabolism deficiency and Parkinson's disease, and also to research any possible correlations between stage of the disease and vitamin B12 and folic acid levels. 33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and 22 male and 20 female age- and sex-matched controls were enrolled in the study. Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and for the females, not being in the menopausal stage were considered as exclusion criteria. Recordings of blood samples of both groups collected after 8 h fasts were assessed in terms of serum iron, ferritin levels and iron-binding capacity, vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine the stage of the disease. No statistically significant difference was found with respect to mean serum iron, median serum ferritin levels and median serum iron-binding capacity between the groups. A statistically significant but inverse correlation was found between symptoms' duration and serum iron and ferritin levels. There was no statistically significant difference between the groups with respect to vitamin B12 and folic acid levels. However, a statistically significant but inverse correlation was determined between the patients' vitamin B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses, serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of these parameters may be the cause of the progression or may be the result of it.

  18. Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells

    PubMed Central

    Brigandi, Sarah A.; Shao, Hong; Qian, Steven Y.; Shen, Yiping; Wu, Bai-Lin; Kang, Jing X.

    2015-01-01

    Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism. PMID:25946342

  19. Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid Levels.

    PubMed

    Sá, Maria João Nabais; Rocha, Júlio C; Almeida, Manuela F; Carmona, Carla; Martins, Esmeralda; Miranda, Vasco; Coutinho, Miguel; Ferreira, Rita; Pacheco, Sara; Laranjeira, Francisco; Ribeiro, Isaura; Fortuna, Ana Maria; Lacerda, Lúcia

    2016-01-01

    Infantile Refsum disease (IRD) is one of the less severe of Zellweger spectrum disorders (ZSDs), a group of peroxisomal biogenesis disorders resulting from a generalized peroxisomal function impairment. Increased plasma levels of very long chain fatty acids (VLCFA) and phytanic acid are biomarkers used in IRD diagnosis. Furthermore, an increased plasma level of phytanic acid is known to be associated with neurologic damage. Treatment of IRD is symptomatic and multidisciplinary.The authors report a 3-year-old child, born from consanguineous parents, who presented with developmental delay, retinitis pigmentosa, sensorineural deafness and craniofacial dysmorphisms. While the relative level of plasma C26:0 was slightly increased, other VLCFA were normal. Thus, a detailed characterization of the phenotype was essential to point to a ZSD. Repeatedly increased levels of plasma VLCFA, along with phytanic acid and pristanic acid, deficient dihydroxyacetone phosphate acyltransferase activity in fibroblasts and identification of the homozygous pathogenic mutation c.2528G>A (p.Gly843Asp) in the PEX1 gene, confirmed this diagnosis. Nutritional advice and follow-up was proposed aiming phytanic acid dietary intake reduction. During dietary treatment, plasma levels of phytanic acid decreased to normal, and the patient's development evaluation showed slow progressive acquisition of new competences.This case report highlights the relevance of considering a ZSD in any child with developmental delay who manifests hearing and visual impairment and of performing a systematic biochemical investigation, when plasma VLCFA are mildly increased. During dietary intervention, a biochemical improvement was observed, and the long-term clinical effect of this approach needs to be evaluated.

  20. Fatty acid compositions of triglycerides and free fatty acids in sebum depend on amount of triglycerides, and do not differ in presence or absence of acne vulgaris.

    PubMed

    Akaza, Narifumi; Akamatsu, Hirohiko; Numata, Shigeki; Matsusue, Miyuki; Mashima, Yasuo; Miyawaki, Masaaki; Yamada, Shunji; Yagami, Akiko; Nakata, Satoru; Matsunaga, Kayoko

    2014-12-01

    To clarify the influence of the fatty acid composition of sebum in acne vulgaris, we investigated the amounts and fatty acid compositions of triglycerides (TG) and free fatty acids (FFA), and the amounts of cutaneous superficial Propionibacterium acnes in acne patients and healthy subjects. The foreheads of 18 female patients, 10 male patients, 10 healthy females and 10 healthy males were studied in a Japanese population. There were significant differences in the amounts of sebum, TG and cutaneous superficial P. acnes, as well as the fatty acid compositions of TG and FFA between acne patients and healthy subjects in females. Their fatty acid compositions were correlated with the amount of TG with or without acne. It was clarified that the fatty acid compositions of TG and FFA depended on the amount of TG, and there were no differences in the fatty acid composition in the presence and absence of acne.

  1. Evaluation of cooling strategies for pumping of milk - impact of fatty acid composition on free fatty acid levels.

    PubMed

    Wiking, Lars; Bertram, Hanne C; Björck, Lennart; Nielsen, Jacob H

    2005-11-01

    Cooling strategies for pumping of raw milk were evaluated. Milk was pumped for 450 s at 31 degrees C, or pumped after cooling to 4 degrees C and subsequently subjected to various incubation times. Two types of milk were used; i.e. milk from cows fed a diet high in saturated fat supplements resulting in significantly larger milk fat globules than the other type of milk which comes from cows fed a low-fat diet that stimulates high de novo fat synthesis. The content of liquid fat was determined by low-field 1H NMR, which showed that milk from cows given the saturated fat diet also contained less liquid fat at both 4 degrees and 31 degrees C than the other type of milk. This can be ascribed to the differences in the fatty acid composition of the milk as a result of the fatty acid composition of the diets. After pumping of the milk at 31 degrees C, measurement of fat globule size distribution revealed a significant coalescence of milk fat globules in the milk obtained from the saturated fat diet due to pumping. Pumping at 4 degrees C or pumping the other type of milk did not result in coalescence of milk fat globules. Formation of free fatty acids increased significantly in both types of milk by pumping at 31 degrees C. Cooling the milk to 4 degrees C immediately before pumping inhibited an increased content of free fatty acids. However, when the milk was incubated at 4 degrees C for 60 min after cooling and then subjected to pumping, a significant increase in the formation of free fatty acids was observed in both types of milk. It is suggested that this increase in free fatty acids is caused by transition of polymorphic crystal forms or higher level of attached lipoprotein lipases to the milk fat globule before pumping.

  2. Alterations in the levels of plasma amino acids in polycystic ovary syndrome- A pilot study

    PubMed Central

    Unni, C. Sumithra N.; Lakshman, Lakshmi R.; Vaidyanathan, Kannan; Subhakumari, K.N.; Menon, N. Leela

    2015-01-01

    Background & objectives: Plasma amino acid levels are known to be altered in conditions like sepsis and burns which are situations of metabolic stress. Polycystic ovary syndrome (PCOS), a condition which affects a woman throughout her life, is said to be associated with metabolic stress. This study was undertaken to assess if there were significant alterations in the levels of plasma amino acids in women with PCOS. Methods: Sixty five women with PCOS along with the similar number of age matched normal controls were included in this study. Levels of 14 amino acids were determined using reverse phase high performance liquid chromatography. Results: The levels of methionine, cystine, isoleucine, phenylalanine, valine, tyrosine, proline, glycine, lysine and histidine were found to be significantly (P<0.001) lower in cases than in controls. Arginine and alanine levels were found to be significantly (P<0.001) higher in cases compared with controls. Interpretation & conclusions: Our findings showed significant derangement in the levels of plasma amino acids in women with PCOS which might be due to the oxidative and metabolic stress associated with it. Further studies need to be done to confirm the findings. PMID:26658589

  3. The environmental light influences the circulatory levels of retinoic acid and associates with hepatic lipid metabolism.

    PubMed

    Pang, Wenqiang; Li, Chunying; Zhao, Yue; Wang, Shiming; Dong, Wei; Jiang, Pengjiu; Zhang, Jianfa

    2008-12-01

    Environmental light is involved in the regulation of photochemical reaction in mouse retina. It remains unclear whether light-mediated increase in all-trans retinoic acid (ATRA) synthesis in retina will result in altering the circulatory levels of ATRA and regulating downstream gene expression and physiological function. Here we showed circulatory levels of ATRA decreased in mice under constant darkness and elevated by light exposure. Fat gene pancreatic lipase-related protein 2 (mPlrp2) and its partner procolipase (mClps), but not hepatic lipase (mHl), activated in livers for responding to lack of light illuminating. Light-triggered alterations in circulatory ATRA levels regulated ecto-5'-nucleotidase gene expression by retinoic acid receptor retinoic acid receptor-alpha and modulated 5'-AMP levels in blood and were associated with mPlrp2 and mClps expression in the livers. Mice deficient in adenosine receptors displayed mPlrp2 and mClps expression in livers under 12-h light, 12-h dark cycles. Caffeine blocked adenosine receptors and induced hepatic mPlrp2 and mClps expression in wild-type mice. Mice activated in hepatic mPlrp2 and mClps expression lowered hepatic and serum lipid levels and markedly elevated circulatory levels of all-trans retinol. Our results suggest environmental light influence hepatic lipid homeostasis by light-modulated retinoic acid signaling associated with mPlrp2 and mClps gene expression in livers.

  4. Ferric sulphate catalysed esterification of free fatty acids in waste cooking oil.

    PubMed

    Gan, Suyin; Ng, Hoon Kiat; Ooi, Chun Weng; Motala, Nafisa Osman; Ismail, Mohd Anas Farhan

    2010-10-01

    In this work, the esterification of free fatty acids (FFA) in waste cooking oil catalysed by ferric sulphate was studied as a pre-treatment step for biodiesel production. The effects of reaction time, methanol to oil ratio, catalyst concentration and temperature on the conversion of FFA were investigated on a laboratory scale. The results showed that the conversion of FFA reached equilibrium after an hour, and was positively dependent on the methanol to oil molar ratio and temperature. An optimum catalyst concentration of 2 wt.% gave maximum FFA conversion of 59.2%. For catalyst loadings of 2 wt.% and below, this catalysed esterification was proposed to follow a pseudo-homogeneous pathway akin to mineral acid-catalysed esterification, driven by the H(+) ions produced through the hydrolysis of metal complex [Fe(H(2)O)(6)](3+) (aq).

  5. Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia.

    PubMed

    Shin, In-Sik; Lee, Mee-Young; Jung, Da-Young; Seo, Chang-Seob; Ha, Hye-Kyung; Shin, Hyeun-Kyoo

    2012-03-01

    Benign prostatic hyperplasia (BPH) is characterized by hyperplasia of prostatic stromal and epithelial cells, which can lead to lower urinary tract symptoms. The prevalence of BPH increases in an age-dependent manner. We investigated the protective effect of ursolic acid in BPH development using a testosterone-induced BPH rat model. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP), for a period of four weeks. Ursolic acid was administrated daily by oral gavage at a dose level of 5mg/kg during the four weeks of TP injections. Animals were sacrificed on the scheduled termination, before prostates were weighed and subjected to histopathological examination. TP and dihydrotestosterone (DHT) levels in the serum and prostate were also measured. BPH-induced animals displayed an increase in prostate weight with increased testosterone and DHT levels in both the serum and prostate. However, ursolic acid treatment resulted in significant reductions in prostate weight and testosterone and DHT levels in both the serum and prostate, compared with BPH-induced animals. Histopathological examination also showed that ursolic acid treatment suppressed TP-induced prostatic hyperplasia. These findings indicate that ursolic acid may effectively inhibit the development of BPH and it may be a useful agent in BPH treatment.

  6. Fatty acid status and its relationship to cognitive decline and homocysteine levels in the elderly.

    PubMed

    Baierle, Marília; Vencato, Patrícia H; Oldenburg, Luiza; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Duarte, Marta M M F; Veit, Juliana C; Somacal, Sabrina; Emanuelli, Tatiana; Grune, Tilman; Breusing, Nicolle; Garcia, Solange C

    2014-09-12

    Polyunsaturated fatty acids (PUFAs), especially the n-3 series, are known for their protective effects. Considering that cardiovascular diseases are risk factors for dementia, which is common at aging, the aim of this study was to evaluate whether fatty acid status in the elderly was associated with cognitive function and cardiovascular risk. Forty-five elderly persons (age ≥ 60 years) were included and divided into two groups based on their Mini-Mental Status Examination score adjusted for educational level: the case group (n = 12) and the control group (n = 33). Serum fatty acid composition, homocysteine (Hcy), hs-CRP, lipid profile and different cognitive domains were evaluated. The case group, characterized by reduced cognitive performance, showed higher levels of 14:0, 16:0, 16:1n-7 fatty acids and lower levels of 22:0, 24:1n-9, 22:6n-3 (DHA) and total PUFAs compared to the control group (p < 0.05). The n-6/n-3 ratio was elevated in both study groups, whereas alterations in Hcy, hs-CRP and lipid profile were observed in the case group. Cognitive function was positively associated with the 24:1n-9, DHA and total n-3 PUFAs, while 14:0, 16:0 and 16:1n-7 fatty acids, the n-6/n-3 ratio and Hcy were inversely associated. In addition, n-3 PUFAs, particularly DHA, were inversely associated with cardiovascular risk, assessed by Hcy levels in the elderly.

  7. Oil palm trunk and sugarcane bagasse derived solid acid catalysts for rapid esterification of fatty acids and moisture-assisted transesterification of oils under pseudo-infinite methanol.

    PubMed

    Ezebor, Francis; Khairuddean, Melati; Abdullah, Ahmad Zuhairi; Boey, Peng Lim

    2014-04-01

    The use of pseudo-infinite methanol in increasing the rate of esterification and transesterification reactions was studied using oil palm trunk (OPT) and sugarcane bagasse (SCB) derived solid acid catalysts. The catalysts were prepared by incomplete carbonisation at 400°C for 8h, followed by sulfonation at 150°C for 15h and characterised using TGA/DTA, XRD, FT-IR, SEM-EDS, EA and titrimetric determinations of acid sites. Under optimal reaction conditions, the process demonstrated rapid esterification of palmitic acid, with FAME yields of 93% and 94% in 45min for OPT and SCB catalysts, respectively. With the process, moisture levels up to 16.7% accelerated the conversion of low FFA oils by sulfonated carbon catalysts, through moisture-induced violent bumping. Moisture assisted transesterification of palm olein containing 1.78% FFA and 8.33% added water gave FAME yield of 90% in 10h, which was two folds over neat oil.

  8. Circulating irisin levels are associated with lipid and uric acid metabolism in a Chinese population.

    PubMed

    Tang, Shanshan; Zhang, Rong; Jiang, Feng; Wang, Jie; Chen, Miao; Peng, Danfeng; Yan, Jing; Wang, Shiyun; Bao, Yuqian; Hu, Cheng; Jia, Weiping

    2015-06-26

    Irisin is a novel hormone secreted by skeletal muscle after exercise, which may ameliorate insulin resistance. In this study, we aimed to explore the relationship between circulating irisin levels and type 2 diabetes (T2DM) as well as related metabolic traits in a Chinese population. A total of 203 subjects were recruited. Of these, 68 subjects with NGT, 63 subjects with IGR and 72 subjects with new-onset T2DM. Circulating irisin levels were measured by ELISA. Detailed clinical investigations and biochemistry measurements were carried out in all of the subjects. Multivariate linear regression analysis was performed to assess the association between irisin levels and related metabolic characteristics. All subjects were classified into normal weight and overweight/obese subgroups according to body mass index (BMI). No significant differences in circulating irisin levels were identified among the three groups (p=0.9741). After adjusting for covariates, multiple linear regression analysis revealed that serum irisin level was independently and significantly associated with total cholesterol (p=0.0005), low-density lipoprotein cholesterol (p=0.0014), fasting fatty acids (p=0.0402) and uric acid (p=0.0062). By dividing the serum irisin levels into three tertile group, the values of total cholesterol, low-density lipoprotein cholesterol, fasting fatty acids and uric acid were all increased significantly with the increase of irisin (p<0.05) . Moreover, serum irisin levels remain closely related to total cholesterol in both normal weight and overweight/obese subgroups. Our study suggests that circulating irisin concentrations are significantly associated with lipid and uric acid metabolism in a Chinese population. This article is protected by copyright. All rights reserved.

  9. Serum uric acid levels and long-term outcomes in chronic kidney disease.

    PubMed

    Miyaoka, Tokiko; Mochizuki, Toshio; Takei, Takashi; Tsuchiya, Ken; Nitta, Kosaku

    2014-07-01

    Hyperuricemia is common in chronic kidney disease (CKD), but data regarding the relationship between serum uric acid levels and the long-term outcomes of CKD patients have been limited. The present study evaluated the associations between baseline serum uric acid levels with mortality and end-stage renal disease (ESRD). The subjects of this study were 551 stage 2-4 CKD patients. Cox proportional hazards models were used to evaluate the relationship between serum uric acid tertiles and all-cause mortality, cardiovascular disease (CVD) mortality, 50 % reduction in estimated glomerular filtration rate (eGFR), and development of ESRD, initially without adjustment, and then after adjusting for several groups of covariates. The mean age of the study subjects was 58.5 years, 59.3 % were men, and 10.0 % had diabetes. The mean eGFR was 42.02 ± 18.52 ml/min/1.73 m(2). In all subjects, the mean serum uric acid level was 6.57 ± 1.35 mg/dl, and 52.2 % of study subjects were on hypouricemic therapy (allopurinol; 48.3 %) at baseline. Thirty-one patients (6.1 %) died during a follow-up period of approximately 6 years. There was no significant association between serum uric acid level and all-cause mortality, CVD mortality, development of ESRD and 50 % reduction in eGFR in the unadjusted Cox models. In the adjusted models, hyperuricemia was found to be associated with all-cause mortality and CVD mortality after adjustment with CVD risk factors, kidney disease factors, and allopurinol, but not associated with development of ESRD and 50 % reduction in eGFR. The results of this study showed that hyperuricemia but not serum uric acid levels were associated with all-cause mortality, CVD mortality after adjustments with CVD risk factors, kidney disease factors, and allopurinol in stage 2-4 CKD patients.

  10. Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function

    PubMed Central

    2012-01-01

    Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms. PMID:22360800

  11. Establishing tolerable dungeness crab (Cancer magister) and razor clam (Siliqua patula) domoic acid contaminant levels.

    PubMed

    Mariën, K

    1996-11-01

    Domoic acid has been found in razor clams (Siliqua patula) and dungeness crabs (Cancer magister) in Washington State and elsewhere on the West Coast of the United States. Due to toxic effects associated with domoic acid exposure, an effort has been made to establish tolerable domoic acid levels in crabs and clams obtained from commercial harvest and sale and from individual recreational harvesting. To accomplish this, the amount of clams and crabs consumed by populations of concern was determined, a tolerable daily intake (TDI) was developed for individuals most sensitive to effects of this compound, and the TDI was equated with consumption patterns to determine tolerable clam and crab domoic acid levels. Results indicate that the primary health effects associated with domoic acid toxicity can be averted in populations of concern and for others consuming crabs or clams less frequently (or in lesser quantity) if domoic acid contaminant concentration does not exceed 30 mg/kg in the hepatopancreas and viscera of dungeness crabs or 20 mg/kg in clams.

  12. Pyruvic acid levels in serum and saliva: A new course for oral cancer screening?

    PubMed Central

    Bhat, Manohara A; Prasad, KVV; Trivedi, Dheeraj; Rajeev, BR; Battur, Hemanth

    2016-01-01

    Objective: Cancerous cells show increased glycolysis rate. This will increase overall levels of pyruvate as it is one of the end products of glycolysis. The present on-going study is to estimate the levels of pyruvate in saliva and serum among healthy and oral cancer subjects. Settings and Design: Hospital-based cross-sectional comparative study. Methodology: A total of 50 subjects among healthy and oral cancer subjects were selected based on clinical and histological criteria. Saliva and serum samples were collected and subjected to pyruvate level estimation using biochemical analysis. Statistical Analysis: Descriptive analysis and Mann-Whitney test were used to find the statistical difference between the two independent groups. Results: Serum pyruvic acid levels of the healthy group were 1.09 ± 0.14 and for oral cancer, it was 2.95 ± 0.59 and salivary level were 3.49 ± 0.47 and 1.32 ± 0.10 respectively. Mann-Whitney test showed statistically significant difference in serum and salivary pyruvate level in between two groups (P < 0.000 respectively). Conclusion: The present study showed noticeable variation in the level of pyruvic acid among healthy and oral cancer subjects. This generates the hypothesis that estimation of the pyruvic acid can be a new tool to screening of the cancer. PMID:27194870

  13. Effect of folic acid and zinc sulphate on endocrine parameters and seminal antioxidant level after varicocelectomy.

    PubMed

    Nematollahi-Mahani, S N; Azizollahi, G H; Baneshi, M R; Safari, Z; Azizollahi, S

    2014-04-01

    Varicocele is among the most common problems which may lead to male infertility. Spermatogenesis is impaired as a consequence of this vascular defect, through mechanisms that are not well described. This study aimed to evaluate serum hormonal level (inhibin B, FSH and testosterone) and seminal plasma antioxidant defence levels after folic acid and zinc sulphate administration in varicocelectomised patients. Participants were randomly allocated to four experimental groups. Our randomisation schedule was as follows: zinc sulphate/folic acid, folic acid, zinc sulphate and placebo. The patients underwent varicocelectomy, before which a blood and semen sample were obtained and also three and six months after varicocelectomy for evaluation of blood hormonal level (FSH, testosterone, inhibin B) and seminal oxidative stress status (nitric oxide, superoxide dismutase, total antioxidant capacity). Patients in different groups took orally one capsule per day after dinner following varicocelectomy for 6 months. A significant rise in peripheral blood inhibin B and seminal plasma activity was detected in the zinc sulphate/folic acid group after 6 months. The present clinical trial indicates a change in the hormonal status of varicocelectomised patients following long-term administration of zinc sulphate and folic acid.

  14. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

  15. Stable Isotope Composition of Fatty Acids in Organisms of Different Trophic Levels in the Yenisei River

    PubMed Central

    Gladyshev, Michail I.; Sushchik, Nadezhda N.; Kalachova, Galina S.; Makhutova, Olesia N.

    2012-01-01

    We studied four-link food chain, periphytic microalgae and water moss (producers), trichopteran larvae (consumers I), gammarids (omnivorous – consumers II) and Siberian grayling (consumers III) at a littoral site of the Yenisei River on the basis of three years monthly sampling. Analysis of bulk carbon stable isotopes and compound specific isotope analysis of fatty acids (FA) were done. As found, there was a gradual depletion in 13C contents of fatty acids, including essential FA upward the food chain. In all the trophic levels a parabolic dependence of δ13C values of fatty acids on their degree of unsaturation/chain length occurred, with 18:2n-6 and 18:3n-3 in its lowest point. The pattern in the δ13C differences between individual fatty acids was quite similar to that reported in literature for marine pelagic food webs. Hypotheses on isotope fractionation were suggested to explain the findings. PMID:22470513

  16. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

    PubMed Central

    Munger, Joshua; Bennett, Bryson D; Parikh, Anuraag; Feng, Xiao-Jiang; McArdle, Jessica; Rabitz, Herschel A; Shenk, Thomas; Rabinowitz, Joshua D

    2010-01-01

    Viruses rely on the metabolic network of their cellular hosts to provide energy and building blocks for viral replication. We developed a flux measurement approach based on liquid chromatography–tandem mass spectrometry to quantify changes in metabolic activity induced by human cytomegalovirus (HCMV). This approach reliably elucidated fluxes in cultured mammalian cells by monitoring metabolome labeling kinetics after feeding cells 13C-labeled forms of glucose and glutamine. Infection with HCMV markedly upregulated flux through much of the central carbon metabolism, including glycolysis. Particularly notable increases occurred in flux through the tricarboxylic acid cycle and its efflux to the fatty acid biosynthesis pathway. Pharmacological inhibition of fatty acid biosynthesis suppressed the replication of both HCMV and influenza A, another enveloped virus. These results show that fatty acid synthesis is essential for the replication of two divergent enveloped viruses and that systems-level metabolic flux profiling can identify metabolic targets for antiviral therapy. PMID:18820684

  17. Fatty acids in berry lipids of six sea buckthorn (Hippophae rhamnoides L., subspecies carpatica) cultivars grown in Romania

    PubMed Central

    2012-01-01

    Background A systematic mapping of the phytochemical composition of different sea buckthorn (Hippophae rhamnoides L.) fruit subspecies is still lacking. No data relating to the fatty acid composition of main lipid fractions from the berries of ssp. carpatica (Romania) have been previously reported. Results The fatty acid composition of the total lipids (oils) and the major lipid fractions (PL, polar lipids; FFA, free fatty acids; TAG, triacylglycerols and SE, sterol esters) of the oils extracted from different parts of six sea buckthorn berry subspecies (ssp. carpatica) cultivated in Romania were investigated using the gas chromatography-mass spectrometry (GC-MS). The dominating fatty acids in pulp/peel and whole berry oils were palmitic (23-40%), oleic (20-53%) and palmitoleic (11-27%). In contrast to the pulp oils, seed oils had higher amount of polyunsaturated fatty acids (PUFAs) (65-72%). The fatty acid compositions of TAGs were very close to the compositions of corresponding seed and pulp oils. The major fatty acids in PLs of berry pulp/peel oils were oleic (20-40%), palmitic (17-27%), palmitoleic (10-22%) and linoleic (10%-20%) acids, whereas in seeds PLs, PUFAs prevailed. Comparing with the other lipid fractions the SEs had the highest contents of saturated fatty acids (SFAs). The fatty acid profiles of the FFA fractions were relatively similar to those of TAGs. Conclusions All parts of the analyzed sea buckthorn berry cultivars (ssp. carpatica) exhibited higher oil content then the other European or Asiatic sea buckthorn subspecies. Moreover, the pulp/peel oils of ssp. carpatica were found to contain high levels of oleic acid and slightly lower amounts of linoleic and α-linolenic acids. The studied cultivars of sea buckthorn from Romania have proven to be potential sources of valuable oils. PMID:22995716

  18. [Ecogenetic aspects of the study of phenotypes and levels of beta-aminoisobutyric acid excretion].

    PubMed

    Spitsyn, V A; Afanas'eva, I S; Alekseeva, N V

    1993-11-01

    The levels of excretion of beta-aminoisobutyric acid (BAIB) in urea were examined in five groups. The distribution of BAIB concentration revealed the existence of high and low excretors in each group. Asbestosis patients had the lowest frequency of high excretors. The BAIB concentration among high excretors was similar for all the groups. The BAIB levels of low excretors varied. The most alike were two children groups, asbestosis patients and the workers from the town Asbest.

  19. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins

    PubMed Central

    Hannukainen, Jarna C; Nuutila, Pirjo; Ronald, Borra; Kaprio, Jaakko; Kujala, Urho M; Janatuinen, Tuula; Heinonen, Olli J; Kapanen, Jukka; Viljanen, Tapio; Haaparanta, Merja; Rönnemaa, Tapani; Parkkola, Riitta; Knuuti, Juhani; Kalliokoski, Kari K

    2007-01-01

    Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 ± 10% higher V˙O2,max (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 ± 4.3 versus 9.0 ± 6.1 μmol (100 ml)−1 min−1, P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

  20. Temporal variability in urinary levels of drinking water disinfection byproducts dichloroacetic acid and trichloroacetic acid among men

    SciTech Connect

    Wang, Yi-Xin; Zeng, Qiang; Wang, Le; Huang, Yue-Hui; Lu, Zhi-Wei; Wang, Peng; He, Meng-Jie; Huang, Xin; Lu, Wen-Qing

    2014-11-15

    Urinary haloacetic acids (HAAs), such as dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), have been suggested as potential biomarkers of exposure to drinking water disinfection byproducts (DBPs). However, variable exposure to and the short elimination half-lives of these biomarkers can result in considerable variability in urinary measurements, leading to exposure misclassification. Here we examined the variability of DCAA and TCAA levels in the urine among eleven men who provided urine samples on 8 days over 3 months. The urinary concentrations of DCAA and TCAA were measured by gas chromatography coupled with electron capture detection. We calculated the intraclass correlation coefficients (ICCs) to characterize the within-person and between-person variances and computed the sensitivity and specificity to assess how well single or multiple urine collections accurately determined personal 3-month average DCAA and TCAA levels. The within-person variance was much higher than the between-person variance for all three sample types (spot, first morning, and 24-h urine samples) for DCAA (ICC=0.08–0.37) and TCAA (ICC=0.09–0.23), regardless of the sampling interval. A single-spot urinary sample predicted high (top 33%) 3-month average DCAA and TCAA levels with high specificity (0.79 and 0.78, respectively) but relatively low sensitivity (0.47 and 0.50, respectively). Collecting two or three urine samples from each participant improved the classification. The poor reproducibility of the measured urinary DCAA and TCAA concentrations indicate that a single measurement may not accurately reflect individual long-term exposure. Collection of multiple urine samples from one person is an option for reducing exposure classification errors in studies exploring the effects of DBP exposure on reproductive health. - Highlights: • We evaluated the variability of DCAA and TCAA levels in the urine among men. • Urinary DCAA and TCAA levels varied greatly over a 3-month

  1. Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival

    PubMed Central

    Villa, Stephanie R.; Priyadarshini, Medha; Fuller, Miles H.; Bhardwaj, Tanya; Brodsky, Michael R.; Angueira, Anthony R.; Mosser, Rockann E.; Carboneau, Bethany A.; Tersey, Sarah A.; Mancebo, Helena; Gilchrist, Annette; Mirmira, Raghavendra G.; Gannon, Maureen; Layden, Brian T.

    2016-01-01

    The regulation of pancreatic β cell mass is a critical factor to help maintain normoglycemia during insulin resistance. Nutrient-sensing G protein-coupled receptors (GPCR) contribute to aspects of β cell function, including regulation of β cell mass. Nutrients such as free fatty acids (FFAs) contribute to precise regulation of β cell mass by signaling through cognate GPCRs, and considerable evidence suggests that circulating FFAs promote β cell expansion by direct and indirect mechanisms. Free Fatty Acid Receptor 2 (FFA2) is a β cell-expressed GPCR that is activated by short chain fatty acids, particularly acetate. Recent studies of FFA2 suggest that it may act as a regulator of β cell function. Here, we set out to explore what role FFA2 may play in regulation of β cell mass. Interestingly, Ffar2−/− mice exhibit diminished β cell mass at birth and throughout adulthood, and increased β cell death at adolescent time points, suggesting a role for FFA2 in establishment and maintenance of β cell mass. Additionally, activation of FFA2 with Gαq/11-biased agonists substantially increased β cell proliferation in in vitro and ex vivo proliferation assays. Collectively, these data suggest that FFA2 may be a novel therapeutic target to stimulate β cell growth and proliferation. PMID:27324831

  2. The TOC159 mutant of Arabidopsis thaliana accumulates altered levels of saturated and polyunsaturated fatty acids.

    PubMed

    Afitlhile, Meshack; Fry, Morgan; Workman, Samantha

    2015-02-01

    We evaluated whether the TOC159 mutant of Arabidopsis called plastid protein import 2-2 (ppi2-2) accumulates normal levels of fatty acids, and transcripts of fatty acid desaturases and galactolipid synthesis enzymes. The ppi2-2 mutant accumulates decreased pigments and total fatty acid content. The MGD1 gene was downregulated and the mutant accumulates decreased levels of monogalactosyldiacylglycerol (MGDG) and 16:3, which suggests that the prokaryotic pathway was impaired in the mutant. The HY5 gene, which encodes long hypocotyl5 transcription factor, was upregulated in the mutant. The DGD1 gene, an HY5 target was marginally increased and the mutant accumulates digalactosyldiacylglycerol at the control level. The mutant had increased expression of 3-ketoacyl-ACP synthase II gene, which encodes a plastid enzyme that elongates 16:0 to 18:0. Interestingly, glycerolipids in the mutant accumulate increased levels of 18:0. A gene that encodes stearoyl-ACP desaturase (SAD) was expressed at the control level and 18:1 was increased, which suggest that SAD may be strongly regulated at the posttranscriptional level. The molar ratio of MGDG to bilayer forming plastid lipids was decreased in the cold-acclimated wild type but not in the ppi2-2 mutant. This indicates that the mutant was unresponsive to cold-stress, and is consistent with increased levels of 18:0, and decreased 16:3 and 18:3 in the ppi2-2 mutant. Overall, these data indicate that a defective Toc159 receptor impaired the synthesis of MGDG, and affected desaturation of 16 and 18-carbon fatty acids. We conclude that expression of the MGD1 gene and synthesis of MGDG are tightly linked to plastid biogenesis.

  3. Residual mitochondrial transmembrane potential decreases unsaturated fatty acid level in sake yeast during alcoholic fermentation.

    PubMed

    Sawada, Kazutaka; Kitagaki, Hiroshi

    2016-01-01

    Oxygen, a key nutrient in alcoholic fermentation, is rapidly depleted during this process. Several pathways of oxygen utilization have been reported in the yeast Saccharomyces cerevisiae during alcoholic fermentation, namely synthesis of unsaturated fatty acid, sterols and heme, and the mitochondrial electron transport chain. However, the interaction between these pathways has not been investigated. In this study, we showed that the major proportion of unsaturated fatty acids of ester-linked lipids in sake fermentation mash is derived from the sake yeast rather than from rice or koji (rice fermented with Aspergillus). Additionally, during alcoholic fermentation, inhibition of the residual mitochondrial activity of sake yeast increases the levels of unsaturated fatty acids of ester-linked lipids. These findings indicate that the residual activity of the mitochondrial electron transport chain reduces molecular oxygen levels and decreases the synthesis of unsaturated fatty acids, thereby increasing the synthesis of estery flavors by sake yeast. This is the first report of a novel link between residual mitochondrial transmembrane potential and the synthesis of unsaturated fatty acids by the brewery yeast during alcoholic fermentation.

  4. Life-history evolution at the molecular level: adaptive amino acid composition of avian vitellogenins

    PubMed Central

    Hughes, Austin L.

    2015-01-01

    Avian genomes typically encode three distinct vitellogenin (VTG) egg yolk proteins (VTG1, VTG2 and VTG3), which arose by gene duplication prior to the most recent common ancestor of birds. Analysis of VTG sequences from 34 avian species in a phylogenetic framework supported the hypothesis that VTG amino acid composition has co-evolved with embryo incubation time. Embryo incubation time was positively correlated with the proportions of dietary essential amino acids (EAAs) in VTG1 and VTG2, and with the proportion of sulfur-containing amino acids in VTG3. These patterns were seen even when only semi-altricial and/or altricial species were considered, suggesting that the duration of embryo incubation is a major selective factor on the amino acid composition of VTGs, rather than developmental mode alone. The results are consistent with the hypothesis that the level of EAAs provided to the egg represents an adaptation to the loss of amino acids through breakdown over the course of incubation and imply that life-history phenotypes and VTG amino acid composition have co-evolved throughout the evolutionary history of birds. PMID:26224713

  5. Effect of excitatory amino acids on serum TSH and thyroid hormone levels in freely moving rats.

    PubMed

    Alfonso, M; Durán, R; Arufe, M C

    2000-01-01

    The actions of glutamate (L-Glu), and glutamate receptor agonists on serum thyroid hormones (T4 and T3) and TSH levels have been studied in conscious and freely moving adult male rats. The excitatory amino acids (EAA), L-Glu, N-methyl-D-aspartate (NMDA), kainic acid (KA) and domoic acid (Dom) were administered intraperitoneally. Blood samples were collected through a cannula implanted in the rats jugular 0--60 min after injection. Thyroid hormone concentrations were measured by enzyme immunoassay, and thyrotrophin (TSH) concentrations were determined by radioimmunoassay. The results showed that L-Glu (20 and 25 mg/kg) and NMDA (25 mg/kg) increased serum thyroxine (T4), triiodothyronine (T3) and TSH concentrations. Serum thyroid hormone levels increased 30 min after treatment, while serum TSH levels increased 5 min after i.p. administration, in both cases serum levels remained elevated during one hour. Injection of the non-NMDA glutamatergic agonists KA (30 mg/kg) and Dom (1 mg/kg) produced an increase in serum thyroid hormones and TSH levels. These results suggest the importance of EAAs in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the importance of the NMDA and non-NMDA receptors in this stimulatory effect.

  6. Vanilmandelic acid and homovanillic acid levels in patients with neural crest tumor: 24-hour urine collection versus random sample.

    PubMed

    Gregianin, L J; McGill, A C; Pinheiro, C M; Brunetto, A L

    1997-01-01

    Neuroblastoma is the most common solid tumor in childhood and is the most frequent neural crest tumor (NCT). More than 90% of the patients excrete high levels of vanilmandelic acid (VMA) and homovanillic acid (HVA) in the urine. Original biochemical methods for measuring these two metabolites of catecholamines employed a collection of urine for 24 hours to avoid errors related to circadian cycle variations. More recently, attempts have been made to replace the 24-hour collections by random samples (RSs). This has practical advantages particularly for young children. The objective of this study is to assess whether urinary VMA related to urinary creatinine levels can be determined reliably by the method of Pisano et al. from RSs in patients with NCT. The determination of the consumption of VMA in urine stored for prolonged periods of time was also studied. We found a good correlation between the values of metabolites of catecholamines in RSs compared with 24-hour urine collections. There was consumption of VMA in urine samples after storage. We conclude that determination of VMA in RSs of urine by Pisano's method may identify NCT production of catecholamines and that the consumption of these catecholamines is an important factor to consider in the interpretation of values obtained with stored urine specimens.

  7. Effect of acidity on the energy level of curcumin dye extracted from Curcuma longa L.

    NASA Astrophysics Data System (ADS)

    Agustia, Yuda Virgantara; Suyitno, Arifin, Zainal; Sutanto, Bayu

    2016-03-01

    The purpose of this research is to investigate the effect of acidity on the energy level of curcumin dye. The natural dye, curcumin, was synthesized from Curcuma longa L. using a simple extraction technique. The purification of curcumin dye was conducted in a column of chromatography and its characteristics were studied. Next, the purified curcumin dye was added by benzoic acids until various acidities of 3.0, 3.5, 4.0, 4.5, and 5.0. The absorbance spectra and the functionality groups found in the dyes were detected by ultraviolet-visible spectroscopy and Fourier-transform infrared spectroscopy, respectively. Meanwhile, the energy level of the dyes, EHOMO and ELUMO was measured by cyclic voltammetry. The best energy level of curcumin dye was achieved at pH 3.5 where Ered = -0.37V, ELUMO = -4.28 eV, Eox = 1.15V, EHOMO = -5.83 eV, and Eband gap = 1.55 eV. Therefore, the purified curcumin dye added by benzoic acid was promising for sensitizing the dye-sensitized solar cells.

  8. Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients.

    PubMed

    Reátegui-Sokolova, C; Ugarte-Gil, Manuel F; Gamboa-Cárdenas, Rocío V; Zevallos, Francisco; Cucho-Venegas, Jorge M; Alfaro-Lozano, José L; Medina, Mariela; Rodriguez-Bellido, Zoila; Pastor-Asurza, Cesar A; Alarcón, Graciela S; Perich-Campos, Risto A

    2017-04-01

    This study aims to determine whether uric acid levels contribute to new renal damage in systemic lupus erythematosus (SLE) patients. This prospective study was conducted in consecutive patients seen since 2012. Patients had a baseline visit and follow-up visits every 6 months. Patients with ≥2 visits were included; those with end-stage renal disease (regardless of dialysis or transplantation) were excluded. Renal damage was ascertained using the SLICC/ACR damage index (SDI). Univariable and multivariable Cox-regression models were performed to determine the risk of new renal damage. Uric acid was included as a continuous and dichotomous (per receiving operating characteristic curve) variable. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, serum creatinine, baseline use of prednisone, antimalarials, and immunosuppressive drugs. One hundred and eighty-six patients were evaluated; their mean (SD) age at diagnosis was 36.8 (13.7) years; nearly all patients were mestizo. Disease duration was 7.7 (6.8) years. Follow-up time was 2.3 (1.1) years. The SLEDAI was 5.2 (4.3) and the SDI 0.8 (1.1). Uric acid levels were 4.5 (1.3) mg/dl. During follow-up, 16 (8.6%) patients developed at least one new point in the renal domain of the SDI. In multivariable analyses, uric acid levels (continuous and dichotomous) at baseline predicted the development of new renal damage (HR 3.21 (1.39-7.42), p 0.006; HR 18.28 (2.80-119.48), p 0.002; respectively). Higher uric acid levels contribute to the development of new renal damage in SLE patients independent of other well-known risk factors for such occurrence.

  9. Correlation between maternal and childhood VitB12, folic acid and ferritin levels

    PubMed Central

    Zeeshan, Fatima; Bari, Attia; Farhan, Saima; Jabeen, Uzma; Rathore, Ahsan Waheed

    2017-01-01

    Objective: To determine the correlation between serum folic acid, vitamin B12 and ferritin of mother and child and to study various neonatal risk factors as a cause of anemia in children. Methods: One hundred eighty children two months to two years of age admitted in the department of Pediatric Medicine of The Children’s Hospital and The Institute of Child Health Lahore from January 2013 to January 2015 with common medical conditions having anemia were included. Complete blood count (CBC), serum ferritin level, folic acid and Vitamin (Vit) B12 level were sent of children and their mothers. Data was analyzed using SPSS version 20. Results: Out of 180 children with anemia, 66.7% were males. Mean age of children was 7.3months. Fifty-five percent children were malnourished according to z scoring. The mean Hemoglobin (Hb) of children was 8 g/dl. Only 4% children had low ferritin level while 60% had low folic acid and 45% had decreased VitB12. There was significant correlation between Hb of mother and child (p =0.02), Vit B12 deficiency (p=0.008) and iron deficiency (p<0.001). Premature children had lower folic acid levels (p =0.02), while prematurity, IUGR, previous admission and history of sepsis showed no association with anemia in our study. Both breast-feeding and top feeding showed significant association with anemia with p-value of 0.042 and 0.003 respectively while dilution showed no impact on anemia. Conclusion: Maternal anemia has a significant impact on child’s hemoglobin. As compared to previous concept of increased iron deficiency in children we found increased occurrence of folic acid and VitB12 deficiency in children and their mothers. PMID:28367192

  10. The effects of different thermal treatments and organic acid levels on nutrient digestibility in broilers.

    PubMed

    Goodarzi Boroojeni, F; Mader, A; Knorr, F; Ruhnke, I; Röhe, I; Hafeez, A; Männer, K; Zentek, J

    2014-05-01

    Poultry feed is a potential vector for pathogens. Heat processing and organic acid treatments may decontaminate feed and can affect bird performance as well as feed digestibility. The present study was performed to investigate the effect of different thermal treatments including pelleting (P), long-term conditioning at 85°C for 3 min (L), or expanding at 110°C (E110) and 130°C for 3 to 5 s (E130) without or with 0.75 and 1.5% organic acid supplementation (63.75% formic acid, 25.00% propionic acid, and 11.25% water) on performance, nutrient digestibility, and organ weights of broilers. In total, 960 one-day-old broiler chicks were randomly assigned to 8 replicates using a 3 × 4 factorial arrangement. Performance variables were determined, and the relative organ weights and ileal and total amino acid (AA) digestibilities were measured at d 35. The organic acid inclusion linearly improved feed efficiency in the first week (P ≤ 0.05). The acid inclusion levels and thermal treatments had no significant effect on the performance variables at later intervals of the growing period of the birds. The L group showed the lowest ileal AA and CP digestibility. The inclusion of organic acids had a quadratic effect on total and ileal digestibility of isoleucine (P ≤ 0.05), whereas it had no significant effect on the ileal digestibility of other AA and nutrients. The relative weights of the jejunum and small intestine were significantly higher in the E130 group compared with P and L (P ≤ 0.05). In conclusion, our study demonstrated that long-term heat conditioning can decrease ileal nutrient digestibility, whereas pelleting and expansion, independently of organic acid addition, seemed to have no negative impact on broiler performance and nutrient digestibilities. Moreover, adding a blend of organic acids to broiler diets had neither positive nor negative effects on nutrient digestibility and final broiler performance. This indicates the feasibility of short-term thermal

  11. Fatty acid and prostaglandin metabolism in children with diabetes mellitus. II. The effect of evening primrose oil supplementation on serum fatty acid and plasma prostaglandin levels.

    PubMed

    Arisaka, M; Arisaka, O; Yamashiro, Y

    1991-07-01

    Our previous study demonstrated that levels of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid in serum total lipids decreased in association with increased plasma levels of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) in patients with insulin-dependent diabetes mellitus. In this study, 11 children with insulin-dependent diabetes mellitus completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid (GLA) on serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. GLA was given as the seed oil from the evening primrose (EPO) and all patients received either EPO capsules (containing 45 mg of GLA and 360 mg of linoleic acid) or indistinguishable placebo capsules for 8 months. Initially patients took 2 capsules daily for 4 months then 4 capsules daily for a further 4 months. All patients were assessed at the start of the study, after 4 months and at the end of the study, by measuring serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. After administration of 4 capsules daily the DGLA levels increased and PGE2 levels decreased significantly (p less than 0.01) in the EPO compared with the placebo group. Neither fatty acid nor PGE2 and PGF2 alpha levels were altered by administration of 2 EPO capsules daily. This suggests that the altered essential fatty acid and PG metabolism in diabetes may be reversed by direct GLA supplementation.

  12. The effects of dietary omega fatty acids on pregnancy rate, plasma prostaglandin metabolite levels, serum progesterone levels, and milk fatty-acid profile in beef cows.

    PubMed

    Richardson, Gavin F; McNiven, Mary A; Petit, Hélène V; Duynisveld, John L

    2013-10-01

    The objectives were to determine the effects of feeding supplements rich in omega-6 or omega-3 fatty acids (FA) during the late gestation to the early postpartum and breeding periods on reproduction and milk FA profile in beef cows. For each of two years, at the beginning of period 1 (mid-December), 72 beef cows, calving in January or February, were assigned to diets supplemented with roasted flaxseed (Flax) or roasted soybean (Soybean). For each of two years, after 11 wk (end of period 1), 18 cows of 36 in the Flax group were switched to the soybean supplement and 18 cows of 36 in the Soybean group were switched to the flax supplement (start of Period 2). Cows were bred by timed artificial insemination (TAI) in week 5 of period 2. The FA composition of the milk reflected the FA profile of the oilseed supplements. There were no differences in pregnancy rates among the 4 groups. The treatments had no effect on plasma prostaglandin metabolite levels or ratios at 4 to 11 d postpartum. At 5 to 6 d post- TAI, pregnant cows fed Flax in period 1 had lower (P < 0.05) plasma prostaglandin F metabolite (PGFM) levels and PGFM to prostaglandin E metabolite (PGEM) ratio than cows fed Soybean, but there were no significant differences at 19 to 20 d post-TAI. Cows pregnant from TAI and fed Flax in period 2 had higher (P < 0.05) serum progesterone levels at 5 to 6 d post-TAI than cows fed Soybean, but there was no difference at 19 to 20 d post-TAI. The dietary treatments had no effect on pregnancy rates, but there were some effects on plasma PGFM levels, PGFM to PGEM ratios, and serum progesterone levels. The FA supplements influenced the FA composition of milk.

  13. Flufenamic acid as an ion channel modulator

    PubMed Central

    Guinamard, Romain; Simard, Christophe; Negro, Christopher Del

    2014-01-01

    Flufenamic acid has been known since the 1960s to have anti-inflammatory properties attributable to the reduction of prostaglandin synthesis. Thirty years later, flufenamic acid appeared to be an ion channel modulator. Thus, while its use in medicine diminished, its use in ionic channel research expanded. Flufenamic acid commonly affects non-selective cation channels and chloride channels, but also modulates potassium, calcium and sodium channels with effective concentrations ranging from 10-6 M in TRPM4 channel inhibition to 10-3 M in two-pore outwardly rectifying potassium channel activation. Because flufenamic acid effects develop and reverse rapidly, it is a convenient and widely used tool. However, given the broad spectrum of its targets, experimental results have to be interpreted cautiously. Here we provide an overview of ion channels targeted by flufenamic acid to aid in interpreting its effects at the molecular, cellular, and systems levels. If it is used with good practices, flufenamic acid remains a useful tool for ion channel research. Understanding the targets of FFA may help reevaluate its physiological impacts and revive interest in its therapeutic potential. PMID:23356979

  14. Determination of ether extract digestibility and energy content of specialty lipids with variable FA and FFA content, and the effect of lecithin, for nursery pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Various specialty lipids are commercially available and used in nursery pig diets, but may have FA profiles and FFA content that affect their caloric value. In each of 2 experiments, 54 barrows (28-d of age) were fed a common diet for 7-d, allotted to dietary treatments and fed their respective expe...

  15. Perceptions of North Carolina High School Agricultural Educators regarding Students with Special Needs Participating in Supervised Agricultural Experience and FFA Activities

    ERIC Educational Resources Information Center

    Johnson, Lendy; Wilson, Elizabeth; Flowers, Jim; Croom, Barry

    2012-01-01

    The purpose of this study was to examine the perceptions of North Carolina high school agricultural educators toward including students with special needs when implementing Supervised Agricultural Experience and participating in FFA activities. The population was all high school agricultural educators in North Carolina with 12 month employment (N…

  16. An Internal Evaluation of the National FFA Agricultural Mechanics Career Development Event through Analysis of Individual and Team Scores from 1996-2006

    ERIC Educational Resources Information Center

    Franklin, Edward A.; Armbruster, James

    2012-01-01

    The purpose of this study was to conduct an internal evaluation of the National FFA Agricultural Mechanics Career Development Event (CDE) through analysis of individual and team scores from 1996-2006. Data were analyzed by overall and sub-event areas scores for individual contestants and team event. To facilitate the analysis process scores were…

  17. Genome-Wide Analysis of Branched-Chain Amino Acid Levels in Arabidopsis Seeds[W

    PubMed Central

    Angelovici, Ruthie; Lipka, Alexander E.; Deason, Nicholas; Gonzalez-Jorge, Sabrina; Lin, Haining; Cepela, Jason; Buell, Robin; Gore, Michael A.; DellaPenna, Dean

    2013-01-01

    Branched-chain amino acids (BCAAs) are three of the nine essential amino acids in human and animal diets and are important for numerous processes in development and growth. However, seed BCAA levels in major crops are insufficient to meet dietary requirements, making genetic improvement for increased and balanced seed BCAAs an important nutritional target. Addressing this issue requires a better understanding of the genetics underlying seed BCAA content and composition. Here, a genome-wide association study and haplotype analysis for seed BCAA traits in Arabidopsis thaliana revealed a strong association with a chromosomal interval containing two BRANCHED-CHAIN AMINO ACID TRANSFERASES, BCAT1 and BCAT2. Linkage analysis, reverse genetic approaches, and molecular complementation analysis demonstrated that allelic variation at BCAT2 is responsible for the natural variation of seed BCAAs in this interval. Complementation analysis of a bcat2 null mutant with two significantly different alleles from accessions Bayreuth-0 and Shahdara is consistent with BCAT2 contributing to natural variation in BCAA levels, glutamate recycling, and free amino acid homeostasis in seeds in an allele-dependent manner. The seed-specific phenotype of bcat2 null alleles, its strong transcription induction during late seed development, and its subcellular localization to the mitochondria are consistent with a unique, catabolic role for BCAT2 in BCAA metabolism in seeds. PMID:24368787

  18. [Pantothenic acid levels in blood of athletes at rest and after aerobic exercise].

    PubMed

    Rokitzki, L; Sagredos, A; Reuss, F; Petersen, G; Keul, J

    1993-12-01

    Ninety-six high-performance athletes of various disciplines were available for this investigation. All athletes had many years of training and competition experience. The pantothenic acid contents in the blood were determined by means of microbiological measurements. In addition to the pantothenic acid level at rest, measurements were made resp. physical exertion in 14 marathon runners and nine body builders. Blood was collected for determination of pantothenic acid before (a), after (b) and 2 h after exercise. Compared to the reference values for untrained persons (1.34 +/- 0.13 nmol/mL), the marathon runners with 0.76 (0.31-0.94) nmol/mL and soccer players with 1.19 (0.37-2.64) nmol/mL were below the reference values. According to relative frequencies, more than 30% of all athletes were below the lower limit (< 1.20 nmol/mL). The values in body builders/racing cyclists differed significantly from those in marathon racers (p < 0.001), which is presumably due to unallowed supplementation. During exercise, there was a significant increase in the pantothenic acid level in marathon runners (p < 0.01).

  19. [A case of megaloblastic anemia with abnormally high urine level of beta-aminoisobutyric acid].

    PubMed

    Konjiki, O; Yoneda, Y; Sato, Y; Oosawa, Y; Imamura, T; Takasaki, M

    1993-01-01

    A 78-year-old man was admitted to our hospital with anemia and jaundice. Hematological studies revealed hyperchromic macrocytic anemia, and biochemical studies revealed findings of hemolysis. The folic acid level was low and megaloblasts were observed in the bone marrow. From these findings, the patient was diagnosed as having megaloblastic anemia due to folic acid deficiency. This patient had been a heavy alcohol drinker in the habit of drinking alcohol without meals. He began to eat regular meals in the hospital, and the anemia and jaundice improved gradually. Since liver cirrhosis was suspected, amino acid analysis of the urine was performed, and abnormal excretion of beta-amino-isobutyric acid (BAIB) was found. According to the amount of BAIB excreted, the Japanese population can be divided into low and high BAIB excretors comprising 65% and 36%, respectively. BAIB is also considered to reflect dissimilation of thymine. The present patient was included in the high excretion group because of the abnormally high urine level of BAIB, which was considered to be caused by ineffective hematopoiesis in the bone marrow as a result of his megaloblastic anemia. For this reason, dissimilation of thymine was considered to have been active in this patient.

  20. The effects of changing dairy intake on trans and saturated fatty acid levels- results from a randomized controlled study

    PubMed Central

    2014-01-01

    Background Dairy food is an important natural source of saturated and trans fatty acids in the human diet. This study evaluates the effect of dietary advice to change dairy food intake on plasma fatty acid levels known to be present in milk in healthy volunteers. Methods Twenty one samples of whole fat dairy milk were analyzed for fatty acids levels. Changes in levels of plasma phospholipid levels were evaluated in 180 healthy volunteers randomized to increase, not change or reduce dairy intake for one month. Fatty acids were measured by gas chromatography–mass spectrometry and levels are normalized to d-4 alanine. Results The long chain fatty acids palmitic (13.4%), stearic (16.7%) and myristic (18.9%) acid were most common saturated fats in milk. Four trans fatty acids constituted 3.7% of the total milk fat content. Increased dairy food intake by 3.0 (± 1.2) serves/ day for 1 month was associated with small increases in plasma levels of myristic (+0.05, 95% confidence level-0.08 to 0.13, p = 0.07), pentadecanoic (+0.014, 95% confidence level -0.016 to 0.048, p = 0.02) and margaric acid (+0.02, -0.03 to 0.05, p = 0.03). There was no significant change in plasma levels of 4 saturated, 4 trans and 10 unsaturated fatty acids. Decreasing dairy food intake by 2.5 (± 1.2) serves per day was not associated with change in levels of any plasma fatty acid levels. Conclusion Dietary advice to change dairy food has a minor effect on plasma fatty acid levels. Trial registration ACTRN12612000574842. PMID:24708591

  1. Abscisic Acid Levels during Early Seed Development in Sechium edule Sw

    PubMed Central

    Vernieri, Paolo; Perata, Pierdomenico; Lorenzi, Roberto; Ceccarelli, Nello

    1989-01-01

    The time-course growth of single tissues in pollinated and unpollinated ovules of Sechium edule Sw. is described in relation to the endogenous levels of abscisic acid. Quantitation of abscisic acid (ABA) in the minute amounts of material obtained after ovule dissection has been performed by using a highly specific and sensitive solid-phase radioimmunoassay based on a monoclonal antibody raised against free (S)-ABA. While the absolute amount of ABA rises in both types of ovules, only in unpollinated ones does this leads to an increase in the hormone concentration. Infact in pollinated ovules the rapid growth following pollination prevents, through a dilution effect, the increase in ABA concentration. Growth patterns and endogenous ABA levels are similar for integuments and nucellus tissues either in pollinated or unpollinated ovules. It is suggested that the growth inhibition induced by the increase in ABA concentration after anthesis could be counteracted by the pollination triggered fast ovule growth. PMID:16667185

  2. Membrane Level of Omega-3 Docosahexaenoic Acid Is Associated with Severity of Obstructive Sleep Apnea

    PubMed Central

    Ladesich, James B.; Pottala, James V.; Romaker, Ann; Harris, William S.

    2011-01-01

    Background: Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular disease (CVD). The omega-3 fatty acid docosahexaenoic acid (DHA) is a major component of neural tissues, and supplementation with fish oils improves autonomic tone and reduces risk for CVD. A link between low DHA status and less mature sleep patterns was observed in newborns. Methods: We investigated the relations between red blood cell (RBC) levels of DHA and OSA severity in 350 sequential patients undergoing sleep studies. Severity categories were defined as none/mild, moderate, and severe, based on apnea hypopnea index (AHI) scores of 0 to 14, 15 to 34, and > 34, respectively. Results: After controlling for age, sex, race, smoking, BMI, alcohol intake, fish intake, and omega-3 supplementation, RBC DHA was inversely related with OSA severity. For each 1-SD increase in DHA levels, a patient was about 50% less likely to be classified with severe OSA. The odds ratios (95% CI) were 0.47 (0.28 to 0.80) and 0.55 (0.31 to 0.99) for being in the severe group versus the none/mild or moderate groups, respectively. Conclusion: These findings suggest that disordered membrane fatty acid patterns may play a causal role in OSA and that the assessment of RBC DHA levels might help in the diagnosis of OSA. The effects of DHA supplementation on OSA should be explored. Citation: Ladesich JB; Pottala JV; Romaker A; Harris WS. Membrane level of omega-3 docosahexaenoic acid is associated with severity of obstructive sleep apnea. J Clin Sleep Med 2011;7(4):391-396. PMID:21897776

  3. Lamotrigine, carbamazepine and phenytoin differentially alter extracellular levels of 5-hydroxytryptamine, dopamine and amino acids.

    PubMed

    Ahmad, Shagufta; Fowler, Leslie J; Whitton, Peter S

    2005-02-01

    We have studied the effects of treatment with the anticonvulsants lamotrigine (LTG), phenytoin (PHN) and carbamazepine (CBZ) on basal and stimulated extracellular aspartate (ASP), glutamate (GLU), taurine (TAU), GABA, 5-hydroxytryptamine (5-HT) and dopamine (DA) in the hippocampus of freely moving rats using microdialysis. All of the drugs investigated have had inhibition of Na(+) channel activity implicated as their principal mechanism of action. Neither LTG (10-20 mg/kg), PHN (20-40 mg/kg) or CBZ (10-20 mg/kg) had an effect on the basal extracellular concentrations of any of the amino acids studied with the exception of glutamate, which was decreased at the highest LTG dose. However, when amino acid transmitter levels were increased with 50 microM veratridine, LTG was found to cause a dose-dependent decrease in dialysate levels of all four amino acids, with the effect being most pronounced for glutamate. In contrast, PHN decreased extracellular aspartate levels but had no effect on evoked-extracellular GLU, TAU or GABA. Somewhat unexpectedly, CBZ did not alter the stimulated increase in the excitatory amino acids, GLU and ASP, but, rather surprisingly for an antiepileptic drug, markedly decreased that of the inhibitory substances TAU and GABA. The three drugs had differing effects on basal extracellular 5-HT and DA. LTG caused a dose-dependent decrease in both, while CBZ and PHN both increased extracellular 5-HT and DA. When extracellular 5-HT and DA was evoked by veratridine LTG had no significant effect on this, while PHN but not CBZ increased stimulated extracellular 5-HT and both PHN and CBZ augmented DA. Thus, the effects of the three drugs studied seemed to depend on whether extracellular transmitter levels are evoked or basal and the particular transmitter in question. This suggests that there are marked differences in the neurochemical mechanisms of antiepileptic drug action of the three compounds studied.

  4. Effect of brown seaweed lipids on fatty acid composition and lipid hydroperoxide levels of mouse liver.

    PubMed

    Airanthi, M K Widjaja-Adhi; Sasaki, Naoya; Iwasaki, Sayaka; Baba, Nobuko; Abe, Masayuki; Hosokawa, Masashi; Miyashita, Kazuo

    2011-04-27

    Brown seaweed lipids from Undaria pinnatifida (Wakame), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) contained several bioactive compounds, namely, fucoxanthin, polyphenols, and omega-3 polyunsaturated fatty acids (PUFA). Fucoxanthin and polyphenol contents of Akamoku and Uganomoku lipids were higher than those of Wakame lipids, while Wakame lipids showed higher total omega-3 PUFA content than Akamoku and Uganomoku lipids. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in liver lipids of KK-A(y) mouse significantly increased by Akamoku and Uganomoku lipid feeding as compared with the control, but not by Wakame lipid feeding. Fucoxanthin has been reported to accelerate the bioconversion of omega-3 PUFA and omega-6 PUFA to DHA and AA, respectively. The higher hepatic DHA and AA level of mice fed Akamoku and Uganomoku lipids would be attributed to the higher content of fucoxanthin of Akamoku and Uganomoku lipids. The lipid hydroperoxide levels of the liver of mice fed brown seaweed lipids were significantly lower than those of control mice, even though total PUFA content was higher in the liver of mice fed brown seaweed lipids. This would be, at least in part, due to the antioxidant activity of fucoxanthin metabolites in the liver.

  5. Normal level of sepsis-associated phenylcarboxylic acids in human serum.

    PubMed

    Beloborodova, N V; Moroz, V V; Osipov, A A; Bedova, A Yu; Olenin, A Yu; Getsina, M L; Karpova, O V; Olenina, E G

    2015-03-01

    Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are accumulated in a septic patient's blood due to increased endogenous and microbial phenylalanine and tyrosine biotransformation. Frequently, biochemical aromatic amino acid transformation into PhCAs is considered functionally insignificant for people without monogenetic hereditary diseases. The blood of healthy people contains the same PhCAs that are typical for septic patients as shown in this paper. The overall serum PhCAs level was 6 µM on average as measured by gas chromatography with flame ionization detection. This level is a stable biochemical parameter indicating the normal metabolism of aromatic amino acids. The concentrations of PhCAs in the metabolic profile of healthy people are distributed as follows: phenylacetic ≈ p-hydroxyphenyllactic > p-hydroxyphenylacetic > phenyllactic ≈ phenylpropionic > benzoic. We conclude that maintaining of stable PhCAs level in the serum is provided as the result of integration of human endogenous metabolic pathways and microbiota.

  6. Association of androgen with gender difference in serum adipocyte fatty acid binding protein levels

    PubMed Central

    Hu, Xiang; Ma, Xiaojing; Pan, Xiaoping; Luo, Yuqi; Xu, Yiting; Xiong, Qin; Bao, Yuqian; Jia, Weiping

    2016-01-01

    Clinical investigations have indicated women have higher levels of adipocyte fatty acid binding protein (A-FABP) than men. The present study aimed to identify factors related to gender difference in serum A-FABP levels. A total of 507 participants (194 men, 132 premenopausal women, and 181 postmenopausal women) were enrolled in the present study. Serum A-FABP levels increased in the order from men to premenopausal women to postmenopausal women in both body mass index categories (<25.0 and ≥25.0 kg/m2; all P < 0.05). Multiple stepwise regression analyses showed that after adjustment for factors related to serum A-FABP levels, the trunk fat mass was an independent and positive factor of serum A-FABP levels. For men, total testosterone was associated independently and inversely with serum A-FABP levels. For pre- and postmenopausal women, bioavailable testosterone and total testosterone were independent and positive factors associated with serum A-FABP levels, respectively. The present study demonstrated that the androgen was correlated with the serum A-FABP levels negatively in men, but positively in women. With these effects on the fat content, especially trunk fat, androgen might contribute to the gender difference in serum A-FABP levels. PMID:27270834

  7. Impact of HIV Infection and Zidovudine Therapy on RBC Parameters and Urine Methylmalonic Acid Levels.

    PubMed

    Adediran, Adewumi; Osunkalu, Vincent; Wakama, Tamunomieibi; John-Olabode, Sarah; Akinbami, Akinsegun; Uche, Ebele; Akanmu, Sulaimon

    2016-01-01

    Background. Anaemia is a common complication of human immunodeficiency virus (HIV) infection. The aim of this study was to investigate the impact of HIV infection and zidovudine on red blood cells (RBC) parameters and urine methylmalonic acid (UMMA) levels in patients with HIV infection. Material and Methods. A cross-sectional study involving 114 subjects, 94 of which are HIV-infected nonanaemic and 20 HIV negative subjects (Cg) as control. Full blood count parameters and urine methylmalonic acid (UMMA) level of each subject were determined. Associations were determined by Chi-square test and logistic regression statistics where appropriate. Results. Subjects on zidovudine-based ART had mean MCV (93 fL) higher than that of control group (82.9 fL) and ART-naïve (85.9 fL) subjects and the highest mean RDW. Mean UMMA level, which reflects vitamin B12 level status, was high in all HIV-infected groups but was significantly higher in ART-naïve subjects than in ART-experienced subjects. Conclusion. Although non-zidovudine therapy may be associated with macrocytosis (MCV > 95 fL), zidovudine therapy and ART naivety may not. Suboptimal level of vitamin B12 as measured by high UMMA though highest in ART-naïve subjects was common in all HIV-infected subjects.

  8. Association between delta-aminolevulinic acid dehydratase polymorphism and placental lead levels.

    PubMed

    Kayaaltı, Zeliha; Sert, Selda; Kaya-Akyüzlü, Dilek; Söylemez, Esma; Söylemezoğlu, Tülin

    2016-01-01

    Lead inhibits the delta-aminolevulinic acid dehydratase (ALAD) activity and results in neurotoxic aminolevulinic acid accumulation in the blood. During pregnancy, lead in the maternal blood can easily cross the placenta. The aim of this study was to determine whether the maternal ALAD G177C polymorphism (rs1800435) was related to the placental lead levels. The study population comprised 97 blood samples taken from mothers to investigate ALAD G177C polymorphism and their placentas to measure lead levels. ALAD G177C polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique and atomic absorption spectrometry (AAS) equipped with a graphite furnace and Zeeman background correction system was used for lead determination. The median placental lead levels for ALAD1-1, ALAD1-2 and ALAD2-2 genotypes were 7.54 μg/kg, 11.78 μg/kg and 18.53 μg/kg, respectively. Statistically significant association was found between the maternal ALAD G177C polymorphism and placental lead levels (p<0.05). This study suggested that maternal ALAD G177C polymorphism was associated with placental lead levels.

  9. The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates reduced levels of hexadecatrienoic acid.

    PubMed

    Afitlhile, Meshack; Duffield-Duncan, Kayla; Fry, Morgan; Workman, Samantha; Hum-Musser, Sue; Hildebrand, David

    2015-11-01

    A null and heterozygous mutant for the Arabidopsis thaliana TOC132 and TOC120 genes accumulates increased levels of 16:0 and decreased 16:3, suggesting altered homeostasis in fatty acid synthesis. The FAD5 gene encodes a plastid desaturase that catalyzes the first step in the synthesis of 16:3 in monogalactosyldiacylglycerol (MGDG). In non-acclimated toc132toc120+/- mutant plants, the FAD5 gene was repressed and this correlated with decreased levels of 16:3. In cold-acclimated mutant however, the FAD5 gene was upregulated and there was a small increase in 16:3 levels relative to the non-acclimated mutant plants. The MGD1 gene was expressed at control levels and the mutant accumulated levels of MGDG that were similar to the wild type. In the mutant however, MGDG had decreased 16:3 levels, suggesting that the activity of FAD5 desaturase was compromised. In the mutant, the FAD2 and FAD3 genes were downregulated but levels of 18:3-PC were increased, suggesting posttranscriptional regulation for the ER-localized fatty acid desaturases. The Toc120 or Toc159 receptor is likely to compensate for a defective Toc132 receptor. In the cold-acclimated mutant, the TOC159 gene was repressed ca. 300-fold, whereas the TOC120 gene was repressed 7-fold relative to the non-acclimated wild type. Thus, the TOC159 gene is more sensitive to cold-stress and might not compensate for defect in the TOC132 gene under these conditions. Overall, these data show that a mutation in the TOC132 gene results in decreased 16:3 levels, indicating the need for an intact Toc132/Toc120 receptor, presumably to facilitate the import of the FAD5 preprotein into chloroplasts.

  10. Influence of age, dietary cholic acid, and calcium levels on performance, utilization of free fatty acids, and bone mineralization in broilers.

    PubMed

    Atteh, J O; Leeson, S

    1985-10-01

    The effects of age on the utilization of dietary palmitic or a 50/50 mixture of palmitic and oleic acid at the 8% inclusion level in the absence or presence of .2% cholic acid and also in the presence of low (.8%) or high (1.2%) calcium were investigated using broiler chicks from 1 to 56 days of age. Significant interactions (P less than .01) were observed between the type of fatty acid supplemented and the presence or absence of cholic acid on weight gain and feed efficiency. Supplementing diets with a mixture of equal weights of palmitic and oleic acid, reduced feed intake relative to control diets and diets supplemented with palmitic acid alone. There was an interaction between the age of the bird and the type of fatty acid supplemented on fat retention and metabolizable energy (ME) of diets (P less than .01). There was also a significant interaction between the type of fatty acid supplemented and the addition of cholic acid on fat retention and ME of diets. While cholic acid reduced soap formation during the process of digestion (P less than .05), increasing dietary calcium level increased the proportion of the digesta fat that was present as soap (P less than .01). The proportion of digesta and excreta fat, present as soap, depended on the type of fatty acid supplemented. The addition of free fatty acids to broiler diets resulted in a decrease in bone ash and bone calcium content relative to those birds fed the control diet. It is concluded that the ability of broilers to utilize dietary free fatty acids depends on the age at which they are fed, although in all cases supplemental cholic acid enhances fatty acid utilization.

  11. Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells.

    PubMed

    Hara, Nobumasa; Yamada, Kazuo; Shibata, Tomoko; Osago, Harumi; Hashimoto, Tatsuya; Tsuchiya, Mikako

    2007-08-24

    NAD plays critical roles in various biological processes through the function of SIRT1. Although classical studies in mammals showed that nicotinic acid (NA) is a better precursor than nicotinamide (Nam) in elevating tissue NAD levels, molecular details of NAD synthesis from NA remain largely unknown. We here identified NA phosphoribosyltransferase (NAPRT) in humans and provided direct evidence of tight link between NAPRT and the increase in cellular NAD levels. The enzyme was abundantly expressed in the small intestine, liver, and kidney in mice and mediated [(14)C]NAD synthesis from [(14)C]NA in human cells. In cells expressing endogenous NAPRT, the addition of NA but not Nam almost doubled cellular NAD contents and decreased cytotoxicity by H(2)O(2). Both effects were reversed by knockdown of NAPRT expression. These results indicate that NAPRT is essential for NA to increase cellular NAD levels and, thus, to prevent oxidative stress of the cells. Kinetic analyses revealed that NAPRT, but not Nam phosphoribosyltransferase (NamPRT, also known as pre-B-cell colony-enhancing factor or visfatin), is insensitive to the physiological concentration of NAD. Together, we conclude that NA elevates cellular NAD levels through NAPRT function and, thus, protects the cells against stress, partly due to lack of feedback inhibition of NAPRT but not NamPRT by NAD. The ability of NA to increase cellular NAD contents may account for some of the clinically observed effects of the vitamin and further implies a novel application of the vitamin to treat diseases such as those associated with the depletion of cellular NAD pools.

  12. Effects of folic acid supplementation on serum homocysteine and lipoprotein (a) levels during pregnancy

    PubMed Central

    Hekmati Azar Mehrabani, Zohreh; Ghorbanihaghjo, Amir; Sayyah Melli, Manizheh; Hamzeh-Mivehroud, Maryam; Fathi Maroufi, Nazila; Bargahi, Nasrin; Bannazadeh Amirkhiz, Maryam; Rashtchizadeh, Nadereh

    2015-01-01

    Introduction:There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum– maximum) levels of serum Hcy from 11.40 μmol/L (4.40-28.70) to 9.70 (1.60-20.80) μmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion:Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women. PMID:26929921

  13. Uric acid plasma level and urine pH in rats treated with ambroxol.

    PubMed

    Drewa, Tomasz; Wolski, Zbigniew; Gruszka, Marzena; Misterek, Bartosz; Lysik, Joanna

    2007-01-01

    It was a chance discovery that ambroxol parenteral administration led to urinary bladder stone formation in rats. This study was undertaken to examine the serum uric acid levels and urine pH in rats after ambroxol parenteral treatment. Ambroxol influence on the uric acid level was measured in 5 rats (Rattus sp.) treated with 60 mg/kg (dissolved in injection water, sc, daily) during 2 weeks. Ambroxol influence on urine pH was examined on 45 rats divided into 3 groups. Rats from the 1st and 2nd group received 30 and 60 mg/kg/24h ambroxol, respectively. Urine was collected once daily and measured with strip kit. All values were presented as the means with standard deviations. The Student t test was used to compare the means, p < 0.05 was considered as significant. Dynamics of pH changes was measured in 4 rats treated with 60 mg/kg/24h of ambroxol. Controls received 1 mL of injection water sc. Serum uric acid level increased up to 8.7 +/- 1.0 mg/dL vs. 5.7 +/- 1.0 mg/dL in control (p < 0.002). In the 1st and 2nd group urine pH increased up to 7.5 +/- 0.5 and 7.6 +/- 0.5 vs. 6.7 +/- 0.4 (p < 0.05). Ambroxol withdrawal resulted in sequential urine pH decrease. 11 days after interruption of ambroxol therapy pH reached the starting value. Urine pH changes and possible disturbances in uric acid metabolic pathway may influence on the stone formation in rats after ambroxol parenteral treatment. The influence of ambroxol on urinary tract GAG layer and the balance between xanthine and CaOx in the urine should be checked.

  14. Oleic acid increases mitochondrial reactive oxygen species production and decreases endothelial nitric oxide synthase activity in cultured endothelial cells.

    PubMed

    Gremmels, Hendrik; Bevers, Lonneke M; Fledderus, Joost O; Braam, Branko; van Zonneveld, Anton Jan; Verhaar, Marianne C; Joles, Jaap A

    2015-03-15

    Elevated plasma levels of free fatty acids (FFA) are associated with increased cardiovascular risk. This may be related to FFA-induced elevation of oxidative stress in endothelial cells. We hypothesized that, in addition to mitochondrial production of reactive oxygen species, endothelial nitric oxide synthase (eNOS)-mediated reactive oxygen species production contributes to oleic acid (OA)-induced oxidative stress in endothelial cells, due to eNOS uncoupling. We measured reactive oxygen species production and eNOS activity in cultured endothelial cells (bEnd.3) in the presence of OA bound to bovine serum albumin, using the CM-H2DCFDA assay and the L-arginine/citrulline conversion assay, respectively. OA induced a concentration-dependent increase in reactive oxygen species production, which was inhibited by the mitochondrial complex II inhibitor thenoyltrifluoroacetone (TTFA). OA had little effect on eNOS activity when stimulated by a calcium-ionophore, but decreased both basal and insulin-induced eNOS activity, which was restored by TTFA. Pretreatment of bEnd.3 cells with tetrahydrobiopterin (BH4) prevented OA-induced reactive oxygen species production and restored inhibition of eNOS activity by OA. Elevation of OA levels leads to both impairment in receptor-mediated stimulation of eNOS and to production of mitochondrial-derived reactive oxygen species and hence endothelial dysfunction.

  15. Chemical inhibition of fatty acid absorption and cellular uptake limits lipotoxic cell death

    PubMed Central

    Ahowesso, Constance; Black, Paul N.; Saini, Nipun; Montefusco, David; Chekal, Jessica; Malosh, Chrysa; Lindsley, Craig W.; Stauffer, Shaun R.; DiRusso, Concetta C.

    2015-01-01

    Chronic elevation of plasma free fatty acid (FFA) levels is commonly associated with obesity, type 2 diabetes, cardiovascular disease and some cancers. Experimental evidence indicates FFA and their metabolites contribute to disease development through lipotoxicity. Previously, we identified a specific fatty acid transport inhibitor CB16.2, a.k.a. Lipofermata, using high throughput screening methods. In this study, efficacy of transport inhibition was measured in four cell lines that are models for myocytes (mmC2C12), pancreatic ß-cells (rnINS-1E), intestinal epithelial cells (hsCaco-2), and hepatocytes (hsHepG2), as well as primary human adipocytes. The compound was effective in inhibiting uptake with IC50s between 3 and 6 µM for all cell lines except human adipocytes (39 µM). Inhibition was specific for long and very long chain fatty acids but had no effect on medium chain fatty acids (C6-C10), which are transported by passive diffusion. Derivatives of Lipofermata were evaluated to understand structural contributions to activity. Lipofermata prevented palmitate-mediated oxidative stress, induction of BiP and CHOP, and cell death in a dose-dependent manner in hsHepG2 and rnINS-1E cells, suggesting it will prevent induction of fatty acid-mediated cell death pathways and lipotoxic disease by channeling excess fatty acids to adipose tissue and away from liver and pancreas. Importantly, mice dosed orally with Lipofermata were not able to absorb 13C-oleate demonstrating utility as an inhibitor of fatty acid absorption from the gut. PMID:26394026

  16. Effects of Uric Acid on Lipid Levels in CKD Patients in a Randomized Controlled Trial

    PubMed Central

    Bowden, Rodney G.; Shelmadine, Brian D.; Moreillon, Jennifer J.; Deike, Erika; Griggs, Jackson O.; Wilson, Ronald L.

    2013-01-01

    Background Few studies have been conducted that compared lipid levels and uric acid in CKD or End-Stage Renal Disease (ESRD) patients with most using animal models. The purpose of the study was to explore effects on lipids while controlling uric acid levels in CKD patients. Methods Twenty-four CKD patients (N = 24) volunteered to participate in this study. The study was conducted using a double-blind, randomized, placebo controlled experimental protocol. The experimental group was prescribed 300 mg of allopurinol PO daily by their treating physician and followed prospectively for 8-weeks. The control group consumed a similar pill once a day for 8-weeks. Results ANCOVA revealed significant differences in total cholesterol (P = 0.009) and Apo B (P = 0.006) with lower levels in the allopurinol group. A trend emerged with LDL (P = 0.052) with lower levels in the allopurinol group. No significant differences were discovered in triglycerides (P = 0.403), HDL (P = 0.762) and total Cholesterol/HDL Ratio (P = 0.455). Conclusions After statistically controlling for compliance and inflammation significant differences between groups were observed for total cholesterol and Apo B. In both instances the allopurinol group had lower concentrations than the placebo group. Similarly, a trend was observed in LDL with the allopurinol group having lower concentrations than the placebo group.

  17. Gallic acid induces HeLa cell death via increasing GSH depletion rather than ROS levels.

    PubMed

    Park, Woo Hyun

    2017-02-01

    Gallic acid (GA; 3,4,5-triphydroxyl-benzoic acid) is widely dispersed in various plants, fruits and foods and it shows various biological properties including anticancer effects. This study investigated the effects of GA on HeLa cervical cancer cells in relation to cell death, reactive oxygen species (ROS) and glutathione (GSH). GA dose-dependently inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC) at 24 or 72 h. The susceptibility of HeLa cells to GA was higher than that of HUVEC. GA induced apoptosis in HeLa cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψm). GA increased ROS levels including O2•- in HeLa cells at 24 h and it also induced GSH depletion. N-acetyl cysteine (NAC) increased the growth inhibition of GA-treated HeLa cells and enhanced the death of these cells. NAC differently influenced ROS levels in GA-treated HeLa cells and significantly increased GSH depletion in these cells. L-buthionine sulfoximine (BSO) increased MMP (∆ψm) loss, ROS levels and GSH depletion in GA-treated HeLa cells. In conclusion, GA significantly inhibited the growth of HeLa cells. GA-induced HeLa cell death was tightly related to GSH depletion rather than ROS level changes.

  18. Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs

    PubMed Central

    Hudson, Brian D.; Christiansen, Elisabeth; Tikhonova, Irina G.; Grundmann, Manuel; Kostenis, Evi; Adams, David R.; Ulven, Trond; Milligan, Graeme

    2012-01-01

    When it is difficult to develop selective ligands within a family of related G-protein-coupled receptors (GPCRs), chemically engineered receptors activated solely by synthetic ligands (RASSLs) are useful alternatives for probing receptor function. In the present work, we explored whether a RASSL of the free fatty acid receptor 2 (FFA2) could be developed on the basis of pharmacological variation between species orthologs. For this, bovine FFA2 was characterized, revealing distinct ligand selectivity compared with human FFA2. Homology modeling and mutational analysis demonstrated a single mutation in human FFA2 of C4.57G resulted in a human FFA2 receptor with ligand selectivity similar to the bovine receptor. This was exploited to generate human FFA2-RASSL by the addition of a second mutation at a known orthosteric ligand interaction site, H6.55Q. The resulting FFA2-RASSL displayed a >100-fold loss of activity to endogenous ligands, while responding to the distinct ligand sorbic acid with pEC50 values for inhibition of cAMP, 5.83 ± 0.11; Ca2+ mobilization, 4.63 ± 0.05; ERK phosphorylation, 5.61 ± 0.06; and dynamic mass redistribution, 5.35 ± 0.06. This FFA2-RASSL will be useful in future studies on this receptor and demonstrates that exploitation of pharmacological variation between species orthologs is a powerful method to generate novel chemically engineered GPCRs.—Hudson, B. D., Christiansen, E., Tikhonova, I. G., Grundmann, M., Kostenis, E., Adams, D. R., Ulven, T., Milligan, G. Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs. PMID:22919070

  19. Extracellular amino acid levels in the interpositus nucleus during classical eyeblink conditioning in alert cats.

    PubMed

    Jiménez-Díaz, Lydia; Gruart, Agnès; Miñano, Francisco Javier; Delgado-García, José María

    2007-10-01

    The extracellular levels of selected amino acids in the cerebellar posterior interpositus nucleus (PIN) during classical eyeblink conditioning was analyzed in alert cats using a delay paradigm. Animals were prepared for the chronic recording of eyelid movements (with the magnetic search-coil technique) and the electromyographic activity of the orbicularis oculi muscle. With the help of a guide and push-pull cannulae, selected PIN sites were perfused daily during classical eyeblink conditioning. The perfusate was sampled at intervals of 5 min and analyzed with a high-pressure liquid chromatography- electrochemical detection (HPLC-EC) method. The analysis of push-pull perfusate revealed a significant increase in the release of glycine, taurine, and glutamate across the successive conditioning sessions, in parallel with the acquisition of eyelid conditioned responses (CRs). Both CRs and extracellular levels of these three amino acids returned to control values during extinction. Other amino acids (alanine, GABA, glutamine, serine, and threonine) did not undergo modifications in their extracellular concentrations across the training. Results are discussed with regard to the role of PIN in this type of associative learning.

  20. Exceptionally crystalline and conducting acid doped polyaniline films by level surface assisted solution casting approach

    NASA Astrophysics Data System (ADS)

    Puthirath, Anand B.; Methattel Raman, Shijeesh; Varma, Sreekanth J.; Jayalekshmi, S.

    2016-04-01

    Emeraldine salt form of polyaniline (PANI) was synthesized by chemical oxidative polymerisation method using ammonium persulfate as oxidant. Resultant emeraldine salt form of PANI was dedoped using ammonia solution and then re-doped with camphor sulphonic acid (CSA), naphthaline sulphonic acid (NSA), hydrochloric acid (HCl), and m-cresol. Thin films of these doped PANI samples were deposited on glass substrates using solution casting method with m-cresol as solvent. A level surface was employed to get homogeneous thin films of uniform thickness. Detailed X-ray diffraction studies have shown that the films are exceptionally crystalline. The crystalline peaks observed in the XRD spectra can be indexed to simple monoclinic structure. FTIR and Raman spectroscopy studies provide convincing explanation for the exceptional crystallinity observed in these polymer films. FESEM and AFM images give better details of surface morphology of doped PANI films. The DC electrical conductivity of the samples was measured using four point probe technique. It is seen that the samples also exhibit quite high DC electrical conductivity, about 287 S/cm for CSA doped PANI, 67 S/cm for NSA doped PANI 65 S/cm for HCl doped PANI, and just below 1 S/cm for m-cresol doped PANI. Effect of using the level surface for solution casting is studied and correlated with the observed crystallinity.

  1. Insulin Signaling Regulates Fatty Acid Catabolism at the Level of CoA Activation

    PubMed Central

    Xu, Xiaojun; Gopalacharyulu, Peddinti; Seppänen-Laakso, Tuulikki; Ruskeepää, Anna-Liisa; Aye, Cho Cho; Carson, Brian P.; Mora, Silvia; Orešič, Matej; Teleman, Aurelio A.

    2012-01-01

    The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS). We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis. PMID:22275878

  2. The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons

    PubMed Central

    Błażej, Paweł; Mackiewicz, Dorota; Wnętrzak, Małgorzata; Mackiewicz, Paweł

    2017-01-01

    There are two main forces that affect usage of synonymous codons: directional mutational pressure and selection. The effectiveness of protein translation is usually considered as the main selectional factor. However, biased codon usage can also be a byproduct of a general selection at the amino acid level interacting with nucleotide replacements. To evaluate the validity and strength of such an effect, we superimposed >3.5 billion unrestricted mutational processes on the selection of nonsynonymous substitutions based on the differences in physicochemical properties of the coded amino acids. Using a modified evolutionary optimization algorithm, we determined the conditions in which the effect on the relative codon usage is maximized. We found that the effect is enhanced by mutational processes generating more adenine and thymine than guanine and cytosine, as well as more purines than pyrimidines. Interestingly, this effect is observed only under an unrestricted model of nucleotide substitution, and disappears when the mutational process is time-reversible. Comparison of the simulation results with data for real protein coding sequences indicates that the impact of selection at the amino acid level on synonymous codon usage cannot be neglected. Furthermore, it can considerably interfere, especially in AT-rich genomes, with other selections on codon usage, e.g., translational efficiency. It may also lead to difficulties in the recognition of other effects influencing codon bias, and an overestimation of protein coding sequences whose codon usage is subjected to adaptational selection. PMID:28122952

  3. Serum uric acid levels in patients with myasthenia gravis are inversely correlated with disability

    PubMed Central

    Yang, Dehao; Weng, Yiyun; Lin, Haihua; Xie, Feiyan; Yin, Fang; Lou, Kangliang; Zhou, Xuan; Han, Yixiang; Li, Xiang

    2016-01-01

    Uric acid (UA), the final product of purine metabolism, has been reported to be reduced in patients with various neurological disorders and is considered to be a possible indicator for monitoring the disability and progression of multiple sclerosis. However, it remains unclear whether there is a close relationship between UA and myasthenia gravis (MG), or whether UA is primarily deficient or secondarily reduced because of its peroxynitrite scavenging activity. We investigated the correlation between serum UA levels and the clinical characteristics of MG. We assessed 338 serum UA levels obtained in 135 patients with MG, 47 patients with multiple sclerosis, and 156 healthy controls. In addition, we compared serum UA levels when MG patients were stratified according to disease activity and classifications performed by the Myasthenia Gravis Foundation of America, age of onset, duration, and thymus histology (by means of MRI or computed tomography). MG patients had significantly lower serum UA levels than the controls (P<0.001). Moreover, UA levels in patients with MG were inversely correlated with disease activity and disease progression (P=0.013). However, UA levels did not correlate significantly with disease duration, age of onset, and thymus histology. Our findings suggest that serum level of UA was reduced in patients with MG and serum UA might be considered a surrogate biomarker of MG disability and progression. PMID:26836463

  4. Factors Influencing an Agricultural Education Student's Perception of the FFA Organization.

    ERIC Educational Resources Information Center

    Croom, D. Barry; Flowers, James L.

    2001-01-01

    A survey of secondary agriscience students in North Carolina (167 Future Farmers of America members, 237 nonmembers) indicated that the decision to join/not join the organization was influenced by its image in the school and its ability to meet affiliation needs. Gender, ethnicity, agriculture coursetaking, and grade level did not influence…

  5. Air and blood lead levels in lead acid battery recycling and manufacturing plants in Kenya.

    PubMed

    Were, Faridah H; Kamau, Geoffrey N; Shiundu, Paul M; Wafula, Godfrey A; Moturi, Charles M

    2012-01-01

    The concentration of airborne and blood lead (Pb) was assessed in a Pb acid battery recycling plant and in a Pb acid battery manufacturing plant in Kenya. In the recycling plant, full-shift area samples taken across 5 days in several production sections showed a mean value ± standard deviation (SD) of 427 ± 124 μg/m(3), while area samples in the office area had a mean ± SD of 59.2 ± 22.7 μg/m(3). In the battery manufacturing plant, full-shift area samples taken across 5 days in several production areas showed a mean value ± SD of 349 ± 107 μg/m(3), while area samples in the office area had a mean ± SD of 55.2 ± 33.2 μg/m(3). All these mean values exceed the U.S. Occupational Safety and Health Administration's permissible exposure limit of 50 μg/m(3) as an 8-hr time-weighted average. In the battery recycling plant, production workers had a mean blood Pb level ± SD of 62.2 ± 12.7 μg/dL, and office workers had a mean blood Pb level ± SD of 43.4 ± 6.6 μg/dL. In the battery manufacturing plant, production workers had a mean blood Pb level ± SD of 59.5 ± 10.1 μg/dL, and office workers had a mean blood Pb level ± SD of 41.6 ± 7.4 μg/dL. All the measured blood Pb levels exceeded 30 μg/dL, which is the maximum blood Pb level recommended by the ACGIH(®). Observations made in these facilities revealed numerous sources of Pb exposure due to inadequacies in engineering controls, work practices, respirator use, and personal hygiene.

  6. Correlation between n-3 polyunsaturated fatty acids consumption and BDNF peripheral levels in adolescents

    PubMed Central

    2014-01-01

    Background Although several studies have reported an association between mental disorders and serum levels of brain-derived neurotrophic factor (BDNF), this association is still poorly understood. The study of factors associated with both BDNF levels and mental disorders, such as n-3 polyunsaturated fatty acids (n-3 PUFAs), may help to elucidate the mechanisms mediating the relationship between the two variables. Therefore, the present study aimed to evaluate whether the intake n-3 PUFAs correlates with serum levels of BDNF. Findings This study involved 137 adolescents drawn from a community sample, including a group with high levels of anxiety, assessed using the Screen for Children and Anxiety Related Emotional Disorders. Blood samples were collected and serum BDNF levels were measured. n-3 PUFAs were estimated using a food frequency questionnaire for adolescents. Correlations were performed to assess the association between n-3 PUFAs intake and BDNF levels. Effects of potential confounders (total fat consumption, age, gender and anxiety) were examined using linear regression models. There was a direct correlation between n-3 PUFAs consumption and serum BDNF levels, which remained significant even after accounting for potential confounders. Conclusions We were able to detect a correlation between n-3 PUFAs intake and peripheral BDNF levels. Our study was limited by its small sample size, and our external validity may be restricted by the oversampling of anxious adolescents. Our findings may help determine the nature of the association between mental disorders and serum levels of BDNF. However, more studies are needed to elucidate the possible mechanisms by which n-3 PUFAs intake affects BDNF levels, and how this may lead to an increased vulnerability to psychiatric disorders. PMID:24593295

  7. Resistance Training in Type 2 Diabetic Patients Improves Uric Acid levels

    PubMed Central

    Sousa, Moisés S.S.R.; Saavedra, Francisco J.F.; Neto, Gabriel R.; Novaes, Giovanni S.; Souza, Antonio C. R.; Salerno, Verônica P.; Novaes, Jefferson S.

    2014-01-01

    Resistance training (RT) can provide several benefits for individuals with Type 2 diabetes. The aim of this study was to investigate the effects of resistance training on the strength levels and uric acid (UA) concentration in individuals with Type 2 diabetes. The study included 68 patients (57.7±9.0 years) that participated in an organized program of RT for 12 weeks. The volunteers were divided into two groups: an experimental group (EG; n=34) that performed the resistance training program consisting of seven exercises executed in an alternating order based on segments; and a control group (CG; n=34) that maintained their normal daily life activities. Muscle strength and uric acid were measured both pre- and post-experiment. The results showed a significant increase in strength of the subjects in the EG for all exercises included in the study (p<0.001). Comparing the strength levels of the post-test, intergroup differences were found in supine sitting (p<0.001), leg extension (p<0.001), shoulder press (p<0.001), leg curl (p=0.001), seated row (p<0.001), leg press (p=0.001) and high pulley (p<0.001). The measured uric acid was significantly increased in both experimental and control groups (p<0.001 and p=0.001, respectively). The intergroup comparison showed a significant increase for the EG (p=0.024). We conclude that the training program was effective for strength gains despite an increase in uric acid in Type 2 diabetics. PMID:25713640

  8. Adenosine plasma level correlates with homocysteine and uric acid concentrations in patients with coronary artery disease.

    PubMed

    Fromonot, J; Deharo, P; Bruzzese, L; Cuisset, T; Quilici, J; Bonatti, S; Fenouillet, E; Mottola, G; Ruf, J; Guieu, R

    2016-03-01

    The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 ± 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 ± 0.5 μmol/L vs 0.53 ± 0.14 μmol/L; p < 0.01), HCys (15 ± 7.6 μmol/L vs 6.8 ± 3 μmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations.

  9. Different effects of cabergoline and bromocriptine on metabolic and cardiovascular risk factors in patients with elevated prolactin levels.

    PubMed

    Krysiak, Robert; Okopien, Bogusław

    2015-03-01

    Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine-resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin-like growth factor-1 (IGF-1) and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA-IR), and circulating levels of IGF-1, free fatty acids (FFA), uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL cholesterol and 25-hydroxyvitamin D. With the exception of a reduction in HOMA-IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2-hr post-challenge plasma glucose levels, HOMA-IR, as well as circulating levels of IGF-1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25-hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine.

  10. Increased presence of monounsaturated fatty acids in the stratum corneum of human skin equivalents.

    PubMed

    Thakoersing, Varsha S; van Smeden, Jeroen; Mulder, Aat A; Vreeken, Rob J; El Ghalbzouri, Abdoelwaheb; Bouwstra, Joke A

    2013-01-01

    Previous results showed that our in-house human skin equivalents (HSEs) differ in their stratum corneum (SC) lipid organization compared with human SC. To elucidate the cause of the altered SC lipid organization in the HSEs, a recently developed liquid chromatography/mass spectrometry method was used to study the free fatty acid (FFA) and ceramide composition in detail. In addition, the SC lipid composition of the HSEs and human skin was examined quantitatively with high-performance thin-layer chromatography. Our results reveal that all our HSEs have an increased presence of monounsaturated FFAs compared with human SC. Moreover, the HSEs display the presence of ceramide species with a monounsaturated acyl chain, which are not detected in human SC. All HSEs also exhibit an altered expression of stearoyl-CoA desaturase, the enzyme that converts saturated FFAs to monounsaturated FFAs. Furthermore, the HSEs show the presence of 12 ceramide subclasses, similar to native human SC. However, the HSEs have increased levels of ceramides EOS and EOH and ceramide species with short total carbon chains and a reduced FFA level compared with human SC. The presence of unsaturated lipid chains in HSE offers new opportunities to mimic the lipid properties of human SC more closely.

  11. Diurnal Changes in Metabolite Levels and Crassulacean Acid Metabolism in Kalanchoë daigremontiana Leaves 1

    PubMed Central

    Kenyon, William H.; Holaday, A. Scott; Black, Clanton C.

    1981-01-01

    Diurnal changes in levels of selected metabolites associated with glycolysis, the C3 cycle, C4-organic acids, and storage carbohydrates were analyzed in active Kalanchoë daigremontiana Crassulacean acid metabolism leaves. Three metabolic transition periods occurred each day. During the first two hours of light, nearly all of the metabolite pools underwent transient changes. Beginning at daylight, stomata opened transiently and closed again within 30 minutes; malate synthesis continued for about 1 hour into the light; C3 photosynthesis began within 30 minutes; and net quantities of starch and glucan began to accumulate after 2 hours, continuing linearly throughout the rest of the day. The second transition occurred in midafternoon: stomata reopened; malate decarboxylation nearly terminated; and the assimilation of ambient CO2 occurred primarily via the C3 cycle. The third transition occurred at dark: stomata transiently closed before opening again; the C3 cycle stopped; malate synthesis started in about 1 hour; starch and glucan degradation began within 1 hour; and the bulk of carbon flow was through glycolysis leading to the synthesis and accumulation of malate throughout the night. At night, the levels of metabolites involved in acidification and glycolysis (except for phosphoenolpyruvate) generally accumulated. Phosphoenolpyruvate levels peaked near midday and were minimal at night. The ribulose 1,5-bisphosphate pool was depleted at night, while sedoheptulose 1,7-bisphosphate, fructose 1,6-bisphosphate, glucose 6-phosphate, and fructose 6-phosphate accumulated. Images PMID:16662040

  12. Axillary versus peripheral blood levels of sialic acid, ferritin, and CEA in patients with breast cancer.

    PubMed

    Monti, M; Catania, S; Locatelli, E; Gandini, R; Reggiani, A; Cunietti, E

    1990-12-01

    Serum levels of total sialic acid, carcinoembryonic antigen (CEA), ferritin, lactate dehydrogenase, and creatine phosphokinase were measured both in tumor drainage blood (axillary vein) and in peripheral blood obtained from 121 breast cancer patients during surgery. No significant differences between mean values in peripheral and tumor draining blood, between cancer patients and healthy controls, or between patients with or without axillary lymph node metastases were found for any of the markers. Both ferritin and CEA levels were higher in axillary and peripheral blood from patients with central breast cancer versus other sites but the difference was significant only for CEA (p less than 0.05). CEA levels were significantly higher (p less than 0.01) in patients with greater than 2 cm diameter carcinomas versus T1 stage patients in axillary but not in peripheral blood. When the cephalic vein was clamped before the axillary sample was taken, ferritin showed a significant increase (p less than 0.05). We conclude that measurement of sialic acid, CEA, and ferritin in axillary venous blood in breast cancer patients is not of clinical benefit, although further data are needed to clarify whether other advantages can be derived.

  13. Effects of domoic acid on serum levels of TSH and thyroid hormones.

    PubMed

    Arufe, M C; Arias, B; Durán, R; Alfonso, M

    1995-08-01

    The actions of Domoic Acid (Dom), a marine toxin, on the levels of serum TSH and thyroid hormones (T4 and T3) has been studied to determine if these actions could be mediated by the serotoninergic system. In all the experiments, adult male Wistar rats were used. The Dom dissolved in saline was administered via i.p. in doses of 0.5 and 1 mg/kg. The T4 and T3 concentrations were determined by enzimoinmunoassay and TSH concentration was determined by radioinmunoassay. The results show that Dom 1 mg/kg increases the serum T4 levels one hour after treatment and decreases these levels 2 and 3 hr after treatment. Dom 0.5 mg/kg decreased the serum T4 levels 2 and 3 hr after treatment. The concentrations of T3 in serum were unchanged by both doses of Dom. The concentration of TSH was increased by Dom. In order to study the possible mediation of the serotoninergic system in the effect of Dom on the hormone levels, PCPA, a tryptophan hydroxylase inhibitor, was administered i.p. 90 min before blood sampling. In this case, with both doses of Dom a decrease in the levels of both hormones occurred with respect to the PCPA group. These results indicate that the serotoninergic system could affect the actions of Dom on TSH and thyroid hormone secretion.

  14. Hypouricemia in severely disabled children II: influence of elemental enteral nutrition on the serum uric acid levels.

    PubMed

    Yoshikawa, Hideto; Yamazaki, Sawako; Abe, Tokinari

    2004-01-01

    The previous study showed that both valproic acid (VPA) and a bedridden state decreased the serum uric acid level, and VPA-induced renal tubular dysfunction was suspected to be one cause of hypouricemia in severely disabled children. However, it was uncertain what factor of bedridden state influences the uric acid level in severely disabled children. Among many factors of a bedridden state that might influence the uric acid level, we examined the influence of elemental nutrition on the serum uric acid level in severely disabled children because many severely disabled children with marked hypouricemia receive elemental nutrition. Thirty-one severely disabled children were included in this study, who were divided into two groups-group A: 11 patients with elemental nutrition; group B: 20 patients with non-elemental nutrition. The laboratory data in both groups were analyzed statistically, using the t-test. The uric acid level was significantly decreased in group A compared with group B (p < 0.01) without elevation of urinary excretion of uric acid. Other laboratory data, except phosphate and potassium, did not differ between the two groups significantly. An elemental diet may be one factor that decreases the uric acid level in severely disabled children.

  15. Differences in the fatty-acid composition of rodent spermatozoa are associated to levels of sperm competition.

    PubMed

    delBarco-Trillo, Javier; Mateo, Rafael; Roldan, Eduardo R S

    2015-03-20

    Sperm competition is a prevalent phenomenon that drives the evolution of sperm function. High levels of sperm competition lead to increased metabolism to fuel higher sperm velocities. This enhanced metabolism can result in oxidative damage (including lipid peroxidation) and damage to the membrane. We hypothesized that in those species experiencing high levels of sperm competition there are changes in the fatty-acid composition of the sperm membrane that makes the membrane more resistant to oxidative damage. Given that polyunsaturated fatty acids (PUFAs) are the most prone to lipid peroxidation, we predicted that higher sperm competition leads to a reduction in the proportion of sperm PUFAs. In contrast, we predicted that levels of sperm competition should not affect the proportion of PUFAs in somatic cells. To test these predictions, we quantified the fatty-acid composition of sperm, testis and liver cells in four mouse species (genus Mus) that differ in their levels of sperm competition. Fatty-acid composition in testis and liver cells was not associated to sperm competition levels. However, in sperm cells, as predicted, an increase in sperm competition levels was associated with an increase in the proportion of saturated fatty-acids (the most resistant to lipid peroxidation) and by a concomitant decrease in the proportion of PUFAs. Two particular fatty acids were most responsible for this pattern (arachidonic acid and palmitic acid). Our findings thus indicate that sperm competition has a pervasive influence in the composition of sperm cells that ultimately may have important effects in sperm function.

  16. Absolute identification of muramic acid, at trace levels, in human septic synovial fluids in vivo and absence in aseptic fluids.

    PubMed

    Fox, A; Fox, K; Christensson, B; Harrelson, D; Krahmer, M

    1996-09-01

    This is the first report of a study employing the state-of-the-art technique of gas chromatography-tandem mass spectrometry for absolute identification of muramic acid (a marker for peptidoglycan) at trace levels in a human or animal body fluid or tissue. Daughter mass spectra of synovial fluid muramic acid peaks (> or = 30 ng/ml) were identical to those of pure muramic acid. Absolute chemical identification at this level represents a 1,000-fold increase in sensitivity over previous gas chromatography-mass spectrometry identifications. Muramic acid was positively identified in synovial fluids during infection and was eliminated over time but was absent from aseptic fluids.

  17. Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid pool parallels increased Cyp7a1 expression levels.

    PubMed

    Burke, Katie T; Horn, Paul S; Tso, Patrick; Heubi, James E; Woollett, Laura A

    2009-07-01

    Intraluminal concentrations of bile acids are low in newborn infants and increase rapidly after birth, at least partly owing to increased bile acid synthesis rates. The expansion of the bile acid pool is critical since bile acids are required to stimulate bile flow and absorb lipids, a major component of newborn diets. The purpose of the present studies was to determine the mechanism responsible for the increase in bile acid synthesis rates and the subsequent enlargement of bile acid pool sizes (BAPS) during the neonatal period, and how changes in circulating hormone levels might affect BAPS. In the hamster, pool size was low just after birth and increased modestly until 10.5 days postpartum (dpp). BAPS increased more significantly ( approximately 3-fold) between 10.5 and 15.5 dpp. An increase in mRNA and protein levels of cholesterol 7alpha-hydroxylase (Cyp7a1), the rate-limiting step in classical bile acid synthesis, immediately preceded an increase in BAPS. In contrast, levels of oxysterol 7alpha-hydroxylase (Cyp7b1), a key enzyme in bile acid synthesis by the alternative pathway, were relatively elevated by 1.5 dpp. farnesyl X receptor (FXR) and short heterodimeric partner (SHP) mRNA levels remained relatively constant at a time when Cyp7a1 levels increased. Finally, although simultaneous increases in circulating cortisol and Cyp7a1 levels occurred, precocious expression of Cyp7a1 could not be induced in neonatal hamsters with dexamethasone. Thus the significant increase in Cyp7a1 levels in neonatal hamsters is due to mechanisms independent of the FXR and SHP pathway and cortisol.

  18. Tissue Specific Expression Levels of Apoptosis Involved Genes Have Correlations with Codon and Amino Acid Usage

    PubMed Central

    Sadeghi, Iman; Salavaty, Abbas; Nasiri, Habib

    2016-01-01

    Different mechanisms, including transcriptional and post transcriptional processes, regulate tissue specific expression of genes. In this study, we report differences in gene/protein compositional features between apoptosis involved genes selectively expressed in human tissues. We found some correlations between codon/amino acid usage and tissue specific expression level of genes. The findings can be significant for understanding the translational selection on these features. The selection may play an important role in the differentiation of human tissues and can be considered for future studies in diagnosis of some diseases such as cancer. PMID:28154517

  19. Justification for Selecting Level A vs. Level B Personal Protective Equipment to Remediate a Room Containing Concentrated Acids, Bases and Radiological Constituents

    SciTech Connect

    Hylko, J. M.; Thompson, A. L.; Walter, J. F.; Deecke, T. A.

    2002-02-25

    Selecting the appropriate personal protective equipment (PPE) is based on providing an adequate level of employee protection relative to the task-specific conditions and hazards. PPE is categorized into four ensembles, based on the degree of protection afforded; e.g., Levels A (most restrictive), B, C, and D (least restrictive). What is often overlooked in preparing an ensemble is that the PPE itself can create significant worker hazards; i.e., the greater the level of PPE, the greater the associated risks. Furthermore, there is confusion as to whether a more ''conservative approach'' should always be taken since Level B provides the same level of respiratory protection as Level A but less skin protection. This paper summarizes the Occupational Safety and Health Administration regulations addressing Level A versus Level B, and provides justification for selecting Level B over Level A without under-protecting the employee during a particular remediation scenario. The scenario consisted of an entry team performing (1) an initial entry into a room containing concentrated acids (e.g., hydrofluoric acid), bases, and radiological constituents; (2) sampling and characterizing container contents; and (3) retrieving characterized containers. The invasive nature of the hydrofluoric acid sampling and characterization scenario created a high potential for splash, immersion, and exposure to hazardous vapors, requiring additional skin protection. The hazards associated with this scenario and the chemical nature of hydrofluoric acid provided qualitative evidence to justify Level A. Once the hydrofluoric acid was removed from the room, PPE performance was evaluated against the remaining chemical inventory. If chemical breakthrough from direct contact was not expected to occur and instrument readings confirmed the absence of any hazardous vapors, additional skin protection afforded by wearing a vapor-tight, totally-encapsulated suit was not required. Therefore, PPE performance and

  20. Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis

    PubMed Central

    Wen, Min; Zhou, Bo; Chen, Yun-Hua; Ma, Zhao-Lei; Gou, Yun; Zhang, Chun-Lin; Yu, Wen-Feng; Jiao, Ling

    2017-01-01

    Background Lower serum uric acid (UA) levels have been reported as a risk factor in Parkinson’s disease (PD). However, the results have been inconsistent so far. Objectives The aim of the present study was to clarify the potential relationship of uric acid with PD. Methods Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger’s regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0. Results Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = −0.65, 95% CI [−0.84, −0.46], Z = 6.75, p <0.001; Non-Asia: SMD = −0.25, 95% CI [−0.43, −0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = −0.53, 95% CI [−0.70, −0.35], z = 5.98, p <0.001; men: SMD = −0.66, 95% CI [−0.87, −0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001). Conclusions Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the

  1. Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype

    PubMed Central

    Huertas, Ismael; Jesús, Silvia; Lojo, José Antonio; García-Gómez, Francisco Javier; Cáceres-Redondo, María Teresa; Oropesa-Ruiz, Juan Manuel; Carrillo, Fátima; Vargas-Gonzalez, Laura; Martín Rodríguez, Juan Francisco; Gómez-Garre, Pilar; García-Solís, David; Mir, Pablo

    2017-01-01

    Parkinson’s disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype. PMID:28358829

  2. Effects of dietary saturated or unsaturated fatty acids and calcium levels on performance and mineral metabolism of broiler chicks.

    PubMed

    Atteh, J O; Leeson, S

    1984-11-01

    The effects of inclusion of 8% oleic, palmitic, or a 50/50 mixture of oleic and palmitic acids as the major source of fat in the presence of .8, 1.2, or 1.6% calcium in broiler diets was investigated using broiler chicks from day-old to 3 weeks of age. Supplementation of broiler diets with oleic acid reduced feed intake (P less than .05) and improved feed efficiency (P less than .01) compared to other treatments. Chicks fed diets supplemented with oleic acid or a mixture of oleic and palmitic acid gained more weight (P less than .01) over a 3-week period. Significant interactions were observed between type of dietary fatty acid and calcium level on metabolizable energy of diets (P less than .01), magnesium retention (P less than .05), calcium and fat retention (P less than .01), and proportion of excreta fatty acid that was present as soap (P less than .01). Although all fatty acids tested formed soap in the small intestine, soaps of oleic acid were efficiently utilized as opposed to soaps of palmitic acid. There was a significant (P less than .05) reduction in bone ash and bone calcium content of chicks fed diets supplemented with palmitic acid. There was a significant interaction (P less than .05) between type of fatty acid and calcium level on bone magnesium content. Increasing the calcium content of diets aggravated the decrease in calcium retention and bone calcium content associated with addition of fat.

  3. Predictors of Urinary 3-Phenoxybenzoic Acid Levels in 50 North Carolina Adults

    PubMed Central

    Morgan, Marsha; Jones, Paul; Sobus, Jon; Boyd Barr, Dana

    2016-01-01

    Limited data are available on the non-chemical stressors that impact adult exposures to pyrethroid insecticides based on urinary biomonitoring. The urinary metabolite, 3-phenoxybenzoic acid (3-PBA), is commonly used to assess human exposure to a number of pyrethroids. In a further analysis of published study data, we quantified urinary 3-PBA levels of 50 adults over a single, 24-h sampling period and examined the associations between the biomarker measurements and selected non-chemical stressors (demographic, lifestyle, and dietary factors). A convenience sample of 50 adults was recruited in North Carolina in 2009–2011. Participants collected individual urine voids (up to 11) and filled out activity, food, and pesticide use diaries over a 24-h sampling period. Urine voids (n = 326) were analyzed for 3-PBA concentrations using high-performance liquid chromatography-tandem mass spectrometry. 3-PBA was detected in 98% of the 24-h composited urine samples. The geometric mean urinary 3-PBA level was 1.68 ng/mL in adults. Time spent outside (p = 0.0006) was a highly significant predictor of natural log-transformed (ln) urinary 3-PBA levels, while consumption of coffee (p = 0.007) and breads (p = 0.019) and ln creatinine levels (p = 0.037) were significant predictors of urinary 3-PBA levels. In conclusion, we identified specific factors that substantially increased adult exposures to pyrethroids in their everyday environments. PMID:27886113

  4. Receptor-level interrelationships of amino acids and the adequate amino acid type hormones in Tetrahymena: a receptor evolution model.

    PubMed

    Csaba, G; Darvas, Z

    1986-01-01

    Histidine stimulates the phagocytosis of Tetrahymena to the same extent as histamine, and also stimulates its division, which histamine does not. Tyrosine and diiodotyrosine equally stimulate the growth of the Tetrahymena. Both amino acids inhibit the characteristic influence of the adequate amino acid hormone when added to Tetrahymena culture 72 h in advance of it. Primary interaction with diiodotyrosine and tyrosine notably increases the cellular growth rate. Histamine has a similar, although less notable effect than histidine. In the light of these experimental observations there is reason to postulate that the receptors of the amino acid hormones have developed from amino acid receptors.

  5. Sulfur-rich geothermal emissions elevate acid aerosol levels in metropolitan Taipei.

    PubMed

    Lin, Chih-Hung; Mao, I-Fang; Tsai, Pei-Hsien; Chuang, Hsin-Yi; Chen, Yi-Ju; Chen, Mei-Lien

    2010-08-01

    Several studies have demonstrated that millions of people globally are potentially exposed to volcanic gases. Hydrogen sulfide is a typical gas in volcanic and geothermal areas. The gas is toxic at high concentrations that predominantly affects the nervous, cardiovascular, and respiratory systems. The WHO air quality guideline for hydrogen sulfide is 150 microg m(-3) (105 ppb). The northwest part of Taipei is surrounded by sulfur-rich geothermal and hot springs. Active fumaroles and bubbling springs around the geothermal area emit acidic gases. In combination with automobile emissions, the pollution of acid aerosols is characteristic of the metropolis. This study considered sulfur-rich geothermal, suburban and downtown locations of this metropolis to evaluate geothermally emitted acid aerosol and H(2)S pollution. Acid aerosols were collected using a honeycomb denuder filter pack sampling system (HDS), and then analyzed by ion chromatography (IC). Results indicated that long-term geothermal emissions, automobile emissions and photochemical reactions have led to significant variations in air pollution among regions of metropolitan Taipei. The highest H(2)S concentration was 1705 ppb in the geothermal area with low traffic density and the mean concentration was 404.06 ppb, which was higher than WHO guideline and might cause eye irritation. The SO(2) concentrations were relatively low (mean concentration was 3.9 ppb) in this area. It may partially result from the chemical reduction reaction in the geothermal emission, which converted the SO(2) gas into SO(4)(2-) and H(2)S. Consequently, very high sulfate concentrations (mean concentration higher than 25.0 microg m(-3)) were also observed in the area. The geothermal areas also emitted relatively high levels of aerosol acidity, Cl(-), F(-), PO(4)(3-), and N-containing aerosols. As a result, concentrations of HNO(3), NO(2)(-), PO(4)(3-), and SO(4)(2-) in metropolitan Taipei are significantly higher than those in other

  6. The Association of Fatty Acid Levels and Gleason Grade among Men Undergoing Radical Prostatectomy

    PubMed Central

    Zhao, Zhiguo; Reinstatler, Lael; Klaassen, Zachary; Xu, Yi; Yang, Xiaoyu; Madi, Rabii; Terris, Martha K.; Qian, Steven Y.; Kelavkar, Uddhav; Moses, Kelvin A.

    2016-01-01

    Background Epidemiological data suggest that omega-6 (ω-6) fatty acids (FAs) may be associated with cancer incidence and/or cancer mortality, whereas ω-3 FAs are potentially protective. We examined the association of the ratio of ω-6 to ω-3 FA (ω-6:ω-3) and individual FA components with pathological results among men with prostate cancer (PCa) undergoing radical prostatectomy. Methods Sixty-nine men were included in the study. Components of ω-6 (linoleic acid (LA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA)) and ω-3 (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) were analyzed by liquid chromatography/mass selective detector separation. Logistic regression analysis was performed to determine association of FA with pathological high grade (Gleason ≥4+3) disease. Results The were 35 men with low grade disease (Gleason ≤3+4) and 34 men with high grade disease. Men with low grade disease were significantly younger (58y vs 61y, p = 0.012) and had lower D’Amico clinical classification (p = 0.001) compared to men with high grade disease. There was no significant association of ω-6:ω-3 with high grade disease (OR 0.93, p = 0.78), however overall ω-6, ω-3, and individual components of ω-6 and ω-3 FAs except EPA were significantly associated with high grade disease (ω-6: OR 3.37, 95% CI: 1.27,8.98; LA: OR 3.33, 95% CI:1.24,8.94; AA: OR 2.93, 95% CI:1.24,6.94; DGLA: OR 3.21, 95% CI:1.28,8.04; ω-3: OR 3.47, 95% CI:1.22,9.83; DHA: OR 3.13, 95% CI:1.26,7.74). ω-6 and ω-3 FA components were highly correlated (Spearman ρ = 0.77). Conclusion Higher levels of individual components of ω-6 and ω-3FAs may be associated with higher-grade PCa. Impact Studies into the causative factors/pathways regarding FAs and prostate carcinogenesis may prove a potential association with PCa aggressiveness. PMID:27880795

  7. Differential modulation of alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors expressed in Xenopus oocytes by flufenamic acid and niflumic acid.

    PubMed

    Zwart, R; Oortgiesen, M; Vijverberg, H P

    1995-03-01

    Effects of flufenamic acid (FFA) and niflumic acid (NFA), which are often used to block Ca(2+)-activated Cl- current, have been investigated in voltage-clamped Xenopus oocytes expressing alpha 3 beta 2 and alpha 3 beta 4 nicotinic ACh receptors (nAChRs). NFA and FFA inhibit alpha 3 beta 2 nAChR-mediated inward currents and potentiate alpha 3 beta 4 nAChR-mediated inward currents in normal, Cl(-)-free and Ca(2+)-free solutions to a similar extent. The concentration-dependence of the inhibition of alpha 3 beta 2 nAChR-mediated ion current yields IC50 values of 90 microM for FFA and of 260 microM for NFA. The potentiation of alpha 3 beta 4 nAChR-mediated ion current by NFA yields an EC50 value of 30 microM, whereas the effect of FFA does not saturate for concentrations of up to 1 mM. At 100 microM, FFA reduces the maximum of the concentration-effect curve of ACh for alpha 3 beta 2 nAChRs, but leaves the EC50 of ACh unaffected. The same concentration of FFA potentiates alpha 3 beta 4 nAChR-mediated ion currents for all ACh concentrations and causes a small shift of the concentration-effect curve of ACh to lower agonist concentrations. The potentiation, like the inhibition, is most likely due to a noncompetitive effect of FFA. Increasing ACh-induced inward current either by raising the agonist concentration from 10 microM to 200 microM or by coapplication of 10 microM ACh and 200 microM FFA causes a similar enhancement of block of the alpha 3 beta 4 nAChR-mediated ion current by Mg2+. This suggests that the effects of FFA and of an increased agonist concentration result in a similar functional modification of the alpha 3 beta 4 nAChR-operated ion channel. It is concluded that alpha 3 beta 4 and alpha 3 beta 2 nAChRs are oppositely modulated by FFA and NFA through a direct beta-subunit-dependent effect.

  8. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

    PubMed

    Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

    2010-04-09

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

  9. Reconsideration of the significance of substrate-level phosphorylation in the citric acid cycle*.

    PubMed

    Lambeth, David O

    2006-01-01

    For nearly 50 years, students of metabolism in animals have been taught that a substrate-level phosphorylation in the Krebs citric acid cycle produces GTP that subsequently undergoes a transphosphorylation with ADP catalyzed by nucleoside diphosphate kinase. Research in the past decade has revealed that animals also express an ADP-forming succinate-CoA ligase whose activity exceeds that of the GDP-forming enzyme in some tissues. Here I argue that the primary fate of GTP is unlikely to be transphosphorylation with ADP. Rather, two succinate-CoA ligases with different nucleotide specificities have evolved to better integrate and regulate the central metabolic pathways that involve the citric acid cycle. The products of substrate-level phosphorylation, ATP and/or GTP, may represent a pool of nucleotide that has a different phosphorylation potential than the ATP made by oxidative phosphorylation and may be channeled to meet specific needs within mitochondria and the cell. Further research is needed to determine the applicable mechanisms and how they vary in tissues.

  10. Salicylic acid enhances antioxidant system in Brassica juncea grown under different levels of manganese.

    PubMed

    Parashar, Akshaya; Yusuf, Mohammad; Fariduddin, Qazi; Ahmad, Aqil

    2014-09-01

    The aim was to explore the responses of varied doses of manganese in mustard plants and also to test the proposition that salicylic acid induced up-regulation of antioxidant system which protect photosynthetic apparatus. Seeds were sown in pots and allowed to germinate under natural environmental conditions. At 10 days stage, soils in the pots were enriched with different levels (0, 3, 6, or 9 mM) of Mn for three days and allowed to grow till 30 day stage. At 31st day, foliage of plants was sprayed with 10 μM of salicylic acid (SA) and then allowed to grow till 45 days. Then plants were harvested to assess various growth, leaf gas exchange traits and biochemical parameters. Mn-treated plants had diminished growth, water relations and photosynthetic attributes along with carbonic anhydrase activity whereas; the level of lipid peroxidation, electrolyte leakage, accumulation of H2O2 along with proline accumulation and antioxidant enzymes increased in a concentration dependent manner. Follow-up application of SA to the Mn-stressed plants improved growth, water relations and photosynthetic traits, accelerated the activity of antioxidant enzymes and also the accumulation of proline. SA mediated tolerance to Mn-stressed plants could have due to up-regulation of antioxidant enzymes and proline accumulation.

  11. Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting

    SciTech Connect

    Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D. )

    1987-10-01

    In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R{sub d}) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R{sub d}. In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using (3-{sup 3}H)glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R{sub d}.

  12. Effects of dietary protein levels for gestating gilts on reproductive performance, blood metabolites and milk composition.

    PubMed

    Jang, Y D; Jang, S K; Kim, D H; Oh, H K; Kim, Y Y

    2014-01-01

    This experiment was conducted to evaluate the effects of dietary CP levels in gestation under equal lysine content on reproductive performance, blood metabolites and milk composition of gilts. A total of 25 gilts (F1, Yorkshire×Landrace) were allotted to 4 dietary treatments at breeding in a completely randomized design, and fed 1 of 4 experimental diets containing different CP levels (11%, 13%, 15%, or 17%) at 2.0 kg/d throughout the gestation. Body weight of gilts at 24 h postpartum tended to increase linearly (p = 0.09) as dietary CP level increased. In lactation, backfat thickness, ADFI, litter size and weaning to estrus interval (WEI) did not differ among dietary treatments. There were linear increases in litter and piglet weight at 21 d of lactation (p<0.05) and weight gain of litter (p<0.01) and piglet (p<0.05) throughout the lactation as dietary CP level increased. Plasma urea nitrogen levels of gilts in gestation and at 24 h postpartum were linearly elevated as dietary CP level increased (p<0.05). Free fatty acid (FFA) levels in plasma of gestating gilts increased as dietary CP level increased up to 15%, and then decreased with quadratic effects (15 d, p<0.01; 90 d, p<0.05), and a quadratic trend (70 d, p = 0.06). There were no differences in plasma FFA, glucose levels and milk composition in lactation. These results indicate that increasing dietary CP level under equal lysine content in gestation increases BW of gilts and litter performance but does not affect litter size and milk composition. Feeding over 13% CP diet for gestating gilts could be recommended to improve litter growth.

  13. Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice

    PubMed Central

    Takahara, Ikuko; Akazawa, Yuko; Tabuchi, Maiko; Matsuda, Katsuya; Miyaaki, Hisamitsu; Kido, Youko; Kanda, Yasuko; Taura, Naota; Ohnita, Ken; Takeshima, Fuminao; Sakai, Yusuke; Eguchi, Susumu; Nakashima, Masahiro; Nakao, Kazuhiko

    2017-01-01

    Background and aims A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD. Methods Huh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed. Results Toyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine-adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes. Conclusions The data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans. PMID:28278289

  14. The Anterior Temporal Face Area Contains Invariant Representations of Face Identity That Can Persist Despite the Loss of Right FFA and OFA.

    PubMed

    Yang, Hua; Susilo, Tirta; Duchaine, Bradley

    2016-03-01

    Macaque neurophysiology found image-invariant representations of face identity in a face-selective patch in anterior temporal cortex. A face-selective area in human anterior temporal lobe (fATL) has been reported, but has not been reliably identified, and its function and relationship with posterior face areas is poorly understood. Here, we used fMRI adaptation and neuropsychology to ask whether fATL contains image-invariant representations of face identity, and if so, whether these representations require normal functioning of fusiform face area (FFA) and occipital face area (OFA). We first used a dynamic localizer to demonstrate that 14 of 16 normal subjects exhibit a highly selective right fATL. Next, we found evidence that this area subserves image-invariant representation of identity: Right fATL showed repetition suppression to the same identity across different images, while other areas did not. Finally, to examine fATL's relationship with posterior areas, we used the same procedures with Galen, an acquired prosopagnosic who lost right FFA and OFA. Despite the absence of posterior face areas, Galen's right fATL preserved its face selectivity and showed repetition suppression comparable to that in controls. Our findings suggest that right fATL contains image-invariant face representations that can persist despite the absence of right FFA and OFA, but these representations are not sufficient for normal face recognition.

  15. Sulforaphane reduces the alterations induced by quinolinic acid: modulation of glutathione levels.

    PubMed

    Santana-Martínez, R A; Galván-Arzáte, S; Hernández-Pando, R; Chánez-Cárdenas, M E; Avila-Chávez, E; López-Acosta, G; Pedraza-Chaverrí, J; Santamaría, A; Maldonado, P D

    2014-07-11

    Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities.

  16. Elevated Serum Uric Acid Levels Are Related to Cognitive Deterioration in an Elderly Japanese Population

    PubMed Central

    Suzuki, Kazushi; Koide, Daisuke; Fujii, Kurumi; Yamazaki, Tsutomu; Tsuji, Shoji; Iwata, Atsushi

    2016-01-01

    Aims The association between serum uric acid (UA) levels and cognitive function is controversial since UA can be a risk factor for cerebral ischemia as well as acting as a neuroprotective antioxidant. Methods We conducted a cross-sectional analysis of 228 elderly participants and examined neuropsychological test results, clinical data as well as brain magnetic resonance imaging data. Patients Overall, 64 participants were diagnosed with cognitive deterioration. To control for the effect of sex differences, 2 independent sets of single-variable and multivariate logistic regression analyses were performed with quartiles divided into non-sex-specific and sex-specific cutoff values for UA. Results In non-sex-specific quartiles, the participants in the highest quartiles of UA levels were found to be at a significantly higher risk of cognitive deterioration than those in the lowest quartiles. In sex-specific quartiles, the highest quartile showed an increased risk of cognitive deterioration, and a greater than fourfold increase in the risk in the highest quartiles was confirmed using multivariate regression models. However, no significant association was observed between serum UA levels and the presence of white matter lesions. Conclusions Elevated serum UA levels were independently associated with cognitive deterioration. UA might have unknown adverse effects on cognitive function, other than causing vascular pathology. PMID:28203247

  17. Effects of composite restorations on nitric oxide and uric acid levels in saliva

    PubMed Central

    Akgul, Nilgun; Gul, Pinar; Alp, Hamit Hakan; Kiziltunc, Ahmet

    2015-01-01

    Background and Aims: Dental materials that are used in dentistry should be harmless to oral tissues, and should, therefore, not contain any leachable toxic and diffusible substances capable of causing side effects. This study was intended to investigate the effects on salivary nitric oxide (NO) and uric acid (UA) levels after application of dental composite filling materials to healthy volunteers. Materials and Methods: A total of 52 individuals (32 female and 20 male) participated in the study. Filtek Z250 composite filling material (3M ESPE, St Paul, MN, USA) was applied to healthy volunteers. Saliva samples were collected before restoration (baseline) and 1 h, 1-day, 7 days, and 30 days after restoration. NO concentrations were measured using the Griess reaction method, and UA was measured using an enzymatic method. Data were analyzed using repeated measures ANOVA and the Bonferroni post-hoc test (α =5%). Results: NO values increased statistically significant after 7 days (P < 0.05). In addition, lower UA levels were determined compared to the baseline levels, but the difference was not statistically significant (P > 0.05). There was no correlation between NO and UA levels in saliva (P > 0.05). Conclusion: Composite resins activated the antioxidant system in saliva. However, further studies are now needed to confirm our findings and to permit a definitive conclusion. PMID:26321839

  18. Synthesis and role of salicylic acid in wheat varieties with different levels of cadmium tolerance.

    PubMed

    Kovács, Viktória; Gondor, Orsolya K; Szalai, Gabriella; Darkó, Eva; Majláth, Imre; Janda, Tibor; Pál, Magda

    2014-09-15

    Wheat genotypes with different endogenous SA contents were investigated, in order to reveal how cadmium influences salicylic acid (SA) synthesis, and to find possible relationships between SA and certain protective compounds (members of the antioxidants and the heavy metal detoxification system) and between the SA content and the level of cadmium tolerance. Cadmium exposure induced SA synthesis, especially in the leaves, and it is suggested that the phenyl-propanoid synthesis pathway is responsible for the accumulation of SA observed after cadmium stress. Cadmium influenced the synthesis and activation of protective compounds to varying extents in wheat genotypes with different levels of tolerance; the roots and leaves also responded differently to cadmium stress. Although a direct relationship was not found between the initial SA levels and the degree of cadmium tolerance, the results suggest that the increase in the root SA level during cadmium stress in the Mv varieties could be related with the enhancement of the internal glutathione cycle, thus inducing the antioxidant and metal detoxification systems, which promote Cd stress tolerance in wheat seedlings. The positive correlation between certain SA-related compounds and protective compounds suggests that SA-related signalling may also play a role in the acclimation to heavy metal stress.

  19. Plasma ammonia levels in preterm infants receiving parenteral nutrition with crystalline L-amino acids.

    PubMed

    Shohat, M; Wielunsky, E; Reisner, S H

    1984-01-01

    In order to investigate the severity and incidence of hyperammonemia in preterm infants receiving total parenteral nutrition (TPN) with crystalline L-amino acids having high arginine content (Travasol), we determined the plasma ammonia (PA) levels in a group of 29 preterm infants on TPN, weekly and 1 wk posttherapy. Their mean gestational age was 29.9 +/- 2.6 wk and mean birth weight 1208 +/- 262 g. Thirty five blood samples obtained from 15 preterm infants not on TPN with mean gestational age 32.2 +/- 1.9 wk and a birth weight of 1495 +/- 161 g served as a control. In the parenteral nutrition group the mean PA level (140 +/- 58 micrograms/100 ml) was significantly higher (p less than 0.001) than that in the same group one week post TPN (97 +/- 34 micrograms/100 ml) and in the control group (86 +/- 35 micrograms/100 ml). The incidence of hyperammonemia (greater than 160 micrograms/100 ml) was 30% in the TPN group versus 3% in the controls (p less than 0.01). Maximal PA level during that treatment was 405 versus 216 micrograms/100 ml 1 wk post-TPN versus 163 micrograms/100 ml in the controls. The data show a significant increase in PA levels in preterm infants receiving TPN with Travasol, possibly because of its high glycine content.

  20. Isobaric Tags for Relative and Absolute Quantitation (iTRAQ)-Based Proteomic Analysis of Hugan Qingzhi and Its Protective Properties against Free Fatty Acid-Induced L02 Hepatocyte Injury

    PubMed Central

    Xia, Fan; Yao, Xiaorui; Tang, Waijiao; Xiao, Chunxin; Yang, Miaoting; Zhou, Benjie

    2017-01-01

    In previous research, Hugan Qingzhi, a traditional Chinese medicine, was shown to have protective effects against hepatic steatosis. However, its activity against non-alcoholic fatty liver disease (NAFLD) and the mechanisms by which it exerts its effects remain unknown. In the present study, the effects of Hugan Qingzhi on free fatty acid (FFA)-induced L02 cells were examined. The techniques of iTRAQ labeling, together with strong cation exchange-non-liquid chromatography–tandem mass spectrometry (SCX-non-LC-MS/MS) analysis and serum pharmacology, were used to evaluate the effects of Hugan Qingzhi-medicated serum on FFA-induced L02 hepatocyte injury. Results identified 355 differentially expressed proteins following FFA treatment, compared with a control group; 359 altered proteins in the Hugan Qingzhi high dose + FFA treatment group, compared with the FFA treatment group; and 365 altered proteins in the Hugan Qingzhi high dose + FFA treatment group, compared with the control group. Based on the Kyoto Encyclopedia of Gene and Genomes pathway enrichment analysis, it is concluded that several pathways including those of microbial metabolism in diverse environments, fatty acid metabolism, peroxisome proliferator activated receptor signaling, and mitogen-activated protein kinase signaling are closely associated with the effects of Hugan Qingzhi-medicated serum in FFA-induced L02 hepatocyte injury. Furthermore, several differentially expressed proteins, including heat shock protein 27 (HSP27), acetyl-CoA acetyltransferase 1, calnexin, and integrin-linked kinase, were validated by western blotting. A target-specific HSP27 siRNA was used to investigate further the function of HSP27, and it was found that HSP27 might have a key role in the observable effects of Hugan Qingzhi-medicated serum in FFA-induced L02 hepatocyte injury. The results not only confirmed that Hugan Qingzhi exhibits a significant protective effect in FFA-induced L02 hepatocyte injury, but also suggest

  1. Salivary total sialic acid levels increase in breast cancer patients: a preliminary study.

    PubMed

    Oztürk, Leyla Koç; Emekli-Alturfan, Ebru; Kaşikci, Emel; Demir, Gokhan; Yarat, Aysen

    2011-09-01

    Breast cancer is the most common cancer in women living in the Western world, even though it occurs worldwide. Cancer and cancer therapy induce multiple oral complications including dental and periodontal disease. Saliva is a complex and dynamic biologic fluid, which reflects both oral and systemic changes. While saliva is easily accessible body fluid, there has been little effort to study its value in cancer diagnosis. Sialic acids (SA), the end moieties of the carbohydrate chains, are biologically important and essential for functions of glycoconjugates that are reported to be altered in both blood and saliva of various cancer patients. Increased sialylation has been shown to be a characteristic feature in cancer tissue and blood in breast cancer patients. However, there is no data about salivary SA in breast cancer. The aim of this study was to evaluate salivary total sialic acid (TSA) levels in breast cancer patients who were under chemotheraphy. The study included 15 breast cancer patients in different stages and 10 healthy individuals as age-matched controls. Unstimulated whole saliva was collected. Salivary total protein and SA levels were determined. Flow rate was calculated from salivary volume by the time of secretion. Salivary SA was significantly higher and total protein was lower in breast cancer patients compared to controls. It is concluded that sialylation may be increased in saliva of patients with breast cancer as the same way for cancer tissue and for blood . Increased salivary SA may therefore be useful as a non-invasive predictive marker for breast cancer patients and for the prevention and management of oral complications of cancer and cancer therapy to improve oral function and quality-of-life. The effects of different types of chemotherapies and different stages of the disease on salivary SA levels and salivary sialo-glycomic are worthy of being further investigated in breast cancer patients.

  2. Serum Uric Acid Levels in Patients with Alzheimer's Disease: A Meta-Analysis

    PubMed Central

    Chen, Xueping; Guo, Xiaoyan; Huang, Rui; Chen, Yongping; Zheng, Zhenzhen; Shang, Huifang

    2014-01-01

    Background Serum uric acid (UA) could exert neuro-protective effects against Alzheimer's disease (AD) via its antioxidant capacities. Many studies investigated serum UA levels in AD patients, but to date, results from these observational studies are conflicting. Methods We conducted a meta-analysis to compare serum UA levels between AD patients and healthy controls by the random-effects model. Studies were identified by searching PubMed, ISI Web of Science, EMBASE, and the Cochrane library databases from 1966 through July 2013 using the Medical Subject Headings and keywords without restriction in languages. Only case-control studies were included if they had data on serum UA levels in AD patients and healthy controls. Begg's funnel plot and Egger's regression test were applied to assess the potential publication bias. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Results A total of 11 studies met the inclusion criteria including 2708 participants were abstracted. Serum UA levels were not significantly different in AD patients compared to healthy controls (standardized mean difference (SMD) = −0.50; 95% confidence interval (CI): −1.23 to 0.22). Little evidence of publication bias was observed. Sensitivity analyses showed that the combined SMD was consistent every time omitting any one study, except only one study which greatly influenced the overall results. Meta-regression showed that year of publication, race, sample size, and mean age were not significant sources of heterogeneity. Conclusion Our meta-analysis of case-control studies suggests that serum UA levels do not differ significantly in AD patients, but there may be a trend toward decreased UA in AD after an appropriate interpretation. More well-designed investigations are needed to demonstrate the potential change of serum UA levels in AD patients. PMID:24714617

  3. Production of yogurt with enhanced levels of gamma-aminobutyric acid and valuable nutrients using lactic acid bacteria and germinated soybean extract.

    PubMed

    Park, Ki-Bum; Oh, Suk-Heung

    2007-05-01

    Yogurt with high levels of gamma-aminobutyric acid (GABA), free amino acids and isoflavones was developed using lactic acid bacteria (LAB) and germinated soybean extract. Fermented soya milk (GABA soya yogurt) produced with starter and substrate had the GABA concentration of 424.67 microg/gDW, whereas fermented milk produced by a conventional method had GABA less than 1.5 microg/gDW. The GABA soya yogurt also contained significantly high levels of free amino acids and isoflavones compared with other conventional yogurts. The results suggested that the Lactobacillus brevis OPY-1 and germinated soybean possessed a prospect to be applied in dairy and other health products with high nutritive values and functional properties.

  4. Plasma long-chain free fatty acids predict mammalian longevity.

    PubMed

    Jové, Mariona; Naudí, Alba; Aledo, Juan Carlos; Cabré, Rosanna; Ayala, Victoria; Portero-Otin, Manuel; Barja, Gustavo; Pamplona, Reinald

    2013-11-28

    Membrane lipid composition is an important correlate of the rate of aging of animals and, therefore, the determination of their longevity. In the present work, the use of high-throughput technologies allowed us to determine the plasma lipidomic profile of 11 mammalian species ranging in maximum longevity from 3.5 to 120 years. The non-targeted approach revealed a specie-specific lipidomic profile that accurately predicts the animal longevity. The regression analysis between lipid species and longevity demonstrated that the longer the longevity of a species, the lower is its plasma long-chain free fatty acid (LC-FFA) concentrations, peroxidizability index, and lipid peroxidation-derived products content. The inverse association between longevity and LC-FFA persisted after correction for body mass and phylogenetic interdependence. These results indicate that the lipidomic signature is an optimized feature associated with animal longevity, emerging LC-FFA as a potential biomarker of longevity.

  5. Elevated systemic glutamic acid level in the non-obese diabetic mouse is Idd linked and induces beta cell apoptosis.

    PubMed

    Banday, Viqar Showkat; Lejon, Kristina

    2017-02-01

    Although type 1 diabetes (T1D) is a T-cell-mediated disease in the effector stage, the mechanism behind the initial beta cell assault is less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in patients with T1D before disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD mice. Serum glutamic acid levels from a (NOD×B6)F2 cohort (n = 182) were measured. By genome-wide and Idd region targeted microsatellite mapping, genetic association was detected for six regions including Idd2, Idd4 and Idd22. In silico analysis of potential enzymes and transporters located in and around the mapped regions that are involved in glutamic acid metabolism consisted of alanine aminotransferase, glutamic-oxaloacetic transaminase, aldehyde dehydrogenase 18 family, alutamyl-prolyl-tRNA synthetase, glutamic acid transporters GLAST and EAAC1. Increased EAAC1 protein expression was observed in lysates from livers of NOD mice compared with B6 mice. Functional consequence of the elevated glutamic acid level in NOD mice was tested by culturing NOD. Rag2(-/-) Langerhans' islets with glutamic acid. Induction of apoptosis of the islets was detected upon glutamic acid challenge using TUNEL assay. Our results support the notion that a dysregulated metabolome could contribute to the initiation of T1D. We suggest that targeting of the increased glutamic acid in pre-diabetic patients could be used as a potential therapy.

  6. Chlorogenic acid increased 5-hydroxymethylfurfural formation when heating fructose alone or with aspartic acid at two pH levels.

    PubMed

    Zhang, Zhenhua; Zou, Yueyu; Wu, Taigang; Huang, Caihuan; Pei, Kehan; Zhang, Guangwen; Lin, Xiaohua; Bai, Weibin; Ou, Shiyi

    2016-01-01

    Chlorogenic acid (CGA) is a phenolic acid that ubiquitously exists in fruits. This work aims to investigate whether and how CGA influences HMF formation during heating fructose alone, or with an amino acid. The results showed that that CGA increased 5-hydroxymethylfurfural (HMF) formation. At pH 5.5 and 7.0, the addition of 5.0 μmol/ml CGA increased HMF formation by 49.4% and 25.2%, respectively when heating fructose alone, and by 9.0% and 16.7%, respectively when heating fructose with aspartic acid. CGA significantly increased HMF formation by promoting 3-deoxosone formation, and its conversion to HMF by inhibiting HMF elimination, especially in the Maillard reaction system. A comparison of the catalytic capacity of CGA with its six analogous compounds showed that both its di-hydroxyphenyl and carboxyl groups function in increasing HMF formation.

  7. The Prevalence of Nonalcoholic Fatty Liver Disease and Relationship with Serum Uric Acid Level in Uyghur Population

    PubMed Central

    Cai, Wen; Song, Jiang-mei; Zhang, Bei; Sun, Yu-ping; Yao, Hua; Zhang, Yue-xin

    2014-01-01

    Objective. To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of serum uric acid level with NAFLD in Uygur people, Xinjiang. Methods. A total of 2241 Uyghur persons (1214 males and 1027 females) were interviewed for physical checkups from 2011 to 2012. The clinical data of questionnaire survey, body mass index (BMI), abdominal circumference, blood pressure, blood sugar, blood lipid, and serum uric acid level were collected for analysis. Results. The prevalence rates of NAFLD determined by abdominal ultrasound examination and hyperuricemia were 43.9% and 8.4%, respectively. The persons with NAFLD had significantly higher serum uric acid levels than those without NAFLD (320 ± 88 versus 254 ± 80 μmol/L; P < 0.001). The prevalence rate of NAFLD was significantly higher in subjects with hyperuricemia than that in those without hyperuricemia (78.19% versus 40.83%; P < 0.001), and the prevalence rate increased with progressively higher serum uric acid levels (P < 0.001). Multiple regression analysis showed that hyperuricemia was associated with an increased risk of NAFLD (odds ratio (OR): 2.628, 95% confidence interval (CI): 1.608–4.294, and P < 0.001). Conclusion. Serum uric acid level was significantly associated with NAFLD, and the prevalence rate of NAFLD increased with progressively higher serum uric acid levels. PMID:24516367

  8. Effects of copper on chlorophyll, proline, protein and abscisic acid level of sunflower (Helianthus annuus L.) seedlings.

    PubMed

    Zengin, Fikriye Kirbag; Kirbag, Sevda

    2007-07-01

    The effect of copperchloride (CuCl2) on the level of chlorophyll (a+b), proline, protein and abscisic acid in sunflower (Helianthus annuus L.) seedlings were investigated Control and copper treated (0.4, 0.5 and 0.6 mM) seedlings were grown for ten days in Hoagland solution. Abscisic acid content was determined in root, shoot and leaf tissues of seedlings by HPLC. Copper stress caused significant increase of the abscisic acid contents in roots, shoots and leaves of seedlings. The increase was dependent on the copper salt concentration. Enhanced accumulation of proline in the leaves of seedlings exposed to copper was determined, as well as a decrease of chlorophyll (a+b) and total protein (p < 0.05 or p < 0.01). It was observed that the level of chlorophyll (a+b) and total protein (p < 0.05 or p < 0.01) remarkably decreased as copper concentration increased to 0.6 mM, although the levels of proline and abscisic acid in the leaves of plants were increased--a dose-depended behavior The same trends were also observed with the level of abscisic acid of stems and roots. Copper has dose- depended effects on chlorophyll, proline, protein and abscisic acid level of sunflower (Helianthus annuus L.) seedlings. Thus, we assumed that copper levels increase above some critical points seedling growth get negative effects. This assumption is in line with previous findings.

  9. Phytochemicals from Tradescantia albiflora Kunth Extracts Reduce Serum Uric Acid Levels in Oxonate-induced Rats

    PubMed Central

    Wang, Wen-Ling; Sheu, Shi-Yuan; Huang, Wen-Dar; Chuang, Ya-Ling; Tseng, Han-Chun; Hwang, Tzann-Shun; Fu, Yuan-Tsung; Kuo, Yueh-Hsiung; Yao, Chun-Hsu; Kuo, Tzong-Fu

    2016-01-01

    Background: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time. Materials and Methods: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration. Results: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 μg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents. SUMMARY Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n-hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP

  10. Effects of allopurinol on plasma uric acid levels in normouricaemic and hyperuricaemic green iguanas (Iguana iguana).

    PubMed

    Hernandez-Divers, S J; Martinez-Jimenez, D; Bush, S; Latimer, K S; Zwart, P; Kroeze, E J B Veldhuis

    2008-01-26

    A two-phase cross-over therapeutic study was performed with 19 green iguanas (Iguana iguana) maintained within a preferred optimum temperature range of 26 to 37 degrees C. During phase 1, they were fed a normal vegetarian diet and medicated orally with either allopurinol or a placebo control once a day for seven days. Uric acid concentrations, total protein, packed-cell volumes (pcv) and bodyweights were recorded from each lizard before and after treatment to determine the effects of allopurinol. In phase 2, after a 10-day washout period, the iguanas were fed a high protein diet to induce hyperuricaemia. Normo- and hyperuricaemic iguanas that received 24.2 (3.2) mg/kg allopurinol had significantly lower mean (sd) uric acid concentrations (100.3 [53.1] micromol/l) than the controls (159.3 [100.3] micromol/l). There were no detectable interactions between the doses of allopurinol or placebo, and the iguanas' diet, weight, pcv or total protein. The allopurinol was well tolerated, and there was no significant clinical, gross or histological evidence of hepatic or renal toxicity in the iguanas that received the drug. However, in the kidneys of the hyperuricaemic iguanas that did not receive allopurinol there were proliferative changes in the glomeruli and degeneration of tubular epithelia. Allopurinol given orally at 25 mg/kg daily is able to reduce plasma uric acid levels by 41 to 45 per cent, and is therefore recommended for the treatment of hyperuricaemia in the green iguana.

  11. Intestinal epithelial cell caveolin 1 regulates fatty acid and lipoprotein cholesterol plasma levels

    PubMed Central

    Shen, Meng-Chieh; Quinlivan, Vanessa; Anderson, Jennifer L.; Farber, Steven A.

    2017-01-01

    ABSTRACT Caveolae and their structural protein caveolin 1 (CAV1) have roles in cellular lipid processing and systemic lipid metabolism. Global deletion of CAV1 in mice results in insulin resistance and increases in atherogenic plasma lipids and cholesterol, but protects from diet-induced obesity and atherosclerosis. Despite the fundamental role of the intestinal epithelia in the regulation of dietary lipid processing and metabolism, the contributions of CAV1 to lipid metabolism in this tissue have never been directly investigated. In this study the cellular dynamics of intestinal Cav1 were visualized in zebrafish and the metabolic contributions of CAV1 were determined with mice lacking CAV1 in intestinal epithelial cells (CAV1IEC-KO). Live imaging of Cav1–GFP and fluorescently labeled caveolae cargos shows localization to the basolateral and lateral enterocyte plasma membrane (PM), suggesting Cav1 mediates transport between enterocytes and the submucosa. CAV1IEC-KO mice are protected from the elevation in circulating fasted low-density lipoprotein (LDL) cholesterol associated with a high-fat diet (HFD), but have increased postprandial LDL cholesterol, total free fatty acids (FFAs), palmitoleic acid, and palmitic acid. The increase in circulating FAs in HFD CAV1IEC-KO mice is mirrored by decreased hepatic FAs, suggesting a non-cell-autonomous role for intestinal epithelial cell CAV1 in promoting hepatic FA storage. In conclusion, CAV1 regulates circulating LDL cholesterol and several FA species via the basolateral PM of enterocytes. These results point to intestinal epithelial cell CAV1 as a potential therapeutic target to lower circulating FFAs and LDL cholesterol, as high levels are associated with development of type II diabetes and cardiovascular disease. PMID:28130355

  12. Free fatty acid and triacylglycerol forms of CLA isomers are not incorporated equally in the liver but do not lead to differences in bone density and biomarkers of bone metabolism.

    PubMed

    DeGuire, Jason R; Weiler, Hope A

    2013-05-01

    Few studies have compared differences between conjugated linoleic acid (CLA) in triacylglycerol (TG) and free fatty acid (FFA) form. This study assessed differences in liver incorporation, mineral mass balance, bone density, and biomarkers of bone metabolism between FFA and TG CLA diets. Rats (n=36) were fed a control (CTRL) or 1% CLA diet in FFA or TG form (1:1 mixture c9, t11: t10, c12). Liver content of c9, t11 CLA from FFA was greater than TG form and CTRL (FFA: 0.05±0.01 vs. TG: 0.02±0.01 vs. CTRL: 0.001±0.001% total fatty acids, P<0.0001). Liver t10, c12 CLA did not differ among groups (P=0.11). No diet differences among groups for growth, bone biomarkers or mass nor mineral balance were found. These findings suggest that c9, t11 CLA in FFA form is preferentially incorporated in the liver but fatty acid forms of CLA do not affect bone or mineral outcomes.

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

    SciTech Connect

    Luo, Yi 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

  14. ClC-7 expression levels critically regulate bone turnover, but not gastric acid secretion.

    PubMed

    Supanchart, C; Wartosch, L; Schlack, C; Kühnisch, J; Felsenberg, D; Fuhrmann, J C; de Vernejoul, M-C; Jentsch, T J; Kornak, U

    2014-01-01

    Mutations in the 2Cl(-)/1H(+)-exchanger ClC-7 impair osteoclast function and cause different types of osteoclast-rich osteopetrosis. However, it is unknown to what extent ClC-7 function has to be reduced to become rate-limiting for bone resorption. In osteoclasts from osteopetrosis patients expression of the mutated ClC-7 protein did not correlate with disease severity and resorption impairment. Therefore, a series of transgenic mice expressing ClC-7 in osteoclasts at different levels was generated. Crossing of these mice with Clcn7(-/-) mutants rescued the osteopetrotic phenotype to variable degrees. One resulting double transgenic line mimicked human autosomal dominant osteopetrosis. The trabecular bone of these mice showed a reduction of osteoblast numbers, osteoid, and osteoblast marker gene expression indicative of reduced osteoblast function. In osteoclasts from these mutants ClC-7 expression levels were 20 to 30% of wildtype levels. These reduced levels not only impaired resorptive activity, but also increased numbers, size and nucleus numbers of osteoclasts differentiated in vitro. Although ClC-7 was expressed in the stomach and PTH levels were high in Clcn7(-/-) mutants loss of ClC-7 did not entail a relevant elevation of gastric pH. In conclusion, we show that in our model a reduction of ClC-7 function by approximately 70% is sufficient to increase bone mass, but does not necessarily enhance bone formation. ClC-7 does not appear to be crucially involved in gastric acid secretion, which explains the absence of an osteopetrorickets phenotype in CLCN7-related osteopetrosis.

  15. A new classification of the amino acid side chains based on doublet acceptor energy levels.

    PubMed Central

    Sneddon, S F; Morgan, R S; Brooks, C L

    1988-01-01

    We describe a new classification of the amino acid side chains based on the potential energy level at which each will accept an extra (doublet) electron. The doublet acceptor energy level, and the doublet acceptor orbital were calculated using semiempirical INDO/2-UHF molecular orbital theory. The results of these calculations show that the side chains fall into four groups. We have termed these groups repulsive, insulating, semiconducting, and attractive in accordance with where each lies on the relative energy scale. We use this classification to examine the role of residues between the donor and acceptor in modulating the rate and mechanism of electron transfer in proteins. With the calculated acceptor levels, we construct a potential barrier for those residues between the donor and acceptor. It is the area beneath this barrier that determines the decay of electronic coupling between donor and acceptor, and thus the transfer rate. We have used this schematic approach to characterize the four electron transfer pathways in myoglobin recently studied by Mayo et al. (Mayo, S.L., W.R. Ellis, R.J. Crutchley, and H.B. Gray. 1986. Science [Wash. DC]. 233:948-952). PMID:3342271

  16. Effect of different levels of supplied cobalt on the fatty acid composition of bovine milk.

    PubMed

    Karlengen, Inger J; Taugbøl, Ole; Salbu, Brit; Aastveit, Are H; Harstad, Odd M

    2013-03-14

    In previous studies, administration of high amounts of Co decreased the proportion of MUFA in bovine milk. The present study was conducted to examine the amount of Co needed to obtain this effect. High-yielding dairy cows (n 4), equipped with ruminal cannulas, were used in a 4 × 4 Latin square design study. The basal diet consisted of concentrate mixture (9 kg/d) without added Co and grass silage (ad libitum). The following four levels of Co were administrated as cobalt acetate dissolved in distilled water: no Co (treatment 1, T1); 4·0 mg Co/d (T2); 380 mg Co/d (T3); 5300 mg Co/d (T4). Each period lasted for 18 d, including 11 d of treatment. During the treatment periods, the solutions were continuously infused into the rumen. Milk yield and milk concentration of fat, fatty acids (FA), protein, lactose, Co, Zn, Fe and Cu were determined. Blood plasma was analysed with respect to FA, Co, Zn, Fe and Cu. Feed intake and total tract digestibility of feed components were also determined. There was a linear effect of increasing the level of Co on milk FA composition. The effects of Co on FA composition in blood were insignificant compared with the effects on milk. In milk fat, the concentration of cis-9-18 : 1 was reduced by as much as 38 % on T4 compared with T1. Feed intake and milk yield were negatively affected by increasing the Co level.

  17. Drought-Induced Increases in Abscisic Acid Levels in the Root Apex of Sunflower 1

    PubMed Central

    Robertson, J. Mason; Pharis, Richard P.; Huang, Yan Y.; Reid, David M.; Yeung, Edward C.

    1985-01-01

    Abscisic acid (ABA) levels in 3-mm apical root segments of slowly droughted sunflower plants (Helianthus annuus L. cv Russian Giant) were analyzed as the methyl ester by selected ion monitoring gas chromatography-mass spectrometry using characteristic ions. An internal standard, hexadeuterated ABA (d6ABA) was used for quantitative analysis. Sunflower seedlings, grown in aeroponic chambers, were slowly droughted over a 7-day period. Drought stress increased ABA levels in the root tips at 24, 72, and 168 hour sample times. Control plants had 57 to 106 nanograms per gram ABA dry weight in the root tips (leaf water potential, −0.35 to −0.42 megapascals). The greatest increase in ABA, about 20-fold, was found after 72 hours of drought (leaf water potential, −1.34 to −1.47 megapascals). Levels of ABA also increased (about 7− to 54-fold) in 3-mm apical root segments which were excised and then allowed to dessicate for 1 hour at room temperature. PMID:16664535

  18. Urinary D-glucaric acid and serum hepatic enzyme levels in chronic alcoholics.

    PubMed

    Tutor, J C; Alvarez-Prechous, A; Bernabeu, F; Pardiñas, M C; Paz, J M; Lareu, V

    1988-06-01

    Urinary D-glucaric acid (DGA) and the activities of gamma-glutamyl transferase (GGT) and other hepatic enzymes in serum were determined in 33 noncirrhotic male alcoholics who had continued to consume alcohol until at least 24 h prior to the taking of samples. DGA excretion was significantly greater in them than in a group of 30 healthy controls (p less than 0.001), exceeding the upper reference level in 38% of the alcoholic cases (as compared with 88% for GGT). In the alcoholic patients, there was highly significant correlation between urinary DGA and serum GGT (r = 0.613, p less than 0.001), suggesting that in both cases the increased levels are due to enzyme induction. None of the biochemical variables studied were significantly correlated with estimated daily alcohol consumption. Urinary DGA levels fell off rapidly with abstinence, and in 31 alcoholic patients who had consumed no alcohol for 5 days, there was no statistically significant correlation between DGA excretion and serum GGT (r = 0.158, p congruent to 0.4).

  19. Lipid-associated sialic acid levels in human breast cyst fluids.

    PubMed

    Mannello, F; Bocchiotti, G; Troccoli, R; Gazzanelli, G

    1992-01-01

    Benign mammary gross cystic disease is the most common breast lesion. Women with apocrine changes of epithelium lining the cysts are at higher risk for developing breast cancer than the normal female population. Sialic acid has drawn considerable interest because of carbohydrate aberrations in malignant cells. The current investigation determined the concentrations of lipid-associated sialic acid (LASA) in 62 breast cyst fluids and sera. Data analyses show a significant increase in the mean values of LASA in metabolically active apocrine cysts when compared to the cysts with Na+/K+ > 3 (flattened cysts) (p < 0.001). The greater LASA levels in cyst fluids with lower intracystic Na+/K+ ratios could represent an altered expression of biosynthetic activity of the surrounding apocrine cell surface sialoglycolipid metabolism, providing a possible explanation of why women with apocrine cysts may be at greater cancer risk and being useful in further studies on functional stage changes in the cysts and their relationship to breast cancer.

  20. [Ascorbic acid consumption and serum levels in smokers and non-smokers adult men in Hermosillo, Sonora, México].

    PubMed

    Méndez, Rosa Olivia; Wyatt, C Jane; Saavedra, Javier; Ornelas, Alicia

    2002-12-01

    Ascorbic acid is one of the important antioxidant nutrients that can aid in the prevention of oxidative cellular damage. Adequate dietary intake is essential as humans can not synthesize this vitamin. It has been reported that smokers require higher dietary intakes to maintain their serum levels. The objective of this study was to determine serum levels of ascorbic acid in young male smokers and non smokers in the city of Hermosillo, Sonora, Mexico. In addition, their dietary intake of ascorbic acid was determined by a 24 h dietary recall. The dietary intake of ascorbic acid in 12 smokers was 64 +/- 11 mg/d and in 13 non smokers it was 70 +/- 12 mg/d. The smokers in this study did not meet the dietary recommendation of 100 mg/d. Serum ascorbic acid values in smokers and non smokers were 24.2 +/- 6.9 mumol/L and 30.9 +/- 3.7 mumol/L respectively. No significant difference was found among the 2 groups. Although the average serum ascorbic acid values fell within the range considered normal, 50% of the smokers had individual values that were below 23 mumol/L, indicating that these subjects have hipovitaminosis. A positive correlation between intake and serum levels was obtained for smokers (r = 0.71; p = 0.03). The results of this study suggest smokers may be at increased risk for chronic diseases due to their low intake and low serum levels of ascorbic acid.

  1. Increased plasma levels of xanthurenic and kynurenic acids in type 2 diabetes

    PubMed Central

    Oxenkrug, Gregory F

    2015-01-01

    About 350 million people worldwide have type 2 diabetes (T2D). The major risk factor of T2D is impaired glucose tolerance (pre-diabetes) with 10% of pre-diabetes subjects develop T2D every year. Understanding of mechanisms of development of T2D from pre-diabetes is important for prevention and treatment of T2D. Chronic stress and chronic low grade inflammation are prominent risk factors for T2D development in pre-diabetic subjects. However, molecular mechanisms mediating effect of stress and inflammation on development of T2D from pre-diabetes remain unknown. One of such mechanisms might involve kynurenine (KYN) pathway (KP) of tryptophan (TRP) metabolism. We suggested that chronic stress- or chronic low grade inflammation-induced upregulation of formation of upstream KTP metabolites, KYN and 3-hydroxyKYN, combined with chronic stress or chronic low grade inflammation-induced deficiency of pyridoxal 5'-phosphate, a cofactor of downstream enzymes of KTP, triggers overproduction of diabetogenic downstream KYN metabolites, kynurenic acid (KYNA) and 3-hydroxyKYNA (also known as xanthurenic acid (XA)). As the initial assessment of our working hypothesis, we evaluated plasma levels of up- and down-stream KP metabolites in the same samples of T2D patients. KYN, XA and KYNA levels in plasma samples of T2D patients were higher than in samples of non-diabetic subjects. Our results provide further support of “kynurenine hypothesis of insulin resistance and its progression to T2D” that suggested that overproduction of diabetogenic KP metabolites, induced by chronic stress- or chronic low grade inflammation, is one of the mechanisms promoting development of T2D from pre-diabetes. Downstream metabolites of KP might serve as biomarkers of T2D and targets for clinical intervention. PMID:26055228

  2. Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.

    PubMed

    Partearroyo, Teresa; Pérez-Miguelsanz, Juliana; Peña-Melián, Ángel; Maestro-de-Las-Casas, Carmen; Úbeda, Natalia; Varela-Moreiras, Gregorio

    2016-06-01

    The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.

  3. Value of random urinary homovanillic acid and vanillylmandelic acid levels in the diagnosis and management of patients with neuroblastoma: comparison with 24-hour urine collections.

    PubMed

    Tuchman, M; Morris, C L; Ramnaraine, M L; Bowers, L D; Krivit, W

    1985-02-01

    Urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) levels were determined in random samples and in 24-hour collections from 13 patients with neuroblastoma and 22 patients without neuroblastoma. Random sample levels were compared with levels in 24-hour collections and showed a positive correlation of 95% for HVA (N = 59) and 93% for VMA (N = 52). No false positives or false negatives occurred using random samples for diagnosis. Nonneuroblastoma (normal) HVA (N = 126) and VMA (N = 119) levels are reported for different age groups. Sequential random HVA and VMA determinations in patients with neuroblastoma during and after therapy are shown. Random urinary HVA and VMA levels are shown to be adequate for utilization in the diagnosis of neuroblastoma and sequential determinations of random HVA and VMA are shown to be helpful in the follow-up of those patients.

  4. A Novel Allosteric Activator of Free Fatty Acid 2 Receptor Displays Unique Gi-functional Bias*

    PubMed Central

    Bolognini, Daniele; Moss, Catherine E.; Nilsson, Karolina; Petersson, Annika U.; Donnelly, Iona; Sergeev, Eugenia; König, Gabriele M.; Kostenis, Evi; Kurowska-Stolarska, Mariola; Miller, Ashley; Dekker, Niek; Tobin, Andrew B.

    2016-01-01

    The short chain fatty acid receptor FFA2 is able to stimulate signaling via both Gi- and Gq/G11-promoted pathways. These pathways are believed to control distinct physiological end points but FFA2 receptor ligands appropriate to test this hypothesis have been lacking. Herein, we characterize AZ1729, a novel FFA2 regulator that acts as a direct allosteric agonist and as a positive allosteric modulator, increasing the activity of the endogenously produced short chain fatty acid propionate in Gi-mediated pathways, but not at those transduced by Gq/G11. Using AZ1729 in combination with direct inhibitors of Gi and Gq/G11 family G proteins demonstrated that although both arms contribute to propionate-mediated regulation of phospho-ERK1/2 MAP kinase signaling in FFA2-expressing 293 cells, the Gq/G11-mediated pathway is predominant. We extend these studies by employing AZ1729 to dissect physiological FFA2 signaling pathways. The capacity of AZ1729 to act at FFA2 receptors to inhibit β-adrenoreceptor agonist-promoted lipolysis in primary mouse adipocytes and to promote chemotaxis of isolated human neutrophils confirmed these as FFA2 processes mediated by Gi signaling, whereas, in concert with blockade by the Gq/G11 inhibitor FR900359, the inability of AZ1729 to mimic or regulate propionate-mediated release of GLP-1 from mouse colonic preparations defined this physiological response as an end point transduced via activation of Gq/G11. PMID:27385588

  5. Effects of weight loss via high fat vs. low fat alternate day fasting diets on free fatty acid profiles.

    PubMed

    Varady, Krista A; Dam, Vi T; Klempel, Monica C; Horne, Matthew; Cruz, Rani; Kroeger, Cynthia M; Santosa, Sylvia

    2015-01-05

    Cardiovascular disease risk is associated with excess body weight and elevated plasma free fatty acid (FFA) concentrations. This study examines how an alternate-day fasting (ADF) diet high (HF) or low (LF) in fat affects plasma FFA profiles in the context of weight loss, and changes in body composition and lipid profiles. After a 2-week weight maintenance period, 29 women (BMI 30-39.9 kg/m(2)) 25-65 years old were randomized to an 8-week ADF-HF (45% fat) diet or an ADF-LF (25% fat) diet with 25% energy intake on fast days and ad libitum intake on feed days. Body weight, BMI and waist circumference were assessed weekly and body composition was measured using dual x-ray absorptiometry (DXA). Total and individual FFA and plasma lipid concentrations were measured before and after weight loss. Body weight, BMI, fat mass, total cholesterol, LDL-C and triglyceride concentrations decreased (P < 0.05) in both groups. Total FFA concentrations also decreased (P < 0.001). In the ADF-LF group, decreases were found in several more FFAs than in the ADF-HF group. In the ADF-HF group, FFA concentrations were positively correlated with waist circumference. Depending on the macronutrient composition of a diet, weight loss with an ADF diet decreases FFA concentrations through potentially different mechanisms.

  6. Purification and identification of bovine cheese whey fatty acids exhibiting in vitro antifungal activity.

    PubMed

    Clément, M; Tremblay, J; Lange, M; Thibodeau, J; Belhumeur, P

    2008-07-01

    Milk lipids contain several bioactive factors exhibiting antimicrobial activity against bacteria, viruses, and fungi. In the present study, we demonstrate that free fatty acids (FFA) derived from the saponification of bovine whey cream lipids are active in vitro at inhibiting the germination of Candida albicans, a morphological transition associated with pathogenicity. This activity was found to be significantly increased when bovine FFA were enriched in non-straight-chain FFA. At low cell density, this non-straight-chain FFA-enriched fraction was also found to inhibit in a dose-dependant manner the growth of both developmental forms of C. albicans as well as the growth of Aspergillus fumigatus. Using an assay-guided fractionation, the main components responsible for these activities were isolated. On the basis of mass spectroscopic and gas chromatographic analysis, antifungal compounds were identified as capric acid (C10:0), lauroleic acid (C12:1), 11-methyldodecanoic acid (iso-C13:0), myristoleic acid (C14:1n-5), and gamma-linolenic acid (C18:3n-6). The most potent compound was gamma-linolenic acid, with minimal inhibitory concentration values of 5.4 mg/L for C. albicans and 1.3 mg/L for A. fumigatus, in standardized conditions. The results of this study indicate that bovine whey contains bioactive fatty acids exhibiting antifungal activity in vitro against 2 important human fungal pathogens.

  7. Blood lead levels among rural Thai children exposed to lead-acid batteries from solar energy conversion systems.

    PubMed

    Swaddiwudhipong, Witaya; Tontiwattanasap, Worawit; Khunyotying, Wanlee; Sanreun, Cherd

    2013-11-01

    We evaluate blood lead levels among Thai children to determine if exposure to lead-acid batteries is associated with elevated blood lead levels (EBLL). We screened 254 children aged 1-14 years old from 2 rural Thai villages for blood lead levels. We also screened 18 of 92 houses in these 2 villages for the presence of environmental lead. The overall prevalence of EBLL (> or = 10 microg/dl) was 43.3% and the mean lead level among study subjects was 9.8 +/- 5.1 microg/dl. The blood lead levels significantly decreased with increasing age. Fifty point eight percent of children who lived in a house with vented lead-acid batteries had EBLL while 23.3% of children who lived in a house without vented lead-acid batteries had EBLL. Multiple logistic regression analysis revealed a significant positive association between the presence of vented lead-acid batteries and EBLL, after adjusting for other variables. Forty-two point nine percent of house floor dust samples collected near the batteries had elevated lead levels, 7.1% of house floor dust samples collected from other areas in the house had elevated lead levels and 0% of the house floor dust samples collected in houses without vented lead-acid batteries had elevated lead levels. In the sampled houses with vented lead-acid batteries, lead contamination was found in the drinking-water kept in household containers, but not in the tap water or other village sources of water. Improper care and placement of vented lead-acid batteries can result in lead contamination in the home environment causing EBLL in exposed children.

  8. Sedimentation properties in density gradients correspond with levels of sperm DNA fragmentation, chromatin compaction and binding affinity to hyaluronic acid.

    PubMed

    Torabi, Forough; Binduraihem, Adel; Miller, David

    2017-03-01

    Mature spermatozoa bind hyaluronic acid in the extracellular matrix via hyaladherins. Immature spermatozoa may be unable to interact because they do not express the appropriate hyaladherins on their surface. Fresh human semen samples were fractionated using differential density gradient centrifugation (DDGC) and the ability of these fractions to bind hyaluronic acid was evaluated. The presence of sperm hyaladherins was also assessed. CD44 was located mainly on the acrosome and equatorial segment and became more restricted to the equatorial segment in capacitated spermatozoa. Hyaluronic acid-TRITC (hyaluronic acid conjugated with tetramethylrhodamine isothiocyanante), a generic hyaluronic-acid-binding reagent, labelled the membrane and the neck region, particularly after capacitation. Sperm populations obtained after DDGC or after interaction with hyaluronic acid were assessed for DNA fragmentation and chromatin maturity. Strong relationships between both measures and sperm sedimentation and hyaluronic-acid-binding profiles were revealed. Capacitation enhanced hyaluronic acid binding of both DDGC-pelleted sperm and sperm washed free of seminal fluid. In conclusion, hyaladherins were detected on human sperm and a higher capacity for sperm hyaluronic-acid-binding was shown to correspond with their DDGC sedimentation profiles and with lower levels of DNA fragmentation and better chromatin maturity. Capacitation induced changes in the distribution and presence of hyaladherins may enhance hyaluronic-acid-binding.

  9. Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study

    PubMed Central

    Chajès, Véronique; Biessy, Carine; Ferrari, Pietro; Romieu, Isabelle; Freisling, Heinz; Huybrechts, Inge; Scalbert, Augustin; Bueno de Mesquita, Bas; Romaguera, Dora; Gunter, Marc J.; Vineis, Paolo; Hansen, Camilla Plambeck; Jakobsen, Marianne Uhre; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verana; Neamat-Allah, Jasmine; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Pala, Valeria; Masala, Giovanna; Mattiello, Amalia; Skeie, Guri; Weiderpass, Elisabete; Agudo, Antonio; Huerta, Jose Maria; Ardanaz, Eva; Sánchez, Maria Jose; Dorronsoro, Miren; Quirós, Jose Ramon; Johansson, Ingegerd; Winkvist, Anna; Sonested, Emily; Key, Tim; Khaw, Kay-Tee; Wareham, Nicolas J.; Peeters, Petra H.M.; Slimani, Nadia

    2015-01-01

    Background Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. Results In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. Conclusions These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids. PMID:25675445

  10. Selective cannabinoid-1 receptor blockade benefits fatty acid and triglyceride metabolism significantly in weight-stable nonhuman primates.

    PubMed

    Vaidyanathan, Vidya; Bastarrachea, Raul A; Higgins, Paul B; Voruganti, V Saroja; Kamath, Subhash; DiPatrizio, Nicholas V; Piomelli, Daniele; Comuzzie, Anthony G; Parks, Elizabeth J

    2012-09-01

    The goal of this study was to determine whether administration of the CB₁ cannabinoid receptor antagonist rimonabant would alter fatty acid flux in nonhuman primates. Five adult baboons (Papio Sp) aged 12.1 ± 4.7 yr (body weight: 31.9 ± 2.1 kg) underwent repeated metabolic tests to determine fatty acid and TG flux before and after 7 wk of treatment with rimonabant (15 mg/day). Animals were fed ad libitum diets, and stable isotopes were administered via diet (d₃₁-tripalmitin) and intravenously (¹³C₄-palmitate, ¹³C₁-acetate). Plasma was collected in the fed and fasted states, and blood lipids were analyzed by GC-MS. DEXA was used to assess body composition and a hyperinsulinemic euglycemic clamp used to assess insulin-mediated glucose disposal. During the study, no changes were observed in food intake, body weight, plasma, and tissue endocannabinoid concentrations or the quantity of liver-TG fatty acids originating from de novo lipogenesis (19 ± 6 vs. 16 ± 5%, for pre- and posttreatment, respectively, P = 0.39). However, waist circumference was significantly reduced 4% in the treated animals (P < 0.04), glucose disposal increased 30% (P = 0.03), and FFA turnover increased 37% (P = 0.02). The faster FFA flux was consistent with a 43% reduction in these fatty acids used for TRL-TG synthesis (40 ± 3 vs. 23 ± 4%, P = 0.02) and a twofold increase in TRL-TG turnover (1.5 ± 0.9 vs. 3.1 ± 1.4 μmol·kg⁻¹·h⁻¹, P = 0.03). These data support the potential for a strong effect of CB₁ receptor antagonism at the level of adipose tissue, resulting in improvements in fasting turnover of fatty acids at the whole body level, central adipose storage, and significant improvements in glucose homeostasis.

  11. A higher baseline plasma uric acid level is an independent predictor of arterial stiffness

    PubMed Central

    Ding, Xiao-Han; Wang, Xiaona; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei; Ye, Ping

    2017-01-01

    Abstract Hyperuricemia has been demonstrated to be a risk factor for cardiovascular diseases. Though the association between uric acid (UA) and arterial stiffness has been investigated previously in patients with basic diseases, the predictive value of baseline UA level for arterial stiffness has not been conducted. We aimed at identifying the predictive role of UA for arterial stiffness prospectively. A longitudinal follow-up study in a routine health check-up population was performed with an average follow-up of 4.8 years. The demographic information, baseline and follow-up anthropometric parameters, arterial stiffness (pulse-wave velocity, PWV), and biomarker variables including UA have been measured and analyzed. A total of 1447 valid follow-ups were available for the final analysis. Both of the baseline and follow-up UA levels were significantly higher in the arterial stiffness groups than that in the nonarterial stiffness groups (all P values <0.001). The follow-up carotid-femoral PWV [(cf-PWV), r = 0.161, P < 0.001] was strongly correlated with baseline UA. At the follow-up cross-section, cf-PWV was also closely associated with UA (r = 0.101, P < 0.001). Logistic regressions revealed that a higher baseline UA level was an independent predictor of follow-up arterial stiffness assessed by cf-PWV [odds ratio (OR): 1.824; P = 0.046]. A higher baseline level of UA is closely related to arterial stiffness and is an independent predictor of arterial stiffening. PMID:28178136

  12. C-reactive protein and alpha 1-acid glycoprotein levels in dogs infected with Ehrlichia canis.

    PubMed Central

    Rikihisa, Y; Yamamoto, S; Kwak, I; Iqbal, Z; Kociba, G; Mott, J; Chichanasiriwithaya, W

    1994-01-01

    To elucidate whether acute-phase protein responses occur in dogs infected with Ehrlichia canis, C-reactive protein (CRP) and alpha 1-acid glycoprotein (AAG) levels were serially measured in the plasma of five dogs experimentally inoculated with E. canis and 10 sham-inoculated or noninoculated control dogs. The CRP concentration was measured by a canine-specific capture enzyme-linked immunosorbent assay, and the AAG concentration was measured by a canine-specific radial immunodiffusion method. In all E. canis-inoculated dogs, a 3.3- to 6.5-fold increase in the plasma CRP concentration and a 1.9- to 8.6-fold increase in the plasma AAG concentration over the preinoculation level occurred at days 4 to 6 postexposure. Despite the persistence of E. canis and high antibody titers, both CRP and AAG concentrations gradually declined to preexposure levels by day 34 postexposure. E. canis-infected dogs had mild and transient clinical signs which resolved without treatment by day 14 postexposure. The CRP and AAG concentrations in control inoculated or nontreated dogs remained within the normal range throughout the experimental period. Of 12 dogs naturally infected with E. canis, 75% had greater than 50 micrograms of CRP per ml and 83% had greater than 500 micrograms of AAG per ml. All of these 12 dogs had chronic and severe clinical signs of canine ehrlichiosis. Thus, elevations in the levels of acute-phase proteins occur in both acute and chronic canine ehrlichiosis. Determination of CRP and AAG concentrations may help in assessing the severity of inflammatory damage in dogs with E. canis infections. PMID:8027343

  13. Trans fatty acids: current contents in Canadian foods and estimated intake levels for the Canadian population.

    PubMed

    Ratnayake, W M Nimal; L'Abbe, Mary R; Farnworth, Sara; Dumais, Lydia; Gagnon, Claude; Lampi, Brian; Casey, Valerie; Mohottalage, Dayani; Rondeau, Isabelle; Underhill, Lynne; Vigneault, Michele; Lillycrop, William; Meleta, Mary; Wong, Lynn Y; Ng, Tran; Gao, Yu; Kwong, Keri; Chalouh, Shirley; Pantazopoulos, Peter; Gunaratna, Hasantha; Rahardja, Adeline; Blagden, Richard; Roscoe, Veronica; Krakalovich, Thomas; Neumann, Gary; Lombaert, Gary A

    2009-01-01

    Research conducted in the mid-1990s indicated that the levels of trans fats in Canadian diets were among the highest in the world. The consumption of trans fats raises blood levels of low-density lipoprotein (LDL)-cholesterol, while reducing levels of high-density lipoprotein (HDL)-cholesterol. In June 2007, Health Canada called on the food industry to voluntarily reduce levels of trans fats in vegetable oils and soft (tub)-margarines to < 2% of total fat, and in all other foods, to < 5%. Industry must show satisfactory progress by June 2009, or Health Canada might have to introduce legislation to ensure that recommended limits are achieved. Since 2005, Health Canada has been performing a national assessment of prepackaged and restaurant foods that likely contain trans fats. From 2005 to 2009, 1120 samples were analyzed, of which 852 or approximately 76% met the recommended trans fat limits. As a result of reformulation, most of the products had decreased trans + saturated fat content. The estimated average intake of trans fatty acids (TFA) in Canada significantly dropped from the high value of 8.4 g/day in the mid-1990s to 3.4 g/day (or 1.4% food energy) in 2008. However, this TFA intake of 1.4% of energy is still above the World Health Organization recommended limit of TFA intake of < 1% of energy, which suggests that the Canadian food industry needs to put more effort into reducing the TFA content in its products, especially in tub-margarines, donuts, and bakery products.

  14. Oral folic acid supplementation decreases palate and/or lip cleft occurrence in Pug and Chihuahua puppies and elevates folic acid blood levels in pregnant bitches.

    PubMed

    Domosławska, A; Jurczak, A; Janowski, T

    2013-01-01

    The aim of this study was to compare the frequency of the occurrence of lip and/or palate cleft (CL/CP) in new-borns of two breeds, Pugs and Chihuahuas, and to measure the folic acid blood levels in bitches during gestations both with and without folic acid oral supplementation. Bitches of 13 Pugs and 17 Chihuahuas with CL/CP cases were used in the study. In trial 1, the animals of the experimental group (n=25) were given additional folic acid from the onset of heat till the 40th day of gestation. The females of the control group (n=12) were fed a traditional diet. From all the animals blood was collected at the onset of heat, 14 days later and on the 30th day of the gestation to estimate folic acid concentration. In trial 2, the prevalence of CP/CL cases in litters from pregnancies before and after supplementation was compared. The percentage of puppies with CL/CP after supplementation decreased in both Pugs and Chihuahua puppies (10.86% and 15.78% vs. 4.76% and 4.8% respectively). On Day 0, the concentrations of folic acid were at a low physiological level (around 8 ng/ml) in all the animals. In bitches of the experimental group the blood level of folic acid on day 14th and 30th of the treatment showed an increase in both breeds (13.65 +/- 4.27 ng/ml in Pugs, 10.79 +/- 2.84 ng/ml in Chihuahuas, and 14.94 +/- 3.22 ng/ml in Pugs, 12.95 +/- 3.58 in Chihuahuas, respectively) while in the control group, this level decreased with time of gestation both in Pugs and in Chihuahuas (around 6 ng/ml). Folic acid supplementation seems to be a simple, effective preventive method to reduce the risk of CL/CP, especially in the predisposed breeds.

  15. Simultaneous hydrolysis-esterification of wet microalgal lipid using acid.

    PubMed

    Takisawa, Kenji; Kanemoto, Kazuyo; Kartikawati, Muliasari; Kitamura, Yutaka

    2013-12-01

    This research demonstrated hydrolysis of wet microalgal lipid and esterification of free fatty acid (FFA) using acid in one-step process. The investigation of simultaneous hydrolysis-esterification (SHE) of wet microalgal lipid was conducted by using L27 orthogonal design and the effects of water content, volume of sulphuric acid, volume of methanol, temperature and time on SHE were examined. As a result, water content was found to be the most effective factor. The effects of various parameters on fatty acid methyl ester (FAME) content and equilibrium relation between FAME and FFA were also examined under water content 80%. Equimolar amounts of sulphuric acid and hydrochloric acid showed similar results. This method has great potential in terms of biodiesel production from microalgae since no organic solvents are used.

  16. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

    PubMed Central

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  17. Early Effects of Boron Deficiency on Indoleacetic Acid Oxidase Levels of Squash Root Tips

    PubMed Central

    Bohnsack, Charles W.; Albert, Luke S.

    1977-01-01

    The indoleacetic acid (IAA) oxidase activity of root tips of boron-sufficient, -deficient, recovering, and IAA-treated boron-sufficient squash plants (Cucurbita pepo L.) was determined. Apical and subapical root sections displayed an increase in IAA oxidase activity between 6 and 9 hours after boron was withheld, and after 24 hours the activity of the apical sections showed a 20-fold increase over +B controls. Root elongation of -B plants was inhibited before an increase in oxidase activity could be detected. Roots of plants subjected to 12 hours of -B treatment and then transferred to +B treatment for recovery regained normal elongation rates and oxidase activity within 18 to 20 hours. IAA treatment of +B plants increased IAA oxidase activity of apical and subapical root sections and also inhibited root elongation and caused symptoms similar to -B treatments. These results have demonstrated the earliest enzymic change for intact boron-deficient plants. The results are in agreement with the theory that boron deficiency symptoms may be the result of supraoptimal endogenous levels of IAA. These high levels of IAA may inhibit cell division and lead to an induction of the IAA oxidase enzyme. PMID:16659990

  18. The putative effects of D-Aspartic acid on blood testosterone levels: A systematic review

    PubMed Central

    Roshanzamir, Farzad; Safavi, Seyyed Morteza

    2017-01-01

    Background: D-Aspartic acid (D-Asp) is in invertebrate and vertebrate neuroendocrine tissues, where it carries out important physiological functions. Recently, it has been reported that D-Asp is involved in the synthesis and release of testosterone and is assumed can be used as a testosterone booster for infertile men, and by athletes to increase muscle mass and strength. Objective: The aim of this review is to summarize available evidence related to the effects of D-Asp on serum testosterone levels. Materials and Methods: We conducted a systematic review of all type studies, which evaluated the effect of the D-Asp on blood testosterone including published papers until October 2015, using PubMed, ISI Web of Science, ProQuest and Scopus database. Results: With 396 retrieved records, 23 animal studies and 4 human studies were included. In vivo and in vitro animal studies revealed the effect of D-Asp depending on species, sex and organ-specific. Our results showed that exogenous D-Asp enhances testosterone levels in male animal’s studies, whereas studies in human yielded inconsistent results. The evidence for this association in man is still sparse, mostly because of limited number and poor quality studies. Conclusion: There is an urgent need for more and well-designed human clinical trials with larger sample sizes and longer duration to investigate putative effects of D-Asp on testosterone concentrations. PMID:28280794

  19. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

    PubMed

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

    2013-11-01

    In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.

  20. In-Use Evaluation of Peracetic Acid for High-Level Disinfection of Endoscopes.

    PubMed

    Chenjiao, Wu; Hongyan, Zhang; Qing, Gu; Xiaoqi, Zhong; Liying, Gu; Ying, Fang

    2016-01-01

    Many high-level disinfectants have been used for disinfection of endoscopes such as 2% glutaraldehyde (GA), 0.55% ortho-phthalaldehyde (OPA), and peracetic acid (PAA). Both GA and OPA are widely used in disinfection of endoscopes and have been previously discussed, but there is little research on the practical use of PAA as an endoscope disinfectant. An experimental model of a flexible gastrointestinal endoscope being contaminated with 9 strains of microorganism was designed. After the cleaning and disinfecting procedure was completed, we evaluated the biocidal activity (850 ppm PAA, 2% GA, and 0.55% OPA) on our flexible gastrointestinal endoscope model. We also evaluated sterilization effectiveness of PAA on other bacteria, including some antibiotic-resistant bacteria (methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile). The residual bacterial colony count number of the PAA-disinfected endoscope was significantly lower than that of the GA- and OPA-disinfected endoscopes. The biocidal effect and efficiency of the endoscope disinfection by PAA appeared to be better than either the GA- or OPA-disinfected endoscope. PAA has demonstrated a good sterilization effect on other bacterial species; of particular note are common antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile. The results of this study demonstrate that PAA is a fast and effective high-level disinfectant for use in the reprocessing of flexible endoscopes.

  1. Effects of Rosuvastatin Alone or in Combination with Omega-3 Fatty Acid on Adiponectin Levels and Cardiometabolic Profile

    PubMed Central

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.

    2016-01-01

    Background: Adiponectin is an important adipocyte-related protein that has been postulated to participate in prevention of the development of metabolic syndrome. The relationship between adiponectin serum levels and risk of coronary artery disease (CAD) has been widely investigated and remains controversial. The aim of the present study was to evaluate the effects of rosuvastatin and/or omega-3 fatty acid on adiponectin serum levels in patients with insulin resistance (IR) and CAD. Patients and Methods: This study involved 87 patients with CADs and IR of different etiology, the patients were divided into three groups; 24 patients on treatment with rosuvastatin, 22 patients on treatment with omega-3 fatty acid, 23 patients on treatment with omega-3 fatty acid and rosuvastatin, 18 patients were not previously or currently treated with either rosuvastatin or omega-3 fatty acid, those regarded as control patients. Anthropometric measures, adiponectin serum levels, and other biochemical parameters were assessed in each treated group. Results: Rosuvastatin therapy leads to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 6.76 ± 1.03 ng/mL compared to control P < 0.01. Omega-3 fatty acid therapy leads to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 6.11 ± 1.29 ng/mL compared to control P < 0.01. Rosuvastatin plus omega-3 fatty acid therapy lead to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 7.99 ± 1.76 ng/mL compared to control P < 0.01. Conclusions: Rosuvastatin and/or omega-3 fatty acid lead to significant cardiometabolic protection through an increment in adiponectin serum levels. PMID:28104968

  2. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    EPA Science Inventory

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  3. Effect of rosmarinic acid on sertoli cells apoptosis and serum antioxidant levels in rats after exposure to electromagnetic fields.

    PubMed

    Hajhosseini, Laleh; Khaki, Arash; Merat, Ehsan; Ainehchi, Nava

    2013-01-01

    Rosmarinic acid belongs to the group of polyphenols; it has antioxidant, anti-inflammatory and antimicrobial activities and help to prevent cell damage caused by free radicals. The objective was to study the effect of Rosmarinic acid on sertolli cells apoptosis and serum antioxidant levels in rats after they were exposed to electromagnetic fields. Male Wistar rats (n=40) were allocated into three groups: control group (n=10) that received 5 cc normal saline (0.9% NaCl) daily by gavage method, Rosmarinic acid group that received 5mg/rat (gavage) (n=10), electromagnetic fields (EMF) group that had exposure with 50 hz (n=20) which was subdivided to two groups of 10; EMF group and treatment group. Treatment group received 5mg/rat (gavage) Rosmarinic acid daily for 6 weeks, respectively. However, the control group just received an equal volume of distilled water daily (gavage). On the 42nd day of research, 5 cc blood was collected to measure testosterone hormones, total antioxidant capacity (TAC), levels from whole group's analysis. Level of malondialdehyde (MDA) levels and sertoli cells apoptosis significantly decreased in the group that received 5mg/rat of Rosmarinic acid (P<0.05) in comparison with experimental groups. Level of testosterone, total antioxidant capacity (TAC), significantly increased in groups that received Rosmarinic acid (P<0.05). Since in our study 5mg/rat of Rosmarinic acid showed significantly preventive effect on cell damages especial sertoli cells apoptosis that caused with EMF, it seems that using Rosmarinic acid as food additive can be effective for supporting people living under EMF environmental pollution.

  4. Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels.

    PubMed

    Barceló-Coblijn, Gwendolyn; Murphy, Eric J

    2009-11-01

    There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n-3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n-3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n-3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes beta-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n-3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n-3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n-3 levels.

  5. CSF levels of heart fatty acid binding protein are altered during early phases of Alzheimer's disease.

    PubMed

    Chiasserini, Davide; Parnetti, Lucilla; Andreasson, Ulf; Zetterberg, Henrik; Giannandrea, David; Calabresi, Paolo; Blennow, Kaj

    2010-01-01

    Heart fatty acid binding protein (HFABP) has been proposed as a putative marker for dementia disorders. To evaluate the value of this protein as an early marker of Alzheimer's disease (AD), we analyzed HFABP level and the classical biomarkers amyloid-β (Aβ)1-42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) followed up for four years (n=41), AD (n=32), and subjects with other neurological diseases without dementia (OND, n=25). HFABP levels were higher in AD patients and in MCI converting to AD (MCI-AD) with respect to OND and to cognitively stable MCI patients (MCI-MCI). The receiver operator characteristics analysis for HFABP alone showed a sensitivity of 87% and a specificity of 81% for AD versus OND (area under the curve, AUC=0.83); sensitivity and specificity were 46% and 94%, respectively, when comparing MCI-MCI versus MCI-AD. CSF HFABP levels showed a strong positive correlation with both t-tau and p-tau. Interestingly, the ratio between HFABP and Aβ1-42 improved the performance in distinguishing AD from OND (sensitivity: 90%; specificity 82%, AUC=0.89), and gave the best accuracy in discriminating MCI-AD from MCI-MCI (sensitivity: 80%; specificity 100%, AUC=0.90). Survival analysis by means of Kaplan-Meier curve showed a significantly higher proportion of MCI patients converting to AD in the group with higher values of HFABP/Aβ1-42 ratio (cut-off=0.7). A significant correlation between HFABP/Aβ1-42 ratio and MMSE annual decrease rate was also documented (p<0.0001). HFABP /Aβ1-42 ratio might be a useful predictor of conversion in MCI patients.

  6. Isoflavone, glyphosate, and aminomethylphosphonic acid levels in seeds of glyphosate-treated, glyphosate-resistant soybean.

    PubMed

    Duke, Stephen O; Rimando, Agnes M; Pace, Patrick F; Reddy, Krishna N; Smeda, Reid J

    2003-01-01

    The estrogenic isoflavones of soybeans and their glycosides are products of the shikimate pathway, the target pathway of glyphosate. This study tested the hypothesis that nonphytotoxic levels of glyphosate and other herbicides known to affect phenolic compound biosynthesis might influence levels of these nutraceutical compounds in glyphosate-resistant soybeans. The effects of glyphosate and other herbicides were determined on estrogenic isoflavones and shikimate in glyphosate-resistant soybeans from identical experiments conducted on different cultivars in Mississippi and Missouri. Four commonly used herbicide treatments were compared to a hand-weeded control. The herbicide treatments were (1) glyphosate at 1260 g/ha at 3 weeks after planting (WAP), followed by glyphosate at 840 g/ha at 6 WAP; (2) sulfentrazone at 168 g/ha plus chlorimuron at 34 g/ha applied preemergence (PRE), followed by glyphosate at 1260 g/ha at 6 WAP; (3) sulfentrazone at 168 g/ha plus chlorimuron at 34 g/ha applied PRE, followed by glyphosate at 1260 g/ha at full bloom; and (4) sulfentrazone at 168 g/ha plus chlorimuron at 34 g/ha applied PRE, followed by acifluorfen at 280 g/ha plus bentazon at 560 g/ha plus clethodim at 140 g/ha at 6 WAP. Soybeans were harvested at maturity, and seeds were analyzed for daidzein, daidzin, genistein, genistin, glycitin, glycitein, shikimate, glyphosate, and the glyphosate degradation product, aminomethylphosphonic acid (AMPA). There were no remarkable effects of any treatment on the contents of any of the biosynthetic compounds in soybean seed from either test site, indicating that early and later season applications of glyphosate have no effects on phytoestrogen levels in glyphosate-resistant soybeans. Glyphosate and AMPA residues were higher in seeds from treatment 3 than from the other two treatments in which glyphosate was used earlier. Intermediate levels were found in treatments 1 and 2. Low levels of glyphosate and AMPA were found in treatment 4 and a

  7. Predictors of urinary levels of 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridinol, 3-phenoxybenzoic acid, and pentachlorophenol in 121 adults in Ohio

    EPA Science Inventory

    Limited data exist on the driving factors that influence the non-occupational exposures of adults to pesticides using urinary biomonitoring. In this work, the objectives were to quantify the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol (TC...

  8. A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes

    PubMed Central

    Dhingra, Radhika; Winquist, Andrea; Darrow, Lyndsey A.; Klein, Mitchel; Steenland, Kyle

    2016-01-01

    Background: Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations.Background: Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations. Objective: We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations.Objective: We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations. Methods: In cross-sectional analyses, we analyzed PFOA in relation to self-reported menopause among women (n = 9,192) 30–65 years old and in relation to kidney function among adults > 20 years old (n = 29,499) in a highly exposed Mid-Ohio Valley cohort. Estimated glomerular filtration rate (eGFR, a marker of kidney function) and serum PFOA concentration were measured in blood samples collected during 2005–2006. Retrospective year-specific serum PFOA estimates were modeled independently of measured PFOA based on residential history and plant emissions. Using measured and modeled PFOA in 2005 or 2006 (predictor variables), cross-sectional associations were assessed for eGFR and menopause (yes/no). We also analyzed measured PFOA (dependent variable) in relation to the number of years since menopause.Methods: In cross-sectional analyses, we analyzed PFOA in relation to self-reported menopause among women (n = 9,192) 30–65 years old and in relation to kidney function among adults > 20 years old (n = 29

  9. Fatty Acid Composition and Levels of Selected Polyunsaturated Fatty Acids in Four Commercial Important Freshwater Fish Species from Lake Victoria, Tanzania

    PubMed Central

    Robert, Agnes; Mfilinge, Prosper; Limbu, Samwel M.; Mwita, Chacha J.

    2014-01-01

    Fatty acids (FAs) particularly ω3 and ω6 polyunsaturated fatty acids (PUFAs) play important role in human health. This study aimed to investigate the composition and levels of selected ω3 PUFAs in four commercial fish species, Nile perch (Lates niloticus), Nile tilapia (Oreochromis niloticus), Tilapia zillii, and dagaa (Rastrineobola argentea) from Mwanza Gulf in Lake Victoria. The results indicated that 36 types of FAs with different saturation levels were detected. These FAs were dominated by docosahexaenoic (DHA), eicosapentaenoic (EPA), docosapentaenoic (DPA), and eicosatetraenoic acids. O. niloticus had the highest composition of FAs (34) compared to L. niloticus (27), T. zillii (26), and R. argentea (21). The levels of EPA differed significantly among the four commercial fish species (F = 6.19,  P = 0.001). The highest EPA levels were found in R. argentea followed by L. niloticus and O. niloticus and the lowest in T. zillii. The DPA levels showed no significant difference among the four fish species studied (F = 0.652,  P = 0.583). The study concluded that all four commercial species collected from Mwanza Gulf are good for human health, but R. argentea is the best for consumption because it contains higher levels of ω3 FAs, mainly EPA. PMID:25610654

  10. Ethanol and fatty acids impair lipid homeostasis in an in vitro model of hepatic steatosis.

    PubMed

    Vecchione, Giulia; Grasselli, Elena; Compalati, Andrea D; Ragazzoni, Milena; Cortese, Katia; Gallo, Gabriella; Voci, Adriana; Vergani, Laura

    2016-04-01

    Excess ethanol consumption and fatty acid intake lead to a cumulative effect on liver steatosis through still unclear mechanisms. This study aimed to characterize the lipid homoeostasis alterations under the exposure of hepatocytes to ethanol alone or combined with fatty acids. FaO hepatoma cells were incubated in the absence (C) or in the presence of 100 mM ethanol (EtOH) or 0.35 mM oleate/palmitate (FFA) alone or in the combination (FFA/EtOH). Content of intra- and extra-cellular triglycerides (TAGs) and of lipid droplets (LDs), expression of lipogenic and lipolytic genes, and oxidative stress-related parameters were evaluated. Exposure to either FFAs or EtOH given separately led to steatosis which was augmented when they were combined. Our results show that FFA/EtOH: (i) increased the LD number, but reduced their size compared to separate treatments; (ii) up-regulated PPARγ and SREBP-1c and down-regulated sirtuin-1 (SIRT1); (iii) impaired FFA oxidation; (iv) did not change lipid secretion and oxidative stress. Our findings indicate that one of the major mechanisms of the metabolic interference between ethanol and fat excess is the impairment of FFA oxidation, in addition to lipogenic pathway stimulation. Interestingly, ethanol combined with FFAs led to a shift from macrovesicular to microvesicular steatosis that represents a more dangerous condition.

  11. Acidification in the Adirondacks: defining the biota in trophic levels of 30 chemically diverse acid-impacted lakes.

    PubMed

    Nierzwicki-Bauer, Sandra A; Boylen, Charles W; Eichler, Lawrence W; Harrison, James P; Sutherland, James W; Shaw, William; Daniels, Robert A; Charles, Donald F; Acker, Frank W; Sullivan, Timothy J; Momen, Bahram; Bukaveckas, Paul

    2010-08-01

    The Adirondack Mountains in New York State have a varied surficial geology and chemically diverse surface waters that are among the most impacted by acid deposition in the U.S. No single Adirondack investigation has been comprehensive in defining the effects of acidification on species diversity, from bacteria through fish, essential for understanding the full impact of acidification on biota. Baseline midsummer chemistry and community composition are presented for a group of chemically diverse Adirondack lakes. Species richness of all trophic levels except bacteria is significantly correlated with lake acid-base chemistry. The loss of taxa observed per unit pH was similar: bacterial genera (2.50), bacterial classes (1.43), phytoplankton (3.97), rotifers (3.56), crustaceans (1.75), macrophytes (3.96), and fish (3.72). Specific pH criteria were applied to the communities to define and identify acid-tolerant (pH<5.0), acid-resistant (pH 5.0-5.6), and acid-sensitive (pH>5.6) species which could serve as indicators. Acid-tolerant and acid-sensitive categories are at end-points along the pH scale, significantly different at P<0.05; the acid-resistant category is the range of pH between these end-points, where community changes continually occur as the ecosystem moves in one direction or another. The biota acid tolerance classification (batc) system described herein provides a clear distinction between the taxonomic groups identified in these subcategories and can be used to evaluate the impact of acid deposition on different trophic levels of biological communities.

  12. Antiepileptic potential of matrine via regulation the levels of gamma-aminobutyric acid and glutamic acid in the brain.

    PubMed

    Xiang, Jun; Jiang, Yugang

    2013-12-05

    Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp), gamma-aminobutyric acid (GABA), glutamic acid (Glu), glycine (Gly) in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAA in the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.

  13. Organosulfates and organic acids in Arctic aerosols: speciation, annual variation and concentration levels

    NASA Astrophysics Data System (ADS)

    Hansen, A. M. K.; Kristensen, K.; Nguyen, Q. T.; Zare, A.; Cozzi, F.; Nøjgaard, J. K.; Skov, H.; Brandt, J.; Christensen, J. H.; Ström, J.; Tunved, P.; Krejci, R.; Glasius, M.

    2014-08-01

    Sources, composition and occurrence of secondary organic aerosols in the Arctic were investigated at Zeppelin Mountain, Svalbard, and Station Nord, northeastern Greenland, during the full annual cycle of 2008 and 2010, respectively. Speciation of organic acids, organosulfates and nitrooxy organosulfates - from both anthropogenic and biogenic precursors were in focus. A total of 11 organic acids (terpenylic acid, benzoic acid, phthalic acid, pinic acid, suberic acid, azelaic acid, adipic acid, pimelic acid, pinonic acid, diaterpenylic acid acetate and 3-methyl-1,2,3-butanetricarboxylic acid), 12 organosulfates and 1 nitrooxy organosulfate were identified in aerosol samples from the two sites using a high-performance liquid chromatograph (HPLC) coupled to a quadrupole Time-of-Flight mass spectrometer. At Station Nord, compound concentrations followed a distinct annual pattern, where high mean concentrations of organosulfates (47 ± 14 ng m-3) and organic acids (11.5 ± 4 ng m-3) were observed in January, February and March, contrary to considerably lower mean concentrations of organosulfates (2 ± 3 ng m-3) and organic acids (2.2 ± 1 ng m-3) observed during the rest of the year. At Zeppelin Mountain, organosulfate and organic acid concentrations remained relatively constant during most of the year at a mean concentration of 15 ± 4 ng m-3 and 3.9 ± 1 ng m-3, respectively. However during four weeks of spring, remarkably higher concentrations of total organosulfates (23-36 ng m-3) and total organic acids (7-10 ng m-3) were observed. Elevated organosulfate and organic acid concentrations coincided with the Arctic haze period at both stations, where northern Eurasia was identified as the main source region. Air mass transport from northern Eurasia to Zeppelin Mountain was associated with a 100% increase in the number of detected organosulfate species compared with periods of air mass transport from the Arctic Ocean, Scandinavia and Greenland. The results from this

  14. Effect of docosahexaenoic acid and furan fatty acids on cytokinesis block micronucleus cytome assay biomarkers in astrocytoma cell lines under conditions of oxidative stress.

    PubMed

    Chua, Ann; Thomas, Philip; Wijesundera, Chakra; Clifton, Peter; Fenech, Michael

    2014-08-01

    Fatty acids from fish such as docosahexaenoic acid (DHA) are associated with improved brain function, whereas furan fatty acids (FFAs) also found in fish oil at low levels (1%) are thought to have antioxidant properties. Understanding their effects in astrocytes is important as these cells are responsible for maintaining healthy neurons via lipid homeostasis and distribution within the brain, and their decline with aging is a possible cause of dementia. We investigated the cytotoxic and genotoxic effects of DHA and FFA using the cytokinesis-block micronucleus cytome assay in in vitro cultures of U87MG (APOE ɛ3/ɛ3) and U118MG (APOE ɛ2/ɛ4) astrocytoma cell lines with and without a hydrogen peroxide (H2O2, 100 µM) challenge. U118MG was found to be more sensitive to the cytostatic, cytotoxic (i.e., apoptosis), and DNA damaging effects [micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs)] of H2O2 (P < 0.01 and P < 0.001) when compared with U87MG. DHA at 100 µg/mL significantly affected cytostasis (P < 0.05) and increased DNA damage in the form of NPBs and MNi (P < 0.05) in both cell lines, whereas it decreased necrosis (P = 0.0251) in U87MG. Significant DHA-H2O2 interactions were observed for decreased necrosis (P = 0.0033) and DNA damage biomarkers (P < 0.0001) in the U87MG cell line and increased cytostasis (P < 0.0001) in the U118MG cell line. The effects of FFA also varied between the cell lines, with significant effects observed in decreased cytostasis (P = 0.0022) in the U87MG cell line, whereas increasing cytostasis (P = 0.0144) in the U118MG cell line. Overall, FFA exerted minimal effects on DNA damage biomarkers.

  15. Effects of dietary folic acid level and symbiotic folate production on fitness and development in the fruit fly Drosophila melanogaster.

    PubMed

    Blatch, Sydella A; Meyer, Kyle W; Harrison, Jon F

    2010-01-01

    Folic acid is a vitamin for probably all animals. When converted to folate forms, it is used in DNA synthesis and amino acid metabolism. Literature suggests insects must consume folates, folates do not affect others, is a toxin for some, and that a few insects synthesize it. It has been reported that Drosophila melanogaster does not consistently need dietary folate because it can synthesize it. This seems unlikely since animals generally lack this ability. More likely, folates thought to have been made by the fly came from microbial symbionts. We aimed to clarify how dietary folic acid affects fitness and development in fruit flies and whether flies may receive folates from microbial symbionts. We found larvae were more viable and developed faster with increasing dietary folic acid, with the surprising exception that larvae fed nearly-zero folic acid developed faster. Their body folate levels did not significantly differ from those that consumed up to 600 times more folic acid. However, these flies fed little folate only achieved normal body folate levels and development times when antibiotics were excluded from the diet. When flies consumed near-zero folates with antibiotics, their body folate levels decreased and development was prolonged. An assay for the endosymbiont Wolbachia in flies used to generate the experimental flies did not show presence of these bacteria. Our data suggest D. melanogaster can harbor unknown bacterial symbiont(s) that provide essential folates to their host when it is scarce in the diet, allowing the fruit fly to maintain growth and development.

  16. Intensive lifestyle intervention provides rapid reduction of serum fatty acid levels in women with severe obesity without lowering omega-3 to unhealthy levels.

    PubMed

    Lin, C; Andersen, J R; Våge, V; Rajalahti, T; Mjøs, S A; Kvalheim, O M

    2016-08-01

    Serum fatty acid (FA) levels were monitored in women with severe obesity during intensive lifestyle intervention. At baseline, total FA levels and most individual FAs were elevated compared to a matching cohort of normal and overweight women (healthy controls). After 3 weeks of intensive lifestyle intervention, total level was only 11-12% higher than in the healthy controls and with almost all FAs being significantly lower than at baseline, but with levels of omega-3 being similar to the healthy controls. This is contrary to observations for patients subjected to bariatric surgery where omega-3 levels dropped to levels significantly lower than in the lifestyle patients and healthy controls. During the next 3 weeks of treatment, the FA levels in lifestyle patients were unchanged, while the weight loss continued at almost the same rate as in the first 3 weeks. Multivariate analysis revealed that weight loss and change of serum FA patterns were unrelated outcomes of the intervention for lifestyle patients. For bariatric patients, these processes were associated probably due to reduced dietary input and increased input from the patients' own fat deposits, causing a higher rate of weight loss and simultaneous reduction of the ratio of serum eicosapentaenoic to arachidonic acid.

  17. Rainwater trifluoroacetic acid (TFA) in Guangzhou, South China: levels, wet deposition fluxes and source implication.

    PubMed

    Wang, Qiaoyun; Wang, Xinming; Ding, Xiang

    2014-01-15

    The origin of trifluoroacetic acid (TFA) occurring in hydrosphere has long been a controversial issue. Hydrochlorofluorocarbons and hydrofluorocarbons (HCFCs/HFCs) as replacements of chlorofluorocarbons (CFCs) are precursors of TFA in the atmosphere, their contribution to rainwater TFA is a concern as their ambient mixing ratios are continually growing. Here we present rainwater TFA monitored from April 2007 to March 2008 in urban Guangzhou, a central city in south China's highly industrialized and densely populated Pearl River Delta region. Rainwater TFA levels ranged 45.8-974 ng L(-1) with a median of 166 ng L(-1). TFA levels negatively correlated with rainfall amount, the yearly rainfall-weighted average for TFA was 152 ng L(-1). The annual TFA wet deposition flux was estimated to be 229 g km(-2) yr(-1), and the total wet deposition of TFA reached ~1.7 tyr(-1) in Guangzhou. The Two-Box model was applied to estimate attributions of HCFCs/HFCs and fluoropolymers to rainwater TFA assuming TFA generated was proportional to gross domestic product (GDP), gross industrial product (GIP) or number of private cars. The results revealed that the degradation of HCFCs/HFCs and fluoropolymers could explain 131.5-152.4 ng L(-1) rainwater TFA, quite near the observed rainfall-weighted annual mean of 152 ng L(-1), suggesting rainwater TFA in Guangzhou was predominantly originated from these anthropogenic precursors. HCFCs/HFCs accounted for 83.3-96.5% of rainwater TFA observed, while fluoropolymers' contributions were minor (~5%). HFC-134a alone could explain 55.9-90.0% of rainwater TFA, and its contribution would be greatly enhanced with its wide use in mobile air conditioning systems and rapid increase in ambient mixing ratios.

  18. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    PubMed

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance.

  19. Serum uric acid levels and freezing of gait in Parkinson's disease.

    PubMed

    Ou, Ruwei; Cao, Bei; Wei, Qianqian; Hou, Yanbing; Xu, Yaqian; Song, Wei; Zhao, Bi; Shang, Huifang

    2017-03-01

    Uric acid (UA) is a natural antioxidant and iron scavenger in the human body, which has been hypothesized to exert an anti-oxidative effect in Parkinson's disease (PD). This study aimed to investigate the relationship between serum UA levels and freezing of gait (FOG) in PD. A total of 321 Chinese PD patients with fasting serum UA evaluated were included in the cross-sectional study. Demographics, clinical features, and therapeutic regimen were collected. The Unified PD Rating Scale (UPDRS) III and Hoehn and Yahr (H and Y) stage were used to evaluate the severity of disease, and the Frontal Assessment Battery (FAB) and Montreal Cognitive Assessment (MoCA) scales were used to assess the cognitive function. Patients with FOG showed lower proportion of male, longer disease duration, lower body mass index, lower concentrations of serum UA, higher total levodopa equivalent daily dosage, higher UPDRS III score, greater median H and Y stage, lower scores of FAB and MoCA, and higher frequencies of motor fluctuation, dyskinesia, falls, and festination compared to patients without FOG (P < 0.05). The binary logistic regression model indicated that high UPDRS III score (OR = 1.049, P < 0.001), fluctuation (OR = 2.677, P = 0.035), dyskinesia (OR = 6.294, P = 0.003), festination (OR = 3.948, P < 0.001), falls (OR = 7.528, P < 0.001), and low serum UA levels (OR = 0.990, P < 0.001) were associated with FOG. Our study suggests that low serum UA concentration is associated with the occurrence of FOG in PD.

  20. Glycyrrhizic acid attenuates growth of Leishmania donovani by depleting ergosterol levels.

    PubMed

    Dinesh, Neeradi; Neelagiri, Soumya; Kumar, Vinay; Singh, Sushma

    2017-02-24

    In the present study, glycyrrhizic acid (GA) the main component of Glycyrrhiza glabra was evaluated for its efficacy as antileishmanial agent and its mode of action explored. GA inhibits promastigotes and intracellular amastigotes in a dose dependent manner at an IC50 value of 34 ± 3.0 μM and 20 ± 4.2 μM respectively. GA was non-toxic against THP-1 macrophage host cell line. GA was found to inhibit recombinant Leishmania donovani HMG-CoA reductase (LdHMGR) enzyme at the half-maximum inhibitory concentration of 24 ± 4.3 μM indicating the sensitivity and specificity of GA towards the enzyme. However, GA could cause only 30% reduction in HMGR activity when measured in Leishmania promastigotes treated with 34 μM of GA. Interestingly western blot analysis revealed fivefold reduced HMGR expression in GLA treated promastigotes. To further study the mode of action of GA, we used transgenic parasites overexpressing LdHMGR. Results indicated that ∼2 fold resistance was exhibited by LdHMGR overexpressing promastigotes to GA with an IC50 value of 74 μM compared to the wild type parasite. This explained the specific binding of GA to LdHMGR enzyme. There was ∼2 fold depletion in ergosterol levels in wild type promastigotes compared to the HMGR overexpressors. This data was further validated by exogenous supplementation of GA treated cells with ergosterol and 40% reversal of growth inhibition was observed. The results obtained suggested that GA kills the parasite by affecting sterol biosynthetic pathway, especially by inhibiting the L. donovani HMGR and altering ergosterol levels. The finding from the current study shows that GA is a potential antileishmanial chemotherapeutic agent.

  1. Deletions of the SACPD-C locus elevate seed stearic acid levels but also result in fatty acid and morphological alterations in nitrogen fixing nodules

    PubMed Central

    2014-01-01

    Background Soybean (Glycine max) seeds are the primary source of edible oil in the United States. Despite its widespread utility, soybean oil is oxidatively unstable. Until recently, the majority of soybean oil underwent chemical hydrogenation, a process which also generates trans fats. An alternative to chemical hydrogenation is genetic modification of seed oil through identification and introgression of mutant alleles. One target for improvement is the elevation of a saturated fat with no negative cardiovascular impacts, stearic acid, which typically constitutes a minute portion of seed oil (~3%). Results We examined radiation induced soybean mutants with moderately increased stearic acid (10-15% of seed oil, ~3-5 X the levels in wild-type soybean seeds) via comparative whole genome hybridization and genetic analysis. The deletion of one SACPD isoform encoding gene (SACPD-C) was perfectly correlated with moderate elevation of seed stearic acid content. However, SACPD-C deletion lines were also found to have altered nodule fatty acid composition and grossly altered morphology. Despite these defects, overall nodule accumulation and nitrogen fixation were unaffected, at least under laboratory conditions. Conclusions Although no yield penalty has been reported for moderate elevated seed stearic acid content in soybean seeds, our results demonstrate that genetic alteration of seed traits can have unforeseen pleiotropic consequences. We have identified a role for fatty acid biosynthesis, and SACPD activity in particular, in the establishment and maintenance of symbiotic nitrogen fixation. PMID:24886084

  2. Effect of dietary starch level and its rumen degradability on lamb meat fatty acid composition.

    PubMed

    Oliveira, Maria A; Alves, Susana P; Santos-Silva, José; Bessa, Rui J B

    2017-01-01

    Forty lambs were fed one of four diets supplemented with a linseed and sunflower oil blend but differing in starch level (mid, ≈35 vs. high, ≈50%) and starch rumen degradability (mid, ≈70 vs. high, ≈80%). The effects of diet on growth, carcass traits and meat fatty acid (FA) composition, with emphasis on biohydrogenation intermediates were evaluated. Lambs stayed on trial for 5weeks until slaughter. Treatment had no effect on animal performance and carcass traits. High-degradability diets decreased (P=0.04) meat shear force compared with mid-degradability diets. Lipid content of meat was unaffected by the diet. Mid-starch diets increased (P<0.05) the saturated FA and cis-MUFA but decreased (P<0.05) the trans-MUFA, particularly the t10-18:1, when compared with high-starch diets. The t11-18:1 (0.7% of total FA) and c9,t11-18:2 (<0.3%) remained low and the 18:3n-3 remained high (1.74%) and unaffected by diet.

  3. Risk factors for suicide among patients with schizophrenia: a cohort study focused on cerebrospinal fluid levels of homovanillic acid and 5-hydroxyindoleacetic acid

    PubMed Central

    Neider, Daniel; Lindström, Leif H; Bodén, Robert

    2016-01-01

    Background The objective of this study was to investigate the association between 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF), bullying, and later suicide among patients with schizophrenia. Methods Ninety-nine patients with schizophrenia were included. Correlations of clinical factors, 5-HIAA and HVA, and later suicide were investigated. Results Twelve patients committed suicide (12%) during a 28-year follow-up period. Later suicide was correlated to bullying in childhood (P=0.02) and a lower quotient of HVA/5-HIAA in CSF (P<0.05). Conclusion Suicide in schizophrenia is related to childhood exposedness and CSF neurotransmitter levels. PMID:27468235

  4. Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males

    PubMed Central

    Shoji, Tatsuya; Shinzawa, Maki; Hasuike, Yukiko; Nagatoya, Katsuyuki; Yamauchi, Atsushi; Hayashi, Terumasa; Kuragano, Takayuki; Moriyama, Toshiki; Isaka, Yoshitaka; Nakanishi, Takeshi

    2016-01-01

    Background Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. Study Design Multicenter retrospective cohort study. Setting & Participants 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. Predictor Uric acid levels at renal biopsy. Outcomes The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". Measurements The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. Results An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. Limitations A cohort analyzed retorospectively. Conclusions This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients. PMID:27560997

  5. EFFECTIVENESS OF USING DILUTE OXALIC ACID TO DISSOLVEHIGH LEVEL WASTE IRON BASED SLUDGE SIMULANT

    SciTech Connect

    Ketusky, E

    2008-07-11

    At the Savannah River Site (SRS), near Aiken South Carolina, there is a crucial need to remove residual quantities of highly radioactive iron-based sludge from large select underground storage tanks (e.g., 19,000 liters of sludge per tank), in order to support tank closure. The use of oxalic acid is planned to dissolve the residual sludge, hence, helping in the removal. Based on rigorous testing, primarily using 4 and 8 wt% oxalic acid solutions, it was concluded that the more concentrated the acid, the greater the amount of residual sludge that would be dissolved; hence, a baseline technology on using 8 wt% oxalic acid was developed. In stark contrast to the baseline technology, reports from other industries suggest that the dissolution will most effectively occur at 1 wt% oxalic acid (i.e., maintaining the pH near 2). The driver for using less oxalic acid is that less (i.e., moles) would decrease the severity of the downstream impacts (i.e., required oxalate solids removal efforts). To determine the initial feasibility of using 1 wt% acid to dissolve > 90% of the sludge solids, about 19,000 liters of representative sludge was modeled using about 530,000 liters of 0 to 8 wt% oxalic acid solutions. With the chemical thermodynamic equilibrium based software results showing that 1 wt% oxalic acid could theoretically work, simulant dissolution testing was initiated. For the dissolution testing, existing simulant was obtained, and an approximate 20 liter test rig was built. Multiple batch dissolutions of both wet and air-dried simulant were performed. Overall, the testing showed that dilute oxalic acid dissolved a greater fraction of the stimulant and resulted in a significantly larger acid effectiveness (i.e., grams of sludge dissolved/mole of acid) than the baseline technology. With the potential effectiveness confirmed via simulant testing, additional testing, including radioactive sludge testing, is planned.

  6. High saturated fatty acid intake induces insulin secretion by elevating gastric inhibitory polypeptide levels in healthy individuals.

    PubMed

    Itoh, Kazue; Moriguchi, Ririko; Yamada, Yuichiro; Fujita, Misuzu; Yamato, Takako; Oumi, Masayo; Holst, Jens Juul; Seino, Yutaka

    2014-08-01

    Insulin resistance is central to the etiology of the metabolic syndrome cluster of diseases. Evidence suggests that a high-fat diet is associated with insulin resistance, which may be modulated by dietary fatty acid composition. We hypothesized that high saturated fatty acid intake increases insulin and gastric inhibitory polypeptide (GIP) secretion. To clarify the effect of ingested fatty acid composition on glucose levels, we conducted an intervention study to investigate the insulin and plasma GIP responses in 11 healthy women, including a dietary control. Subjects were provided daily control meals (F-20; saturated fatty acids/monounsaturated fatty acids/polyunsaturated fatty acids [S/M/P] ratio, 3:4:3) with 20 energy (E) % fat, followed by 2 isoenergetic experimental meals for 7 days each. These meals comprised 60 E% carbohydrate, 15 E% protein, and 30 E% fat (FB-30; high saturated fatty acid meal; S/M/P, 5:4:1; F-30: reduced saturated fatty acid meal; S/M/P, 3:4:3). On the second day of the F-20 and the last day of F-30 and FB-30, blood samples were taken before and 30, 60, and 120 minutes after a meal tolerance test. The plasma glucose responses did not differ between F-20 and FB-30 or F-30. However, insulin levels were higher after the FB-30 than after the F-20 (P < .01). The GIP response after the FB-30 was higher than that after the F-30 (P < .05). In addition, the difference in the incremental GIP between FB-30 and F-30 correlated significantly and positively with that of the insulin. These results suggest that a high saturated fatty acid content stimulates postprandial insulin release via increased GIP secretion.

  7. Differential levels of long chain polyunsaturated fatty acids in women with preeclampsia delivering male and female babies.

    PubMed

    Roy, Suchitra; Dhobale, Madhavi; Dangat, Kamini; Mehendale, Savita; Wagh, Girija; Lalwani, Sanjay; Joshi, Sadhana

    2014-11-01

    Maternal long chain polyunsaturated fatty acids (LCPUFA) play a key role in fetal growth and development. This study for the first time examines the maternal and cord LCPUFA levels in preeclamptic mothers delivering male and female infants. In this study 122 normotensive control pregnant women (gestation≥37 weeks) and 90 women with preeclampsia were recruited. Results indicate lower maternal plasma docosahexaenoic acid (DHA) levels (p<0.05) in women with preeclampsia delivering male babies as compared to normotensive control women delivering male babies. Similarly, cord nervonic acid levels were lower (p<0.01) in women with preeclampsia delivering male babies as compared to normotensive control group. However, cord nervonic acid levels were comparable in women with preeclampsia and normotensive control women delivering female babies. This data suggests that male babies born to mothers with preeclampsia may be at an increased risk of developing neurodevelopmental disorders as compared to female babies. Future studies need to follow up both male and female children born to mothers with preeclampsia since altered levels of LCPUFA at birth may have differential implications for the growth and development.

  8. Co-supplementation of healthy women with fish oil and evening primrose oil increases plasma docosahexaenoic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid levels without reducing arachidonic acid concentrations.

    PubMed

    Geppert, Julia; Demmelmair, Hans; Hornstra, Gerard; Koletzko, Berthold

    2008-02-01

    Fish oil supplementation during pregnancy not only improves maternal and neonatal DHA status, but often reduces gamma-linolenic acid (GLA), dihomo-GLA (DGLA), and arachidonic acid (ARA) levels also, which may compromise foetal and infant development. The present study investigated the effects of a fish oil/evening primrose oil (FSO/EPO) blend (456 mg DHA/d and 353 mg GLA/d) compared to a placebo (mixture of habitual dietary fatty acids) on the plasma fatty acid (FA) composition in two groups of twenty non-pregnant women using a randomised, double-blind, placebo-controlled parallel design. FA were quantified in plasma total lipids, phospholipids, cholesterol esters, and TAG at weeks 0, 4, 6 and 8. After 8 weeks of intervention, percentage changes from baseline values of plasma total lipid FA were significantly different between FSO/EPO and placebo for GLA (+49.9 % v. +2.1 %, means), DGLA (+13.8 % v. +0.7 %) and DHA (+59.6 % v. +5.5 %), while there was no significant difference for ARA ( - 2.2 % v. - 5.9 %). FA changes were largely comparable between plasma lipid fractions. In both groups three subjects reported mild adverse effects. As compared with placebo, FSO/EPO supplementation did not result in any physiologically relevant changes of safety parameters (blood cell count, liver enzymes). In women of childbearing age the tested FSO/EPO blend was well tolerated and appears safe. It increases plasma GLA, DGLA, and DHA levels without impairing ARA status. These data provide a basis for testing this FSO/EPO blend in pregnant women for its effects on maternal and neonatal FA status and infant development.

  9. Compared with stearic acid, palmitic acid increased the yield of milk fat and improved feed efficiency across production level of cows.

    PubMed

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

    2014-02-01

    The effects of dietary palmitic and stearic acids on feed intake, yields of milk and milk components, and feed efficiency of dairy cows were evaluated in an experiment with a crossover arrangement of treatments with a covariate period. Cows with a wide range of milk production (38 to 65 kg/d) were used to determine if response to fat supplementation varied according to production level. Thirty-two Holstein cows (143 ± 61 d in milk) were assigned randomly to a treatment sequence within level of milk production. Treatments were diets supplemented (2% of diet dry matter) with palmitic acid (PA; 97.9% C16:0) or stearic acid (SA; 97.4% C18:0). Treatment periods were 21 d and cows were fed a nonfat supplemented diet for 14 d immediately before the first treatment period. The final 4d of each period were used for sample and data collection. Milk production measured during the covariate period (preliminary milk yield) was used as the covariate. No interactions were detected between treatment and preliminary milk yield for the production response variables measured. Compared with SA, the PA treatment increased milk fat concentration (3.66 vs. 3.55%) and yield (1.68 vs. 1.59 kg/d), and 3.5% fat-corrected milk yield (47.5 vs. 45.6 kg/d). Treatment did not affect dry matter intake, milk yield, milk protein yield, body weight, or body condition score. Milk protein concentration was lower for PA compared with SA treatment (3.24 vs. 3.29%). The PA treatment increased feed efficiency (3.5% fat-corrected milk yield/dry matter intake) compared with SA (1.48 vs. 1.40). The increase in milk fat yield by PA was entirely accounted for by a 24% increase in 16-carbon fatty acid output into milk. Yields of de novo (3.2%) and preformed fatty acids (2.9%) were only slightly decreased by PA relative to SA. The PA treatment increased plasma concentration of nonesterified fatty acids (96.3 vs. 88.2 μEq/L) and glucose (56.6 vs. 55.7 mg/dL) compared with SA, but insulin and

  10. Transcriptome analysis highlights changes in the leaves of maize plants cultivated in acidic soil containing toxic levels of Al(3+).

    PubMed

    Mattiello, Lucia; Begcy, Kevin; da Silva, Felipe Rodrigues; Jorge, Renato A; Menossi, Marcelo

    2014-12-01

    Soil acidity limits crop yields worldwide and is a common result of aluminum (Al) phytotoxicity, which is known to inhibit root growth. Here, we compared the transcriptome of leaves from maize seedlings grown under control conditions (soil without free Al) and under acidic soil containing toxic levels of Al. This study reports, for the first time, the complex transcriptional changes that occur in the leaves of maize plants grown in acidic soil with phytotoxic levels of Al. Our data indicate that 668 genes were differentially expressed in the leaves of plants grown in acidic soil, which is significantly greater than that observed in our previous work with roots. Genes encoding TCA cycle enzymes were upregulated, although no specific transporter of organic acids was differentially expressed in leaves. We also provide evidence for positive roles for auxin and brassinosteroids in Al tolerance, whereas gibberellin and jasmonate may have negative roles. Our data indicate that plant responses to acidic soil with high Al content are not restricted to the root; tolerance mechanisms are also displayed in the aerial parts of the plant, thus indicating that the entire plant responds to stress.

  11. Type IV resistant starch increases cecum short chain fatty acids level in rats.

    PubMed

    Le Thanh-Blicharz, Joanna; Anioła, Jacek; Kowalczewski, Przemysław; Przygoński, Krzysztof; Zaborowska, Zofia; Lewandowicz, Grażyna

    2014-01-01

    Resistant starches are type of dietary fibers. However, their physiological effects depend on the way they resist digestion in the gastrointestinal tract. The objective of this study was to examine the hypothesis that new type of RS4 preparations, of in vitro digestibility of about 50%, obtained by cross-linking and acetylation, acts as a prebiotic by increasing short chain fatty acids content in cecum digesta. The rats were fed with diet containing pregelatinized, cross-linked and acetylated starches as a main carbohydrate source. Pregelatinized, but not chemically modified, potato starch was used in the composition of the control diet. After two weeks of experiment the increase of short chain fatty acids contents in ceceum digesta was observed. The intake of starch A, cross-linked only with adipic acid, resulted in increase of about 40% of short chain fatty acids content, whereas starch PA cross-linked with sodium trimetaphosphate and adipic acid of about 50%. The utmost twofold increase was observed in the case of the production of propionic acid. In contrast, the content of butyric acid increased (12%) only as an effect of consumption of starch PA and even decreased (about 30%) in case of starch A. Both RS4 starches caused an increase of the production of acetic acid by more than 40%. No changes in serum biochemistry, liver cholesterol and organ weights of rats were stated.

  12. Chicoric Acid Levels in Commercial Basil (Ocimum basilicum) and Echinacea purpurea Products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, we reported fresh basil (Ocimum basilicum) leaves contain chicoric acid, which is the principal phenolic compound in Echinacea purpurea and purportedly an active ingredient in dietary supplements derived from E. purpurea. Here we present the results from a study evaluating chicoric acid co...

  13. Childrens' Learning and Behaviour and the Association with Cheek Cell Polyunsaturated Fatty Acid Levels

    ERIC Educational Resources Information Center

    Kirby, A.; Woodward, A.; Jackson, S.; Wang, Y.; Crawford, M. A.

    2010-01-01

    Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs),…

  14. Organosulfates and organic acids in Arctic aerosols: speciation, annual variation and concentration levels

    NASA Astrophysics Data System (ADS)

    Hansen, A. M. K.; Kristensen, K.; Nguyen, Q. T.; Zare, A.; Cozzi, F.; Nøjgaard, J. K.; Skov, H.; Brandt, J.; Christensen, J. H.; Ström, J.; Tunved, P.; Krejci, R.; Glasius, M.

    2014-02-01

    Sources, composition and occurrence of secondary organic aerosols (SOA) in the Arctic were investigated at Zeppelin Mountain, Svalbard, and Station Nord, northeast Greenland, during the full annual cycle of 2008 and 2010 respectively. We focused on the speciation of three types of SOA tracers: organic acids, organosulfates and nitrooxy organosulfates from both anthropogenic and biogenic precursors, here presenting organosulfate concentrations and compositions during a full annual cycle and chemical speciation of organosulfates in Arctic aerosols for the first time. Aerosol samples were analysed using High Performance Liquid Chromatography coupled to a quadrupole Time-of-Flight mass spectrometer (HPLC-q-TOF-MS). A total of 11 organic acids (terpenylic acid, benzoic acid, phthalic acid, pinic acid, suberic acid, azelaic acid, adipic acid, pimelic acid, pinonic acid, diaterpenylic acid acetate (DTAA) and 3-methyl-1,2,3-butanetricarboxylic acid (MBTCA)), 12 organosulfates and one nitrooxy organosulfate were identified at the two sites. Six out of the 12 organosulfates are reported for the first time. Concentrations of organosulfates follow a distinct annual pattern at Station Nord, where high concentration were observed in late winter and early spring, with a mean total concentration of 47 (±14) ng m-3, accounting for 7 (±2)% of total organic matter, contrary to a considerably lower organosulfate mean concentration of 2 (±3) ng m-3 (accounting for 1 (±1)% of total organic matter) observed during the rest of the year. The organic acids followed the same temporal trend as the organosulfates at Station Nord; however the variations in organic acid concentrations were less pronounced, with a total mean organic acid concentration of 11.5 (±4) ng m-3 (accounting for 1.7 (±0.6)% of total organic matter) in late winter and early spring, and 2.2 (±1) ng m-3 (accounting for 0.9 (±0.4)% of total organic matter) during the rest of the year. At Zeppelin Mountain

  15. Health beneficial long chain omega-3 fatty acid levels in Australian lamb managed under extensive finishing systems.

    PubMed

    Ponnampalam, Eric N; Butler, Kym L; Jacob, Robin H; Pethick, David W; Ball, Alex J; Edwards, Janelle E Hocking; Geesink, Geert; Hopkins, David L

    2014-02-01

    The variation in levels of the health claimable long chain omega-3 fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) plus docosahexaenoic acid (DHA, 22:6n-3) across production regions of Australia was studied in 5726 lambs over 3 years completed in 87 slaughter groups. The median level of EPA plus DHA differed dramatically between locations and sometimes between slaughters from the same location. The ratio of EPA plus DHA from lambs with high values (97.5% quantile) to lambs with low values (2.5% quantile) also differed dramatically between locations, and between slaughters from the same location. Consistency between years, at a location, was less for the high to low value ratio of EPA plus DHA than for the median value of EPA plus DHA. To consistently obtain high levels of omega-3 fatty acids in Australian lamb, there must be a focus on lamb finishing diets which are likely to need a supply of α-linolenic acid (18:3n-3), the precursor for EPA and DHA.

  16. Determination of trace levels of haloacetic acids and perchlorate in drinking water by ion chromatography with direct injection.

    PubMed

    Liu, Yongjian; Mou, Shifen

    2003-05-16

    Disinfection by products of haloacetic acids and perchlorate pose significant health risks, even at low microg/l levels in drinking water. A new method for the simultaneous determination of nine haloacetic acids (HAAs) and perchlorate as well as some common anions in one run with ion chromatography was developed. The HAAs tested included mono-, di-, trichloroacetic acids, mono, di-, tribromoacetic acids, bromochloroacetic acid, dibromochloroacetic acid, and bromodichloroacetic acid. Two high-capacity anion-exchange columns, a carbonate-selective column and a hydroxide-selective hydrophilic one, were used for the investigation. With the carbonate-selective column, the nine HAAs as well as fluoride, chloride, nitrite, nitrate, phosphate and sulfate could be well separated and determined in one run. With the very hydrophilic column and a gradient elution of sodium hydroxide, methanol and deionized water, the nine HAAs, fluoride, chloride, nitrite, nitrate as well as perchlorate could be simultaneously determined in one run within 34 min. The detection limits for HAAs were between 1.11 and 9.32 microg/l. For perchlorate, it was 0.60 microg/l.

  17. Effect of modification of the kilning regimen on levels of free ferulic acid and antioxidant activity in malt.

    PubMed

    Inns, Elizabeth L; Buggey, Lesley A; Booer, Christopher; Nursten, Harry E; Ames, Jennifer M

    2011-09-14

    Barley phenolic antioxidants change in response to the kilning regimen used to prepare malt. Green malt was kilned using four different regimens. There were no major differences among the finished malts in parameters routinely used by the malting industry, including, moisture, color, and diastatic activity. Ferulic acid esterase activity and free ferulic acid were higher in malts subjected to the coolest kilning regimen, but malt ethyl acetate extracts (containing ferulic acid) contributed only ∼5% of the total malt antioxidant activity. Finished malt from the hottest kilning regimen possessed the highest antioxidant activity, attributed to higher levels of Maillard reaction products. Modifying kilning conditions leads to changes in release of bound ferulic acid and antioxidant activity with potential beneficial effects on flavor stability in malt and beer.

  18. Two Acyltransferases Contribute Differently to Linolenic Acid Levels in Seed Oil1[OPEN

    PubMed Central

    Stymne, Sten

    2017-01-01

    Acyltransferases are key contributors to triacylglycerol (TAG) synthesis and, thus, are of great importance for seed oil quality. The effects of increased or decreased expression of ACYL-COENZYME A:DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1) or PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) on seed lipid composition were assessed in several Camelina sativa lines. Furthermore, in vitro assays of acyltransferases in microsomal fractions prepared from developing seeds of some of these lines were performed. Decreased expression of DGAT1 led to an increased percentage of 18:3n-3 without any change in total lipid content of the seed. The tri-18:3 TAG increase occurred predominantly in the cotyledon, as determined with matrix-assisted laser desorption/ionization-mass spectrometry, whereas species with two 18:3n-3 acyl groups were elevated in both cotyledon and embryonal axis. PDAT overexpression led to a relative increase of 18:2n-6 at the expense of 18:3n-3, also without affecting the total lipid content. Differential distributions of TAG species also were observed in different parts of the seed. The microsomal assays revealed that C. sativa seeds have very high activity of diacylglycerol-phosphatidylcholine interconversion. The combination of analytical and biochemical data suggests that the higher 18:2n-6 content in the seed oil of the PDAT overexpressors is due to the channeling of fatty acids from phosphatidylcholine into TAG before being desaturated to 18:3n-3, caused by the high activity of PDAT in general and by PDAT specificity for 18:2n-6. The higher levels of 18:3n-3 in DGAT1-silencing lines are likely due to the compensatory activity of a TAG-synthesizing enzyme with specificity for this acyl group and more desaturation of acyl groups occurring on phosphatidylcholine. PMID:28235891

  19. The antiepileptic drug valproic acid and other medium-chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium.

    PubMed

    Chang, Pishan; Orabi, Benoit; Deranieh, Rania M; Dham, Manik; Hoeller, Oliver; Shimshoni, Jakob A; Yagen, Boris; Bialer, Meir; Greenberg, Miriam L; Walker, Matthew C; Williams, Robin S B

    2012-01-01

    Valproic acid (VPA) is the most widely prescribed epilepsy treatment worldwide, but its mechanism of action remains unclear. Our previous work identified a previously unknown effect of VPA in reducing phosphoinositide production in the simple model Dictyostelium followed by the transfer of data to a mammalian synaptic release model. In our current study, we show that the reduction in phosphoinositide [PtdInsP (also known as PIP) and PtdInsP(2) (also known as PIP(2))] production caused by VPA is acute and dose dependent, and that this effect occurs independently of phosphatidylinositol 3-kinase (PI3K) activity, inositol recycling and inositol synthesis. In characterising the structural requirements for this effect, we also identify a family of medium-chain fatty acids that show increased efficacy compared with VPA. Within the group of active compounds is a little-studied group previously associated with seizure control, and analysis of two of these compounds (nonanoic acid and 4-methyloctanoic acid) shows around a threefold enhanced potency compared with VPA for protection in an in vitro acute rat seizure model. Together, our data show that VPA and a newly identified group of medium-chain fatty acids reduce phosphoinositide levels independently of inositol regulation, and suggest the reinvestigation of these compounds as treatments for epilepsy.

  20. The impact of a ketogenic diet and liver dysfunction on serum very long-chain fatty acids levels.

    PubMed

    Stradomska, T J; Bachański, M; Pawłowska, J; Syczewska, M; Stolarczyk, A; Tylki-Szymańska, A

    2013-04-01

    Peroxisomes play an essential role in mammalian cellular metabolism, particularly in oxidation fatty acid pathways. Serum very long-chain fatty acids (VLCFA), the main biochemical diagnostic parameters for peroxisomal disorders, were examined in 25 neurological patients with epilepsy on a ketogenic diet and 27 patients with liver dysfunction. The data show that patients on a ketogenic diet have increased levels of C22:0 and C24:0, but not C26:0, and normal C24:0/C22:0 and C26:0/C22:0. Patients with liver insufficiency showed a slightly elevated level of C26:0, a normal level of C24:0 and a decreased level of C22:0; thus in 21/27 the ratio of C24:0/C22:0 was increased and 15/27 the ratio of C26:0/C22:0 was increased.

  1. Effects of plant species, stage of maturity, and level of formic acid addition on lipolysis, lipid content, and fatty acid composition during ensiling.

    PubMed

    Koivunen, E; Jaakkola, S; Heikkilä, T; Lampi, A-M; Halmemies-Beauchet-Filleau, A; Lee, M R F; Winters, A L; Shingfield, K J; Vanhatalo, A

    2015-09-01

    Forage type and management influences the nutritional quality and fatty acid composition of ruminant milk. Replacing grass silage with red clover (RC; L.) silage increases milk fat 18:3-3 concentration. Red clover has a higher polyphenol oxidase (PPO) activity compared with grasses, which has been suggested to decrease lipolysis and . The present study characterized the abundance and fatty acid composition of esterified lipid and NEFA before and after ensiling of grass and RC to investigate the influence of forage species, growth stage, and extent of fermentation on lipolysis. A randomized block design with a 2 × 3 × 4 factorial arrangement of treatments was used. Treatments comprised RC or a mixture of timothy ( L.) and meadow fescue ( Huds.) harvested at 3 growth stages and treated with 4 levels of formic acid (0, 2, 4, and 6 L/t). Lipid in silages treated with 0 or 6 L/t formic acid were extracted and separated into 4 fractions by TLC. Total PPO activity in fresh herbage and the content of soluble bound phenols in all silages were determined. Concentrations of 18:3-3 and total fatty acids (TFA) were higher ( < 0.001) for RC than for grass. For both forage species, 18:3-3 and TFA content decreased linearly ( < 0.001) with advancing growth stage, with the highest abundance at the vegetative stage. Most of lipid in fresh RC and grass herbage (97%) was esterified, whereas NEFA accounted for 71% of TFA in both silages. Ensiling resulted in marginal increases in TFA content and the amounts of individual fatty acids compared with fresh herbages. Herbage total PPO activity was higher ( < 0.001) for RC than grass (11 vs. 0.11 μkatal/g leaf fresh weight). Net lipolysis during ensiling was extensive for both forage species (660 to 759 g/kg fatty acid for grass and 563 to 737 g/kg fatty acid for RC). Formic acid application (0 vs. 6 L/t) resulted in a marked decrease ( = 0.026) in net lipolysis during the ensiling of RC, whereas the opposite was true ( = 0.026) for grass

  2. Characterization of shortday onion cultivars of 3 pungency levels with flavor precursor, free amino acid, sulfur, and sugar contents.

    PubMed

    Lee, Eun Jin; Yoo, Kil Sun; Jifon, John; Patil, Bhimanagouda S

    2009-08-01

    This study was conducted to characterize shortday onions of 3 pungency levels with regard to the composition of flavor related compounds. A total of 9 onion breeding lines/cultivars were selected, per each of low, medium, and high pungency level, with pyruvic acid contents of 1.9 to 2.8, 4.8 to 5.4, and 7.2 to 8.3 micromoles/mL, respectively. The contents of flavor precursors (S-1-propenyl-L-cysteine sulfoxide [1-PeCSO] and S-methyl-L-cysteine-sulfoxide [MCSO]), free amino acids, free sugars, soluble solids (SSC), and total sulfur (S) in onion bulbs were measured. The flavor precursor contents ranged from 0.03 to 0.16 mg/g fresh weight (FW) for MCSO, 0.07 to 0.65 mg for 1-PeCSO, and 0.12 to 0.77 mg in total, and precursor contents increased with the pungency levels. Onions of different pungency levels did not differ in the contents of individual or total free amino acids, and the most abundant amino acids were glutamine and arginine. The total sugar contents ranged from 50 to 75 mg/g FW, and total S contents (3.5 to 5.1 mg/g dry weight) were not correlated with the pungency levels. However, pungency levels were correlated inversely with bulb weight and positively with SSC, presumably by the effect of dilution. This study indicates that onion pungency is primarily determined by the content of flavor precursor compounds and not by total S, total sugars, or individual/total free amino acids in shortday bulbs.

  3. Shallow hypothermia depends on the level of fatty acid unsaturation in adipose and liver tissues in a tropical heterothermic primate.

    PubMed

    Vuarin, Pauline; Henry, Pierre-Yves; Guesnet, Philippe; Alessandri, Jean-Marc; Aujard, Fabienne; Perret, Martine; Pifferi, Fabien

    2014-07-01

    Optimal levels of unsaturated fatty acids have positive impacts on the use of prolonged bouts of hypothermia in mammalian hibernators, which generally have to face low winter ambient temperatures. Unsaturated fatty acids can maintain the fluidity of fat and membrane phospholipids at low body temperatures. However, less attention has been paid to their role in the regulation of shallow hypothermia, and in tropical species, which may be challenged more by seasonal energetic and/or water shortages than by low temperatures. The present study assessed the relationship between the fatty acids content of white adipose and liver tissues and the expression of shallow hypothermia in a tropical heterothermic primate, the gray mouse lemur (Microcebus murinus). The adipose tissue is the main tissue for fat storage and the liver is involved in lipid metabolism, so both tissues were expected to influence hypothermia dependence on fatty acids. As mouse lemurs largely avoid deep hypothermia (i.e. torpor) use under standard captive conditions, the expression of hypothermia was triggered by food-restricting experimental animals. Hypothermia depth increased with time, with a stronger increase for individuals that exhibited higher contents of unsaturated fatty acids suggesting that they were more flexible in their use of hypothermia. However these same animals delayed the use of long hypothermia bouts relative to individuals with a higher level of saturated fatty acids. This study evidences for the first time that body fatty acids unsaturation levels influence the regulation of body temperature not only in cold-exposed hibernators but also in tropical, facultative heterotherms.

  4. Mutations in a delta9-Stearoyl-ACP-Desaturase Gene Are Associated with Enhanced Stearic Acid Levels in Soybean Seeds

    SciTech Connect

    Zhang, P.; Shanklin, J.; Burton, J. W.; Upchurch, R. G.; Whittle, E.; Dewey, R. E.

    2008-11-01

    Stearic acid (18:0) is typically a minor component of soybean [Glycine max (L.) Merr.] oil, accounting for only 2 to 4% of the total fatty acid content. Increasing stearic acid levels of soybean oil would lead to enhanced oxidative stability, potentially reducing the need for hydrogenation, a process leading to the formation of undesirable trans fatty acids. Although mutagenesis strategies have been successful in developing soybean germplasm with elevated 18:0 levels in the seed oil, the specific gene mutations responsible for this phenotype were not known. We report a newly identified soybean gene, designated SACPD-C, that encodes a unique isoform of {Delta}{sup 9}-stearoyl-ACP-desaturase, the enzyme responsible for converting stearic acid to oleic acid (18:1). High levels of SACPD-C transcript were only detected in developing seed tissue, suggesting that the encoded desaturase functions to enhance oleic acid biosynthetic capacity as the immature seed is actively engaged in triacylglycerol production and storage. The participation of SACPD-C in storage triacylglycerol synthesis is further supported by the observation of mutations in this gene in two independent sources of elevated 18:0 soybean germplasm, A6 (30% 18:0) and FAM94-41 (9% 18:0). A molecular marker diagnostic for the FAM94-41 SACPD-C gene mutation strictly associates with the elevated 18:0 phenotype in a segregating population, and could thus serve as a useful tool in the development of cultivars with oils possessing enhanced oxidative stability.

  5. Effect of Exogenous Indole-3-Acetic Acid and Indole-3-Butyric Acid on Internal Levels of the Respective Auxins and Their Conjugation with Aspartic Acid during Adventitious Root Formation in Pea Cuttings

    PubMed Central

    Nordström, Ann-Caroline; Jacobs, Fernando Alvarado; Eliasson, Lennart

    1991-01-01

    The influence of exogenous indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) on the internal levels of these auxins was studied during the first 4 days of adventitious root formation in cuttings of Pisum sativum L. The quantitations were done by high performance liquid chromatography with spectrofluorometric detection. IBA, identified by combined gas chromatography-mass spectrometry (GC-MS), was found to naturally occur in this plant material. The root inducing ability of exogenous IBA was superior to that of IAA. The IAA level in the tissue increased considerably on the first day after application of IAA, but rapidly decreased again, returning to a level twice the control by day 3. The predominant metabolic route was conjugation with aspartic acid, as reflected by the increase in the level of indole-3-acetylaspartic acid. The IBA treatment resulted in increases in the levels of IBA, IAA, and indole-3-acetylaspartic acid. The IAA content rapidly returned to control levels, whereas the IBA level remained high throughout the experimental period. High amounts of indole-3-butyrylaspartic acid were found in the tissue after feeding with IBA. The identity of the conjugate was confirmed by 1H-nuclear magnetic resonance and GC-MS. IBA was much more stable in solution than IAA. No IAA was detected after 48 hours, whereas 70% IBA was still recovered after this time. The relatively higher root inducing ability of IBA is ascribed to the fact that its level remained elevated longer than that of IAA, even though IBA was metabolized in the tissue. Adventitious root formation is discussed on the basis of these findings. PMID:16668265

  6. S-allyl cysteine attenuates free fatty acid-induced lipogenesis in human HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway.

    PubMed

    Hwang, Yong Pil; Kim, Hyung Gyun; Choi, Jae Ho; Do, Minh Truong; Chung, Young Chul; Jeong, Tae Cheon; Jeong, Hye Gwang

    2013-08-01

    S-Allyl cysteine (SAC), a nontoxic garlic compound, has a variety of pharmacological properties, including antioxidant and hepatoprotective properties. In this report, we provide evidence that SAC prevented free fatty acid (FFA)-induced lipid accumulation and lipotoxicity in hepatocytes. SAC significantly reduced FFA-induced generation of reactive oxygen species, caspase activation and subsequent cell death. Also, SAC mitigated total cellular lipid and triglyceride accumulation in steatotic HepG2 cells. SAC significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Additionally, SAC down-regulated the levels of sterol regulatory element binding protein-1 (SREBP-1) and its target genes, including ACC and fatty acid synthase. Use of a specific inhibitor showed that SAC activated AMPK via calcium/calmodulin-dependent kinase kinase (CaMKK) and silent information regulator T1. Our results demonstrate that SAC activates AMPK through CaMKK and inhibits SREBP-1-mediated hepatic lipogenesis. Therefore, SAC has therapeutic potential for preventing nonalcoholic fatty liver disease.

  7. Effect of dietary supplementation of omega-3 fatty acids and high levels of dietary protein on performance of sows.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was conducted to determine the effect of dietary supplementation of omega-3 fatty acids (O3FA), with or without high levels of dietary protein supplementation, on the performance of sows and their litters during first and subsequent parities. Sixty-four pregnant gilts with body weight (BW...

  8. Effect of dietary supplementation of omega-3 fatty acids and high levels of dietary protein on performance of sows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to determine the effect of dietary supplementation of omega-3 fatty acids (O3FA), with or without high levels of protein, on the performance of sows during first and subsequent parity. Sixty-four pregnant gilts with BW of 195.0 ± 2.1 kg and backfat (BF) thickness of 12.9 ± 0.2 ...

  9. Comparison of physiological and acid-base balance response during uphill, level and downhill running performed at constant velocity.

    PubMed

    Maciejczyk, Marcin; Więcek, M; Szymura, J; Szyguła, Z

    2013-09-01

    The purpose of this study was to compare the physiological and the acid-base balance response to running at various slope angles. Ten healthy men 22.3 ± 1.56 years old participated in the study. The study consisted of completing the graded test until exhaustion and three 45-minute runs. For the first 30 minutes, runs were performed with an intensity of approximately 50% VO2max, while in the final 15 minutes the slope angle of treadmill was adjusted (0°; +4.5°; -4.5°), and a fixed velocity of running was maintained. During concentric exercise, a significant increase in the levels of physiological indicators was reported; during eccentric exercise, a significant decrease in the level of the analyzed indicators was observed. Level running did not cause significant changes in the indicators of acid-base balance. The indicators of acid-base balance changed significantly in the case of concentric muscle work (in comparison to level running) and after the eccentric work, significant and beneficial changes were observed in most of the biochemical indicators. The downhill run can be used for a partial regeneration of the body during exercise, because during this kind of effort an improvement of running economy was observed, and this type of effort did not impair the acid-base balance of body.

  10. Method development for liquid chromatographic/triple quadrupole mass spectrometric analysis of trace level perfluorocarboxylic acids in articles of commerce

    EPA Science Inventory

    An analytical method to identify and quantify trace levels of C5 to C12 perfluorocarboxylic acids (PFCAs) in articles of commerce (AOC) is developed and rigorously validated. Solid samples were extracted in methanol, and liquid samples were diluted with a solvent consisting of 60...

  11. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

    PubMed Central

    2016-01-01

    We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects. PMID:27652270

  12. Vitamin B(12) and folic acid levels as therapeutic target in preserving bone mineral density (BMD) of older men.

    PubMed

    Naharci, Ilkin; Bozoglu, Ergun; Karadurmus, Nuri; Emer, Ozdes; Kocak, Necmettin; Kilic, Selim; Doruk, Huseyin; Serdar, Muhittin

    2012-01-01

    The knowledge about vitamin B(12) and folic acid levels in preserving bone mass in older men is limited. In this retrospective study, we aimed to find out whether levels of vitamin B(12) and folic acid are related to BMD in older men. Two hundred and sixty-nine older men were included in the study. Forty-two (15.6%) of them had osteoporotic, 150 (55.8%) had osteopenic, and 77 (28.6%) had normal BMD. Vitamin B(12) and folic acid levels were categorized as indicating normal, borderline, or low vitamin statuses. Femur neck densities showed statistically significant differences in subjects having low, borderline, and normal vitamin B(12), respectively. There were no significant differences between the three tertiles of vitamin B(12) in femur total, trochanteric, and intertrochanteric densities. After adjustment for age, body mass index (BMI), alcohol, smoking, and exercise with analysis of covariance, the difference was still statistically significant between two groups for femur neck density (p=0.011). No significant difference was observed between the groups of folic acid in any femur sites. We found that the normal level of vitamin B(12) in older men may be related to a decrease of femur neck bone loss.

  13. Genetic Association Mapping Identifies Single Nucleotide Polymorphisms in Genes that Affect Abscisic Acid Levels in Maize Floral Tissues During Drought

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In maize, development of the female inflorescence and its floral parts is vulnerable to water stress at flowering, which causes loss of kernel set and productivity. While changes in the levels of sugars and abscisic acid (ABA) are thought to play a role in this stress response, the mechanistic basi...

  14. Fish oil at low dietary levels enhances physiological activity of sesamin to increase hepatic fatty acid oxidation in rats.

    PubMed

    Ide, Takashi

    2012-11-01

    We previously demonstrated that a diet containing fish oil at a level of 80 g/kg strongly stimulated the physiological activity of a sesame sesamin preparation containing sesamin and episesamin at equal amounts to increase hepatic fatty acid oxidation. This study was conducted to clarify whether fish oil at lower dietary levels enhances the physiological activity of sesamin to increase hepatic fatty acid oxidation. Rats were fed experimental diets supplemented with 0 or 2 g sesamin/kg, and containing 0, 15 or 30 g fish oil/kg for 15 days. Among rats fed sesamin-free diets, diets containing 15 and 30 g fish oil/kg slightly increased the activity of enzymes involved in hepatic fatty acid oxidation. Sesamin increased these values irrespective of the presence or absence of fish oil in diets; however, the extent of the increase of many parameters was much greater in rats given fish oil-containing diets than in those fed a fish oil-free diet. Diets simultaneously containing sesamin and fish oil increased the gene expression of various peroxisomal fatty acid oxidation enzymes in a synergistic manner; but they were ineffective in causing a synergistic increase in mRNA levels of mitochondrial fatty acid oxidation enzymes. The extent of the synergistic increase in the activity of hepatic fatty acid oxidation enzymes and mRNA levels of the peroxisomal enzymes was indistinguishable between diets containing 15 and 30 g fish oil/kg and appeared comparable to that observed previously with a diet containing 80 g fish oil/kg.

  15. Comparison of the Effects of Eicosapentaenoic Acid With Docosahexaenoic Acid on the Level of Serum Lipoproteins in Helicobacter pylori: A Randomized Clinical Trial

    PubMed Central

    Agah, Shahram; Shidfar, Farzad; Khandouzi, Nafiseh; Baghestani, Ahmad Reza; Hosseini, Sharieh

    2014-01-01

    Background: Helicobacter pylori infection is the most common chronic bacterial infection around the world and an important cause of gastrointestinal disorders, which might be involved in the pathogenesis of some extragastrointestinal disturbances as well as changes in serum lipid profile. Hypolipemic properties of omega-3 fatty acids have been studied in several studies. Objectives: The present study aimed to compare the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on the level of serum lipoproteins in H. pylori. Patients and Methods: In a randomized, double-blinded, placebo-controlled clinical trial in Iran, 105 Helicobacter pylori were randomly allocated to receive 2 g of daily EPA (35 patients), DHA (35 patients), or medium-chain triglyceride (MCT) oil as placebo (33 patients) along with conventional tetra-drug H. pylori eradication regimen for 12 weeks. Results: From 105 included patients, 97 (31 in EPA, 33 in DHA, and 33 in control groups) completed the study and were included in final analysis. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and the ratios of TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C were not significantly different among the three groups, while the level of triglyceride (TG) was statistically different. DHA (-16.6 ± 30.34) and control (+ 15.32 ± 56.47) groups were statistically different with regard to changes in TG levels (P = 0.000). Conclusions: There was no difference between the effects of 2 g of EPA or DHA supplementation for 12 weeks on the levels of total cholesterol, LDL-C, HDL-C, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C; however, it had a desirable effect on the level of TG in a way that the effect of DHA was clearer. PMID:25763259

  16. Engineering Escherichia coli to synthesize free fatty acids

    PubMed Central

    Lennen, Rebecca M.; Pfleger, Brian F.

    2013-01-01

    Fatty acid metabolism has received significant attention as a route for producing high-energy density, liquid transportation fuels and high-value oleochemicals from renewable feedstocks. If microbes can be engineered to produce these compounds at yields that approach the theoretical limits of 0.3–0.4 g/g glucose, then processes can be developed to replace current petrochemical technologies. Here, we review recent metabolic engineering efforts to maximize production of free fatty acids (FFA) in Escherichia coli, the first step towards production of downstream products. To date, metabolic engineers have succeeded in achieving higher yields of FFA than any downstream products. Regulation of fatty acid metabolism and the physiological effects of fatty acid production will also be reviewed from the perspective of identifying future engineering targets. PMID:23102412

  17. Effects of conjugated linoleic acid supplementation and feeding level on dairy performance, milk fatty acid composition, and body fat changes in mid-lactation goats.

    PubMed

    Ghazal, S; Berthelot, V; Friggens, N C; Schmidely, P

    2014-11-01

    The objective of this trial was to study the interaction between the supplementation of lipid-encapsulated conjugated linoleic acid (CLA; 4.5 g of cis-9,trans-11 C18:2 and 4.5 g of trans-10,cis-12 C18:2) and feeding level to test if milk performance or milk fatty acid (FA) profile are affected by the interaction between CLA and feeding level. Twenty-four dairy goats were used in an 8-wk trial with a 3-wk adaptation to the experimental ration that contained corn silage, beet pulp, barley, and a commercial concentrate. During the third week, goats were assigned into blocks of 2 goats according to their dry matter intake (DMI), raw milk yield, and fat yield. Each block was randomly allocated to control (45 g of Ca salt of palm oil/d) or CLA treatment. Within each block, one goat was fed to cover 100% (FL100) of the calculated energy requirements and the other was fed 85% of the DMI of the first goat (FL85). Individual milk production and composition were recorded weekly, and milk FA composition was analyzed in wk 3, 5, and 7. Conjugated linoleic acid supplementation reduced milk fat content and fat yield by 17 and 19%, respectively, independent of the feeding level. It reduced both the secretion of milk FA synthesized de novo, and those taken up from the blood. No interaction between CLA and feeding level was observed on milk secretion of any group of FA. The CLA supplementation had no effect on DMI, milk yield, protein, and lactose yields but it improved calculated net energy for lactation balance. Goats fed the FL100 × CLA diet tended to have the highest DMI and protein yield. The interaction between CLA and feeding level was not significant for any other variables. Compared with the goats fed FL100, those fed FL85 had lower DMI, lower net energy for lactation balance, and lower digestible protein in the intestine balance. The body weight; milk yield; milk fat, protein, and lactose yields; and fat, protein, lactose, and urea contents in milk were not affected by

  18. Release of free fatty acids from raw or processed soybeans and subsequent effects on fiber digestibilities.

    PubMed

    Reddy, P V; Morrill, J L; Nagaraja, T G

    1994-11-01

    Two in vitro experiments were conducted to determine the rates of lipolysis and the extent of biohydrogenation of fat from raw or processed soybeans and to examine the subsequent effects on fiber digestibilities. In Experiment 1, substrates containing soy oil, raw soybeans, extruded soybeans, and soybeans roasted at 132, 146, or 163 degrees C were incubated with ruminal contents for 2, 4, 6, 12, or 24 h; and release of FFA was measured. The FFA released from substrates containing soy oil, extruded soybeans, and raw or roasted soybeans reached maxima at incubations of 4, 6, and 12 h, respectively. As the roasting temperature increased from 132 to 163 degrees C, release of FFA decreased at incubations of 2, 12, and 24 h. Fatty acids in roasted soybeans were subjected to less biohydrogenation than those in raw or extruded soybeans, suggesting that FFA of roasted soybeans are partially protected from ruminal bacteria. In Experiment 2, ground alfalfa hay was added to substrates used previously to determine the effect of release rate of FFA on ADF and NDF digestibilities. At all incubation times, the substrates containing soy oil and extruded soybeans had lower digestibilities, and those containing raw or roasted soybeans had higher digestibilities of NDF and ADF.

  19. Nano porous alkaline earth metal silicates as free fatty acid adsorbents from Crude Palm Oil (CPO)

    NASA Astrophysics Data System (ADS)

    Masmur, Indra; Sembiring, Seri Bima; Bangun, Nimpan; Kaban, Jamaran; Putri, Nabila Karina

    2017-01-01

    Free fatty acids(FFA) from Crude Palm Oil (CPO) have been adsorbed by alkaline earth metal silicate (M-silicate : M = Mg, Ca, Sr and Ba) adsorbents in ethanol using batch method. The adsorbents were prepared from the chloride salts of alkaline metals and Na2SiO3. The resulting white solid of the alkaline earth metal silicates were then heated at 800°C for 3 hours to enlarge their porosities. All adsorbents were characterized by SEM-EDX, XRD and BET. The EDX spectrum of SEM-EDX showed the appearance of all elements in the adsorbents, and the XRD spectrum of all adsorbents showed that they have crystobalite structure. The porosity of the adsorbents calculated by BET method showed that the porosities of the adsorbents range from 2.0884 - 2.0969 nm. All the adsorbents were used to adsorb the FFA from CPO containing 4.79%, 7.3%, 10.37% and 13.34% of FFA. The ratio of adsorbent to CPO to be used in adsorption of FFA from CPO were made 1:1, 1:2 and 1:3, with adsorption time of 1 hour. We found that the maximum adsorption of FFA from CPO was given by Ca-Silicate adsorbent which was between 69.86 - 94.78%, while the lowest adsorption was shown by Mg-silicate adsorbent which was 49.32 -74.53%.

  20. Polysorbate 20 Degradation in Biopharmaceutical Formulations: Quantification of Free Fatty Acids, Characterization of Particulates, and Insights into the Degradation Mechanism.

    PubMed

    Tomlinson, Anthony; Demeule, Barthélemy; Lin, Baiwei; Yadav, Sandeep

    2015-11-02

    Polysorbate 20 (PS20), a commonly used surfactant in biopharmaceuticals, showed degradation upon long-term (∼18-36 months) storage of two monoclonal antibody (mAb, mAb-A, and mAb-B) drug products at 2-8 °C. The PS20 degradation resulted in the accumulation of free fatty acids (FFA), which ultimately precipitated to form particles upon long-term storage. This study documents the development, qualification, and application of a method for FFA quantification in soluble and insoluble fraction of protein formulation. The method was applied to the quantification of capric acid, lauric acid, myristic acid, palmitic/oleic acid, and stearic acid in placebo as well as active protein formulations on stability. Quantification of FFA in both the soluble and insoluble fraction of mAb-A and mAb-B provided a better mechanistic understanding of PS20 degradation and the dynamics of subsequent fatty acid particle formation. Additionally, the use of this method for monitoring and quantitation of the FFA on real time storage stability appears to aid in identifying batches with higher probability for particulate formation upon extended storage at 5 °C.

  1. Ageing, adipose tissue, fatty acids and inflammation.

    PubMed

    Pararasa, Chathyan; Bailey, Clifford J; Griffiths, Helen R

    2015-04-01

    A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults.

  2. High-level production of poly (β-L: -malic acid) with a new isolated Aureobasidium pullulans strain.

    PubMed

    Zhang, Huili; Cai, Jin; Dong, Jiaqi; Zhang, Danping; Huang, Lei; Xu, Zhinan; Cen, Peilin

    2011-10-01

    Poly (β-L: -malic acid) (PMLA) is a water-soluble polyester with many attractive properties in chemical industry and medicine development. However, the low titer of PMLA in the available producer strains limits further industrialization efforts and restricts its many potential applications. In order to solve this problem, a new strain with the distinguished high productivity of PMLA was isolated from fresh plants samples. It was characterized as the candidate of Aureobasidium pullulans based on the morphology and phylogenetic analyses of the internal transcribed spacer sequences. After the optimization of culture conditions, the highest PMLA concentration (62.27 g l(-1)) could be achieved in the shake flask scale. In addition, the contribution of the carbon flux to exopolysaccharide (EPS) and PMLA could be regulated by the addition of CaCO₃ in the medium. This high-level fermentation process was further scaled up in the 10 l benchtop fermentor with a high PMLA concentration (57.2 g l(-1)) and productivity (0.35 g l(-1) h(-1)), which are the highest level in all the literature. Finally, the suitable acid hydrolysis conditions of PMLA were also investigated with regard to the production of L: -malic acid, and the kinetics of PMLA acid hydrolysis was modeled to simulate the whole degradation process. The present work paved the road to produce this multifunctional biomaterial (PMLA) at industrial scale and promised one alternative method to produce L: -malic acid in the future.

  3. Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon, 2006-2015.

    PubMed

    Sprague, M; Dick, J R; Tocher, D R

    2016-02-22

    As the global population and its demand for seafood increases more of our fish will come from aquaculture. Farmed Atlantic salmon are a global commodity and, as an oily fish, contain a rich source of the health promoting long-chain omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Replacing the traditional finite marine ingredients, fishmeal and fish oil, in farmed salmon diets with sustainable alternatives of terrestrial origin, devoid of EPA and DHA, presents a significant challenge for the aquaculture industry. By comparing the fatty acid composition of over 3,000 Scottish Atlantic salmon farmed between 2006 and 2015, we find that terrestrial fatty acids have significantly increased alongside a decrease in EPA and DHA levels. Consequently, the nutritional value of the final product is compromised requiring double portion sizes, as compared to 2006, in order to satisfy recommended EPA + DHA intake levels endorsed by health advisory organisations. Nevertheless, farmed Scottish salmon still delivers more EPA + DHA than most other fish species and all terrestrial livestock. Our findings highlight the global shortfall of EPA and DHA and the implications this has for the human consumer and examines the potential of microalgae and genetically modified crops as future sources of these important fatty acids.

  4. Changes in plasma osmolality, cortisol and amino acid levels of tongue sole ( Cynoglossus semilaevis) at different salinities

    NASA Astrophysics Data System (ADS)

    Wang, Guodong; Xu, Kefeng; Tian, Xiangli; Dong, Shuanglin; Fang, Ziheng

    2015-10-01

    A serial of salinity transferring treatments were performed to investigate the osmoregulation of tongue sole ( Cynoglossus semilaevis). Juvenile tongue sole were directly transferred from a salinity of 30 to 0, 10, 20, 30, 40 and 50. Blood sampling was performed for each treatment after 0, 1, 6 and 12 h, as well as after 1, 2, 4, 8, 16 and 32 d. The plasma osmolality, cortisol and free amino acids were assessed. Under the experimental conditions, no fish died after acute salinity transfer. The plasma cortisol level increased 1 h after the abrupt transfer from a salinity of 30 to that of 0, 40 and 50, and decreased from 6 h to 8 d after transfer. Similar trends were observed in the changes of plasma osmolality. The plasma free amino acids concentration showed a `U-shaped' relationship with salinity after being transferred to different salinities for 4 days. More obvious changes of plasma free amino acid concentration occurred under hyper-osmotic conditions than under hypo-osmotic conditions. The concentrations of valine, isoleucine, lysine, glutamic acid, glycine, proline and taurine increased with rising salinity. The plasma levels of threonine, leucine, arginine, serine, and alanine showed a `U-shaped' relationship with salinity. The results of this study suggested that free amino acids might have important effects on osmotic acclimation in tongue sole.

  5. AquaLite, a bioluminescent label for immunoassay and nucleic acid detection: quantitative analyses at the attomol level

    NASA Astrophysics Data System (ADS)

    Smith, David F.; Stults, Nancy L.

    1996-04-01

    AquaLiteR is a direct, bioluminescent label capable of detecting attomol levels of analyte in clinical immunoassays and assays for the quantitative measurement of nucleic acids. Bioluminescent immunoassays (BIAs) require no radioisotopes and avoid complex fluorescent measurements and many of the variables of indirect enzyme immunoassays (EIAs). AquaLite, a recombinant form of the photoprotein aequorin from a bioluminescent jellyfish, is coupled directly to antibodies to prepare bioluminescent conjugates for assay development. When the AquaLite-antibody complex is exposed to a solution containing calcium ions, a flash of blue light ((lambda) max equals 469 nm) is generated. The light signal is measured in commercially available luminometers that simultaneously inject a calcium solution and detect subattomol photoprotein levies in either test tubes or microtiter plates. Immunometric or 'sandwich' type assays are available for the quantitative measurement of human endocrine hormones and nucleic acids. The AquaLite TSH assay can detect 1 attomol of thyroid stimulating hormone (TSH) in 0.2 mL of human serum and is a useful clinical tool for diagnosing hyperthyroid patients. AquaLite-based nucleic acid detection permits quantifying attomol levels of specific nucleic acid markers and represents possible solution to the difficult problem of quantifying the targets of nucleic acid amplification methods.

  6. Boric acid increases the expression levels of human anion exchanger genes SLC4A2 and SLC4A3.

    PubMed

    Akbas, F; Aydin, Z

    2012-04-03

    Boron is an important micronutrient in plants and animals. The role of boron in living systems includes coordinated regulation of gene expression, growth and proliferation of higher plants and animals. There are several well-defined genes associated with boron transportation and tolerance in plants and these genes show close homology with human anion exchanger genes. Mutation of these genes also characterizes some genetic disorders. We investigated the toxic effects of boric acid on HEK293 cells and mRNA expression of anion exchanger (SLC4A1, SLC4A2 and SLC4A3) genes. Cytotoxicity of boric acid at different concentrations was tested by using the methylthiazolyldiphenyl-tetrazolium bromide assay. Gene expression profiles were examined using quantitative real-time PCR. In the HEK293 cells, the nontoxic upper concentration of boric acid was 250 μM; more than 500 μM caused cytotoxicity. The 250 μM boric acid concentration increased gene expression level of SLC4A2 up to 8.6-fold and SLC4A3 up to 2.6-fold, after 36-h incubation. There was no significant effect of boric acid on SLC4A1 mRNA expression levels.

  7. Middle-aged rats orally supplemented with gel-encapsulated catechin favorably increases blood cytosolic NADPH levels.

    PubMed

    Cueno, Marni E; Tamura, Muneaki; Ochiai, Kuniyasu

    2015-04-15

    Green tea catechins are primarily known to function as free radical scavengers and have several beneficial uses. Orally supplemented catechin (OSC) was previously shown to increase mitochondrial heme and catalase levels in rat heart blood, however, its effect in the cytosol has not been elucidated. Here, we determined the effects of OSC in the rat heart blood cytosol. We used middle-aged (40 week-old) and young (4 week-old) rats throughout the study. We isolated blood cytosol, verified its purity, and determined heme, hydrogen peroxide (H2O2) levels, catalase (CAT) activities, gp91(phox) amounts, NADP and NAD pools, sirtuin 1 (SIRT1) and glutathione reductase (GR) activities, and free fatty acids (FFA). We established that OSC is associated with decreased heme-dependent H2O2 amounts while increasing heme-independent CAT activity. Moreover, we found that OSC-related decrease in NAD(+) amounts among middle-aged rats is associated to increased NADPH levels and SIRT1 activity. In contrast, we associated OSC-related decrease in NAD(+) amounts among young rats to decreased NADPH levels and increased SIRT1 activity. This highlights a major difference between catechin-treated middle-aged and young rats. Furthermore, we observed that cytosolic FFA and GR levels were significantly increased only among OSC-treated middle-aged rats which we hypothesize are related to increased NADPH levels. This insinuates that OSC treatment allows higher catechin amounts to enter the bloodstream of middle-aged rats. We propose that this would favorably increase NADPH amounts and lead to the simultaneous decrease in NADPH-related pro-oxidant activity and increase in NADPH-related biomolecules and anti-oxidant activities.

  8. Performance of dairy cows fed high levels of acetic acid or ethanol.

    PubMed

    Daniel, J L P; Amaral, R C; Sá Neto, A; Cabezas-Garcia, E H; Bispo, A W; Zopollatto, M; Cardoso, T L; Spoto, M H F; Santos, F A P; Nussio, L G

    2013-01-01

    Ethanol and acetic acid are common end products from silages. The main objective of this study was to determine whether high concentrations of ethanol or acetic acid in total mixed ration would affect performance in dairy cow