Sample records for acid aa release

  1. Hydrocortisone selectively inhibits IgE-dependent arachidonic acid release from rat peritoneal mast cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Heiman, A.S.; Crews, F.T.

    Purified rat mst cells were used to study the effects of antiinflammatory steroids on the release of (1-14C)-arachidonic acid ((1-14C)AA) and metabolites. Mast cell were incubated overnight with glucocorticoids, (1-14C)AA incorporated into cellular phospholipids and the release of (1-14C)AA, and metabolites determined using a variety of secretagogues. Release of (1-14C)AA and metabolites by concanavalin A, the antigen ovalbumin and anti-immunoglobulin E antibody was markedly reduced by glucocorticoid treatment. Neither the total incorporation of (1-14C)AA nor the distribution into phospholipids was altered by hydrocortisone pretreatment. Glucocorticoid pretreatment did not alter (1-14C)AA release stimulated by somatostatin, compound 48/80, or the calcium ionophore,more » A23187. These data indicate that antiinflammatory steroids selectively inhibit immunoglobulin dependent release of arachidonic acid from rat mast cells. These findings question the role of lipomodulin and macrocortin as general phospholipase inhibitors and suggest that they may be restricted to immunoglobulin stimuli.« less

  2. Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite.

    PubMed

    Elliott Donaghue, Irja; Shoichet, Molly S

    2015-10-01

    Polymer excipients, such as low molar mass poly(ethylene glycol) (PEG), have shown contradictory effects on protein stability when co-encapsulated in polymeric nanoparticles. To gain further insight into these effects, platelet-derived growth factor (PDGF-AA) was encapsulated in polymeric nanoparticles with vs. without PEG. PDGF-AA is a particularly compelling protein, as it has been demonstrated to promote cell survival and induce the oligodendrocyte differentiation of neural stem/progenitor cells (NSPCs) both in vitro and in vivo. Here we show, for the first time, the controlled release of bioactive PDGF-AA from an injectable nanoparticle/hydrogel drug delivery system (DDS). PDGF-AA was encapsulated, with high efficiency, in poly(lactide-co-glycolide) nanoparticles, and its release from the drug delivery system was followed over 21 d. Interestingly, the co-encapsulation of low molecular weight poly(ethylene glycol) increased the PDGF-AA loading but, unexpectedly, accelerated the aggregation of PDGF-AA, resulting in reduced activity and detection by enzyme-linked immunosorbent assay (ELISA). In the absence of PEG, released PDGF-AA remained bioactive as demonstrated with NSPC oligodendrocyte differentiation, similar to positive controls, and significantly different from untreated controls. This work presents a novel delivery method for differentiation factors, such as PDGF-AA, and provides insights into the contradictory effects reported in the literature of excipients, such as PEG, on the loading and release of proteins from polymeric nanoparticles. Previously, the polymer poly(ethylene glycol) (PEG) has been used in many biomaterials applications, from surface coatings to the encapsulation of proteins. In this work, we demonstrate that, unexpectedly, low molecular weight PEG has a deleterious effect on the release of the encapsulated protein platelet-derived growth factor AA (PDGF-AA). We also demonstrate release of bioactive PDGF-AA (in the absence of PEG

  3. Characterization of the radical-scavenging reaction of 2-O-substituted ascorbic acid derivatives, AA-2G, AA-2P, and AA-2S: a kinetic and stoichiometric study.

    PubMed

    Takebayashi, Jun; Tai, Akihiro; Gohda, Eiichi; Yamamoto, Itaru

    2006-04-01

    The aim of this study was to characterize the antioxidant activity of three ascorbic acid (AA) derivatives O-substituted at the C-2 position of AA: ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S). The radical-scavenging activities of these AA derivatives and some common low molecular-weight antioxidants such as uric acid or glutathione against 1,1-diphenyl-picrylhydrazyl (DPPH) radical, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS+), or galvinoxyl radical were kinetically and stoichiometrically evaluated under pH-controlled conditions. Those AA derivatives slowly and continuously reacted with DPPH radical and ABTS+, but not with galvinoxyl radical. They effectively reacted with DPPH radical under acidic conditions and with ABTS+ under neutral conditions. In contrast, AA immediately quenched all species of radicals tested at all pH values investigated. The reactivity of Trolox, a water-soluble vitamin E analogue, was comparable to that of AA in terms of kinetics and stoichiometrics. Uric acid and glutathione exhibited long-lasting radical-scavenging activity against these radicals under certain pH conditions. The radical-scavenging profiles of AA derivatives were closer to those of uric acid and glutathione rather than to that of AA. The number of radicals scavenged by one molecule of AA derivatives, uric acid, or glutathione was equal to or greater than that by AA or Trolox under the appropriate conditions. These data suggest the potential usage of AA derivatives as radical scavengers.

  4. Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF-AA release kinetics in a 3D microparticle-hydrogel drug delivery system.

    PubMed

    Pinezich, Meghan R; Russell, Lauren N; Murphy, Nicholas P; Lampe, Kyle J

    2018-04-16

    Biomaterial drug delivery systems (DDS) can be used to regulate growth factor release and combat the limited intrinsic regeneration capabilities of central nervous system (CNS) tissue following injury and disease. Of particular interest are systems that aid in oligodendrocyte regeneration, as oligodendrocytes generate myelin which surrounds neuronal axons and helps transmit signals throughout the CNS. Oligodendrocyte precursor cells (OPCs) are found in small numbers in the adult CNS, but are unable to effectively differentiate following CNS injury. Delivery of signaling molecules can initiate a favorable OPC response, such as proliferation or differentiation. Here, we investigate the delivery of one such molecule, platelet derived growth factor-AA (PDGF-AA), from poly(lactic-co-glycolic) acid microparticles to OPCs in a 3D polyethylene glycol-based hydrogel. The goal of this DDS was to better understand the relationship between PDGF-AA release kinetics and OPC fate. The system approximates native brain tissue stiffness, while incorporating PDGF-AA under seven different delivery scenarios. Within this DDS, supply of PDGF-AA followed by PDGF-AA withdrawal caused OPCs to upregulate gene expression of myelin basic protein (MBP) by factors of 1.6-9.2, whereas continuous supply of PDGF-AA caused OPCs to remain proliferative. At the protein expression level, we observed an upregulation in O1, a marker for mature oligodendrocytes. Together, these results show that burst release followed by withdrawal of PDGF-AA from a hydrogel DDS stimulates survival, proliferation, and differentiation of OPCs in vitro. Our results could inform the development of improved neural regeneration strategies that incorporate delivery of PDGF-AA to the injured CNS. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

  5. Group X secreted phospholipase A2 proenzyme is matured by a furin-like proprotein convertase and releases arachidonic acid inside of human HEK293 cells.

    PubMed

    Jemel, Ikram; Ii, Hiromi; Oslund, Rob C; Payré, Christine; Dabert-Gay, Anne-Sophie; Douguet, Dominique; Chargui, Khaoula; Scarzello, Sabine; Gelb, Michael H; Lambeau, Gérard

    2011-10-21

    Among mammalian secreted phospholipases A(2) (sPLA(2)s), group X sPLA(2) has the most potent hydrolyzing activity toward phosphatidylcholine and is involved in arachidonic acid (AA) release. Group X sPLA(2) is produced as a proenzyme and contains a short propeptide of 11 amino acids ending with a dibasic motif, suggesting cleavage by proprotein convertases. Although the removal of this propeptide is clearly required for enzymatic activity, the cellular location and the protease(s) involved in proenzyme conversion are unknown. Here we have analyzed the maturation of group X sPLA(2) in HEK293 cells, which have been extensively used to analyze sPLA(2)-induced AA release. Using recombinant mouse (PromGX) and human (ProhGX) proenzymes; HEK293 cells transfected with cDNAs coding for full-length ProhGX, PromGX, and propeptide mutants; and various permeable and non-permeable sPLA(2) inhibitors and protease inhibitors, we demonstrate that group X sPLA(2) is mainly converted intracellularly and releases AA before externalization from the cell. Most strikingly, the exogenous proenzyme does not elicit AA release, whereas the transfected proenzyme does elicit AA release in a way insensitive to non-permeable sPLA(2) inhibitors. In transfected cells, a permeable proprotein convertase inhibitor, but not a non-permeable one, prevents group X sPLA(2) maturation and partially blocks AA release. Mutations at the dibasic motif of the propeptide indicate that the last basic residue is required and sufficient for efficient maturation and AA release. All together, these results argue for the intracellular maturation of group X proenzyme in HEK293 cells by a furin-like proprotein convertase, leading to intracellular release of AA during secretion.

  6. Group X Secreted Phospholipase A2 Proenzyme Is Matured by a Furin-like Proprotein Convertase and Releases Arachidonic Acid inside of Human HEK293 Cells*

    PubMed Central

    Jemel, Ikram; Ii, Hiromi; Oslund, Rob C.; Payré, Christine; Dabert-Gay, Anne-Sophie; Douguet, Dominique; Chargui, Khaoula; Scarzello, Sabine; Gelb, Michael H.; Lambeau, Gérard

    2011-01-01

    Among mammalian secreted phospholipases A2 (sPLA2s), group X sPLA2 has the most potent hydrolyzing activity toward phosphatidylcholine and is involved in arachidonic acid (AA) release. Group X sPLA2 is produced as a proenzyme and contains a short propeptide of 11 amino acids ending with a dibasic motif, suggesting cleavage by proprotein convertases. Although the removal of this propeptide is clearly required for enzymatic activity, the cellular location and the protease(s) involved in proenzyme conversion are unknown. Here we have analyzed the maturation of group X sPLA2 in HEK293 cells, which have been extensively used to analyze sPLA2-induced AA release. Using recombinant mouse (PromGX) and human (ProhGX) proenzymes; HEK293 cells transfected with cDNAs coding for full-length ProhGX, PromGX, and propeptide mutants; and various permeable and non-permeable sPLA2 inhibitors and protease inhibitors, we demonstrate that group X sPLA2 is mainly converted intracellularly and releases AA before externalization from the cell. Most strikingly, the exogenous proenzyme does not elicit AA release, whereas the transfected proenzyme does elicit AA release in a way insensitive to non-permeable sPLA2 inhibitors. In transfected cells, a permeable proprotein convertase inhibitor, but not a non-permeable one, prevents group X sPLA2 maturation and partially blocks AA release. Mutations at the dibasic motif of the propeptide indicate that the last basic residue is required and sufficient for efficient maturation and AA release. All together, these results argue for the intracellular maturation of group X proenzyme in HEK293 cells by a furin-like proprotein convertase, leading to intracellular release of AA during secretion. PMID:21878635

  7. Clinical implications of eicosapentaenoic acid/arachidonic acid ratio (EPA/AA) in adult patients with congenital heart disease.

    PubMed

    Kanoh, Miki; Inai, Kei; Shinohara, Tokuko; Tomimatsu, Hirofumi; Nakanishi, Toshio

    2017-12-01

    Recent studies showed that a low ratio between the levels of eicosapentaenoic acid and those of arachidonic acid (EPA/AA) is associated with higher incidence of coronary artery disease and poor prognosis of heart failure, arrhythmia, and cardiac sudden death. However, the clinical implications of EPA/AA in adult patients with congenital heart disease remain unclear. We aimed to assess the prognostic value of EPA/AA regarding cardiac events in adult patients with congenital heart disease. We measured the serum levels of eicosapentaenoic acid and arachidonic acid in 130 adult patients (median age, 31 years) stratified into two groups according to their EPA/AA (low, ≤0.22; high, >0.22). We prospectively analyzed the association between EPA/AA and incidence of cardiac events during a mean observation period of 15 months, expressed in terms of hazard ratio (HR) with 95% confidence interval (95% CI). In the subgroup of patients with biventricular circulation (2VC) (n = 76), we analyzed the same clinical endpoints. In our study population, EPA/AA was not associated with the incidence of arrhythmic events (HR, 1.52; 95% CI, 0.82-2.85; p = 0.19), but low EPA/AA was a predictor of heart failure hospitalization (HR, 2.83; 95% CI, 1.35-6.30; p < 0.01). Among patients with 2VC, an EPA/AA of ≤0.25 was associated with a significantly higher risk of arrhythmic events (HR, 2.55; 95% CI, 1.11-6.41; p = 0.03) and heart failure hospitalization (HR, 5.20; 95% CI, 1.78-18.1; p < 0.01). EPA/AA represents a useful predictor of cardiac events in adult patients with congenital heart disease.

  8. [Risk control of traditional Chinese medicines containing aristolochis acids (AAs) based on influencing factors of content of AAs].

    PubMed

    Tian, Jing-Zhuo; Liang, Ai-Hua; Liu, Jing; Zhang, Bo-Li

    2017-12-01

    Aristolochic acids (AAs) widely exist in such plants as Aristolochia and Asarum. The renal toxicity of AAs as well as its carcinogenicity to urinary system have been widely known. In 2003 and 2004, China prohibited the use of Aristolochiae Radix, Aristolochiae Manshuriensis Caulis and Aristolochiae Fangchi Radix, and required administering other AAs-containing medicines in accordance with the regulations for prescription drugs. In this paper, we retrieved literatures on the content determination of AAs in recent 10 years in China. It suggested that the AAs content is lower in Asarum herb, especially in its roots and rhizomes, and most of which do not show detectable amount of AA-I. Some of traditional Chinese medicines show fairly small amount of detectable AA-I. The AAs content in Aristolochia herb (including Fructus Aristolochiae, kaempfer dutchmanspipe root) is relatively high; however, there are fewer literatures for studying the content determination of AAs in Chinese patent medicines. There were many factors affecting AAs content, including the parts used, origins, processing methods, extraction process. It suggested that we should pay attention to the toxicity of Chinese medicines containing AAs and use these decoction pieces and traditional Chinese medicines cautiously. In addition, basic studies for the origins, processing methods and extraction process of Chinese patent medicines containing AAs, as well as supervision and detection of AAs content in traditional Chinese medicinal materials, decoction pieces and Chinese patent medicines shall be strengthened for reducing medication risk and guaranteeing clinical medication safety. Copyright© by the Chinese Pharmaceutical Association.

  9. Phospholipid sources for adrenic acid mobilization in RAW 264.7 macrophages. Comparison with arachidonic acid.

    PubMed

    Guijas, Carlos; Astudillo, Alma M; Gil-de-Gómez, Luis; Rubio, Julio M; Balboa, María A; Balsinde, Jesús

    2012-11-01

    Cells metabolize arachidonic acid (AA) to adrenic acid (AdA) via 2-carbon elongation reactions. Like AA, AdA can be converted into multiple oxygenated metabolites, with important roles in various physiological and pathophysiological processes. However, in contrast to AA, there is virtually no information on how the cells regulate the availability of free AdA for conversion into bioactive products. We have used a comparative lipidomic approach with both gas chromatography and liquid chromatography coupled to mass spectrometry to characterize changes in the levels of AA- and AdA-containing phospholipid species in RAW 264.7 macrophage-like cells. Incubation of the cells with AA results in an extensive conversion to AdA but both fatty acids do not compete with each other for esterification into phospholipids. AdA but not AA, shows preference for incorporation into phospholipids containing stearic acid at the sn-1 position. After stimulation of the cells with zymosan, both AA and AdA are released in large quantities, albeit AA is released to a greater extent. Finally, a variety of phosphatidylcholine and phosphatidylinositol molecular species contribute to AA; however, AdA is liberated exclusively from phosphatidylcholine species. Collectively, these results identify significant differences in the cellular utilization of AA and AdA by the macrophages, suggesting non-redundant biological actions for these two fatty acids. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Role of protein kinase C alpha in endothelin-1 stimulation of cytosolic phospholipase A2 and arachidonic acid release in cultured cat iris sphincter smooth muscle cells.

    PubMed

    Husain, S; Abdel-Latif, A A

    1998-05-20

    We have investigated the role and mechanism of protein kinase C (PKC) isoforms in endothelin-1 (ET-1)-induced arachidonic acid (AA) release in cat iris sphincter smooth muscle (CISM) cells. ET-1 increased AA release in a concentration (EC50=8 nM) and time-dependent (t1/2=1.2 min) manner. Cytosolic phospholipase A2 (cPLA2), but not phospholipase C (PLC), is involved in the liberation of AA in the stimulated cells. This conclusion is supported by the findings that ET-1-induced AA release is inhibited by AACOCF3, quinacrine and manoalide, PLA2 inhibitors, but not by U-73122, a PLC inhibitor, or by RHC-80267, a diacylglycerol lipase inhibitor. A role for PKC in ET-1-induced AA release is supported by the findings that the phorbol ester, PDBu, increased AA release by 96%, that prolonged treatment of the cells with PDBu resulted in the selective down regulation of PKCalpha and the complete inhibition of ET-1-induced AA release, and that pretreatment of the cells with staurosporine or RO 31-8220, PKC inhibitors, blocked the ET-1-induced AA release. Gö-6976, a compound that inhibits PKCalpha and beta specifically, blocked ET-1-induced AA release in a concentration-dependent manner with an IC50 value of 8 nM. Thymeatoxin (0.1 microM), a specific activator of PKCalpha, beta, and gamma induced a 150% increase in AA release. Treatment of the cells with ET-1 caused significant translocation of PKCalpha, but not PKCbeta, from cytosol to the particulate fraction. These results suggest that PKCalpha plays a critical role in ET-1-induced AA release in these cells. Immunochemical analysis revealed the presence of cPLA2, p42mapk and p44mapk in the CISM cells. The data presented are consistent with a role for PKCalpha, but not for p42/p44 mitogen-activated protein kinase (MAPK), in cPLA2 activation and AA release in ET-1-stimulated CISM cells since: (i) the PKC inhibitor, RO 31-8220, inhibited ET-1-induced AA release, cPLA2 phosphorylation and cPLA2 activity, but had no inhibitory

  11. Mildly abnormal general movement quality in infants is associated with higher Mead acid and lower arachidonic acid and shows a U-shaped relation with the DHA/AA ratio.

    PubMed

    van Goor, S A; Schaafsma, A; Erwich, J J H M; Dijck-Brouwer, D A J; Muskiet, F A J

    2010-01-01

    We showed that docosahexaenoic acid (DHA) supplementation during pregnancy and lactation was associated with more mildly abnormal (MA) general movements (GMs) in the infants. Since this finding was unexpected and inter-individual DHA intakes are highly variable, we explored the relationship between GM quality and erythrocyte DHA, arachidonic acid (AA), DHA/AA and Mead acid in 57 infants of this trial. MA GMs were inversely related to AA, associated with Mead acid, and associated with DHA/AA in a U-shaped manner. These relationships may indicate dependence of newborn AA status on synthesis from linoleic acid. This becomes restricted during the intrauterine period by abundant de novo synthesis of oleic and Mead acids from glucose, consistent with reduced insulin sensitivity during the third trimester. The descending part of the U-shaped relation between MA GMs and DHA/AA probably indicates DHA shortage next to AA shortage. The ascending part may reflect a different developmental trajectory that is not necessarily unfavorable. Copyright 2009 Elsevier Ltd. All rights reserved.

  12. Performance of AA5052 alloy anode in alkaline ethylene glycol electrolyte with dicarboxylic acids additives for aluminium-air batteries

    NASA Astrophysics Data System (ADS)

    Wang, DaPeng; Zhang, DaQuan; Lee, KangYong; Gao, LiXin

    2015-11-01

    Dicarboxylic acid compounds, i.e. succinic acid (SUA), adipic acid (ADA) and sebacic acid (SEA), are used as electrolyte additives in the alkaline ethylene glycol solution for AA5052 aluminium-air batteries. It shows that the addition of dicarboxylic acids lowers the hydrogen gas evolution rate of commercial AA5052 aluminium alloy anode. AA5052 aluminium alloy has wide potential window for electrochemical activity and better discharge performance in alkaline ethylene glycol solution containing dicarboxylic acid additives. ADA has the best inhibition effect for the self-corrosion of AA5052 anode among the three dicarboxylic acid additives. Fourier transform infrared spectroscopy (FT-IR) reveals that dicarboxylic acids and aluminium ions can form coordination complexes. Quantum chemical calculations shows that ADA has a smaller energy gap (ΔE, the energy difference between the lowest unoccupied orbital and the highest occupied orbital), indicating that ADA has the strongest interaction with aluminium ions.

  13. Binary release of ascorbic acid and lecithin from core-shell nanofibers on blood-contacting surface for reducing long-term hemolysis of erythrocyte.

    PubMed

    Shi, Qiang; Fan, Qunfu; Ye, Wei; Hou, Jianwen; Wong, Shing-Chung; Xu, Xiaodong; Yin, Jinghua

    2015-01-01

    There is an urgent need to develop blood-contacting biomaterials with long-term anti-hemolytic capability. To obtain such biomaterials, we coaxially electrospin [ascorbic acid (AA) and lecithin]/poly (ethylene oxide) (PEO) core-shell nanofibers onto the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) that has been grafted with poly (ethylene glycol) (PEG) chains. Our strategy is based on that the grafted layers of PEG render the surface hydrophilic to reduce the mechanical injure to red blood cells (RBCs) while the AA and lecithin released from nanofibers on blood-contacting surface can actively interact with RBCs to decrease the oxidative damage to RBCs. We demonstrate that (AA and lecithin)/PEO core-shell structured nanofibers have been fabricated on the PEG grafted surface. The binary release of AA and lecithin in the distilled water is in a controlled manner and lasts for almost 5 days; during RBCs preservation, AA acts as an antioxidant and lecithin as a lipid supplier to the membrane of erythrocytes, resulting in low mechanical fragility and hemolysis of RBCs, as well as high deformability of stored RBCs. Our work thus makes a new approach to fabricate blood-contacting biomaterials with the capability of long-term anti-hemolysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Water- and Fertilizer-Integrated Hydrogel Derived from the Polymerization of Acrylic Acid and Urea as a Slow-Release N Fertilizer and Water Retention in Agriculture.

    PubMed

    Cheng, Dongdong; Liu, Yan; Yang, Guiting; Zhang, Aiping

    2018-05-31

    To reduce the preparation cost of superabsorbent and improve the N release rate at the same time, a novel low-cost superabsorbent (SA) with the function of N slow release was prepared by chemical synthesis with neutralized acrylic acid (AA), urea, potassium persulfate (KPS), and N, N'-methylenebis(acrylamide) (MBA). The order of influence factors on the water absorbency property was determined by an orthogonal L 18 (3) 7 experiment. On the basis of the optimization results of the orthogonal experiment, the effects of a single factor on the water absorption were investigated, and the highest water absorbency (909 g/g) was achieved for the conditions of 1.0 mol urea/mol AA ratio, 100% of AA neutralized, K + , 1.5% KPS to AA mass fraction, 0.02% MBA to AA mass fraction, 45 °C reaction temperature, and 4.0 h reaction time. The optimal sample was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Swelling behaviors of the superabsorbent were investigated in distilled water and various soil and salt solutions. The water-release kinetics of SA in different negative pressures and soils were systematically investigated. Additionally, the maize seed germination in various types of soil with different amounts of SA was proposed, and the N could release 3.71% after being incubated in distilled water for 40 days. After 192 h, the relative water content of SA-treated sandy loam, loam, and paddy soil were 42, 56, and 45%, respectively. All of the results in this work showed that SA had good water retention and slow N-release properties, which are expected to have potential applications in sustainable modern agriculture.

  15. pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil.

    PubMed

    Bashir, Shahid; Teo, Yin Yin; Naeem, Sumaira; Ramesh, S; Ramesh, K

    2017-01-01

    There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug

  16. pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil

    PubMed Central

    Bashir, Shahid; Teo, Yin Yin; Naeem, Sumaira; Ramesh, S.; Ramesh, K.

    2017-01-01

    There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug

  17. Effects of synthetic sphingosine-1-phosphate analogs on cytosolic phospholipase A2alpha-independent release of arachidonic acid and cell toxicity in L929 fibrosarcoma cells: the structure-activity relationship.

    PubMed

    Shimizu, Masaya; Muramatsu, Yuki; Tada, Eiko; Kurosawa, Takeshi; Yamaura, Erika; Nakamura, Hiroyuki; Fujino, Hiromichi; Houjyo, Yuuya; Miyasaka, Yuri; Koide, Yuuki; Nishida, Atsushi; Murayama, Toshihiko

    2009-03-01

    Sphingolipid metabolites including ceramide, sphingosine, and their phosphorylated products [sphingosine-1-phosphate (S1P) and ceramide-1-phosphate] regulate cell functions including arachidonic acid (AA) metabolism and cell death. The development of analogs of S1P may be useful for regulating these mediator-induced cellular responses. We synthesized new analogs of S1P and examined their effects on the release of AA and cell death in L929 mouse fibrosarcoma cells. Among the analogs tested, several compounds including DMB-mC11S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMB-mC9S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-nonyl)phenylpropyl phosphate] released AA within 1 h and caused cell death 6 h after treatment. The release of AA was observed in C12 cells [a L929 variant lacking a type alpha cytosolic phospholipase A(2) (cPLA(2)alpha)] and L929-cPLAalpha-siRNA cells (L929 cells treated with small interference RNA for cPLA(2)alpha). Treatment with pharmacological inhibitors of secretory and Ca(2+)-independent PLA(2)s decreased the DMB-mC11S-induced release of AA. The effect of the S1P analogs tested on the release of AA was comparable to that on cell death in L929 cells, and a high correlation coefficient was observed. Two analogs lacking a butoxycarbonyl moiety [DMAc-mC11S (dimethyl (2S,3R)-2-acetamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMAm-mC11S [dimethyl (2S,3R)-2-amino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate)] had inhibitory effects on the release of AA and cell toxicity induced by DMB-mC11S. Synthetic phosphorylated lipid analogs may be useful for studying PLA(2) activity and its toxicity in cells. [Supplementary Fig. 1: available only at http://dx.doi.org/10.1254/jphs.08284FP].

  18. AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells.

    PubMed

    Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

    2016-01-01

    Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.

  19. Multifunctional slow-release organic-inorganic compound fertilizer.

    PubMed

    Ni, Boli; Liu, Mingzhu; Lü, Shaoyu; Xie, Lihua; Wang, Yanfang

    2010-12-08

    Multifunctional slow-release organic-inorganic compound fertilizer (MSOF) has been investigated to improve fertilizer use efficiency and reduce environmental pollution derived from fertilizer overdosage. The special fertilizer is based on natural attapulgite (APT) clay used as a matrix, sodium alginate used as an inner coating and sodium alginate-g-poly(acrylic acid-co-acrylamide)/humic acid (SA-g-P(AA-co-AM)/HA) superabsorbent polymer used as an outer coating. The coated multielement compound fertilizer granules were produced in a pan granulator, and the diameter of the prills was in the range of 2.5-3.5 mm. The structural and chemical characteristics of the product, as well as its efficiency in slowing the nutrients release, were examined. In addition, a mathematical model for nutrient release from the fertilizer was applied to calculate the diffusion coefficient D of nutrients in MSOF. The degradation of the SA-g-P(AA-co-AM)/HA coating was assessed by examining the weight loss with incubation time in soil. It is demonstrated that the product prepared by a simple route with good slow-release property may be expected to have wide potential applications in modern agriculture and horticulture.

  20. AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells

    PubMed Central

    Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

    2016-01-01

    Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy. PMID:27073325

  1. Arachidonic Acid: An Evolutionarily Conserved Signaling Molecule Modulates Plant Stress Signaling Networks[C][W

    PubMed Central

    Savchenko, Tatyana; Walley, Justin W.; Chehab, E. Wassim; Xiao, Yanmei; Kaspi, Roy; Pye, Matthew F.; Mohamed, Maged E.; Lazarus, Colin M.; Bostock, Richard M.; Dehesh, Katayoon

    2010-01-01

    Fatty acid structure affects cellular activities through changes in membrane lipid composition and the generation of a diversity of bioactive derivatives. Eicosapolyenoic acids are released into plants upon infection by oomycete pathogens, suggesting they may elicit plant defenses. We exploited transgenic Arabidopsis thaliana plants (designated EP) producing eicosadienoic, eicosatrienoic, and arachidonic acid (AA), aimed at mimicking pathogen release of these compounds. We also examined their effect on biotic stress resistance by challenging EP plants with fungal, oomycete, and bacterial pathogens and an insect pest. EP plants exhibited enhanced resistance to all biotic challenges, except they were more susceptible to bacteria than the wild type. Levels of jasmonic acid (JA) were elevated and levels of salicylic acid (SA) were reduced in EP plants. Altered expression of JA and SA pathway genes in EP plants shows that eicosapolyenoic acids effectively modulate stress-responsive transcriptional networks. Exogenous application of various fatty acids to wild-type and JA-deficient mutants confirmed AA as the signaling molecule. Moreover, AA treatment elicited heightened expression of general stress-responsive genes. Importantly, tomato (Solanum lycopersicum) leaves treated with AA exhibited reduced susceptibility to Botrytis cinerea infection, confirming AA signaling in other plants. These studies support the role of AA, an ancient metazoan signaling molecule, in eliciting plant stress and defense signaling networks. PMID:20935246

  2. Structure, molecular simulation, and release of aspirin from intercalated Zn-Al-layered double hydroxides.

    PubMed

    Meng, Zilin; Li, Xiaowei; Lv, Fengzhu; Zhang, Qian; Chu, Paul K; Zhang, Yihe

    2015-11-01

    Aspirin or acetylsalicylic acid (AA), a non-steroidal anti-inflammatory drug, is intercalated into Zn-Al-layered double hydroxides (ZnAl-LDHs) by co-precipitation and reconstruction methods. The composition, structure, and morphology of the intercalated products as well as their release behavior are determined experimentally and theoretically by Material Studio 5.5. Experimental results disclose the strong interaction between the LDHs sheets and AA in the intercalated ZnAl-LDHs produced by co-precipitation and slow release of AA from the intercalated ZnAl-LDHs in both phosphate buffered saline (PBS) and borate buffered saline (BBS) solutions. The percentage of AA released from the ZnAl-LDHs prepared by both methods in PBS (96.87% and 98.12%) are much more than those in BBS (68.59% and 81.22%) implying that both H4BO4(-) and H2PO4(-) can exchange with AA in the ZnAl-LDHs. After AA is released to PBS, ZnAl-LDHs break into small pieces. The experimental results are explained theoretically based on the calculation of the bonding energy between the anions and LDHs sheets as well as the AlO bond length change in the LDHs sheets. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Effects of prostaglandin F(2alpha)and carbachol on MAP kinases, cytosolic phospholipase A(2)and arachidonic acid release in cat iris sphincter smooth muscle cells.

    PubMed

    Husain, S; Abdel-Latif, A A

    2001-05-01

    The signal transduction pathways initiated by Ca(2+)-mobilizing agonists, such as prostaglandin F(2alpha)(PGF(2alpha)) and carbachol (CCh), leading to activation of cytosolic phospholipase A(2)(cPLA(2)) and arachidonic acid (AA) release in a wide variety of tissues remain obscure. To further define the role of protein kinases in receptor mediated stimulation of cPLA(2)and consequently AA release we have investigated the role of mitogen-activated protein (MAP) kinases and protein kinase C (PKC) in PGF(2alpha)- and CCh-induced cPLA(2)phosphorylation and AA release in cat iris sphincter smooth muscle (CISM) cells. The cells were prelabeled with [(3)H]AA for 24 hr and incubated in the absence or presence of the agonist for 5-10 min as indicated. MAP kinases activities and cPLA(2)phosphorylation were determined in immunoprecipitates obtained by using anti-p38 MAP kinase and anti-cPLA(2)antibodies. We found that: (a) PGF(2alpha)and CCh increased p38 MAP kinase activity by 197 and 215%, respectively, and increased p42/p44 MAP kinase activity by 200 and 125%, respectively. (b) SB202190, a p38 MAP kinase specific inhibitor, inhibited PGF(2alpha)- and CCh-induced cPLA(2)phosphorylation by 92 and 85%, respectively, and AA release by 62 and 78%, respectively. (c) PD98059, a p42/p44 MAP kinase inhibitor, inhibited CCh-induced cPLA(2)phosphorylation by 70% and AA release by 71%, but had no effect on that of PGF(2alpha). (d) Inhibition of PKC activity by RO 31-8220 inhibited both PGF(2alpha)- and CCh-stimulation of p38 MAP kinase, p42/p44 MAP kinases and cPLA(2)phosphorylation. We conclude from these results that in CISM cells PGF(2alpha)-induced cPLA(2)phosphorylation and AA release is mediated through p38 MAP kinase, but not through p42/p44 MAP kinases, whereas that of CCh is mediated through both p38 MAP kinase and p42/p44 MAP kinases. These effects of PGF(2alpha)and CCh are regulated by the MAP kinases in a PKC-dependent manner. Studies aimed at elucidating the role of

  4. Variation of amino acid sequences of serum amyloid a (SAA) and immunohistochemical analysis of amyloid a (AA) in Japanese domestic cats.

    PubMed

    Tei, Meina; Uchida, Kazuyuki; Chambers, James K; Watanabe, Ken-Ichi; Tamamoto, Takashi; Ohno, Koichi; Nakayama, Hiroyuki

    2018-02-02

    Amyloid A (AA) amyloidosis, a fatal systemic amyloid disease, occurs secondary to chronic inflammatory conditions in humans. Although persistently elevated serum amyloid A (SAA) levels are required for its pathogenesis, not all individuals with chronic inflammation necessarily develop AA amyloidosis. Furthermore, many diseases in cats are associated with the elevated production of SAA, whereas only a small number actually develop AA amyloidosis. We hypothesized that a genetic mutation in the SAA gene may strongly contribute to the pathogenesis of feline AA amyloidosis. In the present study, genomic DNA from four Japanese domestic cats (JDCs) with AA amyloidosis and from five without amyloidosis was analyzed using polymerase chain reaction (PCR) amplification and direct sequencing. We identified the novel variation combination of 45R-51A in the deduced amino acid sequences of four JDCs with amyloidosis and five without. However, there was no relationship between amino acid variations and the distribution of AA amyloid deposits, indicating that differences in SAA sequences do not contribute to the pathogenesis of AA amyloidosis. Immunohistochemical analysis using antisera against the three different parts of the feline SAA protein-i.e., the N-terminal, central, and C-terminal regions-revealed that feline AA contained the C-terminus, unlike human AA. These results indicate that the cleavage and degradation of the C-terminus are not essential for amyloid fibril formation in JDCs.

  5. Eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio as an associated factor of high risk plaque on coronary computed tomography in patients without coronary artery disease.

    PubMed

    Nagahara, Yasuomi; Motoyama, Sadako; Sarai, Masayoshi; Ito, Hajime; Kawai, Hideki; Takakuwa, Yoko; Miyagi, Meiko; Shibata, Daisuke; Takahashi, Hiroshi; Naruse, Hiroyuki; Ishii, Junichi; Ozaki, Yukio

    2016-07-01

    Coronary computed tomography angiography (CCTA)-verified high risk plaque (HRP) characteristics including positive remodeling and low attenuation plaque have been associated with acute coronary syndromes. Several studies reported that the n-3 polyunsaturated fatty acids have been associated with cardiovascular events. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and CCTA-verified HRP in patients without known coronary artery disease (CAD) is unclear. We aimed at investigating the relation between EPA/AA and CCTA-verified HRP in patients without known CAD. We included 193 patients undergoing CCTA without known CAD (65.5 ± 12.0 years, 55.0% male). No patient has been treated with EPA. The relation of coronary risk factors, lipid profile, high-sensitivity C-reactive protein, coronary artery calcification score (CACS), number of vessel disease, plaque burden, and EPA/AA with the presence of HRP was evaluated by logistic regression analysis. Incremental value of EPA/AA to predict HRP was also analyzed by C-index, NRI, and IDI. A Cox proportional hazards model was used to estimate the time to cardiovascular event. HRP was observed in 37 (19%) patients. Multivariable logistic regression analysis revealed that current smoking (OR 2.58; p=0.046), number of vessel disease (OR 1.87; p=0.031), and EPA/AA ratio (OR 0.65; p=0.0006) were independent associated factors of HRP on CCTA. Although the addition of EPA/AA to the baseline model did not significantly improve C-index, both NRI (0.60, p=0.0049) and IDI (0.054, p=0.0072) were significantly improved. Patients with HRP had significantly higher rate of events compared with patients without HRP (14% vs. 3%, Logrank p=0.0004). On multivariable Cox hazard analysis, baseline EPA/AA ratio was an independent predictor (HR 0.57, p=0.047). Low EPA/AA was an associated factor of HRP on CCTA in patients without CAD. In addition to conventional coronary risk factors and CACS, EPA/AA

  6. Targeted antitumoral dehydrocrotonin nanoparticles with L-ascorbic acid 6-stearate.

    PubMed

    Frungillo, Lucas; Martins, Dorival; Teixeira, Sérgio; Anazetti, Maristela Conti; Melo, Patrícia da Silva; Durán, Nelson

    2009-12-01

    Tumoral cells are known to have a higher ascorbic acid uptake than normal cells. Therefore, the aim of this study was to obtain polymeric nanoparticles containing the antitumoral compound trans-dehydrocrotonin (DHC) functionalized with L-ascorbic acid 6-stearate (AAS) to specifically target this system tumoral cells. Nanoparticle suspensions (NP-AAS-DHC) were prepared by the nanoprecipitation method. The systems were characterized for AAS presence by thin-layer chromatography and for drug loading (81-88%) by UV-Vis spectroscopy. To further characterize these systems, in vitro release kinetics, size distribution (100-140 nm) and Zeta potential by photon-correlation spectroscopic method were used. In vitro toxicity against HL60 cells was evaluated by tetrazolium reduction and Trypan blue exclusion assays. Cell death by apoptosis was quantified and characterized by flow cytometry and caspase activity. Zeta potential analyses showed that the system has a negatively charged outer surface and also indicate that AAS is incorporated on the external surface of the nanoparticles. In vitro release kinetics assay showed that DHC loaded in nanoparticles had sustained release behavior. In vitro toxicity assays showed that NP-AAS-DHC suspension was more effective as an antitumoral than free DHC or NP-DHC and increased apoptosis induction by receptor-mediated pathway. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  7. Fluoride release from fluoride varnishes under acidic conditions.

    PubMed

    Lippert, F

    2014-01-01

    The aim was to investigate the in vitro fluoride release from fluoride varnishes under acidic conditions. Poly(methyl methacrylate) blocks (Perspex, n=3 per group) were painted with 80 ± 5 mg fluoride varnish (n=10) and placed into artificial saliva for 30 min. Then, blocks were placed into either 1% citric acid (pH 2.27) or 0.3% citric acid (pH 3.75) solutions (n=3 per solution and varnish) for 30 min with the solutions being replaced every 5 min. Saliva and acid solutions were analyzed for fluoride content. Data were analyzed using three-way ANOVA (varnish, solution, time). The three-way interaction was significant (p>0.0001). Fluoride release and release patterns varied considerably between varnishes. Fluoride release in saliva varied by a factor of more than 10 between varnishes. Some varnishes (CavityShield, Nupro, ProFluorid, Vanish) showed higher fluoride release in saliva than during the first 5 min of acid exposure, whereas other varnishes (Acclean, Enamel-Pro, MI Varnish, Vella) showed the opposite behavior. There was little difference between acidic solutions. Fluoride release from fluoride varnishes varies considerably and also depends on the dissolution medium. Bearing in mind the limitations of laboratory research, the consumption of acidic drinks after fluoride varnish application should be avoided to optimize the benefit/risk ratio.

  8. LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction.

    PubMed

    Dancs, Péter Tibor; Ruisanchez, Éva; Balogh, Andrea; Panta, Cecília Rita; Miklós, Zsuzsanna; Nüsing, Rolf M; Aoki, Junken; Chun, Jerold; Offermanns, Stefan; Tigyi, Gábor; Benyó, Zoltán

    2017-04-01

    Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA 1 , LPA 2 , LPA 4 , and LPA 6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA 1-3 agonist VPC31143 induced dose-dependent vasoconstriction. VPC31143-induced AA contraction was sensitive to pertussis toxin (PTX), the LPA 1&3 antagonist Ki16425, and genetic deletion of LPA 1 but not that of LPA 2 or inhibition of LPA 3 , by diacylglycerol pyrophosphate. Surprisingly, vasoconstriction was also diminished in vessels lacking cyclooxygenase-1 [COX1 knockout (KO)] or the thromboxane prostanoid (TP) receptor (TP KO). VPC31143 increased thromboxane A 2 (TXA 2 ) release from TA of wild-type, TP-KO, and LPA 2 -KO mice but not from LPA 1 -KO or COX1-KO mice, and PTX blocked this effect. Our findings indicate that LPA causes vasoconstriction in VSMCs, mediated by LPA 1 -, G i -, and COX1-dependent autocrine/paracrine TXA 2 release and consequent TP activation. We propose that this new-found interaction between the LPA/LPA 1 and TXA 2 /TP pathways plays significant roles in vasoregulation, hemostasis, thrombosis, and vascular remodeling.-Dancs, P. T., Ruisanchez, E., Balogh, A., Panta, C. R., Miklós, Z., Nüsing, R. M., Aoki, J., Chun, J., Offermanns, S., Tigyi, G., Benyó, Z. LPA 1 receptor-mediated thromboxane A 2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction. © FASEB.

  9. Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages.

    PubMed

    da Silva-Souza, Hercules Antônio; Lira, Maria Nathalia de; Costa-Junior, Helio Miranda; da Cruz, Cristiane Monteiro; Vasconcellos, Jorge Silvio Silva; Mendes, Anderson Nogueira; Pimenta-Reis, Gabriela; Alvarez, Cora Lilia; Faccioli, Lucia Helena; Serezani, Carlos Henrique; Schachter, Julieta; Persechini, Pedro Muanis

    2014-07-01

    We have previously described that arachidonic acid (AA)-5-lipoxygenase (5-LO) metabolism inhibitors such as NDGA and MK886, inhibit cell death by apoptosis, but not by necrosis, induced by extracellular ATP (ATPe) binding to P2X7 receptors in macrophages. ATPe binding to P2X7 also induces large cationic and anionic organic molecules uptake in these cells, a process that involves at least two distinct transport mechanisms: one for cations and another for anions. Here we show that inhibitors of the AA-5-LO pathway do not inhibit P2X7 receptors, as judged by the maintenance of the ATPe-induced uptake of fluorescent anionic dyes. In addition, we describe two new transport phenomena induced by these inhibitors in macrophages: a cation-selective uptake of fluorescent dyes and the release of ATP. The cation uptake requires secreted ATPe, but, differently from the P2X7/ATPe-induced phenomena, it is also present in macrophages derived from mice deficient in the P2X7 gene. Inhibitors of phospholipase A2 and of the AA-cyclooxygenase pathway did not induce the cation uptake. The uptake of non-organic cations was investigated by measuring the free intracellular Ca(2+) concentration ([Ca(2+)]i) by Fura-2 fluorescence. NDGA, but not MK886, induced an increase in [Ca(2+)]i. Chelating Ca(2+) ions in the extracellular medium suppressed the intracellular Ca(2+) signal without interfering in the uptake of cationic dyes. We conclude that inhibitors of the AA-5-LO pathway do not block P2X7 receptors, trigger the release of ATP, and induce an ATP-dependent uptake of organic cations by a Ca(2+)- and P2X7-independent transport mechanism in macrophages. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tang, Yuting; Zhou, Lubing; Gunnet, Joseph W.

    2006-06-23

    HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. The molecular mechanisms whereby niacin exerts its pleiotropic effects on lipid metabolism remain largely unknown. In addition, the most common side effect in niacin therapy is skin flushing that is caused by prostaglandin release, suggesting that the phospholipase A{sub 2} (PLA{sub 2})/arachidonic acid (AA) pathway is involved. Various eicosanoids have been shown to activate peroxisome-proliferator activated receptors (PPAR) that play a diverse array of roles in lipid metabolism. To further elucidate the potential roles of HM74A in mediating the therapeuticmore » effects and/or side effects of niacin, we sought to explore the signaling events upon HM74A activation. Here we demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells. Activation of HM74A also led to Ca{sup 2+}-mobilization and enhanced bradykinin-promoted Ca{sup 2+}-mobilization through Gi protein. While HM74A increased ERK1/2 activation by the bradykinin receptor, it had no effects on UTP-promoted ERK1/2 activation.Furthermore, UTP- and bradykinin-mediated AA release was significantly decreased in the presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF 109203X. However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. Finally, stimulation of A431 cells transiently transfected with PPRE-luciferase with AA significantly induced luciferase activity, mimicking the effects of PPAR{gamma} agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs.« less

  11. 40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (40 CFR Part 63, Subpart A) to Subpart AA A Appendix A to Subpart AA of Part 63 Protection of... Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to Subpart AA of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA 40 CFR...

  12. 40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (40 CFR Part 63, Subpart A) to Subpart AA A Appendix A to Subpart AA of Part 63 Protection of... Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to Subpart AA of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA 40 CFR...

  13. Preparation and characterization of pH sensitive crosslinked Linseed polysaccharides-co-acrylic acid/methacrylic acid hydrogels for controlled delivery of ketoprofen.

    PubMed

    Shabir, Farya; Erum, Alia; Tulain, Ume Ruqia; Hussain, Muhammad Ajaz; Ahmad, Mahmood; Akhter, Faiza

    2017-01-01

    Some pH responsive polymeric matrix of Linseed ( Linum usitatissimum ), L. hydrogel (LSH) was prepared by free radical polymerization using potassium persulfate (KPS) as an initiator, N,N -methylene bisacrylamide (MBA) as a crosslinker, acrylic acid (AA) and methacrylic acid (MAA) as monomers; while ketoprofen was used as a model drug. Different formulations of LSH-co-AA and LSH-co-MAA were formulated by varying the concentration of crosslinker and monomers. Structures obtained were thoroughly characterized using Fourier transforms infrared (FTIR) spectroscopy, XRD analysis and Scanning electron microscopy. Sol-gel fractions, porosity of the materials and ketoprofen loading capacity were also measured. Swelling and in vitro drug release studies were conducted at simulated gastric fluids, i.e., pH 1.2 and 7.4. FTIR evaluation confirmed successful grafting of AA and MAA to LSH backbone. XRD studies showed retention of crystalline structure of ketoprofen in LSH-co-AA and its amorphous dispersion in LSH-co-MAA. Gel content was increased by increasing MBA and monomer content; whereas porosity of hydrogel was increased by increasing monomer concentration and decreased by increasing MBA content. Swelling of copolymer hydrogels was high at pH 7.4 and low at pH 1.2. Ketoprofen release showed an increasing trend by increasing monomer content; however it was decreased with increasing MBA content. Sustained release of ketoprofen was noted from copolymers and release followed Korsmeyer-Peppas model.

  14. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway.

    PubMed

    Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Youjia; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

    2014-04-06

    Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Radar investigation of barium releases over Arecibo Observatory, Puerto Rico

    NASA Technical Reports Server (NTRS)

    Djuth, Frank T.

    1995-01-01

    The NASA Combined Release and Radiation Effects Satellite (CRRES) El Coqui rocket campaign was successfully carried out in Puerto Rico during the period 18 May through 12 July 1992. This report describes five chemical release experiments in the upper ionosphere supported by Geospace Research, Inc. during the El Coqui campaign. Additional spin-off science is also discussed. The El Coqui releases are designated AA-1 (rocket 36-082), AA-2 (rocket 36-081), AA-3b (rocket 36-064), AA-4 (rocket 36-065), and AA-7 (rocket 36-083). Particular attention is paid to releases AA-2 and AA-4. These two experiments involved the illumination of ionospheric release regions with powerful high-frequency (HF) radio waves transmitted from the Arecibo HF facility. In the AA-2 experiment, microinstabilities excited by the HF wave in a Ba(+) plasma were examined. This release yielded a smooth plasma cloud that helped clarify several fundamental issues regarding the physics of wave plasma instabilities. During AA-2 extremely strong HF-induced Langmuir turbulence was detected with the Arecibo 430 MHz radar. CF3Br was released in the AA-4 study to create an ionospheric hole that focused the HF beam. This experiment successfully explored wave-plasma coupling in an O(+) ionosphere under conditions of very high HF electric field strengths.

  16. Iron Release from Soybean Seed Ferritin Induced by Cinnamic Acid Derivatives.

    PubMed

    Sha, Xuejiao; Chen, Hai; Zhang, Jingsheng; Zhao, Guanghua

    2018-05-04

    Plant ferritin represents a novel class of iron supplement, which widely co-exists with phenolic acids in a plant diet. However, there are few reports on the effect of these phenolic acids on function of ferritin. In this study, we demonstrated that cinnamic acid derivatives, as widely occurring phenolic acids, can induce iron release from holo soybean seed ferritin (SSF) in a structure-dependent manner. The ability of the iron release from SSF by five cinnamic acids follows the sequence of Cinnamic acid > Chlorogenic acid > Ferulic acid > p -Coumaric acid > Trans -Cinnamic acid. Fluorescence titration in conjunction with dialysis results showed that all of these five compounds have a similar, weak ability to bind with protein, suggesting that their protein-binding ability is not related to their iron release activity. In contrast, both Fe 2+ -chelating activity and reducibility of these cinnamic acid derivatives are in good agreement with their ability to induce iron release from ferritin. These studies indicate that cinnamic acid and its derivatives could have a negative effect on iron stability of holo soybean seed ferritin in diet, and the Fe 2+ -chelating activity and reducibility of cinnamic acid and its derivatives have strong relations to the iron release of soybean seed ferritin.

  17. Hyperforin induces Ca(2+)-independent arachidonic acid release in human platelets by facilitating cytosolic phospholipase A(2) activation through select phospholipid interactions.

    PubMed

    Hoffmann, Marika; Lopez, Jakob J; Pergola, Carlo; Feisst, Christian; Pawelczik, Sven; Jakobsson, Per-Johan; Sorg, Bernd L; Glaubitz, Clemens; Steinhilber, Dieter; Werz, Oliver

    2010-04-01

    Here, we investigated the modulation of cytosolic phospholipase A(2) (cPLA(2))-mediated arachidonic acid (AA) release by the polyprenylated acylphloroglucinol hyperforin. Hyperforin increased AA release from human platelets up to 2.6 fold (maximal effect at 10microM) versus unstimulated cells, which was blocked by cPLA(2)alpha-inhibition, and induced translocation of cPLA(2) to a membrane compartment. Interestingly, these stimulatory effects of hyperforin were even more pronounced after depletion of intracellular Ca(2+) by EDTA plus BAPTA/AM. Hyperforin induced phosphorylation of cPLA(2) at Ser505 and activated p38 mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK by SB203580 prevented cPLA(2) phosphorylation. However, neither AA release nor translocation of cPLA(2) was abrogated by SB203580. In cell-free assays using liposomes prepared from different lipids, hyperforin failed to stimulate phospholipid hydrolysis by isolated cPLA(2) in the presence of Ca(2+). However, when Ca(2+) was omitted, hyperforin caused a prominent increase in cPLA(2) activity using liposomes composed of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphoethanolamine but not of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PAPC) unless the PAPC liposomes were enriched in cholesterol (20 to 50%). Finally, two-dimensional (1)H-MAS-NMR analysis visualized the directed insertion of hyperforin into POPC liposomes. Together, hyperforin, through insertion into phospholipids, may facilitate cPLA(2) activation by enabling its access towards select lipid membranes independent of Ca(2+) ions. Such Ca(2+)- and phosphorylation-independent mechanism of cPLA(2) activation may apply also to other membrane-interfering molecules. 2010 Elsevier B.V. All rights reserved.

  18. Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior.

    PubMed

    Zuo, Dai-Ying; Zhang, Ya-Hong; Cao, Yue; Wu, Chun-Fu; Tanaka, Masatoshi; Wu, Ying-Liang

    2006-04-04

    The present study was designed to investigate the effects of acute and chronic administration of MK-801 (0.6 mg/kg), a noncompetitive NMDA-receptor antagonist on extracellular glutamate (Glu) and ascorbic acid (AA) release in the prefrontal cortex (PFC) of freely moving mice using in vivo microdialysis with open-field behavior. In line with earlier studies, acute administration of MK-801 induced an increase of Glu in the PFC. We also observed single MK-801 treatment increased AA release in the PFC. In addition, our results indicated that the basal AA levels in the PFC after MK-801 administration for 7 consecutive days were significantly decreased, and basal Glu levels also had a decreased tendency. After chronic administration (0.6 mg/kg, 7 days), MK-801 (0.6 mg/kg) challenge significantly decreased dialysate levels of AA and Glu. Our study also found that both acute and chronic administration of MK-801 induced hyperactivity in mice, but the intensity of acute administration was more than that of chronic administration. Furthermore, in all acute treatment mice, individual changes in Glu dialysate concentrations and the numbers of locomotion were positively correlated. In conclusion, this study may provide new evidence that a single MK-801 administration induces increases of dialysate AA and Glu concentrations in the PFC of freely moving mice, which are opposite to those induced by repeated MK-801 administration, with an unknown mechanism. Our results suggested that redox-response might play an important role in the model of schizophrenic symptoms induced by MK-801.

  19. Canine bombesin-like gastrin releasing peptides stimulate gastrin release and acid secretion in the dog.

    PubMed Central

    Bunnett, N W; Clark, B; Debas, H T; Del Milton, R C; Kovacs, T O; Orloff, M S; Pappas, T N; Reeve, J R; Rivier, J E; Walsh, J H

    1985-01-01

    The synthetic mammalian bombesin-like peptides, canine gastrin releasing peptide 27, 23 and 10, and porcine gastrin releasing peptide 27 were compared with amphibian bombesin 14 and 10 during intravenous infusions into six conscious dogs with chronic gastric cannulae. Gastrin and gastrin releasing peptide were measured in peripherally sampled venous blood by radioimmunoassay and gastric acid secretions were collected. All forms of gastrin releasing peptide stimulated gastrin release and gastric acid secretion in a dose-dependent manner. The larger canine and porcine peptides were more potent than the decapeptide. Bombesin 14 was more potent than bombesin 10. A rise in the venous concentration of immunoreactive gastrin releasing peptide of only 20 fmol ml-1 stimulated gastrin release to about 50% of maximal. Gastrin releasing peptide 10 was cleared from the circulation three times faster than the larger forms and this may account for the apparent differences in potency. PMID:3839849

  20. Ammonia-Nitrogen Added to Low-Crude-Protein Diets Deficient in Dispensable Amino Acid-Nitrogen Increases the Net Release of Alanine, Citrulline, and Glutamate Post-Splanchnic Organ Metabolism in Growing Pigs.

    PubMed

    Mansilla, Wilfredo D; Silva, Kayla E; Zhu, Cuilan; Nyachoti, Charles M; Htoo, John K; Cant, John P; de Lange, Cornelis F M

    2018-06-07

    Dietary ammonia is rapidly absorbed but poorly used for urea synthesis in pigs fed low-crude-protein (low-CP) diets deficient in dispensable amino acid (DAA)-nitrogen. We explored the effect of dietary ammonia on net amino acid (AA) balances in portal-drained viscera (PDV) and livers of pigs fed a diet deficient in DAA-nitrogen. Eight barrows with an initial body weight (BW) of 26.5 ± 1.4 kg (mean + SD) were surgically fitted with 4 catheters each (portal, hepatic, and mesenteric veins and carotid artery). The pigs were restricted-fed (2.8 × 191 kcal/kg BW0.60) for 7 d, and every 8 h a diet deficient in DAA-nitrogen supplemented with increasing amounts of ammonia-nitrogen (CP = 7.76%, 9.27%, and 10.77% for the control and low- and high-ammonia diets, respectively). The treatment sequence was based on a 3 × 3 Latin-square design with 3 consecutive periods. On the last day of each period, blood flows in portal and hepatic veins were determined with a continuous infusion of ρ-amino hippuric acid into the mesenteric vein. Consecutive blood samples were taken for AA concentration in blood plasma, and AA balances were calculated for PDV and the liver. Cumulative release of citrulline (Cit) and proline (Pro) increased with ammonia supplementation in PDV but decreased for glutamine (Gln) and glycine (Gly) (Gln: -19.32 ± 3.56, -32.50 ± 3.73, and -42.11 ± 3.55 mmol/meal for the control and low- and high-ammonia groups, respectively; P ≤ 0.05). Cumulative release of alanine (Ala), glutamic acid (Glu), and Gln increased with ammonia supplementation across the liver (P ≤ 0.05). When combined, PDV+liver, the cumulative release of Ala, Cit, and Glu increased with ammonia-nitrogen supplementation (P ≤ 0.05). Dietary ammonia could be used as a nitrogen supplement to increase the synthesis of Ala, Cit, and Glu across splanchnic organs in pigs fed a diet deficient in DAA-nitrogen.

  1. Hydrotropic polymer micelles containing acrylic acid moieties for oral delivery of paclitaxel

    PubMed Central

    Kim, Sungwon; Kim, Ji Young; Huh, Kang Moo; Acharya, Ghanshyam; Park, Kinam

    2008-01-01

    Hydrotropic polymers (HPs) and their micelles have been recently developed as vehicles for delivery of poorly water-soluble drugs, such as paclitaxel (PTX), by oral administration. The release of PTX from HP micelles, however, was slow and it took more than a day for complete release of the loaded PTX. Since the gastrointestinal (GI) transit time is known to be only several hours, pH-sensitive HP micelles were prepared for fast release of the loaded PTX responding to pH changes along the GI tract. Acrylic acid (AA) was introduced, as a release modulator, into HPs by copolymerization with 4-(2-vinylbenzyloxy)-N,N-(diethylnicotinamide) (VBODENA). The AA content was varied from 0% to 50 % (in the molar ratio to VBODENA). HPs spontaneously produced micelles in water, and their critical micelle concentrations (CMCs) ranged from 31 μg/mL to 86 μg/mL. Fluorescence probe study using pyrene showed that blank HP micelles possessed a good pH-sensitivity, which was clearly observed at relatively high AA contents and pH > 6. The pH sensitivity also affected the PTX loading property. Above pH 5, the PTX loading content and loading efficiency in HP micelles were significantly reduced. Although this may be primarily due to the AA moieties, other factors may include PTX degradation and polymer aggregation. The PTX release from HP micelles with more than 20% (mol) AA contents was completed within 12 h in a simulated intestinal fluid (SIF, pH=6.5). The HP micelles without any AA moiety showed very slow release profiles. In the simulated gastric fluid (SGF, pH=1.6), severe degradation of the released PTX was observed. The pH-dependent release of PTX from HP micelles can be used to increase the bioavailability of PTX upon oral delivery. PMID:18672013

  2. Oral gold compound auranofin triggers arachidonate release and cyclooxygenase metabolism in the alveolar macrophage

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peters-Golden, M.; Shelly, C.

    1988-12-01

    We examined the effect of in vitro incubation with the oral gold compound auranofin (AF) on arachidonic acid (AA) release and metabolism by rat alveolar macrophages (AMs). AF stimulated dose- and time-dependent release of /sup 14/C-AA from prelabeled AMs, which reached 4.7 +/- 0.3% (mean +/- SEM) of incorporated radioactivity at 10 micrograms/ml for 90 min, as compared to 0.5 +/- 0.1% release following control incubation for 90 min (p less than 0.001). Similar dose- and time-dependent synthesis of thromboxane (Tx) A2 (measured as TxB2) and prostaglandin (PG) E2 was demonstrated by radioimmunoassay of medium from unlabeled cultures, reaching 18-foldmore » and 9-fold, respectively, of the control values at 10 micrograms/ml AF for 90 min (p less than 0.001 for both). AF-induced TxB2 and PGE2 synthesis was inhibited by indomethacin as well as by pretreatment with methylprednisolone. No increase in the synthesis of immunoreactive leukotrienes (LT) B4 or C4 was noted at any dose or time of AF. High performance liquid chromatographic separation of /sup 14/C-eicosanoids synthesized by prelabeled AMs confirmed that AF induced the release of free AA and its metabolism to cyclooxygenase, but not 5-lipoxygenase, metabolites. The ability of AF to trigger macrophage AA metabolism may be relevant to the exacerbation of certain inflammatory processes which sometimes accompany gold therapy.« less

  3. Synthesis and release of fatty acids by human trophoblast cells in culture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Coleman, R.A.; Haynes, E.B.

    1987-11-01

    In order to determine whether placental cells can synthesize and release fatty acids, trophoblast cells from term human placentas were established in monolayer culture. The cells continued to secrete placental lactogen and progesterone and maintained specific activities of critical enzymes of triacylglycerol and phosphatidylcholine biosynthesis for 24 to 72 hr in culture. Fatty acid was rapidly synthesized from (/sup 14/C)acetate and released by the cells. Palmitoleic, palmitic, and oleic acids were the major fatty acids synthesized from (/sup 14/C)acetate and released. Small amounts of lauric, myristic, and stearic acids were also identified. (/sup 14/C)acetate was also incorporated into cellular triacylglycerol,more » phospholipid, and cholesterol, but radiolabeled free fatty acid did not accumulate intracellularly. In a pulse-chase experiment, cellular glycerolipids were labeled with (1-/sup 14/C)oleate; trophoblast cells then released /sup 14/C-labeled fatty acid into the media as the cellular content of labeled phospholipid and triacylglycerol decreased without intracellular accumulation of free fatty acid. Twenty percent of the /sup 14/C-label lost from cellular glycerolipid could not be recovered as a chloroform-extractable product, suggesting that some of the hydrolyzed fatty acid had been oxidized. These data indicate that cultured placenta trophoblast cells can release fatty acids that have either been synthesized de novo or that have been hydrolyzed from cellular glycerolipids. Trophoblast cells in monolayer culture should provide an excellent model for molecular studies of placental fatty acid metabolism and release.« less

  4. Chemical evolution. XXI - The amino acids released on hydrolysis of HCN oligomers

    NASA Technical Reports Server (NTRS)

    Ferris, J. P.; Wos, J. D.; Nooner, D. W.; Oro, J.

    1974-01-01

    Major amino acids released by hydrolysis of acidic and basic HCN oligomers are identified by chromatography as Gly, Asp, and diaminosuccinic acid. Smaller amounts of Ala, Ile and alpha-aminoisobutyric acid are also detected. The amino acids released did not change appreciably when the hydrolysis medium was changed from neutral to acidic or basic. The presence of both meso and d, l-diaminosuccinic acids was established by paper chromatography and on an amino acid analyzer.

  5. Amino acid repletion does not decrease muscle protein catabolism during hemodialysis.

    PubMed

    Raj, Dominic S C; Adeniyi, Oladipo; Dominic, Elizabeth A; Boivin, Michel A; McClelland, Sandra; Tzamaloukas, Antonios H; Morgan, Nancy; Gonzales, Lawrence; Wolfe, Robert; Ferrando, Arny

    2007-06-01

    Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol.min(-1).100 ml (-1)) was more negative during HD-O compared with pre-HD (-33.7 +/- 1.5 vs. -6.0 +/- 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (-16.9 +/- 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively (P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

  6. Corticostriatal dysfunction underlies diminished striatal ascorbate release in the R6/2 mouse model of Huntington’s disease

    PubMed Central

    Dorner, Jenelle L.; Miller, Benjamin R.; Klein, Emma L.; Murphy-Nakhnikian, Alexander; Andrews, Rachel L.; Barton, Scott J.; Rebec, George V.

    2009-01-01

    A behavior-related deficit in the release of ascorbate (AA), an antioxidant vitamin, occurs in the striatum of R6/2 mice expressing the human mutation for Huntington’s disease (HD), a dominantly inherited condition characterized by striatal dysfunction. To determine the role of corticostriatal fibers in AA release, we combined slow-scan voltammetry with electrical stimulation of cortical afferents to measure evoked fluctuations in extracellular AA in wild-type (WT) and R6/2 striatum. Although cortical stimulation evoked a rapid increase in AA release in both groups, the R6/2 response had a significantly shorter duration and smaller magnitude than WT. To determine if corticostriatal dysfunction also underlies the behavior-related AA deficit in R6/2s, we measured striatal AA release in separate groups of mice treated with d-amphetamine (5 mg/kg), a psychomotor stimulant known to release AA from corticostriatal terminals independently of dopamine. Relative to WT, both AA release and behavioral activation were diminished in R6/2 mice. Collectively, our results show that the corticostriatal pathway is directly involved in AA release and that this system is dysfunctional in HD. Moreover, because AA release requires glutamate uptake, a failure of striatal AA release in HD is consistent with an overactive glutamate system and diminished glutamate transport, both of which are thought to be central to HD pathogenesis. PMID:19616518

  7. The Pasadena Recommendations: Five Years After AAS Endorsement

    NASA Astrophysics Data System (ADS)

    Knezek, Patricia; Frattare, L.; Ulvestad, J.

    2010-01-01

    It has been five years since the AAS Council unanimously endorsed the document, known as "Equity Now: The Pasadena Recommendations for Gender Equality in Astronomy," in January 2005. This document was the main product of the conference entitled "Women in Astronomy II: Ten Years After” (WIA II), held in June 2003 in Pasadena, CA. Participants of that 2003 meeting assessed the progress for women in science, offering insights into causes of the slower advancement of women, and discussed strategies to accelerate the achievement of equality. These insights and strategies were then incorporated into the "Pasadena Recommendations" by the CSWA. It was subsequently released to the entire AAS community for review and comments prior to its endorsement by the AAS. We will discuss the Recommendations and their impact since the endorsement by the AAS, including the process that is in place for organizations and departments to formally endorse the Pasadena Recommendations, thus making an organizational commitment to their implementation (see http://www.aas.org/cswa/pasadena_endorse.html).

  8. Net Flux of Amino Acids Across the Portal-drained Viscera and Liver of the Ewe During Abomasal Infusion of Protein and Glucose

    USDA-ARS?s Scientific Manuscript database

    Decreasing the fraction of amino acids metabolized by the mucosal cells may increase the fraction of AA being released into the blood. A potential mechanism to reduce AA catabolism by mucosal cells is to provide an alternative source of energy. We hypothesized that increasing glucose flow to the s...

  9. The cytochrome P450 2AA gene cluster in zebrafish (Danio rerio): Expression of CYP2AA1 and CYP2AA2 and response to phenobarbital-type inducers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kubota, Akira; Bainy, Afonso C.D.; Departamento de Bioquímica, CCB, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900

    2013-10-01

    The cytochrome P450 (CYP) 2 gene family is the largest and most diverse CYP gene family in vertebrates. In zebrafish, we have identified 10 genes in a new subfamily, CYP2AA, which does not show orthology to any human or other mammalian CYP genes. Here we report evolutionary and structural relationships of the 10 CYP2AA genes and expression of the first two genes, CYP2AA1 and CYP2AA2. Parsimony reconstruction of the tandem duplication pattern for the CYP2AA cluster suggests that CYP2AA1, CYP2AA2 and CYP2AA3 likely arose in the earlier duplication events and thus are most diverged in function from the other CYP2AAs.more » On the other hand, CYP2AA8 and CYP2AA9 are genes that arose in the latest duplication event, implying functional similarity between these two CYPs. A molecular model of CYP2AA1 showing the sequence conservation across the CYP2AA cluster reveals that the regions with the highest variability within the cluster map onto CYP2AA1 near the substrate access channels, suggesting differing substrate specificities. Zebrafish CYP2AA1 transcript was expressed predominantly in the intestine, while CYP2AA2 was most highly expressed in the kidney, suggesting differing roles in physiology. In the liver CYP2AA2 expression but not that of CYP2AA1, was increased by 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) and, to a lesser extent, by phenobarbital (PB). In contrast, pregnenolone 16α-carbonitrile (PCN) increased CYP2AA1 expression, but not CYP2AA2 in the liver. The results identify a CYP2 subfamily in zebrafish that includes genes apparently induced by PB-type chemicals and PXR agonists, the first concrete in vivo evidence for a PB-type response in fish. - Highlights: • A tandemly duplicated cluster of ten CYP2AA genes was described in zebrafish. • Parsimony and duplication analyses suggest pathways to CYP2AA diversity. • Homology models reveal amino acid positions possibly related to functional diversity. • The CYP2AA locus does not share

  10. Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery

    PubMed Central

    Woo, J. O.; Misran, M.; Lee, P. F.; Tan, L. P.

    2014-01-01

    Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release. PMID:24578624

  11. Arachidonic Acid Stress Impacts Pneumococcal Fatty Acid Homeostasis

    PubMed Central

    Eijkelkamp, Bart A.; Begg, Stephanie L.; Pederick, Victoria G.; Trapetti, Claudia; Gregory, Melissa K.; Whittall, Jonathan J.; Paton, James C.; McDevitt, Christopher A.

    2018-01-01

    Free fatty acids hold dual roles during infection, serving to modulate the host immune response while also functioning directly as antimicrobials. Of particular importance are the long chain polyunsaturated fatty acids, which are not commonly found in bacterial organisms, that have been proposed to have antibacterial roles. Arachidonic acid (AA) is a highly abundant long chain polyunsaturated fatty acid and we examined its effect upon Streptococcus pneumoniae. Here, we observed that in a murine model of S. pneumoniae infection the concentration of AA significantly increases in the blood. The impact of AA stress upon the pathogen was then assessed by a combination of biochemical, biophysical and microbiological assays. In vitro bacterial growth and intra-macrophage survival assays revealed that AA has detrimental effects on pneumococcal fitness. Subsequent analyses demonstrated that AA exerts antimicrobial activity via insertion into the pneumococcal membrane, although this did not increase the susceptibility of the bacterium to antibiotic, oxidative or metal ion stress. Transcriptomic profiling showed that AA treatment also resulted in a dramatic down-regulation of the genes involved in fatty acid biosynthesis, in addition to impacts on other metabolic processes, such as carbon-source utilization. Hence, these data reveal that AA has two distinct mechanisms of perturbing the pneumococcal membrane composition. Collectively, this work provides a molecular basis for the antimicrobial contribution of AA to combat pneumococcal infections. PMID:29867785

  12. AaCAT1 of the Yellow Fever Mosquito, Aedes aegypti

    PubMed Central

    Hansen, Immo A.; Boudko, Dmitri Y.; Shiao, Shin-Hong; Voronov, Dmitri A.; Meleshkevitch, Ella A.; Drake, Lisa L.; Aguirre, Sarah E.; Fox, Jeffrey M.; Attardo, Geoffrey M.; Raikhel, Alexander S.

    2011-01-01

    Insect yolk protein precursor gene expression is regulated by nutritional and endocrine signals. A surge of amino acids in the hemolymph of blood-fed female mosquitoes activates a nutrient signaling system in the fat bodies, which subsequently derepresses yolk protein precursor genes and makes them responsive to activation by steroid hormones. Orphan transporters of the SLC7 family were identified as essential upstream components of the nutrient signaling system in the fat body of fruit flies and the yellow fever mosquito, Aedes aegypti. However, the transport function of these proteins was unknown. We report expression and functional characterization of AaCAT1, cloned from the fat body of A. aegypti. Expression of AaCAT1 transcript and protein undergoes dynamic changes during postembryonic development of the mosquito. Transcript expression was especially high in the third and fourth larval stages; however, the AaCAT1 protein was detected only in pupa and adult stages. Functional expression and analysis of AaCAT1 in Xenopus oocytes revealed that it acts as a sodium-independent cationic amino acid transporter, with unique selectivity to l-histidine at neutral pH (K0.5l-His = 0.34 ± 0.07 mm, pH 7.2). Acidification to pH 6.2 dramatically increases AaCAT1-specific His+-induced current. RNAi-mediated silencing of AaCAT1 reduces egg yield of subsequent ovipositions. Our data show that AaCAT1 has notable differences in its transport mechanism when compared with related mammalian cationic amino acid transporters. It may execute histidine-specific transport and signaling in mosquito tissues. PMID:21262963

  13. Interactions of collagen molecules in the presence of N-hydroxysuccinimide activated adipic acid (NHS-AA) as a crosslinking agent.

    PubMed

    Zhang, Min; Wu, Kun; Li, Guoying

    2011-11-01

    The effect of crosslinking agent on pepsin-soluble bovine collagen solution was examined using N-hydroxysuccinimide activated adipic acid (NHS-AA) as a crosslinker. Electrophoretic patterns indicated that crosslinks formed when NHS-AA was added. A higher polarity level deduced from the changes in the fluorescence emission spectrum of pyrene in the crosslinked collagen solution indicated that the formation of well-ordered aggregates was suppressed. The random aggregation of collagens was also observed by atomic force microscopy (AFM). Furthermore, the association of collagens into fibrils was influenced by crosslinking. Self-assembly was suppressed at 37°C; however, as temperature was increased to 39°C, a small amount of NHS-AA leaded to an improvement in the ability of self-aggregation. Although more random structure was brought about by crosslinking, self-aggregation might still be promoted as temperature was increased, accompanying by the thermal stability improvement of fibrils. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Interaction between Al3+ and acrylic acid and polyacrylic acid in acidic aqueous solution: a model experiment for the behavior of Al3+ in acidified soil solution.

    PubMed

    Etou, Mayumi; Masaki, Yuka; Tsuji, Yutaka; Saito, Tomoyuki; Bai, Shuqin; Nishida, Ikuko; Okaue, Yoshihiro; Yokoyama, Takushi

    2011-01-01

    From the viewpoint of the phytotoxicity and mobility of Al(3+) released from soil minerals due to soil acidification, the interaction between Al(3+) and acrylic acid (AA) and polyacrylic acid (PAA) as a model compound of fulvic acid was investigated. The interaction was examined at pH 3 so as to avoid the hydrolysis of Al(3+). The interaction between Al(3+) and AA was weak. However, the interaction between Al(3+) and PAA was strong and depended on the initial (COOH in PAA)/Al molar ratio (R(P)) of the solution. For the range of 1/R(P), the interaction between Al(3+) and PAA can be divided into three categories: (1) 1:1 Al-PAA-complex (an Al(3+) combines to a carboxyl group), (2) intermolecular Al-PAA-complex (an Al(3+) combines to more than 2 carboxyl groups of other Al-PAA-complexes) in addition to the 1:1 Al-PAA-complex and (3) precipitation of intermolecular complexes. In conclusion, R(P) is an important factor affecting the behavior of Al(3+) in acidic soil solution.

  15. Macrophage activation by factors released from acetaminophen-injured hepatocytes: Potential role of HMGB1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dragomir, Ana-Cristina; Laskin, Jeffrey D.; Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu

    2011-06-15

    Toxic doses of acetaminophen (AA) cause hepatocellular necrosis. Evidence suggests that activated macrophages contribute to the pathogenic process; however, the factors that activate these cells are unknown. In these studies, we assessed the role of mediators released from AA-injured hepatocytes in macrophage activation. Treatment of macrophages with conditioned medium (CM) collected 24 hr after treatment of mouse hepatocytes with 5 mM AA (CM-AA) resulted in increased production of reactive oxygen species (ROS). Macrophage expression of heme oxygenase-1 (HO-1) and catalase mRNA was also upregulated by CM-AA, as well as cyclooxygenase (COX)-2 and 12/15-lipoxygenase (LOX). CM-AA also upregulated expression of themore » proinflammatory chemokines, MIP-1{alpha} and MIP-2. The effects of CM-AA on expression of COX-2, MIP-1{alpha} and MIP-2 were inhibited by blockade of p44/42 MAP kinase, suggesting a biochemical mechanism mediating macrophage activation. Hepatocytes injured by AA were found to release HMGB1, a potent macrophage activator. This was inhibited by pretreatment of hepatocytes with ethyl pyruvate (EP), which blocks HMGB1 release. EP also blocked CM-AA induced ROS production and antioxidant expression, and reduced expression of COX-2, but not MIP-1{alpha} or MIP-2. These findings suggest that HMGB1 released by AA-injured hepatocytes contributes to macrophage activation. This is supported by our observation that expression of the HMGB1 receptor RAGE is upregulated in macrophages in response to CM-AA. These data indicate that AA-injured hepatocytes contribute to the inflammatory environment in the liver through the release of mediators such as HMGB1. Blocking HMGB1/RAGE may be a useful approach to limiting classical macrophage activation and AA-induced hepatotoxicity. - Research Highlights: > These studies analyze macrophage activation by mediators released from acetaminophen-damaged hepatocytes. > Factors released from acetaminophen-injured hepatocytes induce

  16. Humic acids enhance the microbially mediated release of sedimentary ferrous iron.

    PubMed

    Chang, Chun-Han; Wei, Chia-Cheng; Lin, Li-Hung; Tu, Tzu-Hsuan; Liao, Vivian Hsiu-Chuan

    2016-03-01

    Iron (Fe) is an essential element for many organisms, but high concentrations of iron can be toxic. The complex relation between iron, arsenic (As), bacteria, and organic matter in sediments and groundwater is still an issue of environmental concern. The present study addresses the effects of humic acids and microorganisms on the mobilization of iron in sediments from an arsenic-affected area, and the microbial diversity was analyzed. The results showed that the addition of 50, 100, and 500 mg/L humic acids enhanced ferrous iron (Fe(II)) release in a time-dependent and dose-dependent fashion under anaerobic conditions. A significant increase in the soluble Fe(II) concentrations occurred in the aqueous phases of the samples during the first 2 weeks, and aqueous Fe(II) reached its maximum concentrations after 8 weeks at the following Fe(II) concentrations: 28.95 ± 1.16 mg/L (original non-sterilized sediments), 32.50 ± 0.71 mg/L (50 mg/L humic acid-amended, non-sterilized sediments), 37.50 ± 1.85 mg/L (100 mg/L humic acid-amended, non-sterilized sediments), and 39.00 ± 0.43 mg/L (500 mg/L humic acid-amended, non-sterilized sediments). These results suggest that humic acids can further enhance the microbially mediated release of sedimentary iron under anaerobic conditions. By contrast, very insignificant amounts of iron release were observed from sterilized sediments (the abiotic controls), even with the supplementation of humic acids under anaerobic incubation. In addition, the As(III) release was increased from 50 ± 10 μg/L (original non-sterilized sediments) to 110 ± 45 μg/L (100 mg/L humic acid-amended, non-sterilized sediments) after 8 weeks of anaerobic incubation. Furthermore, a microbial community analysis indicated that the predominant class was changed from Alphaproteobacteria to Deltaproteobacteria, and clearly increased populations of Geobacter sp., Paludibacter sp., and Methylophaga sp. were found after adding humic acids

  17. Effect of palmitic acid on the characteristics and release profiles of rotigotine-loaded microspheres.

    PubMed

    Wang, Aiping; Liang, Rongcai; Liu, Wanhui; Sha, Chunjie; Li, Youxin; Sun, Kaoxiang

    2016-01-01

    The initial burst release is a major obstacle to the development of microsphere-formulated drug products. To investigate the influence of palmitic acid on the characteristics and release profiles of rotigotine-loaded poly(d,l-lactide-co-glycolide) microspheres. Rotigotine-loaded microspheres (RMS) were prepared using the oil-in-water emulsion solvent evaporation technique. The in vitro characteristics of the RMS were evaluated with scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and a particle size analyzer. The in vitro drug release and in vivo pharmacokinetics of the RMS were investigated. The SEM results showed that the addition of palmitic acid changed the surface morphology of the microspheres from smooth to dimpled and then to non-smooth as the palmitic acid content increased. DSC revealed the existence of molecularly dispersed forms of palmitic acid in the microspheres. The in vitro and in vivo release profiles indicated that the addition of 5% and 8% palmitic acid significantly decreased the burst release of rotigotine from the microspheres, and the late-stage release was delayed as the palmitic acid content increased across the investigated range (5-15%). The addition of palmitic acid to the microspheres significantly affects the release profile of rotigotine from RMS.

  18. Indexing Anatomical Phrases in Neuro-Radiology Reports to the UMLS 2005AA

    PubMed Central

    Bashyam, Vijayaraghavan; Taira, Ricky K.

    2005-01-01

    This work describes a methodology to index anatomical phrases to the 2005AA release of the Unified Medical Language System (UMLS). A phrase chunking tool based on Natural Language Processing (NLP) was developed to identify semantically coherent phrases within medical reports. Using this phrase chunker, a set of 2,551 unique anatomical phrases was extracted from brain radiology reports. These phrases were mapped to the 2005AA release of the UMLS using a vector space model. Precision for the task of indexing unique phrases was 0.87. PMID:16778995

  19. Inhibition of noradrenaline release by lysergic acid diethylamide

    PubMed Central

    Hughes, J.

    1973-01-01

    Lysergic acid diethylamide (LSD) inhibits the release of labelled noradrenaline from the guinea-pig vas deferens during intramural nerve stimulation and causes a corresponding reduction in the contractions of the smooth muscle. These effects of LSD are most prominent at low stimulus frequencies and they are prevented by treatment with phentolamine. It is concluded that LSD inhibits noradrenaline release by interacting with presynaptic α-adrenoceptors. PMID:4788042

  20. Radar investigation of barium releases over Arecibo Observatory, Puerto Rico. Final report, 12 August 1991-30 June 1994

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Djuth, F.T.

    1995-07-01

    The NASA Combined Release and Radiation Effects Satellite (CRRES) El Coqui rocket campaign was successfully carried out in Puerto Rico during the period 18 May through 12 July 1992. This report describes five chemical release experiments in the upper ionosphere supported by Geospace Research, Inc. during the El Coqui campaign. Additional spin-off science is also discussed. The El Coqui releases are designated AA-1 (rocket 36-082), AA-2 (rocket 36-081), AA-3b (rocket 36-064), AA-4 (rocket 36-065), and AA-7 (rocket 36-083). Particular attention is paid to releases AA-2 and AA-4. These two experiments involved the illumination of ionospheric release regions with powerful high-frequencymore » (HF) radio waves transmitted from the Arecibo HF facility. In the AA-2 experiment, microinstabilities excited by the HF wave in a Ba(+) plasma were examined. This release yielded a smooth plasma cloud that helped clarify several fundamental issues regarding the physics of wave plasma instabilities. During AA-2 extremely strong HF-induced Langmuir turbulence was detected with the Arecibo 430 MHz radar. CF3Br was released in the AA-4 study to create an ionospheric hole that focused the HF beam. This experiment successfully explored wave-plasma coupling in an O(+) ionosphere under conditions of very high HF electric field strengths.« less

  1. Adsorption and release of ofloxacin from acid- and heat-treated halloysite.

    PubMed

    Wang, Qin; Zhang, Junping; Zheng, Yue; Wang, Aiqin

    2014-01-01

    Halloysite nanotube is an ideal vehicle of the controlled release of drugs. In this study, we systematically investigated the effects of acid- and heat-treatments on the physicochemical properties, structure and morphology of halloysite by XRD, FTIR, SEM and TEM. Afterwards, the adsorption and in vitro release properties of halloysite for cationic ofloxacin (OFL) were evaluated. The results indicate that HCl treatment has no influence on the crystal structure of halloysite, whereas it becomes amorphous after calcined at temperature higher than 500 °C. Both acid- and heat-treatments have no evident influence on the tubular structure of halloysite. OFL was adsorbed onto halloysite via electrostatic interaction between protonated OFL and negative halloysite surface, cation exchange as well as electrostatic interaction between the OFL-Al(3+) complexes and the negative halloysite surface. Acid-treatment facilitates the release of the adsorbed OFL compared with the natural halloysite in spite of a slight decrease of adsorption capacity. However, heat-treatment results in a sharp decrease of adsorption capacity for OFL owning to the OFL-promoted dissolution of aluminum and the disappearance of the porous structure. Although heat-treatment also facilitates release of the adsorbed OFL, the amount of OFL released is in fact less than the natural halloysite owing to the very low adsorption capacity. Thus, acid-activation is an effective protocol to improve the adsorption and release of halloysite for cationic drug molecules. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Amino acid neurotransmitter release and learning: a study of visual imprinting.

    PubMed

    Meredith, R M; McCabe, B J; Kendrick, K M; Horn, G

    2004-01-01

    The intermediate and medial part of the hyperstriatum ventrale (IMHV) is an area of the domestic chick forebrain that stores information acquired through the learning process of imprinting. The effects of visual imprinting on the release of the amino acids aspartate, arginine, citrulline, gamma-aminobutyric acid (GABA), glutamate, glycine and taurine from the left and right IMHVs in vitro were measured at 3.5, 10 and 24 h after training. Chicks were exposed to an imprinting stimulus for 1 h, their preferences measured 10 min afterward and a preference score calculated as a measure of the strength of learning. Potassium stimulation was used to evoke amino acid release from the IMHVs of trained and untrained chicks in the presence and absence of extracellular Ca2+. Ca2+-dependent, K+-evoked release of glutamate was significantly (34.4%) higher in trained than in untrained chicks. This effect was not influenced by time after training or by side (left or right IMHV). Training influenced the evoked release of GABA and taurine from the left IMHV at both 3.5 and 10 h. The training effects at the two times were statistically homogeneous so data (< or = 10 h group) were combined for each amino acid respectively. For this < or = 10 h group, evoked release increased significantly with preference score. In contrast, for the 24 h group, evoked release of GABA and taurine was not significantly correlated with preference score. There were no significant correlations between preference score and GABA or taurine release in the right IMHV at any time, nor in the absence of extracellular calcium. No significant effects of training condition, time or side were observed for any other amino acid in the study. The present findings suggest that soon after chicks have been exposed to an imprinting stimulus glutamatergic excitatory transmission in IMHV is enhanced, and remains enhanced for at least 24 h. In contrast, the learning-related elevations in taurine and GABA release are not

  3. Capture and release of mixed acid gasses with binding organic liquids

    DOEpatents

    Heldebrant, David J.; Yonker, Clement R.

    2010-09-21

    Reversible acid-gas binding organic liquid systems that permit separation and capture of one or more of several acid gases from a mixed gas stream, transport of the liquid, release of the acid gases from the ionic liquid and reuse of the liquid to bind more acid gas with significant energy savings compared to current aqueous systems. These systems utilize acid gas capture compounds made up of strong bases and weak acids that form salts when reacted with a selected acid gas, and which release these gases when a preselected triggering event occurs. The various new materials that make up this system can also be included in various other applications such as chemical sensors, chemical reactants, scrubbers, and separators that allow for the specific and separate removal of desired materials from a gas stream such as flue gas.

  4. The unique self-assembly/disassembly property of Archaeoglobus fulgidus ferritin and its implications on molecular release from the protein cage.

    PubMed

    Sana, Barindra; Johnson, Eric; Lim, Sierin

    2015-12-01

    In conventional in vitro encapsulation of molecular cargo, the multi-subunit ferritin protein cages are disassembled in extremely acidic pH and re-assembled in the presence of highly concentrated cargo materials, which results in poor yields due to the low-pH treatment. In contrast, Archaeoglobus fulgidus open-pore ferritin (AfFtn) and its closed-pore mutant (AfFtn-AA) are present as dimeric species in neutral buffers that self-assemble into cage-like structure upon addition of metal ions. To understand the iron-mediated self-assembly and ascorbate-mediated disassembly properties, we studied the iron binding and release profile of the AfFtn and AfFtn-AA, and the corresponding oligomerization of their subunits. Fe(2+) binding and conversion to Fe(3+) triggered the self-assembly of cage-like structures from dimeric species of AfFtn and AfFtn-AA subunits, while disassembly was induced by dissolving the iron core with reducing agents. The closed-pore AfFtn-AA has identical iron binding kinetics but lower iron release rates when compared to AfFtn. While the iron binding rate is proportional to Fe(2+) concentration, the iron release rate can be controlled by varying ascorbate concentrations. The AfFtn and AfFtn-AA cages formed by iron mineralization could be disassembled by dissolving the iron core. The open-pores of AfFtn contribute to enhanced reductive iron release while the small channels located at the 3-fold symmetry axis (3-fold channels) are used for iron uptake. The iron-mediated self-assembly/disassembly property of AfFtn offers a new set of molecular trigger for formation and dissociation of the protein cage, which can potentially regulate uptake and release of molecular cargo from protein cages. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Activity of vegetative insecticidal proteins Vip3Aa58 and Vip3Aa59 of Bacillus thuringiensis against lepidopteran pests.

    PubMed

    Baranek, Jakub; Kaznowski, Adam; Konecka, Edyta; Naimov, Samir

    2015-09-01

    Vegetative insecticidal proteins (Vips) secreted by some isolates of Bacillus thuringiensis show activity against insects and are regarded as insecticides against pests. A number of B. thuringiensis strains harbouring vip3A genes were isolated from different sources and identified by using a PCR based approach. The isolates with the highest insecticidal activity were indicated in screening tests, and their vip genes were cloned and sequenced. The analysis revealed two polymorphic Vip protein forms, which were classified as Vip3Aa58 and Vip3Aa59. After expression of the vip genes, the proteins were isolated and characterized. The activity of both toxins was estimated against economically important lepidopteran pests of woodlands (Dendrolimus pini), orchards (Cydia pomonella) and field crops (Spodoptera exigua). Vip3Aa58 and Vip3Aa59 were highly toxic and their potency surpassed those of many Cry proteins used in commercial bioinsecticides. Vip3Aa59 revealed similar larvicidal activity as Vip3Aa58 against S. exigua and C. pomonella. Despite 98% similarity of amino acid sequences of both proteins, Vip3Aa59 was significantly more active against D. pini. Additionally the effect of proteolytic activation of Vip58Aa and Vip3Aa59 on toxicity of D. pini and S. exigua was studied. Both Vip3Aa proteins did not show any activity against Tenebrio molitor (Coleoptera) larvae. The results suggest that the Vip3Aa58 and Vip3Aa59 toxins might be useful for controlling populations of insect pests of crops and forests. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. A feedback regulatory loop between G3P and lipid transfer proteins DIR1 and AZI1 mediates azelaic-acid-induced systemic immunity.

    PubMed

    Yu, Keshun; Soares, Juliana Moreira; Mandal, Mihir Kumar; Wang, Caixia; Chanda, Bidisha; Gifford, Andrew N; Fowler, Joanna S; Navarre, Duroy; Kachroo, Aardra; Kachroo, Pradeep

    2013-04-25

    Systemic acquired resistance (SAR), a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced by the dicarboxylic acid azelaic acid (AA) requires the phosphorylated sugar derivative glycerol-3-phosphate (G3P). Pathogen inoculation induced the release of free unsaturated fatty acids (FAs) and thereby triggered AA accumulation, because these FAs serve as precursors for AA. AA accumulation in turn increased the levels of G3P, which is required for AA-conferred SAR. The lipid transfer proteins DIR1 and AZI1, both of which are required for G3P- and AA-induced SAR, were essential for G3P accumulation. Conversely, reduced G3P resulted in decreased AZI1 and DIR1 transcription. Our results demonstrate that an intricate feedback regulatory loop among G3P, DIR1, and AZI1 regulates SAR and that AA functions upstream of G3P in this pathway. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy.

    PubMed

    Jurkić, Lela Munjas; Cepanec, Ivica; Pavelić, Sandra Kraljević; Pavelić, Krešimir

    2013-01-08

    Silicon (Si) is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K), the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel), silica gel (amorphous silicon dioxide), and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4) in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation)-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.

  8. Temporal dynamics of amino and fatty acid composition in the razor clam Ensis siliqua (Mollusca: Bivalvia)

    NASA Astrophysics Data System (ADS)

    Baptista, Miguel; Repolho, Tiago; Maulvault, Ana Luísa; Lopes, Vanessa M.; Narciso, Luis; Marques, António; Bandarra, Narcisa; Rosa, Rui

    2014-12-01

    Few studies have been conducted on the temporal dynamics of both amino acid (AA) and fatty acid (FA) profiles in marine bivalves. We investigated the seasonal variation of these compounds in the pod razor clam Ensis siliqua in relation to food availability, salinity, water temperature and reproductive cycle. AA content varied between 46.94 and 54.67 % dry weight (DW), and the AAs found in greater quantity were glutamic acid, glycine and aspartic acid. FA content varied between 34.02 and 87.94 mg g-1 DW and the FAs found in greater quantity were 16:0 and 22:6 n-3. Seasonal trends were observed for AAs and FAs. FAs increased with gametogenesis and decreased with spawning while AA content increased throughout spawning. The effect of increasing temperature and high food availability during the spawning season masked the loss of AAs resulting from gamete release. Still, a comparatively greater increase in the contents of glutamic acid and leucine with spawning indicate their possible involvement in a post-spawning gonad recovery mechanism. A post-spawning decrease in 14:0, 16:0, 16:1 n-7, 18:1 n-7 and 18:1 n-9 is indicative of the importance of these FAs in bivalve eggs. An increase in 18:3 n-3, 18:4 n-3, 20:1 n-9 and 20:2 n-6 during gametogenesis suggests their involvement in oocyte maturation. The FA 22:4 n-6, while increasing with spawning, appears to play a role in post-spawning gonad recovery. Salinity did not have an effect on the AA composition. None of the environmental parameters measured had an effect on FA composition.

  9. Enhancement of neurite outgrowth in PC12 cells stimulated with cyclic AMP and NGF by 6-acylated ascorbic acid 2-O-alpha-glucosides (6-Acyl-AA-2G), novel lipophilic ascorbate derivatives.

    PubMed

    Zhou, Xiaohua; Tai, Akihiro; Yamamoto, Itaru

    2003-03-01

    It has been shown that ascorbate (AsA) and its stable derivative, ascorbic acid 2-O-alpha-glucoside (AA-2G), do not elicit neurite outgrowth in PC12 cells. However, these ascorbates are synergistically enhanced by both dibutyryl cyclic AMP (Bt(2)cAMP)- and nerve growth factor (NGF)-induced neurite outgrowth in this model. In the present study, the effects of a series of novel lipophilic ascorbate derivatives, 6-acylated ascorbic acid 2-O-alpha-glucosides (6-Acyl-AA-2G), on neurite outgrowth induced by Bt(2)cAMP and NGF were examined in PC12 cells. We found that all the tested acylated ascorbate derivatives enhanced neurite formation induced by both agents in a dose-dependent manner. Of the 6-Acyl-AA-2G derivatives, 6-octanoyl ascorbic acid 2-O-alpha-glucoside (6-Octa-AA-2G) enhanced the Bt(2)cAMP-induced phosphorylated MAPK p44 and p42 expression. A alpha-glucosidase inhibitor, castanospermine, completely abrogated the promotion of neurite outgrowth and MAPK expression by 6-Octa-AA-2G. Addition of 6-Octa-AA-2G (0.5 mM) to PC12 cells caused a rapid and significant increase in intracellular AsA content, which reached a maximum and was maintained from 12 to 24 h after the culture. These findings suggest that 6-Acyl-AA-2G is rapidly hydrolyzed to AsA within the cell and enhances neurite differentiation through the interaction with the inducer-activated MAPK pathway.

  10. Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin.

    PubMed

    Gabboun, N H; Najib, N M; Ibrahim, H G; Assaf, S

    2001-01-05

    Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.

  11. Release kinetics of esterified p-coumaric acid and ferulic acid from rice straw in mild alkaline solution.

    PubMed

    Linh, Tran Ngoc; Fujita, Hirokata; Sakoda, Akiyoshi

    2017-05-01

    The release kinetics of esterified p-coumaric acid (PCA) and ferulic acid (FA) from rice straw under a mild alkaline condition were investigated to collect fundamental data for the design of a recovery process. The results showed that the straw size, NaOH concentration, and temperature were the key parameters governing release kinetics. The analysis demonstrated that FA is released considerably faster than PCA. The close relationship between lignin and the PCA dissolution indicates a reciprocal and/or simultaneous release. Moreover, PCA is broadly distributed in the lignin network but tends to be located more densely in the lignin fraction which is not easily solubilized by alkaline treatment. In contrast, the release of FA is strongly affected by removal of lignin fraction which is easily solubilized. These results suggest that the release kinetics are controlled by the accessibility of NaOH to their ester sites in the lignin/hemicellulose network, and by their localization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Control of arachidonic acid release in chick muscle cultures

    NASA Technical Reports Server (NTRS)

    Templeton, G. H.; Padalino, M.; Wright, W.

    1985-01-01

    Cultures from thigh muscles of 12 day old embryonic chicks are utilized to examine arachidonic release, prostaglandin (PG) biosynthesis, and protein synthesis. The preparation of the cultures is described. It is observed that exogenous arachidonic acid is formed into photsphatidylethanolamine and phosphatidylcholine, is released by a calcium ionosphere or phospholiphase simulator, and is the substrate for the biosynthesis of PG; the epidermal growth factor and PGF do not stimulate protein synthesis over the basal levels. The relationship between arachidonate release and melittin is studied. The data reveal that a change in intracellular calcium stimulates phospholiphase activity, arachidonate release, and PG synthesis in chick muscle culture.

  13. Systemic AA amyloidosis in the red fox (Vulpes vulpes).

    PubMed

    Rising, Anna; Cederlund, Ella; Palmberg, Carina; Uhlhorn, Henrik; Gaunitz, Stefan; Nordling, Kerstin; Ågren, Erik; Ihse, Elisabet; Westermark, Gunilla T; Tjernberg, Lars; Jörnvall, Hans; Johansson, Jan; Westermark, Per

    2017-11-01

    Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model. © 2017 The Protein Society.

  14. Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

    PubMed Central

    Hines, Daniel J.; Kaplan, David L.

    2013-01-01

    Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

  15. IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

    PubMed Central

    Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

    2012-01-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

  16. Amino Acid Transporters and Release of Hydrophobic Amino Acids in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120.

    PubMed

    Pernil, Rafael; Picossi, Silvia; Herrero, Antonia; Flores, Enrique; Mariscal, Vicente

    2015-04-23

    Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can use inorganic compounds such as nitrate or ammonium as nitrogen sources. In the absence of combined nitrogen, it can fix N2 in differentiated cells called heterocysts. Anabaena also shows substantial activities of amino acid uptake, and three ABC-type transporters for amino acids have been previously characterized. Seven new loci encoding predicted amino acid transporters were identified in the Anabaena genomic sequence and inactivated. Two of them were involved in amino acid uptake. Locus alr2535-alr2541 encodes the elements of a hydrophobic amino acid ABC-type transporter that is mainly involved in the uptake of glycine. ORF all0342 encodes a putative transporter from the dicarboxylate/amino acid:cation symporter (DAACS) family whose inactivation resulted in an increased uptake of a broad range of amino acids. An assay to study amino acid release from Anabaena filaments to the external medium was set up. Net release of the alanine analogue α-aminoisobutyric acid (AIB) was observed when transport system N-I (a hydrophobic amino acid ABC-type transporter) was engaged in the uptake of a specific substrate. The rate of AIB release was directly proportional to the intracellular AIB concentration, suggesting leakage from the cells by diffusion.

  17. Acid-Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release.

    PubMed

    Mao, Dake; Liang, Yajun; Liu, Yamin; Zhou, Xianhao; Ma, Jiaqi; Jiang, Biao; Liu, Jia; Ma, Da

    2017-10-02

    Stimuli-responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n]uril (CB[n]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5-6.5). These containers retain the excellent recognition properties of CB[n]-type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine-tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Dysregulation of Corticostriatal Ascorbate Release and Glutamate Uptake in Transgenic Models of Huntington's Disease

    PubMed Central

    2013-01-01

    Abstract Significance: Dysregulation of cortical and striatal neuronal processing plays a critical role in Huntington's disease (HD), a dominantly inherited condition that includes a progressive deterioration of cognitive and motor control. Growing evidence indicates that ascorbate (AA), an antioxidant vitamin, is released into striatal extracellular fluid when glutamate is cleared after its release from cortical afferents. Both AA release and glutamate uptake are impaired in the striatum of transgenic mouse models of HD owing to a downregulation of glutamate transporter 1 (GLT1), the protein primarily found on astrocytes and responsible for removing most extracellular glutamate. Improved understanding of an AA–glutamate interaction could lead to new therapeutic strategies for HD. Recent Advances: Increased expression of GLT1 following treatment with ceftriaxone, a beta-lactam antibiotic, increases striatal glutamate uptake and AA release and also improves the HD behavioral phenotype. In fact, treatment with AA alone restores striatal extracellular AA to wild-type levels in HD mice and not only improves behavior but also improves the firing pattern of neurons in HD striatum. Critical Issues: Although evidence is growing for an AA-glutamate interaction, several key issues require clarification: the site of action of AA on striatal neurons; the precise role of GLT1 in striatal AA release; and the mechanism by which HD interferes with this role. Future Directions: Further assessment of how the HD mutation alters corticostriatal signaling is an important next step. A critical focus is the role of astrocytes, which express GLT1 and may be the primary source of extracellular AA. Antioxid. Redox Signal. 19, 2115–2128. PMID:23642110

  19. Branched-chain amino acids and brain function.

    PubMed

    Fernstrom, John D

    2005-06-01

    Branched-chain amino acids (BCAAs) influence brain function by modifying large, neutral amino acid (LNAA) transport at the blood-brain barrier. Transport is shared by several LNAAs, notably the BCAAs and the aromatic amino acids (ArAAs), and is competitive. Consequently, when plasma BCAA concentrations rise, which can occur in response to food ingestion or BCAA administration, or with the onset of certain metabolic diseases (e.g., uncontrolled diabetes), brain BCAA concentrations rise, and ArAA concentrations decline. Such effects occur acutely and chronically. Such reductions in brain ArAA concentrations have functional consequences: biochemically, they reduce the synthesis and the release of neurotransmitters derived from ArAAs, notably serotonin (from tryptophan) and catecholamines (from tyrosine and phenylalanine). The functional effects of such neurochemical changes include altered hormonal function, blood pressure, and affective state. Although the BCAAs thus have biochemical and functional effects in the brain, few attempts have been made to characterize time-course or dose-response relations for such effects. And, no studies have attempted to identify levels of BCAA intake that might produce adverse effects on the brain. The only "model" of very high BCAA exposure is a very rare genetic disorder, maple syrup urine disease, a feature of which is substantial brain dysfunction but that probably cannot serve as a useful model for excessive BCAA intake by normal individuals. Given the known biochemical and functional effects of the BCAAs, it should be a straightforward exercise to design studies to assess dose-response relations for biochemical and functional effects and, in this context, to explore for adverse effect thresholds.

  20. Effect of resveratrol, tyrosol and beta-sitosterol on oxidised low-density lipoprotein-stimulated oxidative stress, arachidonic acid release and prostaglandin E2 synthesis by RAW 264.7 macrophages.

    PubMed

    Vivancos, Marta; Moreno, Juan J

    2008-06-01

    Oxidation of LDL is hypothesised as an early and critical event in atherogenesis. Oxidised LDL (oxLDL) favour the transformation of macrophages into foam cells, an important cell involved in atherosclerosis. Furthermore, oxLDL cause multiple changes in macrophage functions. Thus, oxLDL induces certain genes, suppresses others and alters cell lipid metabolism. Consumption of a Mediterranean diet is associated with a low incidence of atherosclerotic disease, but data about the specific dietary constituents involved and mechanisms conferring cardioprotection are still sparse. The aim of the present study was to determine the effect of representative minor components of wine and olive oil on reactive oxygen species and eicosanoid synthesis induced by oxLDL-stimulated macrophages. We observed that exposure to non-toxic oxLDL concentrations leads to the production of H2O2 by RAW 264.7 macrophages and this effect was reverted by apocynin, a NADPH oxidase inhibitor. Moreover, oxLDL induced arachidonic acid (AA) release, cyclo-oxygenase-2 overexpression and subsequent PGE2 release. We observed that resveratrol and tyrosol revert H2O2 production induced by oxLDL as well as AA release and PGE2 synthesis and that these effects were not as a consequence of these compounds interfering with the oxLDL binding to their receptors. Interestingly, beta-sitosterol presence enhances these polyphenol actions. Thus, we found a synergistic action of polyphenols of olive oil and wine and beta-sitosterol of olive oil led to the modulation of the effects of oxLDL on oxidative stress and PGE2 synthesis.

  1. The preparation and the sustained release of titanium dioxide hollow particles encapsulating L-ascorbic acid

    NASA Astrophysics Data System (ADS)

    Tominaga, Yoko; Kadota, Kazunori; Shimosaka, Atsuko; Yoshida, Mikio; Oshima, Kotaro; Shirakawa, Yoshiyuki

    2018-05-01

    The preparation of the titanium dioxide hollow particles encapsulating L-ascorbic acid via sol-gel process using inkjet nozzle has been performed, and the sustained release and the effect protecting against degradation of L-ascorbic acid in the particles were investigated. The morphology of titanium dioxide particles was evaluated by scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). The sustained release and the effect protecting against degradation of L-ascorbic acid were estimated by dialysis bag method in phosphate buffer saline (PBS) (pH = 7.4) as release media. The prepared titanium dioxide particles exhibited spherical porous structures. The particle size distribution of the titanium dioxide particles was uniform. The hollow titanium dioxide particles encapsulating L-ascorbic acid showed the sustained release. It was also found that the degradation of L-ascorbic acid could be inhibited by encapsulating L-ascorbic acid in the titanium dioxide hollow particles.

  2. Increasing the fidelity of noncanonical amino acid incorporation in cell-free protein synthesis.

    PubMed

    Gan, Qinglei; Fan, Chenguang

    2017-11-01

    Cell-free protein synthesis provides a robust platform for co-translational incorporation of noncanonical amino acid (ncAA) into proteins to facilitate biological studies and biotechnological applications. Recently, eliminating the activity of release factor 1 has been shown to increase ncAA incorporation in response to amber codons. However, this approach could promote mis-incorporation of canonical amino acids by near cognate suppression. We performed a facile protocol to remove near cognate tRNA isoacceptors of the amber codon from total tRNAs, and used the phosphoserine (Sep) incorporation system as validation. By manipulating codon usage of target genes and tRNA species introduced into the cell-free protein synthesis system, we increased the fidelity of Sep incorporation at a specific position. By removing three near cognate tRNA isoacceptors of the amber stop codon [tRNA Lys , tRNA Tyr , and tRNA Gln (CUG)] from the total tRNA, the near cognate suppression decreased by 5-fold without impairing normal protein synthesis in the cell-free protein synthesis system. Mass spectrometry analyses indicated that the fidelity of ncAA incorporation was improved. Removal of near cognate tRNA isoacceptors of the amber codon could increase ncAA incorporation fidelity towards the amber stop codon in release factor deficiency systems. We provide a general strategy to improve fidelity of ncAA incorporation towards stop, quadruplet and sense codons in cell-free protein synthesis systems. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Effect of different polyphenol sources on the efficiency of ellagic acid release by Aspergillus niger.

    PubMed

    Sepúlveda, Leonardo; de la Cruz, Reynaldo; Buenrostro, José Juan; Ascacio-Valdés, Juan Alberto; Aguilera-Carbó, Antonio Francisco; Prado, Arely; Rodríguez-Herrera, Raúl; Aguilar, Cristóbal Noé

    2016-01-01

    Fungal hydrolysis of ellagitannins produces hexahydroxydiphenic acid, which is considered an intermediate molecule in ellagic acid release. Ellagic acid has important and desirable beneficial health properties. The aim of this work was to identify the effect of different sources of ellagitannins on the efficiency of ellagic acid release by Aspergillus niger. Three strains of A. niger (GH1, PSH and HT4) were assessed for ellagic acid release from different polyphenol sources: cranberry, creosote bush, and pomegranate used as substrate. Polyurethane foam was used as support for solid-state culture in column reactors. Ellagitannase activity was measured for each of the treatments. Ellagic acid was quantified by high performance liquid chromatography. When pomegranate polyphenols were used, a maximum value of ellagic acid (350.21 mg/g) was reached with A. niger HT4 in solid-state culture. The highest amount of ellagitannase (5176.81 U/l) was obtained at 8h of culture when cranberry polyphenols and strain A. niger PSH were used. Results demonstrated the effect of different polyphenol sources and A. niger strains on ellagic acid release. It was observed that the best source for releasing ellagic acid was pomegranate polyphenols and A. niger HT4 strain, which has the ability to degrade these compounds for obtaining a potent bioactive molecule such as ellagic acid. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Presence of gonadotropin-releasing hormone and its messenger ribonucleic acid in human ovarian epithelial carcinoma.

    PubMed

    Ohno, T; Imai, A; Furui, T; Takahashi, K; Tamaya, T

    1993-09-01

    The purpose of this study was to investigate the expression of gonadotropin-releasing hormone messenger ribonucleic acid and the presence of gonadotropin-releasing hormone in human ovarian carcinoma known to have gonadotropin-releasing hormone binding sites and to be affected by gonadotropin-releasing hormone analog. Human ovarian carcinomas surgically removed and human ovarian carcinoma cell lines were examined. Gonadotropin-releasing hormone was determined by a radioimmunoassay and a bioassay. Gonadotropin-releasing hormone messenger ribonucleic acid was determined by reverse transcription polymerase chain reaction using oligonucleotide primers synthesized according to the published human gonadotropin-releasing hormone sequence. Gonadotropin-releasing hormone was shown to be present in extracts of ovarian mucinous cystadenocarcinoma sample (0.8 +/- 0.12 pg/mg of protein) and ovarian adenocarcinoma cell line SK-OV3 (0.92 +/- 0.17 pg/mg of protein) but not in the normal ovary and placenta. Two of two extract samples from individual cases evoked dose-dependent phosphoinositide breakdown in rat granulosa cells similar to that caused by authentic gonadotropin-releasing hormone. Gonadotropin-releasing hormone messenger ribonucleic acid was detected in two of two mucinous cystadenocarcinoma specimens, one of one serous cystadenocarcinoma, and SK-OV3 cells but not in the dysgerminoma, mucinous cystadenoma, and normal ovary and placenta. The demonstration of gonadotropin-releasing hormone and its messenger ribonucleic acid raises the possibility that gonadotropin-releasing hormone may play an autocrine regulatory role in the growth of ovarian carcinoma.

  5. Synthesis of ST7612AA1, a Novel Oral HDAC Inhibitor, via Radical 
Thioacetic Acid Addition.

    PubMed

    Battistuzzi, Gianfranco; Giannini, Giuseppe

    2016-12-01

    In the expanding field of anticancer drugs, HDAC inhibitors are playing an increasingly important role. To date, four/five HDAC inhibitors have been approved by FDA. All these compounds fit the widely accepted HDAC inhibitors pharmacophore model characterized by a cap group, a linker chain and a zinc binding group (ZBG), able to bind the Zn 2+ ion in a pocket of the HDAC active site. Romidepsin, a natural compound, is the only thiol derivative. We have selected a new class of synthetic HDAC inhibitors, the thio-ω(lactam-carboxamide) derivatives, with ST7612AA1 as drug candidate, pan-inhibitor active in the range of single- to two-digit nanomolar concentrations. Preliminary results of a synthetic optimization attempt towards a fast scale-up process are here proposed. In the four steps of synthesis, from unsaturated amino acid intermediate to the final product, we explored different synthetic conditions in order to have a transferable process for a scale-up synthetic laboratory. In the first step, isobutyl chloroformate was used and, after a simple work up with 1M HCl, 2 (96% yield) was obtained as a white solid, which was used directly in the next step. For thioacetic acid addition to the double bond of intermediate 2 , two different routes were possible, with addition reaction in the first (D') or last step (D). Reactions of 2 to give 5 or of 4 to give ST7612AA1 were both performed in dioxane. Reactions were fast and did not need the usually advised radical quenching with cyclohexene. The corresponding products were obtained in good yields (step D', 89%; step D, 81%) after a flash chromatography. , a thiol derivative prodrug of ST7464AA1 , is the first of a new generation of HDAC inhibitors, very potent, orally administered, and well tolerated. Here, we have identified a synthetic route, competitive, versatile and easily transferable to industrial processes.

  6. The 9aaTAD Transactivation Domains: From Gal4 to p53.

    PubMed

    Piskacek, Martin; Havelka, Marek; Rezacova, Martina; Knight, Andrea

    2016-01-01

    The family of the Nine amino acid Transactivation Domain, 9aaTAD family, comprises currently over 40 members. The 9aaTAD domains are universally recognized by the transcriptional machinery from yeast to man. We had identified the 9aaTAD domains in the p53, Msn2, Pdr1 and B42 activators by our prediction algorithm. In this study, their competence to activate transcription as small peptides was proven. Not surprisingly, we elicited immense 9aaTAD divergence in hundreds of identified orthologs and numerous examples of the 9aaTAD species' convergence. We found unforeseen similarity of the mammalian p53 with yeast Gal4 9aaTAD domains. Furthermore, we identified artificial 9aaTAD domains generated accidentally by others. From an evolutionary perspective, the observed easiness to generate 9aaTAD transactivation domains indicates the natural advantage for spontaneous generation of transcription factors from DNA binding precursors.

  7. Micromotors Spontaneously Neutralize Gastric Acid for pH-Responsive Payload Release.

    PubMed

    Li, Jinxing; Angsantikul, Pavimol; Liu, Wenjuan; Esteban-Fernández de Ávila, Berta; Thamphiwatana, Soracha; Xu, Mingli; Sandraz, Elodie; Wang, Xiaolei; Delezuk, Jorge; Gao, Weiwei; Zhang, Liangfang; Wang, Joseph

    2017-02-13

    The highly acidic gastric environment creates a physiological barrier for using therapeutic drugs in the stomach. While proton pump inhibitors have been widely used for blocking acid-producing enzymes, this approach can cause various adverse effects. Reported herein is a new microdevice, consisting of magnesium-based micromotors which can autonomously and temporally neutralize gastric acid through efficient chemical propulsion in the gastric fluid by rapidly depleting the localized protons. Coating these micromotors with a cargo-containing pH-responsive polymer layer leads to autonomous release of the encapsulated payload upon gastric-acid neutralization by the motors. Testing in a mouse model demonstrate that these motors can safely and rapidly neutralize gastric acid and simultaneously release payload without causing noticeable acute toxicity or affecting the stomach function, and the normal stomach pH is restored within 24 h post motor administration. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Effect of the Microstructure on Diffusion Bonded AA5083, AA6082 and AA7075 Aluminium Alloys

    NASA Astrophysics Data System (ADS)

    Venugopal, S.; Mahendran, G.

    2018-05-01

    Rolled plates of aluminium alloys AA5083, AA6082 and AA7075 of 5 mm thickness are joined by diffusion bonding at varied parameters. The microstructure evolution of AA5083, AA6082 and AA7075 aluminium alloys is characterized by Transmission Electron Microscopy (TEM). Metallurgical investigations and mechanical tests are also performed to correlate the results of the TEM investigations with the mechanical properties of the produced diffusion bonded joints. It is observed that the bonding and shear strength of the alloys increase with the increase in bonding temperature, due to the diffusion of micro-constituents in the interface. High temperature enhances the uniform distribution of secondary phase particles and reduces pore formation/defects in the bonded joints.

  9. Controlled release properties of zein-fatty acid blend films for multiple bioactive compounds.

    PubMed

    Arcan, Iskender; Yemenicioğlu, Ahmet

    2014-08-13

    To develop edible films having controlled release properties for multiple bioactive compounds, hydrophobicity and morphology of zein films were modified by blending zein with oleic (C18:1)Δ⁹, linoleic (C18:2)Δ(9,12), or lauric (C₁₂) acids in the presence of lecithin. The blend zein films showed 2-8.5- and 1.6-2.9-fold lower initial release rates for the model active compounds, lysozyme (LYS) and (+)-catechin (CAT), than the zein control films, respectively. The change of fatty acid chain length affected both CAT and LYS release rates while the change of fatty acid double bond number affected only the CAT release rate. The film morphologies suggested that the blend films owe their controlled release properties mainly to the microspheres formed within their matrix and encapsulation of active compounds. The blend films showed antilisterial activity and antioxidant activity up to 81 μmol Trolox/cm². The controlled release of multiple bioactive compounds from a single film showed the possibility of combining application of active and bioactive packaging technologies and improving not only safety and quality but also health benefits of packed food.

  10. Simulating the Fate and Transport of an Acid Mine Drainage Release

    EPA Science Inventory

    On August 5, 2015, approximately 3 million gallons of acid mine drainage were released from the Gold King Mine into Cement Creek in the San Juan River watershed (CO, NM, UT). The release further mobilized additional metals, which resulted in a large mass of solids and dissolved m...

  11. Active food packaging based on molecularly imprinted polymers: study of the release kinetics of ferulic acid.

    PubMed

    Otero-Pazos, Pablo; Rodríguez-Bernaldo de Quirós, Ana; Sendón, Raquel; Benito-Peña, Elena; González-Vallejo, Victoria; Moreno-Bondi, M Cruz; Angulo, Immaculada; Paseiro-Losada, Perfecto

    2014-11-19

    A novel active packaging based on molecularly imprinted polymer (MIP) was developed for the controlled release of ferulic acid. The release kinetics of ferulic acid from the active system to food simulants (10, 20, and 50% ethanol (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v) and isooctane), and real food samples at different temperatures were studied. The key parameters of the diffusion process were calculated by using a mathematical modeling based on Fick's second law. The ferulic acid release was affected by the temperature as well as the percentage of ethanol of the simulant. The fastest release occurred in 95% ethanol (v/v) at 20 °C. The diffusion coefficients (D) obtained ranged between 1.8 × 10(-11) and 4.2 × 10(-9) cm(2)/s. A very good correlation between experimental and estimated data was obtained, and consequently the model could be used to predict the release of ferulic acid into food simulants and real food samples.

  12. Controlled release of tyrosol and ferulic acid encapsulated in chitosan-gelatin films after electron beam irradiation

    NASA Astrophysics Data System (ADS)

    Benbettaïeb, Nasreddine; Assifaoui, Ali; Karbowiak, Thomas; Debeaufort, Frédéric; Chambin, Odile

    2016-01-01

    This work deals with the study of the release kinetics of antioxidants (ferulic acid and tyrosol) incorporated into chitosan-gelatin edible films after irradiation processes. The aim was to determine the influence of electron beam irradiation (at 60 kGy) on the retention of antioxidants in the film, their release in water (pH=7) at 25 °C, in relation with the barrier and mechanical properties of biopolymer films. The film preparation process coupled to the irradiation induced a loss of about 20% of tyrosol but did not affect the ferulic acid content. However, 27% of the ferulic acid remained entrapped in the biopolymer network during the release experiments whereas all tyrosol was released. Irradiation induced a reduction of the release rate for both compounds, revealing that cross-linking occurred during irradiation. This was confirmed by the mechanical properties enhancement which tensile strength value significantly increased and by the reduction of permeabilities. Although molecular weights, molar volume and molecular radius of the two compounds are very similar, the effective diffusivity of tyrosol was 40 times greater than that of ferulic acid. The much lower effective diffusion coefficient of ferulic acid as determined from the release kinetics was explained by the interactions settled between ferulic acid molecules and the gelatin-chitosan matrix. As expected, the electron beam irradiation allowed modulating the retention and then the release of antioxidants encapsulated.

  13. Fluorescence turn-on detection of alkaline phosphatase activity based on controlled release of PEI-capped Cu nanoclusters from MnO2 nanosheets.

    PubMed

    Zhang, Yunyi; Li, Yongxin; Zhang, Cuiyun; Zhang, Qingfeng; Huang, Xinan; Yang, Meiding; Shahzad, Sohail Anjum; Lo, Kenneth Kam-Wing; Yu, Cong; Jiang, Shichun

    2017-08-01

    A fluorescence turn-on assay for alkaline phosphatase (ALP) activity is developed through the controlled release of polyethyleneimine-capped copper nanoclusters (PEI-capped CuNCs) from the MnO 2 nanosheets. In an aqueous solution, the positively charged PEI-capped CuNCs could be adsorbed onto the surface of the negatively charged MnO 2 nanosheets. Such adsorption through favorable electrostatic interactions could efficiently quench the nanocluster fluorescence emission via resonance energy transfer from the PEI-capped CuNCs to the MnO 2 nanosheets. 2-Phospho-L-ascorbic acid (AAP) could be hydrolyzed to L-ascorbic acid (AA) in the presence of ALP. AA could reduce MnO 2 into Mn 2+ and trigger the disintegration of the MnO 2 nanosheets. As a result, the CuNCs were released and the quenched fluorescence was recovered efficiently. The detection strategy is simple, inexpensive, sensitive, selective, with low toxicity, and has better biocompatibility. The newly fabricated biosensor for ALP activity will potentially make it a robust candidate for numerous biological and biomedical applications.

  14. Bacterial cellulose based hydrogel (BC-g-AA) and preliminary result of swelling behavior

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hakam, Adil; Lazim, Azwan Mat; Abdul Rahman, I. Irman

    2013-11-27

    In this study, hydrogel based on Bacterial cellulose (BC) or local known as Nata de Coco, which grafted with monomer: Acrylic acid (AA) is synthesis by using gamma radiation technique. These hydrogel (BC-g-AA) has unique characteristic whereby responsive to pH buffer solution.

  15. Effect of Dietary L-ascorbic Acid (L-AA) on Production Performance, Egg Quality Traits and Fertility in Japanese Quail (Coturnix japonica) at Low Ambient Temperature.

    PubMed

    Shit, N; Singh, R P; Sastry, K V H; Agarwal, R; Singh, R; Pandey, N K; Mohan, J

    2012-07-01

    Environmental stress boosts the levels of stress hormones and accelerates energy expenditure which subsequently imbalance the body's homeostasis. L-ascorbic acid (L-AA) has been recognized to mitigate the negative impact of environmental stress on production performances in birds. The present investigation was carried out to elucidate the effect of different dietary levels of L-AA on production performance, egg quality traits and fertility in Japanese quail at low ambient temperature. Sixty matured females (15 wks) were equally divided into three groups (20/group) based on the different dietary levels of L-AA (0, 250 and 500 ppm) and coupled with an equal number of males (1:1) obtained from the same hatch. They were managed in uniform husbandry conditions without restriction of feed and water at 14 h photo-schedule. Except for feed efficiency, body weight change, feed consumption and hen-day egg production were recorded highest in 500 ppm L-AA supplemented groups. Among the all egg quality traits studied, only specific gravity, shell weight and thickness differed significantly (p<0.05) in the present study. Fertility was improved significantly (p<0.01) to a dose dependent manner of L-AA. The findings of the present study concluded that dietary L-AA can be a caring management practice at least in part to alleviate the adverse effect of cold induced stress on production performance in Japanese quail.

  16. Enhancement of nitric oxide release and hemocompatibility by surface chirality of D-tartaric acid grafting

    NASA Astrophysics Data System (ADS)

    Han, Honghong; Wang, Ke; Fan, Yonghong; Pan, Xiaxin; Huang, Nan; Weng, Yajun

    2017-12-01

    Nitric Oxide (NO) generation from endogenous NO-donors catalyzed by diselenide modified biomaterials has been reported. Here we reported surface chirality by L-tartaric acid and D-tartaric acid grafting on the outermost showed a significant impact on diselenide modified biomaterials, which modulated protein adsorption, NO release and anti-platelet adhesion properties. D-tartaric acid grafted surface showed more blood protein adsorption than that of L-surfaces by QCM analysis, however, ELISA analysis disclosed less fibrinogen denatured on the D surfaces. Due to the surface ratio of selenium decreasing, NO release catalyzed by L-tartaric acid grafting on the outermost significantly decreased in comparison to that of only selenocystamine immobilized surfaces. While NO release catalyzed by D-tartaric acid grafting on the outermost didn't decrease and was similar with that of selenocystamine immobilized surfaces. Surface chirality combined with NO release had synergetic effects on platelet adhesion, and it showed the lowest number of platelets adhered on the D-tartaric acid grafted surfaces. Thus surface chirality from D-tartaric acid grafting enhanced hemocompatibility of the surface in this study. Our work provides new insights into engineering novel blood contacting biomaterials by taking into account surface chirality.

  17. Utilization of wheat straw for the preparation of coated controlled-release fertilizer with the function of water retention.

    PubMed

    Xie, Lihua; Liu, Mingzhu; Ni, Boli; Wang, Yanfang

    2012-07-18

    With the aim of improving fertilizer use efficiency and minimizing the negative impact on the environment, a new coated controlled-release fertilizer with the function of water retention was prepared. A novel low water solubility macromolecular fertilizer, poly(dimethylourea phosphate) (PDUP), was "designed" and formulated from N,N'-dimethylolurea (DMU) and potassium dihydrogen phosphate. Simultaneously, an eco-friendly superabsorbent composite based on wheat straw (WS), acrylic acid (AA), 2-acryloylamino-2-methyl-1-propanesulfonic acid (AMPS), and N-hydroxymethyl acrylamide (NHMAAm) was synthesized and used as the coating to control the release of nutrient. The nitrogen release profile and water retention capacity of the product were also investigated. The degradation of the coating material in soil solution was studied. Meanwhile, the impact of the content of N-hydroxymethyl acrylamide on the degradation extent was examined. The experimental data showed that the product with good water retention and controlled-release capacities, being economical and eco-friendly, could be promising for applications in agriculture and horticulture.

  18. Arachidonic acid, but not its metabolites, is essential for FcγR-stimulated intracellular killing of Staphylococcus aureus by human monocytes

    PubMed Central

    Zheng, L; Zomerdijk, T P L; Van Den Barselaar, M T; Geertsma, M F; Van Furth, R; Nibbering, P H

    1999-01-01

    Since arachidonic acid (AA) production by phospholipase A2 (PLA2) is essential for the Fcγ receptor (FcγR)-mediated respiratory burst and phagocytosis of opsonized erythrocytes by monocytes and macrophages, we focused in this study on the role of AA and its metabolites in the FcγR-stimulated intracellular killing of Staphylococcus aureus by human monocytes. The results revealed that the PLA2 inhibitors, but not inhibitors of cyclo-oxygenase and lipoxygenase, markedly suppressed the FcγR-mediated killing process. The production of O−2 by monocytes upon FcγR cross-linking was inhibited by 4-bromophenacyl bromide in a dose-dependent fashion, indicating that inhibition of PLA2 activity impairs the oxygen-dependent bactericidal mechanisms of monocytes, which could be partially restored by addition of exogenous AA and docosahexaenoic acid, but not myristic acid. These polyunsaturated fatty acids, but not myristic acid, stimulated the intracellular killing of S. aureus by monocytes, although not as effectively as FcγR cross-linking. Furthermore, FcγR cross-linking stimulated the release of AA from monocytes. Studies with selective inhibitors revealed that the FcγR-mediated activation of PLA2 is dependent on Ca2+ and tyrosine kinase activity. Together these results indicate a key role for PLA2/AA, but not its major metabolites, in mediating the FcγR-stimulated intracellular killing of S. aureus by monocytes. PMID:10233682

  19. Amino acid fingerprint in the rhizosphere of Pisum sativum in response to water stress

    NASA Astrophysics Data System (ADS)

    Bobille, Hélène; Fustec, Joëlle; Robins, Richard J.; Cukier, Caroline; Limami, Anis M.

    2017-04-01

    In cropping systems, legumes release substantial amounts of nitrogen (N) into the soil, via rhizodeposition, and constitute a sustainable source of N, instead of synthetic N fertilisers (Fustec et al. 2010). More frequent or/and intense droughts and floodings, due to climate change and intensification of agriculture, may affect N rhizodeposition (Preece & Peñuelas 2016). However, the effects of water stress on this process are poorly documented. A part of N derived from root exudates, mainly in amino acids (AAs) form, is suspected shape and regulate rhizosphere microbial community, thus playing a potential role in maintaining plant health in case of abiotic stress (Moe 2013). We hypothesized that root AA exudation could change significantly, according to water availability, and would help to understand N metabolism changes in plant-rhizosphere interactions. Because studying exudation from plant grown in unsterilized soil is challenging (Oburger et al. 2013), we have measured the rhizosphere AA fingerprint (RAAF), as the result of interactions between AA exudation and rhizospheric environment. In addition, plants were stem-labeled (cotton-wick) with 15N-urea for 72 h to provide direct evidence of a link between root AA and exudation in the soil. The RAAF was measured in Pisum sativum rhizosphere, under either a water deficit or a water excess for 72 h. Water deficit decreases biomass accumulation in shoots but not in roots. Then, water deficit had no significant effect on total AAs released into the rhizosphere but, it significantly modified the composition of RAAF, with a preferential increase of proline, alanine and glutamate and a rise in isotopic enrichment of AAs derived from oxaloacetate in tricarboxylic acidic cycle (asparagine, aspartate, threonine and isoleucine). These results support the idea that, under the early stages of water deficit, recently assimilated N is rapidly translocated to the roots, and part of it is exudated in AAs. Most of the exudated

  20. Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets.

    PubMed

    Cheng, Qilai; Liao, Meixiang; Hu, Haibo; Li, Hongliang; Wu, Longhuo

    2018-01-01

    P-glycoprotein (P-gp, i.e., MDR1) is associated with the phenotype of multidrug resistance (MDR) and causes chemotherapy failure in the management of cancers. Searching for effective MDR modulators and combining them with anticancer drugs is a promising strategy against MDR. Asiatic acid (AA), a natural triterpene isolated from the plant Centella asiatica, may have an antitumor activity. The present study assessed the reversing effect of AA on MDR and possible molecular mechanisms of AA action in MDR1-overexpressing cisplatin (DDP)-resistant lung cancer cells, A549/DDP. Human lung adenocarcinoma A549/DDP cells were either exposed to different concentrations of AA or treated with DDP, and their viability was measured by the MTT assay. A Rhodamine 123 efflux assay, immunofluorescent staining, ATPase assay, reverse-transcription PCR (RT-PCR), and western blot analysis were conducted to elucidate the mechanisms of action of AA on MDR. Our results showed that AA significantly enhanced the cytotoxicity of DDP toward A549/DDP cells but not its parental A549 cells. Furthermore, AA strongly inhibited P-gp expression by blocking MDR1 gene transcription and increased the intracellular accumulation of the P-gp substrate Rhodamine 123 in A549/DDP cells. Nuclear factor (NF)-kB (p65) activity, IkB degradation, and NF-kB/p65 nuclear translocation were markedly inhibited by pretreatment with AA. Additionally, AA inhibited the MAPK-ERK pathway, as indicated by decreased phosphorylation of ERK1 and -2, AKT, p38, and JNK, thus resulting in reduced activity of the Y-box binding protein 1 (YB1) via blockage of its nuclear translocation. AA reversed P-gp-mediated MDR by inhibition of P-gp expression. This effect was likely related to downregulation of YB1, and this effect was mediated by the NF-kB and MAPK-ERK pathways. AA may be useful as an MDR reversal agent for combination therapy in clinical trials. © 2018 The Author(s). Published by S. Karger AG, Basel.

  1. Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

    PubMed Central

    Zhang, Beiru; Une, Yumi; Fu, Xiaoying; Yan, Jingmin; Ge, FengXia; Yao, Junjie; Sawashita, Jinko; Mori, Masayuki; Tomozawa, Hiroshi; Kametani, Fuyuki; Higuchi, Keiichi

    2008-01-01

    AA amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, but little is known about the underlying mechanisms. Given the transmissible characteristics of AA amyloidosis, transmission between captive cheetahs may be a possible mechanism involved in the high incidence of AA amyloidosis. In this study of animals with AA amyloidosis, we found that cheetah feces contained AA amyloid fibrils that were different from those of the liver with regard to molecular weight and shape and had greater transmissibility. The infectious activity of fecal AA amyloid fibrils was reduced or abolished by the protein denaturants 6 M guanidine·HCl and formic acid or by AA immunodepletion. Thus, we propose that feces are a vehicle of transmission that may accelerate AA amyloidosis in captive cheetah populations. These results provide a pathogenesis for AA amyloidosis and suggest possible measures for rescuing cheetahs from extinction. PMID:18474855

  2. Novel sustained-release dosage forms of proteins using polyglycerol esters of fatty acids.

    PubMed

    Yamagata, Y; Iga, K; Ogawa, Y

    2000-02-03

    In order to develop a novel delivery system for proteins based on polyglycerol esters of fatty acids (PGEFs), we studied a model system using interferon-alpha (IFN-alpha) as the test protein. A cylindrical matrix was prepared by a heat extrusion technique using a lyophilized powder of the protein and 11 different types of synthetic PGEFs, which varied in degree of glycerol polymerization (di- and tetra-), chain length of fatty acids (myristate, palmitate and stearate) and degree of fatty acid esterification (mono-, di- and tri-). In an in-vitro release study using an enzyme-linked immunosorbent assay (ELISA) as a detection method, the matrices prepared from a monoglyceride (used for comparison) and from diglycerol esters exhibited a biphasic release pattern with a large initial burst followed by slow release. In contrast, the matrices prepared from tetraglycerol esters showed a steady rate of release without a large initial burst. In an in vivo release study, initial bursts of IFN-alpha release were, also, dramatically reduced when the matrices were prepared from the tetraglycerol esters of palmitate and stearate, and the mean residence time (MRT) of IFN-alpha was prolonged, whereas the matrices prepared from monoglyceride and from diglycerol esters showed large initial bursts of IFN-alpha release. Since the release rates from the matrices prepared from the tetraglycerol esters of palmitate and stearate were governed by Jander's equation modified for a cylindrical matrix, the release from those matrices was concluded to be a diffusion-controlled process. The bioavailability of IFN-alpha after implantation of the matrix formulation prepared using all types of PGEFs, except for tetraglycerol triesters, was almost equivalent to that after injection of IFN-alpha solution; consequently, IFN-alpha in these matrices appears to remain stable during the release period.

  3. [Shikimic acid inhibits the degranulation and histamine release in RBL-2H3 cells].

    PubMed

    Chen, Xianyong; Zheng, Qianqian; Liu, Wei; Yu, Lingling; Wang, Jinling; Li, Shigang

    2017-05-01

    Objective To study the effects of shikimic acid on the proliferation of rat RBL-2H3 cells and the degranulation of the cells induced by C48/80 and its mechanism. Methods MTT assay was performed to measure the proliferation of RBL-2H3 cells treated with 3, 10, 30 μg/mL shikimic acid. Toluidine blue staining was used to observe the degranulation of RBL-2H3 cells. The release of β-hexosaminidase from RBL-2H3 cells treated with 0, 12.5, 25, 50, 80, 100 μg/mL C48/80 was determined by substrate assay. ELISA was used to detect the histamine content in the supernatant of each treated group. Results Shikimic acid at 3, 10, 300 μg/mL had no obvious inhibitory effect on the proliferation of RBL-2H3 cells. There was a dose-effect relationship between the degranulation of RBL-2H3 cells and C48/80 concentration. Shikimic acid inhibited the degranulation of RBL-2H3 cells compared with the positive control group, the β-hexosaminidase release rate and histamine release were significantly reduced in RBL-2H3 cells treated with shikimic acid and C48/80. Conclusion Shikimic acid can inhibit the degranulation of RBL-2H3 cells and reduce histamine release.

  4. Diazeniumdiolate-doped poly(lactic-co-glycolic acid)-based nitric oxide releasing films as antibiofilm coatings.

    PubMed

    Cai, Wenyi; Wu, Jianfeng; Xi, Chuanwu; Meyerhoff, Mark E

    2012-11-01

    Nitric oxide (NO) releasing films with a bilayer configuration are fabricated by doping dibutyhexyldiamine diazeniumdiolate (DBHD/N2O2) in a poly(lactic-co-glycolic acid) (PLGA) layer and further encapsulating this base layer with a silicone rubber top coating. By incorporating pH sensitive dyes within the films, pH changes in the PLGA layer are visualized and correlated with the NO release profiles (flux vs. time). It is demonstrated that PLGA acts as both a promoter and controller of NO release from the coating by providing protons through its intrinsic acid residues (both end groups and monomeric acid impurities) and hydrolysis products (lactic acid and glycolic acid). Control of the pH changes within the PLGA layer can be achieved by adjusting the ratio of DBHD/N2O2 and utilizing PLGAs with different hydrolysis rates. Coatings with a variety of NO release profiles are prepared with lifetimes of up to 15 d at room temperature (23 °C) and 10 d at 37 °C. When incubated in a CDC flow bioreactor for a one week period at RT or 37 °C, all the NO releasing films exhibit considerable antibiofilm properties against gram-positive Staphylococcus aureus and gram-negative Escherichia coli. In particular, compared to the silicone rubber surface alone, an NO releasing film with a base layer of 30 wt% DBHD/N2O2 mixed with poly(lactic acid) exhibits an ∼98.4% reduction in biofilm biomass of S. aureus and ∼99.9% reduction for E. coli at 37 °C. The new diazeniumdiolate-doped PLGA-based NO releasing coatings are expected to be useful antibiofilm coatings for a variety of indwelling biomedical devices (e.g., catheters). Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. 40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to...

  6. 40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to...

  7. 40 CFR Appendix A to Subpart Aa of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart AA

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphoric Acid Manufacturing Plants Pt. 63, Subpt. AA, App. A Appendix A to...

  8. Ferulic Acid Suppresses Glutamate Release Through Inhibition of Voltage-Dependent Calcium Entry in Rat Cerebrocortical Nerve Terminals

    PubMed Central

    Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu-Kuei

    2013-01-01

    Abstract This study investigated the effects and possible mechanism of ferulic acid, a naturally occurring phenolic compound, on endogenous glutamate release in the nerve terminals of the cerebral cortex in rats. Results show that ferulic acid inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). The effect of ferulic acid on the evoked glutamate release was prevented by chelating the extracellular Ca2+ ions, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Ferulic acid suppressed the depolarization-induced increase in a cytosolic-free Ca2+ concentration, but did not alter 4-AP–mediated depolarization. Furthermore, the effect of ferulic acid on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na+/Ca2+ exchange. These results show that ferulic acid inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca2+ entry. PMID:23342970

  9. Targeting fatty acid amide hydrolase and transient receptor potential vanilloid-1 simultaneously to modulate colonic motility and visceral sensation in the mouse: A pharmacological intervention with N-arachidonoyl-serotonin (AA-5-HT).

    PubMed

    Bashashati, M; Fichna, J; Piscitelli, F; Capasso, R; Izzo, A A; Sibaev, A; Timmermans, J-P; Cenac, N; Vergnolle, N; Di Marzo, V; Storr, M

    2017-12-01

    Endocannabinoid anandamide (AEA) inhibits intestinal motility and visceral pain, but it may also be proalgesic through transient receptor potential vanilloid-1 (TRPV1). AEA is degraded by fatty acid amide hydrolase (FAAH). This study explored whether dual inhibition of FAAH and TRPV1 reduces diarrhea and abdominal pain. Immunostaining was performed on myenteric plexus of the mouse colon. The effects of the dual FAAH/TRPV1 inhibitor AA-5-HT on electrically induced contractility, excitatory junction potential (EJP) and fast (f) and slow (s) inhibitory junction potentials (IJP) in the mouse colon, colonic propulsion and visceromotor response (VMR) to rectal distension were studied. The colonic levels of endocannabinoids and fatty acid amides were measured. CB1-positive neurons exhibited TRPV1; only some TRPV1 positive neurons did not express CB1. CB1 and FAAH did not colocalize. AA-5-HT (100 nM-10 μM) decreased colonic contractility by ~60%; this effect was abolished by TRPV1 antagonist 5'-IRTX, but not by CB1 antagonist, SR141716. AA-5-HT (1 μM-10 μM) inhibited EJP by ~30% and IJPs by ~50%. The effects of AA-5-HT on junction potentials were reversed by SR141716 and 5`-IRTX. AA-5-HT (20 mg/kg; i.p.) inhibited colonic propulsion by ~30%; SR141716 but not 5`-IRTX reversed this effect. AA-5-HT decreased VMR by ~50%-60%; these effects were not blocked by SR141716 or 5`-IRTX. AA-5-HT increased AEA in the colon. The effects of AA-5-HT on visceral sensation and colonic motility are differentially mediated by CB1, TRPV1 and non-CB1/TRPV1 mechanisms, possibly reflecting the distinct neuromodulatory roles of endocannabinoid and endovanilloid FAAH substrates in the mouse intestine. © 2017 John Wiley & Sons Ltd.

  10. Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

    PubMed

    Hofsäss, Martin A; Souza, Jacqueline de; Silva-Barcellos, Neila M; Bellavinha, Karime R; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Parr, Alan; Langguth, Peter; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Mehta, Mehul U; Dressman, Jennifer B

    2017-12-01

    This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive. Following a conservative approach, folic acid is classified as a Biopharmaceutics Classification System class IV compound until more reliable data become available. Commensurate with its solubility characteristics, the results of dissolution studies indicated that none of the folic acid products evaluated showed rapid dissolution in media at pH 1.2 or 4.5. Therefore, according to the current criteria of the Biopharmaceutics Classification System, the biowaiver approval procedure cannot be recommended for immediate-release solid oral dosage forms containing folic acid. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  11. Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes.

    PubMed

    O'Dwyer, Aoife M; Lajczak, Natalia K; Keyes, Jennifer A; Ward, Joseph B; Greene, Catherine M; Keely, Stephen J

    2016-08-01

    Monocytes are critical to the pathogenesis of inflammatory bowel disease (IBD) as they infiltrate the mucosa and release cytokines that drive the inflammatory response. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with anti-inflammatory actions, has been proposed as a potential new therapy for IBD. However, its effects on monocyte function are not yet known. Primary monocytes from healthy volunteers or cultured U937 monocytes were treated with either the proinflammatory cytokine, TNFα (5 ng/ml) or the bacterial endotoxin, lipopolysaccharide (LPS; 1 μg/ml) for 24 h, in the absence or presence of UDCA (25-100 μM). IL-8 release into the supernatant was measured by ELISA. mRNA levels were quantified by qPCR and changes in cell signaling proteins were determined by Western blotting. Toxicity was assessed by measuring lactate dehydrogenase (LDH) release. UDCA treatment significantly attenuated TNFα-, but not LPS-driven, release of IL-8 from both primary and cultured monocytes. UDCA inhibition of TNFα-driven responses was associated with reduced IL-8 mRNA expression. Both TNFα and LPS stimulated NFκB activation in monocytes, while IL-8 release in response to both cytokines was attenuated by an NFκB inhibitor, BMS-345541. Interestingly, UDCA inhibited TNFα-, but not LPS-stimulated, NFκB activation. Finally, TNFα, but not LPS, induced phosphorylation of TNF receptor associated factor (TRAF2), while UDCA cotreatment attenuated this response. We conclude that UDCA specifically inhibits TNFα-induced IL-8 release from monocytes by inhibiting TRAF2 activation. Since such actions would serve to dampen mucosal immune responses in vivo, our data support the therapeutic potential of UDCA for IBD. Copyright © 2016 the American Physiological Society.

  12. Arachidonic acid enhances intracellular [Ca2+]i increase and mitochondrial depolarization induced by glutamate in cerebellar granule cells.

    PubMed

    Surin, A M; Bolshakov, A P; Mikhailova, M M; Sorokina, E G; Senilova, Ya E; Pinelis, V G; Khodorov, B I

    2006-08-01

    Maturation of primary neuronal cultures is accompanied by an increase in the proportion of cells that exhibit biphasic increase in free cytoplasmic Ca2+ ([Ca2+]i) followed by synchronic decrease in electrical potential difference across the inner mitochondrial membrane (DeltaPsim) in response to stimulation of glutamate receptors. In the present study we have examined whether the appearance of the second phase of [Ca2+]i change can be attributed to arachidonic acid (AA) release in response to the effect of glutamate (Glu) on neurons. Using primary culture of rat cerebellar granule cells we have investigated the effect of AA (1-20 microM) on [Ca2+]i, DeltaPsim, and [ATP] and changes in these parameters induced by neurotoxic concentrations of Glu (100 microM, 10-40 min). At =10 microM, AA caused insignificant decrease in DeltaPsim without any influence on [Ca2+]i. The mitochondrial ATPase inhibitor oligomycin enhanced AA-induced decrease in DeltaPsim; this suggests that AA may inhibit mitochondrial respiration. Addition of AA during the treatment with Glu resulted in more pronounced augmentation of [Ca2+]i and the decrease in DeltaPsim than the changes in these parameters observed during independent action of AA; removal of Glu did not abolish these changes. An inhibitor of the cyclooxygenase and lipoxygenase pathways of AA metabolism, 5,8,11,14-eicosatetraynoic acid, increased the proportion of neurons characterized by Glu-induced biphasic increase in [Ca2+]i and the decrease in DeltaPsim. Palmitic acid (30 microM) did not increase the percentage of neurons exhibiting biphasic response to Glu. Co-administration of AA and Glu caused 2-3 times more pronounced decrease in ATP concentrations than that observed during the independent effect of AA and Glu. The data suggest that AA may influence the functional state of mitochondria, and these changes may promote biphasic [Ca2+]i and DeltaPsim responses of neurons to the neurotoxic effect of Glu.

  13. Inhibition of free radical-induced erythrocyte hemolysis by 2-O-substituted ascorbic acid derivatives.

    PubMed

    Takebayashi, Jun; Kaji, Hiroaki; Ichiyama, Kenji; Makino, Kazutaka; Gohda, Eiichi; Yamamoto, Itaru; Tai, Akihiro

    2007-10-15

    Inhibitory effects of 2-O-substituted ascorbic acid derivatives, ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S), on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of sheep erythrocytes were studied and were compared with those of ascorbic acid (AA) and other antioxidants. The order of the inhibition efficiency was AA-2S> or =Trolox=uric acid> or =AA-2P> or =AA-2G=AA>glutathione. Although the reactivity of the AA derivatives against AAPH-derived peroxyl radical (ROO(*)) was much lower than that of AA, the derivatives exerted equal or more potent protective effects on AAPH-induced hemolysis and membrane protein oxidation. In addition, the AA derivatives were found to react per se with ROO(*), not via AA as an intermediate. These findings suggest that secondary reactions between the AA derivative radical and ROO(*) play a part in hemolysis inhibition. Delayed addition of the AA derivatives after AAPH-induced oxidation of erythrocytes had already proceeded showed weaker inhibition of hemolysis compared to that of AA. These results suggest that the AA derivatives per se act as biologically effective antioxidants under moderate oxidative stress and that AA-2G and AA-2P may be able to act under severe oxidative stress after enzymatic conversion to AA in vivo.

  14. Propylisopropylacetic acid (PIA), a constitutional isomer of valproic acid, uncompetitively inhibits arachidonic acid acylation by rat acyl-CoA synthetase 4: a potential drug for bipolar disorder

    PubMed Central

    Modi, Hiren R.; Basselin, Mireille; Taha, Ameer Y.; Li, Lei O.; Coleman, Rosalind A.; Bialer, Meir; Rapoport, Stanley I.

    2013-01-01

    Background Mood stabilizers used for treating bipolar disorder (BD) selectively downregulate arachidonic acid (AA) turnover (deacylation-reacylation) in brain phospholipids, when given chronically to rats. In vitro studies suggest that one of these, valproic acid (VPA), which is teratogenic, reduces AA turnover by inhibiting the brain acyl-CoA synthetase (Acsl)-4 mediated acylation of AA to AA-CoA. We tested whether non-teratogenic VPA analogues might also inhibit Acsl-4 catalyzed acylation, and thus have potential anti-BD action. Methods Rat Acsl4-flag protein was expressed in E. coli, and the ability of three VPA analogues, propylisopropylacetic acid (PIA), propylisopropylacetamide (PID) and N-methyl-2,2,3,3-tetramethylcyclopropanecarboxamide (MTMCD), and of sodium butyrate, to inhibit conversion of AA to AA-CoA by Acsl4 was quantified using Michaelis-Menten kinetics. Results Acsl4-mediated conversion of AA to AA-CoA in vitro was inhibited uncompetitively by PIA, with a Ki of 11.4 mM compared to a published Ki of 25 mM for VPA, while PID, MTMCD and sodium butyrate had no inhibitory effect. Conclusions PIA's ability to inhibit conversion of AA to AA-CoA by Acsl4 in vitro suggests that, like VPA, PIA may reduce AA turnover in brain phospholipids in unanesthetized rats, and if so, may be effective as a non-teratogenic mood stabilizer in BD patients. PMID:23354024

  15. Dipicolinic Acid Release by Germinating Clostridium difficile Spores Occurs through a Mechanosensing Mechanism.

    PubMed

    Francis, Michael B; Sorg, Joseph A

    2016-01-01

    Classically, dormant endospores are defined by their resistance properties, particularly their resistance to heat. Much of the heat resistance is due to the large amount of dipicolinic acid (DPA) stored within the spore core. During spore germination, DPA is released and allows for rehydration of the otherwise-dehydrated core. In Bacillus subtilis , 7 proteins are encoded by the spoVA operon and are important for DPA release. These proteins receive a signal from the activated germinant receptor and release DPA. This DPA activates the cortex lytic enzyme CwlJ, and cortex degradation begins. In Clostridium difficile , spore germination is initiated in response to certain bile acids and amino acids. These bile acids interact with the CspC germinant receptor, which then transfers the signal to the CspB protease. Activated CspB cleaves the cortex lytic enzyme, pro-SleC, to its active form. Subsequently, DPA is released from the core. C. difficile encodes orthologues of spoVAC , spoVAD , and spoVAE . Of these, the B. subtilis SpoVAC protein was shown to be capable of mechanosensing. Because cortex degradation precedes DPA release during C. difficile spore germination (opposite of what occurs in B. subtilis ), we hypothesized that cortex degradation would relieve the osmotic constraints placed on the inner spore membrane and permit DPA release. Here, we assayed germination in the presence of osmolytes, and we found that they can delay DPA release from germinating C. difficile spores while still permitting cortex degradation. Together, our results suggest that DPA release during C. difficile spore germination occurs though a mechanosensing mechanism. IMPORTANCE Clostridium difficile is transmitted between hosts in the form of a dormant spore, and germination by C. difficile spores is required to initiate infection, because the toxins that are necessary for disease are not deposited on the spore form. Importantly, the C. difficile spore germination pathway

  16. [Effect of glucocorticoides on the release of amino acids in the perfused rat hindquarter (author's transl)].

    PubMed

    Thienhaus, R; Tharandt, L; Zais, U; Staib, W

    1975-06-01

    The release of amino acids by skeletal muscle was studied in the isolated perfused rat hindquarter. Adrenalectomy depressed the formation of glutamine and alanine as well as the efflux of all other amino acids measured. Betamethasone--a synthetic glucocorticoid--caused a significant increase in the efflux of nearly all amino acids up to the level of normal controls. The release of amino acids was also increased in perfused hindquarters of diabetic rats. On the other hand, insulin exhibited a depressing effect on the release of amino acids by hindquarters of normal rats. The metabolic integrity of the muscle tissue was proved by measuring creatine phosphate, ATP, ADP and water content as well as by the significant insulin effect on glucose uptake and on [14C]leucine incorporation into muscle proteins.

  17. Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats.

    PubMed

    Yilmaz, Okkeş; Ozkan, Yusuf; Yildirim, Mehmet; Oztürk, A Ihsan; Erşan, Yasemin

    2002-01-01

    In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P < 0.01), D + ALA, and D + AA6P groups (P < 0.001). Malonaldehyde (MA) level increased in diabetes (P < 0.05), D + FO, and D + COM groups (P < 0.001), but its level in D + AA6P and D + ALA groups was lower in diabetes group (P < 0.01). Total lipid level in diabetes and diabetes plus antioxidant administered groups were higher than control. Total cholesterol level was high in diabetes and D + ALA groups (P < 0.05), but its level reduced in D + FO compared to control and diabetes groups, P < 0.05, < 0.001, respectively. Total triglyceride (TTG) level was high in the D + ALA (P < 0.05) and D + COM (P < 0.001) groups. In contrast, TTG level in blood of diabetes group was higher than diabetes plus antioxidant and FO administered groups (P < 0.001). According to gas chromatography analysis results, while the palmitic acid raised in diabetes group (P < 0.05), stearic acid in D + FO, D + ALA, and diabetes groups was lower than control (P < 0.05), oleic acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P < 0.01). As the linoleic acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P < 0.001). Arachidonic acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P < 0.01), but its level in D + COM and D + FO was higher than control (P < 0.05). Docosahexaenoic acid (DHA) increased in D + AA6P and D + COM (P < 0.05). While the total saturated fatty acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P < 0.05). In contrast, total

  18. Hypochlorous acid regulates neutrophil extracellular trap release in humans

    PubMed Central

    Palmer, L J; Cooper, P R; Ling, M R; Wright, H J; Huissoon, A; Chapple, I L C

    2012-01-01

    Neutrophil extracellular traps (NETs) comprise extracellular chromatin and granule protein complexes that immobilize and kill bacteria. NET release represents a recently discovered, novel anti-microbial strategy regulated non-exclusively by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generation of reactive oxygen intermediates (ROIs), particularly hydrogen peroxide. This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to record their effect fluorometrically on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in situ from sodium hypochlorite) established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which, due to the lack of a functional NADPH oxidase, also lack the capacity for NET release in response to classical stimuli. Moreover, the exogenous addition of taurine, abundantly present within the neutrophil cytosol, abrogated NET production stimulated by phorbol myristate acetate (PMA) and HOCl, providing a novel mode of cytoprotection by taurine against oxidative stress by taurine. PMID:22236002

  19. Determination of D- and L-amino acids produced by cyanobacteria using gas chromatography on Chirasil-Val after derivatization with pentafluoropropyl chloroformate.

    PubMed

    Zahradnícková, Helena; Husek, Petr; Simek, Petr; Hartvich, Petr; Marsálek, Blahoslav; Holoubek, Ivan

    2007-08-01

    A rapid and simple method was developed for the determination of free amino acids (AAs) released from cyanobacteria. The procedure involves trapping of AAs from the centrifuged cyanobacterial culture fluid on a cation-exchange resin, their release together with the resin by direct treatment with the reaction medium, followed by immediate derivatization with a corresponding chloroformate. The extractive alkylation transfers the analytes into an organic phase, an aliquot of which is subjected to GC analysis. Identification and quantification of AAs was performed by GC/MS and GC/FID, respectively, using propyl chloroformate (PCF) as the derivatization reagent. For chiral analysis, the cyanobacteria extracts were treated with 2,2,3,3,3-pentafluoropropyl chloroformate (PFPCF) to create more volatile analytes. Separation of the AA enantiomers was accomplished on a Chirasil-Val capillary column and the D/L enantiomeric ratios were determined. AAs of cyanobacteria are considered to be important for the assessment of energy flow in an aquatic food web, nutrition value of cyanobacteria in a food web and for cell-cell communication within cyanobacteria. The highest levels of AAs were found in the summer period at the beginning of the season (July). In the September and October samples, the amount of AAs was lower, the number of D-AAs decreased and the D/L ratio was higher than in the July sample. Based on the obtained results it can be assumed that young populations excrete AAs in higher concentrations and a different composition compared to actively growing populations.

  20. Controlling the Mesostructure Formation within the Shell of Novel Cubic/Hexagonal Phase Cetyltrimethylammonium Bromide-Poly(acrylamide-acrylic acid) Capsules for pH Stimulated Release.

    PubMed

    Tangso, Kristian J; Patel, Hetika; Lindberg, Seth; Hartley, Patrick G; Knott, Robert; Spicer, Patrick T; Boyd, Ben J

    2015-11-11

    The self-assembly of ordered structures in mixtures of oppositely charged surfactant and polymer systems has been exploited in various cleaning and pharmaceutical applications and continue to attract much interest since their discovery in the late twentieth century. The ability to control the electrostatic and hydrophobic interactions that dictate the formation of liquid crystalline phases in these systems is advantageous in manipulation of structure and rendering them responsive to external stimuli. Nanostructured capsules comprised of the cationic surfactant, cetyltrimethylammonium bromide (CTAB), and the diblock copolymer poly(acrylamide-acrylic acid) (PAAm-AA) were prepared to assess their potential as pH responsive nanomaterials. Crossed-polarizing light microscopy (CPLM) and small-angle X-ray scattering (SAXS) identified coexisting Pm3n cubic and hexagonal phases at the surfactant-polymer interface. The hydrophobic and electrostatic interactions between the oppositely charged components were studied by varying temperature and solution pH, respectively, and were found to influence the liquid crystalline nanostructure formed. The lattice parameter of the mesophases and the fraction of cubic phase in the system decreased upon heating. Acidic conditions resulted in the loss of the highly ordered structures due to protonation of the carboxylic acid group, and subsequent reduction of attractive forces previously present between the oppositely charged molecules. The rate of release of the model hydrophilic drug, Rhodamine B (RhB), from nanostructured macro-sized capsules significantly increased when the pH of the solution was adjusted from pH 7 to pH 2. This allowed for immediate release of the compound of interest "on demand", opening new options for structured materials with increased functionality over typical layer-by-layer capsules.

  1. FadD Is Required for Utilization of Endogenous Fatty Acids Released from Membrane Lipids ▿ †

    PubMed Central

    Pech-Canul, Ángel; Nogales, Joaquina; Miranda-Molina, Alfonso; Álvarez, Laura; Geiger, Otto; Soto, María José; López-Lara, Isabel M.

    2011-01-01

    FadD is an acyl coenzyme A (CoA) synthetase responsible for the activation of exogenous long-chain fatty acids (LCFA) into acyl-CoAs. Mutation of fadD in the symbiotic nitrogen-fixing bacterium Sinorhizobium meliloti promotes swarming motility and leads to defects in nodulation of alfalfa plants. In this study, we found that S. meliloti fadD mutants accumulated a mixture of free fatty acids during the stationary phase of growth. The composition of the free fatty acid pool and the results obtained after specific labeling of esterified fatty acids with a Δ5-desaturase (Δ5-Des) were in agreement with membrane phospholipids being the origin of the released fatty acids. Escherichia coli fadD mutants also accumulated free fatty acids released from membrane lipids in the stationary phase. This phenomenon did not occur in a mutant of E. coli with a deficient FadL fatty acid transporter, suggesting that the accumulation of fatty acids in fadD mutants occurs inside the cell. Our results indicate that, besides the activation of exogenous LCFA, in bacteria FadD plays a major role in the activation of endogenous fatty acids released from membrane lipids. Furthermore, expression analysis performed with S. meliloti revealed that a functional FadD is required for the upregulation of genes involved in fatty acid degradation and suggested that in the wild-type strain, the fatty acids released from membrane lipids are degraded by β-oxidation in the stationary phase of growth. PMID:21926226

  2. Uranium Release from Acidic Weathered Hanford Sediments: Single-Pass Flow-Through and Column Experiments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Guohui; Um, Wooyong; Wang, Zheming

    The reaction of acidic radioactive waste with sediments can induce mineral transformation reactions that, in turn, control contaminant fate. Here, sediment weathering by synthetic uranium-containing acid solutions was investigated using bench-scale experiments to simulate waste disposal conditions at Hanford’s cribs, USA. During acid weathering, the presence of phosphate exerted a strong influence over uranium mineralogy and a rapidly precipitated, crystalline uranium phosphate phase (meta-ankoleite [K(UO2)(PO4)·3H2O]) was identified using spectroscopic and diffraction-based techniques. In phosphate-free system, uranium oxyhydroxide minerals such as K-compreignacite [K2(UO2)6O4(OH)6·7H2O] were formed. Single-pass flow-through (SPFT) and column leaching experiments using synthetic Hanford pore water showed that uranium precipitatedmore » as meta-ankoleite during acid weathering was strongly retained in the sediments, with an average release rate of 2.67E-12 mol g-1 s-1. In the absence of phosphate, uranium release was controlled by dissolution of uranium oxyhydroxide (compreignacite-type) mineral with a release rate of 1.05-2.42E-10 mol g-1 s-1. The uranium mineralogy and release rates determined for both systems in this study support the development of accurate U-release models for prediction of contaminant transport. These results suggest that phosphate minerals may be a good candidate for uranium remediation approaches at contaminated sites.« less

  3. Uranium Release from Acidic Weathered Hanford Sediments: Single-Pass Flow-Through and Column Experiments.

    PubMed

    Wang, Guohui; Um, Wooyong; Wang, Zheming; Reinoso-Maset, Estela; Washton, Nancy M; Mueller, Karl T; Perdrial, Nicolas; O'Day, Peggy A; Chorover, Jon

    2017-10-03

    The reaction of acidic radioactive waste with sediments can induce mineral transformation reactions that, in turn, control contaminant fate. Here, sediment weathering by synthetic uranium-containing acid solutions was investigated using bench-scale experiments to simulate waste disposal conditions at Hanford's cribs (Hanford, WA). During acid weathering, the presence of phosphate exerted a strong influence over uranium mineralogy and a rapidly precipitated, crystalline uranium phosphate phase (meta-ankoleite [K(UO 2 )(PO 4 )·3H 2 O]) was identified using spectroscopic and diffraction-based techniques. In phosphate-free system, uranium oxyhydroxide minerals such as K-compreignacite [K 2 (UO 2 ) 6 O 4 (OH) 6 ·7H 2 O] were formed. Single-pass flow-through (SPFT) and column leaching experiments using synthetic Hanford pore water showed that uranium precipitated as meta-ankoleite during acid weathering was strongly retained in the sediments, with an average release rate of 2.67 × 10 -12 mol g -1 s -1 . In the absence of phosphate, uranium release was controlled by dissolution of uranium oxyhydroxide (compreignacite-type) mineral with a release rate of 1.05-2.42 × 10 -10 mol g -1 s -1 . The uranium mineralogy and release rates determined for both systems in this study support the development of accurate U-release models for the prediction of contaminant transport. These results suggest that phosphate minerals may be a good candidate for uranium remediation approaches at contaminated sites.

  4. The Acp26Aa seminal fluid protein is a modulator of early egg hatchability in Drosophila melanogaster.

    PubMed

    Chapman, T; Herndon, L A; Heifetz, Y; Partridge, L; Wolfner, M F

    2001-08-22

    Drosophila melanogaster male accessory gland proteins (Acps) that are transferred in the ejaculate with sperm mediate post-mating competition for fertilizations between males. The actions of Acps include effects on oviposition and ovulation, receptivity and sperm storage. Two Acps that modulate egg production are Acp26Aa (ovulin) and Acp70A (the sex peptide). Acp26Aa acts specifically on the process of ovulation (the release of mature eggs from the ovaries), which is initiated 1.5 h after mating. In contrast, sperm storage can take as long as 6-9 h to complete. Initial ovulations after matings by virgin females will therefore occur before all sperm are fully stored and the extra eggs initially laid as a result of Acp26Aa transfer are expected to be inefficiently fertilized. Acp26Aa-mediated release of existing eggs should not cause a significant energetic cost or lead to a decrease in female lifespan assuming, as seems likely, that the energetic cost of egg laying comes from de novo egg synthesis (oogenesis) rather than from ovulation. We tested these predictions using Acp26Aa(1) mutant males that lack Acp26Aa but are normal for other Acps and Acp26Aa(2) males that transfer a truncated but fully functional Acp26Aa protein. Females mating with Acp26Aa(2) (truncation) males that received functional Acp26Aa produced significantly more eggs following their first matings than did mates of Acp26Aa(1) (null) males. However, as predicted above, these extra eggs, which were laid as a result of Acp26Aa transfer to virgin females, showed significantly lower egg hatchability. Control experiments indicated that this lower hatchability was due to lower rates of fertilization at early post-mating times. There was no drop in egg hatchability in subsequent non-virgin matings. In addition, as predicted above, females that did or did not receive Acp26Aa did not differ in survival, lifetime fecundity or lifetime progeny, indicating that Acp26Aa transfer does not represent a

  5. Laser-triggered release of encapsulated molecules from polylactic-co-glycolic acid microcapsules

    NASA Astrophysics Data System (ADS)

    Ariyasu, Kazumasa; Ishii, Atsuhiro; Umemoto, Taiga; Terakawa, Mitsuhiro

    2016-08-01

    The controlled release of encapsulated molecules from a microcapsule is a promising method of targeted drug delivery. Laser-triggered methods for the release of encapsulated molecules have the advantage of spatial and temporal controllability. In this study, we demonstrated the release of encapsulated molecules from biodegradable polymer-based microcapsules using near-infrared femtosecond laser pulses. The polylactic-co-glycolic acid microcapsules encapsulating fluorescein isothiocyanate-dextran molecules were fabricated using a dual-coaxial nozzle system. Irradiation of femtosecond laser pulses enhanced the release of the molecules from the microcapsules, which was accompanied by a decrease in the residual ratio of the microcapsules. The laser-induced modification of the surface of the shell of the microcapsules indicated the potential for sustained release as well as burst release.

  6. Ruminal bacteria and protozoa composition, digestibility, and amino acid profile determined by multiple hydrolysis times.

    PubMed

    Fessenden, S W; Hackmann, T J; Ross, D A; Foskolos, A; Van Amburgh, M E

    2017-09-01

    Microbial samples from 4 independent experiments in lactating dairy cattle were obtained and analyzed for nutrient composition, AA digestibility, and AA profile after multiple hydrolysis times ranging from 2 to 168 h. Similar bacterial and protozoal isolation techniques were used for all isolations. Omasal bacteria and protozoa samples were analyzed for AA digestibility using a new in vitro technique. Multiple time point hydrolysis and least squares nonlinear regression were used to determine the AA content of omasal bacteria and protozoa, and equivalency comparisons were made against single time point hydrolysis. Formalin was used in 1 experiment, which negatively affected AA digestibility and likely limited the complete release of AA during acid hydrolysis. The mean AA digestibility was 87.8 and 81.6% for non-formalin-treated bacteria and protozoa, respectively. Preservation of microbe samples in formalin likely decreased recovery of several individual AA. Results from the multiple time point hydrolysis indicated that Ile, Val, and Met hydrolyzed at a slower rate compared with other essential AA. Singe time point hydrolysis was found to be nonequivalent to multiple time point hydrolysis when considering biologically important changes in estimated microbial AA profiles. Several AA, including Met, Ile, and Val, were underpredicted using AA determination after a single 24-h hydrolysis. Models for predicting postruminal supply of AA might need to consider potential bias present in postruminal AA flow literature when AA determinations are performed after single time point hydrolysis and when using formalin as a preservative for microbial samples. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Liquid-Phase Heat-Release Rates of the Systems Hydrazine-Nitric Acid and Unsymmetrical Dimethylhydrazine-Nitric Acid

    NASA Technical Reports Server (NTRS)

    Somogyi, Dezso; Feiler, Charles E.

    1960-01-01

    The initial rates of heat release produced by the reactions of hydrazine and unsymmetrical dimethylhydrazine with nitric acid were determined in a bomb calorimeter under conditions of forced mixing. Fuel-oxidant weight ratio and injection velocity were varied. The rate of heat release apparently depended on the interfacial area between the propellants. Above a narrow range of injection velocities representing a critical amount of interfacial area, the rates reached a maximum and were almost constant with injection velocity. The maximum rate for hydrazine was about 70 percent greater than that for unsymmetrical dimethylhydrazine. The total heat released did not vary with mixture ratio over the range studied.

  8. Oxidative potential of ambient water-soluble PM2.5 in the southeastern United States: contrasts in sources and health associations between ascorbic acid (AA) and dithiothreitol (DTT) assays

    NASA Astrophysics Data System (ADS)

    Fang, Ting; Verma, Vishal; Bates, Josephine T.; Abrams, Joseph; Klein, Mitchel; Strickland, Matthew J.; Sarnat, Stefanie E.; Chang, Howard H.; Mulholland, James A.; Tolbert, Paige E.; Russell, Armistead G.; Weber, Rodney J.

    2016-03-01

    The ability of certain components of particulate matter to induce oxidative stress through the generation of reactive oxygen species (ROS) in vivo may be one mechanism accounting for observed linkages between ambient aerosols and adverse health outcomes. A variety of assays have been used to measure this so-called aerosol oxidative potential. We developed a semi-automated system to quantify oxidative potential of filter aqueous extracts utilizing the dithiothreitol (DTT) assay and report here the development of a similar semi-automated system for the ascorbic acid (AA) assay. Approximately 500 PM2.5 filter samples collected in contrasting locations in the southeastern US were analyzed for a host of aerosol species, along with AA and DTT activities. We present a detailed contrast in findings from these two assays. Water-soluble AA activity was higher in summer and fall than in winter, with highest levels near heavily trafficked highways, whereas DTT activity was higher in winter compared to summer and fall and more spatially homogeneous. AA activity was nearly exclusively correlated with water-soluble Cu (r = 0.70-0.94 at most sites), whereas DTT activity was correlated with organic and metal species. Source apportionment models, positive matrix factorization (PMF) and a chemical mass balance method with ensemble-averaged source impact profiles (CMB-E), suggest a strong contribution from traffic emissions and secondary processes (e.g., organic aerosol oxidation or metals mobilization by secondary acids) to both AA and DTT activities in urban Atlanta. In contrast, biomass burning was a large source for DTT activity, but insignificant for AA. AA activity was not correlated with PM2.5 mass, while DTT activity co-varied strongly with mass (r = 0.49-0.86 across sites and seasons). Various linear models were developed to estimate AA and DTT activities for the central Atlanta Jefferson Street site, based on the CMB-E sources. The models were then used to estimate daily

  9. Flavonoids preservation and release by methacrylic acid-grafted (N-vinyl-pyrrolidone).

    PubMed

    Parisi, Ortensia Ilaria; Puoci, Francesco; Iemma, Francesca; Curcio, Manuela; Cirillo, Giuseppe; Spizzirri, Umile Gianfranco; Picci, Nevio

    2013-01-01

    Flavonoids preservation and release. Synthesis of a polymeric material able to prevent thermal and photo degradation of a flavonoid model compound, such as (+)-catechin, and suitable for a controlled/sustained delivery of this molecule in gastro-intestinal simulating fluids. Methacrylic acid (MAA) was grafted onto poly(N-vinyl-pyrrolidone) (PVP) by a free radical grafting procedure involving a single-step reaction at room temperature. For this purpose, hydrogen peroxide/ascorbic acid redox pair was employed as water-soluble and biocompatible initiator system. FT-IR spectra confirmed the insertion of MAA onto the polymeric chain. Stability studies, performed under various conditions, such as freeze-thaw cycles, exposure to strong light, thermal stability studies under constant humidity and with light protection at different temperatures, showed the preservative properties of the polymeric material towards flavonoids. Furthermore, the biocompatibility was highlighted by Hen's Egg Test-Chorioallantoic Membrane assay and in vitro release studies demonstrated the possibility to employ PVP-MAA copolymer as a device for gastro-intestinal release of flavonoids. The coupling of good preservative properties together with biocompatibility and the usefulness as carrier in controlled release make this kind of material very interesting from an industrial point of view for different applications in food, pharmaceutical, and cosmetic fields.

  10. Laboratory study on the behaviour of spent AA household alkaline batteries in incineration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Almeida, Manuel F.; Xara, Susana M.; Delgado, Julanda

    2009-01-15

    The quantitative evaluation of emissions from incineration is essential when Life Cycle Assessment (LCA) studies consider this process as an end-of-life solution for some wastes. Thus, the objective of this work is to quantify the main gaseous emissions produced when spent AA alkaline batteries are incinerated. With this aim, batteries were kept for 1 h at 1273 K in a refractory steel tube hold in a horizontal electric furnace with temperature control. At one end of the refractory steel tube, a constant air flow input assures the presence of oxygen in the atmosphere and guides the gaseous emissions to amore » filter system followed by a set of two bubbler flasks having an aqueous solution of 10% (v/v) nitric acid. After each set of experiments, sulphur, chlorides and metals (As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Sb, Tl and Zn) were analyzed in both the solutions obtained from the steel tube washing and from the bubblers. Sulphur, chlorides and metals were quantified, respectively, using barium sulfate gravimetry, the Volhard method and atomic absorption spectrometry (AAS). The emissions of zinc, the most emitted metal, represent about 6.5% of the zinc content in the batteries. Emissions of manganese (whose oxide is the main component of the cathode) and iron (from the cathode collector) are negligible when compared with their amount in AA alkaline batteries. Mercury is the metal with higher volatility in the composition of the batteries and was collected even in the second bubbler flask. The amount of chlorides collected corresponds to about 36% of the chlorine in the battery sleeve that is made from PVC. A considerable part of the HCl formed in PVC plastic sleeve incineration is neutralized with KOH, zinc and manganese oxides and, thus, it is not totally released in the gas. Some of the emissions are predictable through a thermodynamic data analysis at temperatures in the range of 1200-1300 K taking into account the composition of the batteries. This analysis

  11. Associations With Eicosapentaenoic Acid to Arachidonic Acid Ratio and Mortality in Hospitalized Heart Failure Patients.

    PubMed

    Watanabe, Shunsuke; Yoshihisa, Akiomi; Kanno, Yuki; Takiguchi, Mai; Yokokawa, Tetsuro; Sato, Akihiko; Miura, Shunsuke; Shimizu, Takeshi; Abe, Satoshi; Sato, Takamasa; Suzuki, Satoshi; Oikawa, Masayoshi; Sakamoto, Nobuo; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-Ichi; Takeishi, Yasuchika

    2016-12-01

    Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) lowers the risk of atherosclerotic cardiovascular events, particularly ischemic heart disease. In addition, the ratio of eicosapentaenoic acid (EPA; n-3 PUFA) to arachidonic acid (AA; n-6 PUFA) has recently been recognized as a risk marker of cardiovascular disease. In contrast, the prognostic impact of the EPA/AA ratio on patients with heart failure (HF) remains unclear. A total of 577 consecutive patients admitted for HF were divided into 2 groups based on median of the EPA/AA ratio: low EPA/AA (EPA/AA <0.32 mg/dl, n = 291) and high EPA/AA (EPA/AA ≥0.32, n = 286) groups. We compared laboratory data and echocardiographic findings and followed cardiac mortality. Although body mass index, blood pressure, B-type natriuretic peptide, hemoglobin, estimated glomerular filtration rate, total protein, albumin, sodium, C-reactive protein, and left ventricular ejection fraction did not differ between the 2 groups, cardiac mortality was significantly higher in the low EPA/AA group than in the high EPA/AA group (12.7 vs 5.9%, log-rank P = .004). Multivariate Cox proportional hazard analysis revealed that the EPA/AA ratio was an independent predictor of cardiac mortality (hazard ratio 0.677, 95% confidence interval 0.453-0.983, P = .041) in patients with HF. The EPA/AA ratio was an independent predictor of cardiac mortality in patients with HF; therefore, the prognosis of patients with HF may be improved by taking appropriate management to control the EPA/AA balance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins.

    PubMed

    Gan, Rui; Perez, Jessica G; Carlson, Erik D; Ntai, Ioanna; Isaacs, Farren J; Kelleher, Neil L; Jewett, Michael C

    2017-05-01

    The ability to site-specifically incorporate non-canonical amino acids (ncAAs) into proteins has made possible the study of protein structure and function in fundamentally new ways, as well as the bio synthesis of unnatural polymers. However, the task of site-specifically incorporating multiple ncAAs into proteins with high purity and yield continues to present a challenge. At the heart of this challenge lies the lower efficiency of engineered orthogonal translation system components compared to their natural counterparts (e.g., translation elements that specifically use a ncAA and do not interact with the cell's natural translation apparatus). Here, we show that evolving and tuning expression levels of multiple components of an engineered translation system together as a whole enhances ncAA incorporation efficiency. Specifically, we increase protein yield when incorporating multiple p-azido-phenylalanine(pAzF) residues into proteins by (i) evolving the Methanocaldococcus jannaschii p-azido-phenylalanyl-tRNA synthetase anti-codon binding domain, (ii) evolving the elongation factor Tu amino acid-binding pocket, and (iii) tuning the expression of evolved translation machinery components in a single vector. Use of the evolved translation machinery in a genomically recoded organism lacking release factor one enabled enhanced multi-site ncAA incorporation into proteins. We anticipate that our approach to orthogonal translation system development will accelerate and expand our ability to site-specifically incorporate multiple ncAAs into proteins and biopolymers, advancing new horizons for synthetic and chemical biotechnology. Biotechnol. Bioeng. 2017;114: 1074-1086. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Aa Ah Nak

    ERIC Educational Resources Information Center

    Tha, Na Gya; Wus, Thay

    2017-01-01

    In this article, Aa Ah Nak, the authors' methodology presents not only various reflections but also diverse contradictions about the Aa Nii language as well as language revitalization. This article explores language foundation and how the Aa Nii language revitalization is inextricably linked to the genocide and resulting historic trauma pervasive…

  14. Data on the effect of oral feeding of Arachidonic acid or Docosahexanoic acid on haematopoiesis in mice.

    PubMed

    Limbkar, Kedar; Dhenge, Ankita; Jadhav, Dipesh D; Thulasiram, Hirekodathakallu V; Kale, Vaijayanti; Limaye, Lalita

    2017-10-01

    Stem cells have peculiar property to self-renew and differentiate. It is important to control their fate in safe and effective ways for their therapeutic use. The mediators of essential polyunsaturated fatty acids (PUFAs) namely Arachidonic acid (AA) and Docosahexanoic acid (DHA) are known to play a role in haematopoiesis via various metabolic pathways [1]. However the direct effect of purified AA or DHA on haematopoiesis has not been well investigated yet. We have reported that oral administration of PUFAs enhanced haematopoiesis in mice [2]. Signaling Leukocyte Antigen Molecule (SLAM) (CD48 - CD150 + ) phenotype consists of pure population of haematopoietic stem cells (HSCs). Herein we observed higher percentage of SLAM (CD48 - CD150 + ) phenotype in the bone marrow (BM) cells of mice fed with AA or DHA compared to PBS fed control mice. Data from engraftment study depicts that BM from AA/DHA-fed mice showed higher absolute number of donor cells in recipient mice compared to control. The enhanced hematopoiesis observed in AA/DHA-fed mice was returned to normal when the mice were kept on normal diet for six weeks (after ten days of oral feeding). We confirmed GCMS (Gas Chromatography-Mass Spectroscopy) retention times of AA and DHA by co-injecting fatty acid extract from AA or DHA fed mice with purified AA or DHA standards respectively. Representative flow cytometry profile of Lin - Sca-1 + c-kit + (LSK) cells showed higher expression of CXCR4 protein and ligands of Wnt, Notch1 signaling in BM of AA/DHA-fed mice.

  15. Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

    PubMed Central

    Stroup, Bridget M.; Sawin, Emily A.; Murali, Sangita G.; Binkley, Neil; Hansen, Karen E.

    2017-01-01

    Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258. PMID:28546877

  16. Oxidative potential of ambient water-soluble PM2.5 measured by Dithiothreitol (DTT) and Ascorbic Acid (AA) assays in the southeastern United States: contrasts in sources and health associations

    NASA Astrophysics Data System (ADS)

    Fang, T.; Verma, V.; Bates, J. T.; Abrams, J.; Klein, M.; Strickland, M. J.; Sarnat, S. E.; Chang, H. H.; Mulholland, J. A.; Tolbert, P. E.; Russell, A. G.; Weber, R. J.

    2015-11-01

    The ability of certain components of particulate matter to induce oxidative stress through catalytic generation of reactive oxygen species (ROS) in vivo may be one mechanism accounting for observed linkages between ambient aerosols and adverse health outcomes. A variety of assays have been used to measure this so-called aerosol oxidative potential. We developed a semi-automated system to quantify oxidative potential of filter aqueous extracts utilizing the dithiothreitol (DTT) assay and have recently developed a similar semi-automated system using the ascorbic acid (AA) assay. Approximately 500 PM2.5 filter samples collected in contrasting locations in the southeastern US were analyzed using both assays. We found that water-soluble DTT activity on a per air volume basis was more spatially uniform than water-soluble AA activity. DTT activity was higher in winter than in summer/fall, whereas AA activity was higher in summer/fall compared to winter, with highest levels near highly trafficked highways. DTT activity was correlated with organic and metal species, whereas AA activity was correlated with water-soluble metals (especially water-soluble Cu, r=0.70-0.91 at most sites). Source apportionment models, Positive Matrix Factorization (PMF) and a Chemical Mass Balance Method with ensemble-averaged source impact profiles (CMB-E), suggest a strong contribution from secondary processes (e.g., organic aerosol oxidation or metal mobilization by formation of an aqueous particle with secondary acids) and traffic emissions to both DTT and AA activities in urban Atlanta. Biomass burning was a large source for DTT activity, but insignificant for AA. DTT activity was well correlated with PM2.5 mass (r=0.49-0.86 across sites/seasons), while AA activity did not co-vary strongly with mass. A linear model was developed to estimate DTT and AA activities for the central Atlanta Jefferson Street site, based on the CMB-E sources that are statistically significant with positive

  17. Phosphatidic acid (PA) binds PP2AA1 to regulate PP2A activity and PIN1 polar localization.

    PubMed

    Gao, Hong-Bo; Chu, Yu-Jia; Xue, Hong-Wei

    2013-09-01

    Phospholipase D (PLD) exerts broad biological functions in eukaryotes through regulating downstream effectors by its product, phosphatidic acid (PA). Protein kinases and phosphatases, such as mammalian target of rapamycin (mTOR), Protein Phosphatase 1 (PP1) and Protein Phosphatase 2C (PP2C), are PA-binding proteins that execute crucial regulatory functions in both animals and plants. PA participates in many signaling pathways by modulating the enzymatic activity and/or subcellular localization of bound proteins. In this study, we demonstrated that PLD-derived PA interacts with the scaffolding A1 subunit of Protein Phosphatase 2A (PP2A) and regulates PP2A-mediated PIN1 dephosphorylation in Arabidopsis. Genetic and pharmacological studies showed that both PA and PP2A participate in the regulation of auxin distribution. In addition, both the phosphorylation status and polar localization of PIN1 protein were affected by PLD inhibitors. Exogenous PA triggered the membrane accumulation of PP2AA1 and enhanced the PP2A activity at membrane, while PLD inhibition resulted in the reduced endosomal localization and perinuclear aggregation of PP2AA1. These results demonstrate the important role of PLD-derived PA in normal PP2A-mediated PIN dephosphorylation and reveal a novel mechanism, in which PA recruits PP2AA1 to the membrane system and regulates PP2A function on membrane-targeted proteins. As PA and PP2A are conserved among eukaryotes, other organisms might use similar mechanisms to mediate multiple biological processes.

  18. Chronic nicotine exposure selectively activates a carrier-mediated release of endogenous glutamate and aspartate from rat hippocampal synaptosomes.

    PubMed

    Marchi, Mario; Zappettini, Stefania; Olivero, Guendalina; Pittaluga, Anna; Grilli, Massimo

    2012-05-01

    The effect of chronic nicotine treatment on the release of endogenous glutamate (GLU), aspartate (ASP) and GABA evoked in vitro by KCl, 4-aminopyridine (4AP) and nicotinic agonists in synaptosomes of rat hippocampus was investigated. Rats were chronically administered with nicotine bitartrate or saline vehicle each for 14 days using osmotic mini-pumps. Hippocampal synaptosomes were stimulated with KCl, 4AP, nicotine or with choline (Ch) and 5-iodo-A-85380 dihydrochloride (5IA85380). The GLU and ASP overflow evoked by Ch, nicotine, KCl and 4AP were increased in treated animals while the nicotine-evoked GABA overflow was reduced and that evoked by Ch, KCl and 4AP was unaffected. The 5IA85380-evoked overflow of the three aminoacids (AAs) was always reduced. The increase of ASP and GLU overflow evoked by KCl, 4AP or Ch was blocked by dl-threo-β-benzyloxyaspartic acid (dl-TBOA), a carrier transporter inhibitor, and by inhibitors of the Na(+)/Ca(2+) exchangers 2-[[4-[(4-nitrophenyl)methoxy]phenyl]methyl]-4-thiazolidinecarboxylic acid ethyl ester (SN-6) and 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea mesylate (KB-R7943). In conclusion long-term nicotine treatment may selectively increase GLU and ASP overflow elicited by KCl, 4AP and Ch through the activation of a carrier-mediated release mechanism and completely abolished the stimulatory effects of α4β2 nAChRs which modulate the release of all the three AA. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. HCOOH-induced Controlled-release Hydrolysis of Microalgae (Scenedesmus) to Lactic Acid over Sn-Beta Catalyst.

    PubMed

    Zan, Yifan; Sun, Yuanyuan; Kong, Lingzhao; Miao, Gai; Bao, Liwei; Wang, Hao; Li, Shenggang; Sun, Yuhan

    2018-06-12

    Formic acid induced controlled-release hydrolysis of sugar-rich microalgae (Scenedesmus) over the Sn-Beta catalyst was found to be a highly efficient process for producing lactic acid as a platform chemical. One-pot reaction with a very high lactic acid yield of 83.0% was realized in a batch reactor using water as the solvent. Under the attack of formic acid, the cell wall of Scenedesmus was disintegrated, and hydrolysis of the starch inside the cell was strengthened in a controlled-release mode, resulting in a stable and relatively low glucose concentration. Subsequently, the Sn-Beta catalyst was employed for the efficient conversion of glucose into lactic acid with stable catalytic performance through isomerization, retro-aldol and de-/rehydration reactions. Thus, the hydrolysis of polysaccharides and the catalytic conversion of the monosaccharide into lactic acid was realized by the synergy between an organic Brønsted acid and a heterogeneous Lewis acid catalyst. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Altered macrophage arachidonic acid metabolism induced by endotoxin tolerance: characterization and mechanisms

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rogers, T.S.

    Altered macrophage arachidonic acid (AA) metabolism may play a role in endotoxic shock and the phenomenon of endotoxin tolerance induced by repeated injections of endotoxin. Studies were initiated to characterize both lipoxygenase and cyclooxygenase metabolite formation by endotoxin tolerant and non-tolerant macrophages in response to 4 different stimuli, i.e., endotoxin, glucan, zymosan, and the calcium ionophore A23187. In contrast to previous reports of decreased prostaglandin synthesis by tolerant macrophages, A23187-stimulated immunoreactive (i) leukotriene (LT) C/sub 4/D/sub 4/ and prostaglandin (PG) E/sub 2/ production by tolerant cells was greater than that by non-tolerant controls (p <0.001). However, A23187-stimulated i6-keto PGF/sub 1a/more » levels were lower in tolerant macrophages compared to controls (P < 0.05). iL TC/sub 4/D/sub 4/ production was not significantly stimulated by endotoxin or glucan, but was stimulated by zymosan in non-tolerant cells. Synthesis of iLTB/sub 4/ by control macrophages was stimulated by endotoxin (p <0.01). The effect of tolerance on factors that affect AA release was investigated by measuring /sup 14/C-AA incorporation and release and phospholipase A/sub 2/ activity« less

  1. Development of Poly Lactic/Glycolic Acid (PLGA) Microspheres for Controlled Release of Rho-Associated Kinase Inhibitor.

    PubMed

    Koda, Sho; Okumura, Naoki; Kitano, Junji; Koizumi, Noriko; Tabata, Yasuhiko

    2017-01-01

    The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA) as a drug delivery carrier of Rho kinase (ROCK) inhibitor for the treatment of corneal endothelial disease. ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1), and a double emulsion [(W1/O)/W2] was formed with dichloromethane (O) and polyvinyl alcohol (W2). Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography. PLGA was injected into the anterior chamber or subconjunctiva in rabbit eyes, and ocular complication was evaluated by slitlamp microscope and histological analysis. Y-27632 incorporated PLGA microspheres with different molecular weights, and different composition ratios of lactic acid and glycolic acid were fabricated. A high molecular weight and low content of glycolic acid produced a slower and longer release. The Y-27632 released from PLGA microspheres significantly promoted the cell proliferation of cultured corneal endothelial cells. The injection of PLGA did not induce any evident eye complication. ROCK inhibitor-incorporated PLGA microspheres were fabricated, and the microspheres achieved the sustained release of ROCK inhibitor over 7-10 days in vitro. Our data should encourage researchers to use PLGA microspheres for treating corneal endothelial diseases.

  2. A study of marine pollution caused by the release of metals into seawater following acid spills.

    PubMed

    Cabon, Jean-Yves; Giamarchi, Philippe; Le Floch, Stephane

    2010-07-01

    This study examined the potential metal pollution induced by the accidental spill of different acids into seawater. The acids sink to the bottom according to their densities and subsequently react with marine sediments. The acids selected for this study were acetic, hydrochloric, nitric, sulfuric, and phosphoric acids; the metallic elements selected were Cr, Cu, Fe, Mn, Pb and Zn. The sediment was collected in Brest Harbour. The percentages of metals released from this sediment in the presence of various concentrations of acids in seawater were important; concentrations of approximately 7 mg L(-1) for Mn and 60 mg L(-1) for Zn were observed under our experimental conditions. We also examined the rate of release of these metals from the sediment into the seawater in the presence of the different acids and under different experimental conditions. We found that most of the metallic elements were released from the sediments into the seawater during the first fifteen minutes of exposure. After this time, a high degree of pollution was induced if acids leached into seawater were not rapidly diluted. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Analysis of abietic acid and dehydroabietic acid residues in raw ducks and cooked ducks.

    PubMed

    Zhu, Yongzhi; Zhang, Suzhen; Geng, Zhiming; Wang, Daoying; Liu, Fang; Zhang, Muhan; Bian, Huan; Xu, Weimin

    2014-10-01

    Rosin was once widely used for removal of duck feathers in China and is still being used secretly in some poultry processing enterprises. Abietic acid (AA) and dehydroabietic acid (DHAA) are the major compounds of rosin. In the present study, 90 duck samples were collected for investigation of AA and DHAA residues. Abietic acid and DHAA were simultaneously detected in 13 out 40 raw ducks, 8 out of 26 water-boiled salted ducks, and 7 out of 24 roasted ducks, respectively. In positive samples, averages of AA were significantly higher than those of DHAA in positive samples of the 3 types of ducks (P < 0.05). Averages of AA and DHAA in positive raw ducks were significantly higher than those in positive roasted ducks (P < 0.05). The results indicated that almost one-third of raw ducks were defeathered by means of rosin-containing defeathering agent, and cooking processes could reduce the AA and DHAA residues to some extent, but could not eliminate them completely. ©2014 Poultry Science Association Inc.

  4. Stimuli responsive charge-switchable lipids: Capture and release of nucleic acids.

    PubMed

    Hersey, Joseph S; LaManna, Caroline M; Lusic, Hrvoje; Grinstaff, Mark W

    2016-03-01

    Stimuli responsive lipids, which enable control over the formation, transformation, and disruption of supramolecular assemblies, are of interest for biosensing, diagnostics, drug delivery, and basic transmembrane protein studies. In particular, spatiotemporal control over a supramolecular structure can be achieved using light activated compounds to induce significant supramolecular rearrangements. As such, a family of cationic lipids are described which undergo a permanent switch in charge upon exposure to 365 nm ultraviolet (UV) light to enable the capture of negatively charged nucleic acids within the self-assembled supramolecular structure of the lipids and subsequent release of these macromolecules upon exposure to UV light and disruption of the assemblies. The lipids are composed of either two different tripeptide head groups, Lysine-Glycine-Glycine (KGG) and Glycine-Glycine-Glycine (GGG) and three different hydrocarbon chain lengths (C6, C10, or C14) terminated by a UV light responsive 1-(2-nitrophenyl)ethanol (NPE) protected carboxylic acid. The photolysis of the NPE protected lipid is measured as a function of time, and the resulting changes in net molecular charge are observed using zeta potential analysis for each head group and chain length combination. A proof of concept study for the capture and release of both linear DNA (calf thymus) and siRNA is presented using an ethidium bromide quenching assay where a balance between binding affinity and supramolecular stability are found to be the key to optimal nucleic acid capture and release. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Portable electrochemical sensor based on 4-aminobenzoic acid-functionalized herringbone carbon nanotubes for the determination of ascorbic acid and uric acid in human fluids.

    PubMed

    Abellán-Llobregat, A; González-Gaitán, C; Vidal, L; Canals, A; Morallón, E

    2018-06-30

    A new portable electrochemical sensor based on 4-aminobenzoic acid-modified herringbone carbon nanotubes (hCNTs-4ABA/Au-IDA) has been developed for the simultaneous determination of ascorbic acid (AA) and uric acid (UA) in physiological fluids. AA and UA were quantified by chronoamperometry at 0.1 and 0.32 V, respectively, in phosphate buffer solution (PBS 0.25 M, pH 7.0). Significant results were obtained for the separate quantification of AA and UA, with a limit of detection (LOD) of 0.65 μM for both analytes, and sensitivities of (9.0 ± 0.4) A g -1 mM -1 and (8.8 ± 0.3) A g -1 mM -1 for AA and UA, respectively. Repeatability was studied at 50 μM for AA and UA, providing relative standard deviations (RSD) lower than 9%. Additions of glucose, dopamine and epinephrine did not interfere with the AA and UA determination. Furthermore, UA did not interfere with AA determination at 0.1 V, although AA additions increased the current recorded at 0.32 V. The method has been successfully applied to human urine, perspiration and serum samples, without significant matrix effects, which allows for the use of an external calibration and the analysis of all the matrices investigated. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Release of Polyphenols Is the Major Factor Influencing the Bioconversion of Rice Straw to Lactic Acid.

    PubMed

    Chen, Xingxuan; Xue, Yiyun; Hu, Jiajun; Tsang, Yiu Fai; Gao, Min-Tian

    2017-11-01

    In this study, we found that p-coumaric acid (p-CA), ferulic acid (FA), and condensed tannins were released from rice straw during saccharification. The presence of polyphenols prolonged the lag phase and lowered the productivity of lactic acid. p-CA was identified as a key inhibitor. Tannins had a lower inhibitory effect than p-CA; FA had little inhibitory effect. Acid, alkaline, and ball milling pretreatments elicited different levels of polyphenol release from rice straw. Due to the different levels of polyphenol release in the pretreatment step, the enzymatic hydrolysates contained different concentrations of polyphenols. Compared with fermentation with a synthetic medium, fermentation with the hydrolysates of ball-milled rice straw provided much lower productivity and yield of lactic acid due to the presence of polyphenols. Removal of these compounds played an important role in lactic acid fermentation. When rice straw was alkaline pretreated, the hydrolysates contained few phenolic compounds, resulting in high productivity and yield of lactic acid (1.8 g/L/h and 26.7 g/100 g straw), which were comparable to those in a synthetic medium. This indicates that there is a correlation between removal of phenolic compounds and efficiency in lactic acid fermentation.

  7. Carbon-11 and Fluorine-18 Labeled Amino Acid Tracers for Positron Emission Tomography Imaging of Tumors

    NASA Astrophysics Data System (ADS)

    Sun, Aixia; Liu, Xiang; Tang, Ganghua

    2017-12-01

    Tumor cells have an increased nutritional demand for amino acids(AAs) to satisfy their rapid proliferation. Positron-emitting nuclide labeled AAs are interesting probes and are of great importance for imaging tumors using positron emission tomography (PET). Carbon-11 and fluorine-18 labeled AAs include the [1-11C] amino acids, labeling alpha-C- amino acids, the branched-chain of amino acids and N-substituted carbon-11 labeled amino acids. These tracers target protein synthesis or amino acid(AA) transport, and their uptake mechanism mainly involves AA transport. AA PET tracers have been widely used in clinical settings to image brain tumors, neuroendocrine tumors, prostate cancer, breast cancer, non–small cell lung cancer (NSCLC) and hepatocellular carcinoma. This review focuses on the fundamental concepts and the uptake mechanism of AAs, AA PET tracers and their clinical applications.

  8. Effect of low-molecular-weight organic acids on kinetics release and fractionation of phosphorus in some calcareous soils of western Iran.

    PubMed

    Taghipour, M; Jalali, M

    2013-07-01

    Organic acid has been related to nutrient mobilization, mainly in phosphorus (P) insoluble utilization, and therefore enhances P bioavailability. In this study, we examined the effect of low-molecular-weight organic acids (malic, citric, and oxalic acids) on P release of some calcareous soils from western Iran. Fractionation and speciation of P in the soil solution were studied at the initial and final P release. Significantly different quantities of P were extracted by the organic acids. On average the maximum (1,554.9 mg kg(-1)) and the minimum (1,260.5 mg kg(-1)) P were extracted by 10 mM oxalic and malic acid, respectively. Power equation described well P release. In the initial stage of P release, the solution samples in soils were supersaturated with respect to hydroxyapatite and β-TCP. At the end of P release, all solutions were undersaturated with phosphate minerals. The percentage of Fe-Al oxide fraction generally increased after P release, while carbonate and residual P fractions were decreased in all organic acids. Compared with the native soils, adding malic and citric acids had no effect on Fe-Al oxide fraction, but oxalic acid significantly reduced this fraction.

  9. Inhibition by somatostatin (growth-hormone release-inhibiting hormone, GH-RIH) of gastric acid and pepsin and G-cell release of gastrin.

    PubMed Central

    Barros D'sa, A A; Bloom, S R; Baron, J H

    1978-01-01

    Somatostatin (cyclic growth-hormone release-inhibiting hormone--GH-RIH) was infused into dogs with gastric fistulae. Somatostatin inhibited gastric acid response to four gastric stimulants--insulin, food, histamine, and pentagastrin. Histamine- and pentagastrin-stimulated pepsins were inhibited similarly to inhibition of acid. Somatostatin inhibited the gastrin response to insulin and food. PMID:348581

  10. Release of free amino acids upon oxidation of peptides and proteins by hydroxyl radicals.

    PubMed

    Liu, Fobang; Lai, Senchao; Tong, Haijie; Lakey, Pascale S J; Shiraiwa, Manabu; Weller, Michael G; Pöschl, Ulrich; Kampf, Christopher J

    2017-03-01

    Hydroxyl radical-induced oxidation of proteins and peptides can lead to the cleavage of the peptide, leading to a release of fragments. Here, we used high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) and pre-column online ortho-phthalaldehyde (OPA) derivatization-based amino acid analysis by HPLC with diode array detection and fluorescence detection to identify and quantify free amino acids released upon oxidation of proteins and peptides by hydroxyl radicals. Bovine serum albumin (BSA), ovalbumin (OVA) as model proteins, and synthetic tripeptides (comprised of varying compositions of the amino acids Gly, Ala, Ser, and Met) were used for reactions with hydroxyl radicals, which were generated by the Fenton reaction of iron ions and hydrogen peroxide. The molar yields of free glycine, aspartic acid, asparagine, and alanine per peptide or protein varied between 4 and 55%. For protein oxidation reactions, the molar yields of Gly (∼32-55% for BSA, ∼10-21% for OVA) were substantially higher than those for the other identified amino acids (∼5-12% for BSA, ∼4-6% for OVA). Upon oxidation of tripeptides with Gly in C-terminal, mid-chain, or N-terminal positions, Gly was preferentially released when it was located at the C-terminal site. Overall, we observe evidence for a site-selective formation of free amino acids in the OH radical-induced oxidation of peptides and proteins, which may be due to a reaction pathway involving nitrogen-centered radicals.

  11. ARISTOLOCHIC ACID I METABOLISM IN THE ISOLATED PERFUSED RAT KIDNEY

    PubMed Central

    Priestap, Horacio A.; Torres, M. Cecilia; Rieger, Robert A.; Dickman, Kathleen G.; Freshwater, Tomoko; Taft, David R.; Barbieri, Manuel A.; Iden, Charles R.

    2012-01-01

    Aristolochic acids are natural nitro-compounds found globally in the plant genus Aristolochia that have been implicated in the severe illness in humans termed aristolochic acid nephropathy (AAN). Aristolochic acids undergo nitroreduction, among other metabolic reactions, and active intermediates arise that are carcinogenic. Previous experiments with rats showed that aristolochic acid I (AA-I), after oral administration or injection, is subjected to detoxication reactions to give aristolochic acid Ia, aristolactam Ia, aristolactam I and their glucuronide and sulfate conjugates that can be found in urine and faeces. Results obtained with whole rats do not clearly define the role of liver and kidney in such metabolic transformation. In this study, in order to determine the specific role of the kidney on the renal disposition of AA-I and to study the biotransformations suffered by AA-I in this organ, isolated kidneys of rats were perfused with AA-I. AA-I and metabolite concentrations were determined in perfusates and urines using HPLC procedures. The isolated perfused rat kidney model showed that AA-I distributes rapidly and extensively in kidney tissues by uptake from the peritubular capillaries and the tubules. It was also established that the kidney is able to metabolize AA-I into aristolochic acid Ia, aristolochic acid Ia O-sulfate, aristolactam Ia, aristolactam I and aristolactam Ia O-glucuronide. Rapid demethylation and sulfation of AA-I in the kidney generate aristolochic acid Ia and its sulfate conjugate that are voided to the urine. Reduction reactions to give the aristolactam metabolites occur to a slower rate. Renal clearances showed that filtered AA-I is reabsorbed at the tubules whereas the metabolites are secreted. The unconjugated metabolites produced in the renal tissues are transported to both urine and perfusate whereas the conjugated metabolites are almost exclusively secreted to the urine. PMID:22118289

  12. AAS Publishing News: Astronomical Software Citation Workshop

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-07-01

    Do you write code for your research? Use astronomical software? Do you wish there were a better way of citing, sharing, archiving, or discovering software for astronomy research? You're not alone! In April 2015, AAS's publishing team joined other leaders in the astronomical software community in a meeting funded by the Sloan Foundation, with the purpose of discussing these issues and potential solutions. In attendance were representatives from academic astronomy, publishing, libraries, for-profit software sharing platforms, telescope facilities, and grantmaking institutions. The goal of the group was to establish “protocols, policies, and platforms for astronomical software citation, sharing, and archiving,” in the hopes of encouraging a set of normalized standards across the field. The AAS is now collaborating with leaders at GitHub to write grant proposals for a project to develop strategies for software discoverability and citation, in astronomy and beyond. If this topic interests you, you can find more details in this document released by the group after the meeting: http://astronomy-software-index.github.io/2015-workshop/ The group hopes to move this project forward with input and support from the broader community. Please share the above document, discuss it on social media using the hashtag #astroware (so that your conversations can be found!), or send private comments to julie.steffen@aas.org.

  13. An investigation into the mechanisms of drug release from taste-masking fatty acid microspheres.

    PubMed

    Qi, Sheng; Deutsch, David; Craig, Duncan Q M

    2008-09-01

    Fatty acid microspheres based on stearic and palmitic acids are known to form effective taste masking systems, although the mechanisms by which the drug is preferentially released in the lower gastrointestinal tract are not known. The objective of the present study was to identify the mechanisms involved, with a particular view to clarify the role of acid soap formation in the dissolution process. Microspheres were prepared by a spray chilling process. Using benzoic acid as a model drug and an alkaline dissolution medium, a faster drug release was observed in the mixed fatty acid formulation (50:50 stearic:palmitic acid (w/w)) compared to the single fatty acid component systems. Thermal and powder X-ray diffraction studies indicated a greater degree of acid soap formation for the mixed formulation in alkaline media compared to the single fatty acid systems. Particle size and porosity studies indicated a modest reduction in size for the mixed systems and an increase in porosity on immersion in the dissolution medium. It is proposed that the mixed fatty acid system form a mixed crystal system which in turn facilitates interaction with the dissolution medium, thereby leading to a greater propensity for acid soap formation which in turn forms a permeable liquid crystalline phase through which the drug may diffuse. The role of dissolution of palmitic acid into the dissolution medium is also discussed as a secondary mechanism.

  14. Polyaspartic acid-anchored mesoporous silica nanoparticles for pH-responsive doxorubicin release

    PubMed Central

    Zhan, Guiting; Yi, Ping; Yang, Hai; Gan, Lu; Yang, Xiangliang

    2018-01-01

    Background Nanotechnology-based drug delivery systems exhibit promising therapeutic efficacy in cancer chemotherapy. However, ideal nano drug carriers are supposed to be sufficiently internalized into cancer cells and then release therapeutic cargoes in response to certain intracellular stimuli, which has never been an easy task to achieve. Objective This study is to design mesoporous silica nanoparticles (MSNs)-based pH-responsive nano drug delivery system that is effectively internalized into cancer cells and then release drug in response to lysosomal/endosomal acidified environment. Methods We synthesized MSNs by sol-gel method. Doxorubicin (DOX) was encapsulated into the pores as a model drug. Polyaspartic acid (PAsA) was anchored on the surface of mesoporous MSNs (P-MSNs) as a gatekeeper via amide linkage and endowed MSNs with positive charge. Results In vitro release analysis demonstrated enhanced DOX release from DOX-loaded PAsA-anchored MSNs (DOX@P-MSNs) under endosomal/lysosomal acidic pH condition. Moreover, more DOX@P-MSNs were internalized into HepG2 cells than DOX-loaded MSNs (DOX@MSNs) and free DOX revealed by flow cytometry. Likewise, confocal microscopic images revealed that DOX@P-MSNs effectively released DOX and translocated to the nucleus. Much stronger cytotoxicity of DOX@P-MSNs against HepG2 cells was observed compared with DOX@MSNs and free DOX. Conclusion DOX@P-MSNs were successfully fabricated and achieved pH-responsive DOX release. We anticipated this nanotherapeutics might be suitable contenders for future in vivo cancer chemotherapeutic applications. PMID:29497295

  15. Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids.

    PubMed

    Lotrich, Francis E; Sears, Barry; McNamara, Robert K

    2013-11-01

    Anger worsens in some patients during interferon-alpha (IFN-α) therapy. Elevated anger has also been associated with lower long-chain omega-3 (LCn-3) fatty acid levels. We examined whether fatty acids could influence vulnerability to anger during IFN-α exposure. Plasma arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were determined prior to IFN-α therapy by mass spectroscopy. Repeated-measure analyses examined the relationship between AA/EPA+DHA and the subsequent development of labile anger and irritability in 82 subjects who prospectively completed the Anger, Irritability, and Assault Questionnaire (AIAQ) during the first eight weeks of IFN-α therapy. Prior to IFN-α therapy, AA/EPA+DHA did not correlate with either labile anger or irritability. Pre-treatment AA/EPA+DHA did correlate with the subsequent maximal increase in labile anger during IFN-α therapy (r=0.33; p=0.005). Over time, labile anger increased more in subjects with above median AA/EPA+DHA ratios (p<0.05). Of the 17 subjects ultimately requiring psychiatric intervention for anger, 14/17 had above-median AA/EPA+DHA ratios (p=0.009). There was also an interaction with the tumor necrosis factor-alpha (TNF-α) promoter polymorphism (A-308G), such that only those with both elevated AA/EPA+DHA and the A allele had increased labile anger (p=0.001). In an additional 18 subjects, we conversely observed that selective serotonin reuptake inhibitor treatment was associated with increased irritability during IFN-α therapy. LCn-3 fatty acid status may influence anger development during exposure to elevated inflammatory cytokines, and may interact with genetic risk for increased brain TNF-α. LCn-3 supplements may be one strategy for minimizing this adverse side effect of IFN-α. © 2013.

  16. Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release

    PubMed Central

    Chu, David S.H.; Johnson, Russell N.; Pun, Suzie H.

    2011-01-01

    Degradable cationic polymers are desirable for in vivo nucleic acid delivery because they offer significantly decreased toxicity over non-degradable counterparts. Peptide linkers provide chemical stability and high specificity for particular endopeptidases but have not been extensively studied for nucleic acid delivery applications. In this work, enzymatically degradable peptide-HPMA copolymers were synthesized by RAFT polymerization of HPMA with methacrylated peptide macromonomers, resulting in polymers with low polydispersity and near quantitative incorporation of peptides. Three peptide-HPMA copolymers were evaluated: (i) pHCathK10, containing peptides composed of the linker phe-lys-phe-leu (FKFL), a substrate of the endosomal/lysosomal endopeptidase cathepsin B, connected to oligo-(l)-lysine for nucleic acid binding, (ii) pHCath(d)K10, containing the FKFL linker with oligo-(d)-lysine, and (iii) pH(d)Cath(d)K10, containing all (d) amino acids. Cathepsin B degraded copolymers pHCathK10 and pHCath(d)K10 within one hour while no degradation of pH(d)Cath(d)K10 was observed. Polyplexes formed with pHCathK10 copolymers show DNA release by 4 hrs of treatment with cathepsin B; comparatively, polyplexes formed with pHCath(d)K10 and pH(d)Cath(d)K10 show no DNA release within 8 hrs. Transfection efficiency in HeLa and NIH/3T3 cells were comparable between the copolymers but pHCathK10 was less toxic. This work demonstrates the successful application of peptide linkers for degradable cationic polymers and DNA release. PMID:22036879

  17. A Novel Colletotrichum graminicola Raffinose Oxidase in the AA5 Family

    PubMed Central

    Mollerup, Filip; Parikka, Kirsti; Koutaniemi, Sanna; Boer, Harry; Juvonen, Minna; Master, Emma; Tenkanen, Maija; Kruus, Kristiina

    2017-01-01

    ABSTRACT We describe here the identification and characterization of a copper radical oxidase from auxiliary activities family 5 (AA5_2) that was distinguished by showing preferential activity toward raffinose. Despite the biotechnological potential of carbohydrate oxidases from family AA5, very few members have been characterized. The gene encoding raffinose oxidase from Colletotrichum graminicola (CgRaOx; EC 1.1.3.−) was identified utilizing a bioinformatics approach based on the known modular structure of a characterized AA5_2 galactose oxidase. CgRaOx was expressed in Pichia pastoris, and the purified enzyme displayed the highest activity on the trisaccharide raffinose, whereas the activity on the disaccharide melibiose was three times lower and more than ten times lower activity was detected on d-galactose at a 300 mM substrate concentration. Thus, the substrate preference of CgRaOx was distinguished clearly from the substrate preferences of the known galactose oxidases. The site of oxidation for raffinose was studied by 1H nuclear magnetic resonance and mass spectrometry, and we confirmed that the hydroxyl group at the C-6 position was oxidized to an aldehyde and that in addition uronic acid was produced as a side product. A new electrospray ionization mass spectrometry method for the identification of C-6 oxidized products was developed, and the formation mechanism of the uronic acid was studied. CgRaOx presented a novel activity pattern in the AA5 family. IMPORTANCE Currently, there are only a few characterized members of the CAZy AA5 protein family. These enzymes are interesting from an application point of view because of their ability to utilize the cheap and abundant oxidant O2 without the requirement of complex cofactors such as FAD or NAD(P). Here, we present the identification and characterization of a novel AA5 member from Colletotrichum graminicola. As discussed in the present study, the bioinformatics approach using the modular structure of

  18. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats

    PubMed Central

    YILMAZ, Okkes; ERSAN, Yasemin; Dilek OZSAHIN, Ayse; Ihsan OZTURK, Ali; OZKAN, Yusuf

    2013-01-01

    Objective(s): Our objective was to evaluate the effects of a triple antioxidant combination [α-tocopherol (AT), ascorbic acid (AA) and α-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. Materials and Methods: Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fourth and fifth groups were injected with intraperitoneal (IP) 50 mg/kg DL-AT and 50 mg /kg DL-LA four times per week and received water-soluble vitamin C (50 mg/kg) in their drinking water for a period of six weeks. Results: Liver cholesterol levels in the AT+AA+LA group were lower than the control (P<0.05). Glutathione level was lower in D-2 (P<0.05) and were higher in D+AT+AA+LA and AT+AA+LA groups than the control groups (P≤ 0.05). The muscle cholesterol levels in the D-1 and D+AT+AA+LA groups were higher than the control group (P≤ 0.05). The levels of oleic acid were higher in the D-1 group and lower in the D-2 group (P<0.001). The arachidonic acid level in the D-1 and D-2 groups were lower (P<0.05), and higher in the D+AT+AA+LA group. Conclusion: Our results revealed that glutathione levels and the Stearoyl CoA Desaturase enzyme products in liver tissues of diabetic and non-diabetic rats were increased by triple antioxidant mixture. PMID:24298385

  19. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats.

    PubMed

    Yilmaz, Okkes; Ersan, Yasemin; Dilek Ozsahin, Ayse; Ihsan Ozturk, Ali; Ozkan, Yusuf

    2013-02-01

    Our objective was to evaluate the effects of a triple antioxidant combination [α-tocopherol (AT), ascorbic acid (AA) and α-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fourth and fifth groups were injected with intraperitoneal (IP) 50 mg/kg DL-AT and 50 mg /kg DL-LA four times per week and received water-soluble vitamin C (50 mg/kg) in their drinking water for a period of six weeks. Liver cholesterol levels in the AT+AA+LA group were lower than the control (P<0.05). Glutathione level was lower in D-2 (P<0.05) and were higher in D+AT+AA+LA and AT+AA+LA groups than the control groups (P≤ 0.05). The muscle cholesterol levels in the D-1 and D+AT+AA+LA groups were higher than the control group (P≤ 0.05). The levels of oleic acid were higher in the D-1 group and lower in the D-2 group (P<0.001). The arachidonic acid level in the D-1 and D-2 groups were lower (P<0.05), and higher in the D+AT+AA+LA group. Our results revealed that glutathione levels and the Stearoyl CoA Desaturase enzyme products in liver tissues of diabetic and non-diabetic rats were increased by triple antioxidant mixture.

  20. Antiangiogenic effects of AA-PMe on HUVECs in vitro and zebrafish in vivo

    PubMed Central

    Xiao, Qi; Zhou, Yachun; Wei, Yingjie; Gong, Zhunan

    2018-01-01

    Angiogenesis plays a vital role in many physiological and pathological processes and several diseases are connected with its dysregulation. Asiatic acid (AA) has demonstrated anticancer properties and we suspect this might be attributable to an effect on angio-genesis. A modified derivative of AA, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-L-proline methyl ester (AA-PMe), has improved efficacy over its parent compound, but its effect on blood vessel development remains unclear. Methods In this study, we investigated the antiangiogenic activity of AA and AA-PMe in zebrafish embryos and human umbilical vein endothelial cells (HUVECs). First of all, we treated HUVECs with increasing concentrations of AA-PMe or AA, with or without vascular endothelial growth factor (VEGF) present, and assessed cell viability, tube formation, and cell migration and invasion. Quantitative real-time polymerase chain reaction and Western blot analysis were later used to determine the role of vascular endothelial growth factor receptor 2 (VEGFR2)-mediated signaling in AA-PMe inhibition of angiogenesis. We extended these studies to follow angiogenesis using Tg(fli:EGFP) transgenic zebrafish embryos. For these experiments, embryos were treated with varying concentrations of AA-PMe or AA from 24 to 72 hours postfertilization prior to morphological observation, angiogenesis assessment, and endogenous alkaline phosphatase assay. VEGFR2 expression in whole embryos following AA-PMe treatment was also determined. Results We found AA-PMe decreased cell viability and inhibited migration and tube formation in a dose-dependent manner in HUVECs. Similarly, AA-PMe disrupted the formation of intersegmental vessels, the dorsal aorta, and the posterior cardinal vein in zebrafish embryos. Both in vitro and in vivo AA-PMe surpassed AA in its ability to block angiogenesis by suppressing VEGF-induced phosphorylation of VEGFR2 and disrupting downstream extracellular regulated protein kinase and AKT signaling

  1. Antiangiogenic effects of AA-PMe on HUVECs in vitro and zebrafish in vivo.

    PubMed

    Jing, Yue; Wang, Gang; Xiao, Qi; Zhou, Yachun; Wei, Yingjie; Gong, Zhunan

    2018-01-01

    Angiogenesis plays a vital role in many physiological and pathological processes and several diseases are connected with its dysregulation. Asiatic acid (AA) has demonstrated anticancer properties and we suspect this might be attributable to an effect on angio-genesis. A modified derivative of AA, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-L-proline methyl ester (AA-PMe), has improved efficacy over its parent compound, but its effect on blood vessel development remains unclear. In this study, we investigated the antiangiogenic activity of AA and AA-PMe in zebrafish embryos and human umbilical vein endothelial cells (HUVECs). First of all, we treated HUVECs with increasing concentrations of AA-PMe or AA, with or without vascular endothelial growth factor (VEGF) present, and assessed cell viability, tube formation, and cell migration and invasion. Quantitative real-time polymerase chain reaction and Western blot analysis were later used to determine the role of vascular endothelial growth factor receptor 2 (VEGFR2)-mediated signaling in AA-PMe inhibition of angiogenesis. We extended these studies to follow angiogenesis using Tg(fli:EGFP) transgenic zebrafish embryos. For these experiments, embryos were treated with varying concentrations of AA-PMe or AA from 24 to 72 hours postfertilization prior to morphological observation, angiogenesis assessment, and endogenous alkaline phosphatase assay. VEGFR2 expression in whole embryos following AA-PMe treatment was also determined. We found AA-PMe decreased cell viability and inhibited migration and tube formation in a dose-dependent manner in HUVECs. Similarly, AA-PMe disrupted the formation of intersegmental vessels, the dorsal aorta, and the posterior cardinal vein in zebrafish embryos. Both in vitro and in vivo AA-PMe surpassed AA in its ability to block angiogenesis by suppressing VEGF-induced phosphorylation of VEGFR2 and disrupting downstream extracellular regulated protein kinase and AKT signaling. For the first time

  2. Vitamin-C delivery from CoCr alloy surfaces using polymer-free and polymer-based platforms for cardiovascular stent applications.

    PubMed

    Thiruppathi, Eagappanath; Mani, Gopinath

    2014-06-03

    Antiproliferative drugs such as paclitaxel and sirolimus are delivered from stents to inhibit the growth of smooth muscle cells (SMCs) for preventing neointimal hyperplasia. However, these drugs delay the growth of endothelial cells (ECs) as well and cause late stent thrombosis. We recently demonstrated the use of Vitamin-C (l-ascorbic acid, l-AA) over paclitaxel and sirolimus for inhibiting SMCs growth and promoting EC growth simultaneously. In this study, we have investigated the delivery of l-AA from CoCr alloy surfaces for potential use in stents. A polymer-free phosphoric acid (PA) platform and a polymer-based poly(lactic-co-glycolic acid) (PLGA) platform were used for coating l-AA onto CoCr surfaces. For the PA platform, FTIR confirmed that the PA was coated on CoCr, while the AFM showed that the PA coating on the CoCr surface was homogeneous. The successful deposition of l-AA on PA-coated CoCr was also confirmed by FTIR. The uniform distribution of l-AA crystals on PA-coated CoCr was shown by SEM, optical profilometer, and AFM. The drug release studies showed that l-AA (276 μg/cm(2)) was burst released from the PA platform by 1 h. For the PLGA platform, SEM showed that the l-AA incorporated polymer films were smoothly and uniformly coated on CoCr. FTIR showed that l-AA was incorporated into the bulk of the PLGA film. DSC showed that the l-AA was present in an amorphous form and formed an intermolecular bonding interaction with PLGA. The drug release studies showed that l-AA was sustained released from the PLGA coated CoCr for up to 24 h. The SEM, FTIR, and DSC characterizations of samples collected post drug release shed light on the mechanism of l-AA release from PLGA coated CoCr. Thus, this study demonstrated the delivery of l-AA from biomaterial surfaces for potential applications in stents and other implantable medical devices.

  3. Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds.

    PubMed

    Leach, Jennie B; Schmidt, Christine E

    2005-01-01

    The goal of this work was to utilize the naturally derived bioactive polymer hyaluronic acid (HA) to create a combination tissue engineering scaffold and protein delivery device. HA is a non-immunogenic, non-adhesive glycosaminoglycan that plays significant roles in several cellular processes, including angiogenesis and the regulation of inflammation. In previous work, we created photopolymerizable glycidyl methacrylate-hyaluronic acid (GMHA) hydrogels that had controlled degradation rates, were cytocompatible, and were able to be modified with peptide moieties. In the present studies, we characterized the release of a model protein, bovine serum albumin (BSA), from GMHA and GMHA-polyethylene glycol (PEG) hydrogels. Although BSA could be released rapidly (> 60% within 6 h) from 1% GMHA hydrogels, we found that increasing either the GMHA or the PEG concentrations could lengthen the duration of protein delivery. Preliminary size exclusion chromatography studies indicated that the released BSA was almost entirely in its native monomeric form. Lastly, protein release was extended to several weeks by suspending BSA-poly(lactic-co-glycolic acid) microspheres within the hydrogel bulk. These initial studies indicate that the naturally derived biopolymer HA can be employed to design novel photopolymerizable composites that are suitable for delivering stable proteins from scaffolding in tissue engineering applications.

  4. Preparation and Characterization of Thermoresponsive Poly(N-isopropylacrylamide-co-acrylic acid)-Grafted Hollow Fe3O4/SiO2 Microspheres with Surface Holes for BSA Release

    PubMed Central

    Zhao, Jing; Zeng, Ming; Zheng, Kaiqiang; He, Xinhua; Xie, Minqiang; Fu, Xiaoyi

    2017-01-01

    Thermoresponsive P(NIPAM-AA)/Fe3O4/SiO2 microspheres with surface holes serving as carriers were prepared using p-Fe3O4/SiO2 microspheres with a thermoresponsive copolymer. The p-Fe3O4/SiO2 microspheres was obtained using a modified Pickering method and chemical etching. The surface pore size of p-Fe3O4/SiO2 microspheres was in the range of 18.3 nm~37.2 nm and the cavity size was approximately 60 nm, which are suitable for loading and transporting biological macromolecules. P(NIPAM-AA) was synthesized inside and outside of the p-Fe3O4/SiO2 microspheres via atom transfer radical polymerization of NIPAM, MBA and AA. The volume phase transition temperature (VPTT) of the specifically designed P(NIPAM-AA)/Fe3O4/SiO2 microspheres was 42.5 °C. The saturation magnetization of P(NIPAM-AA)/Fe3O4/SiO2 microspheres was 72.7 emu/g. The P(NIPAM-AA)/Fe3O4/SiO2 microspheres were used as carriers to study the loading and release behavior of BSA. This microsphere system shows potential for the loading of proteins as a drug delivery platform. PMID:28772770

  5. Enhancement of the release of azelaic acid through the synthetic membranes by inclusion complex formation with hydroxypropyl-beta-cyclodextrin.

    PubMed

    Manosroi, Jiradej; Apriyani, Maria Goretti; Foe, Kuncoro; Manosroi, Aranya

    2005-04-11

    The aim of this study was to investigate the release rates of azelaic acid and azelaic acid-hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion complex through three types of synthetic membranes, namely cellophane, silicone and elastomer membranes. Solid inclusion complexes of azelaic acid-HPbetaCD at the molar ratio of 1:1 were prepared by coevaporation and freeze-drying methods, subsequently characterized by differential scanning calorimetry, X-ray diffractometry and dissolution studies. Solid inclusion complex obtained by coevaporation method which exhibited the inclusion of azelaic acid in the HPbetaCD cavity and gave the highest dissolution rate of azelaic acid was selected for the release study. Release studies of azelaic acid and this complex through the synthetic membranes were conducted using vertical Franz diffusion cells at 30 degrees C for 6 days. The release rates of azelaic acid through the synthetic membranes were enhanced by the formation of inclusion complex with HPbetaCD at the molar ratio of 1:1, with the increasing fluxes of about 41, 81 and 28 times of the uncomplexed system in cellophane, silicone and elastomer membranes, respectively. The result from this study can be applied for the development of azelaic acid for topical use.

  6. The potent inhibition of vapiprost, a novel thromboxane A2 receptor antagonist, on the secondary aggregation and ATP release of human platelets.

    PubMed

    Horie, S; Yamada, M; Satoh, M; Noritake, S; Hiraishi, S; Kizaki, K; Kurusu, O; Nakahara, T; Ishii, H; Kazama, M

    1997-06-01

    The inhibitory effects of vapiprost hydrochloride (vapiprost), a novel thromboxane A2 receptor antagonist, on platelet aggregation and ATP release were studied using platelet rich plasma (PRP) of humans, guinea pigs, rabbits and rats. In in vitro experiments with human platelet, vapiprost inhibited the aggregation and ATP release stimulated with U-46619, collagen or arachidonic acid (AA) at an IC50 of less than 2.1 x 10(-8) M. Vapiprost did not inhibit the primary aggregation or ATP release of human platelets stimulated with adenosine 5'-diphosphate (ADP), epinephrine (Epi) or platelet activating factor (PAF), but inhibited the secondary aggregation stimulated with those agonists at an IC50 of less than 1.3 x 10(-7) M. The sensitivity of platelets in various species of animals to vapiprost was in the following order: human > or = guinea pigs > rats > rabbits. In ex vivo experiments with guinea pigs which received a single oral dose of vapiprost, the agent demonstrated strong inhibition of ATP release from platelets stimulated with U-46619, collagen or AA at an ID50 of less than 25.8 micrograms/kg. These inhibitory effects were observed within 30 min and sustained for 24 h at a single dosage of 5 mg/kg of vapiprost. In AA-induced pulmonary infarction models of mice, the sudden death rates decreased significantly with the oral administration of 10 mg/kg or more of vapiprost. These results indicate that vapiprost effectively inhibits the secondary aggregation and ATP release of human platelets stimulated with various agonists, and that guinea pig and human platelets are similar in response to vapiprost. Furthermore, it was demonstrated in ex vivo experiments with guinea pigs that the inhibitory action of vapiprost appears rapidly and lasts for long periods.

  7. Effects of low molecular weight organic acids on (137)Cs release from contaminated soils.

    PubMed

    Chiang, Po Neng; Wang, Ming Kuang; Huang, Pan Ming; Wang, Jeng Jong

    2011-06-01

    Radio pollutant removal is one of several priority restoration strategies for the environment. This study assessed the effect of low molecular weight organic acid on the lability and mechanisms for release of (137)Cs from contaminated soils. The amount of (137)Cs radioactivity released from contaminated soils reacting with 0.02 M low molecular weight organic acids (LMWOAs) specifically acetic, succinic, oxalic, tartaric, and citric acid over 48 h were 265, 370, 760, 850, and 1002 Bq kg(-1), respectively. The kinetic results indicate that (137)Cs exhibits a two-step parabolic diffusion equation and a good linear relationship, indicating that the parabolic diffusion equation describes the data quite well, as shown by low p and high r(2) values. The fast stage, which was found to occur within a short period of time (0.083-3 h), corresponds to the interaction of LMWOAs with the surface of clay minerals; meanwhile, during the slow stage, which occurs over a much longer time period (3-24 h), desorption primarily is attributed to inter-particle or intra-particle diffusion. After a fifth renewal of the LMWOAs, the total levels of (137)Cs radioactivity released by acetic, succinic, oxalic, tartaric, and citric acid were equivalent to 390, 520, 3949, 2061, and 4422 Bq kg(-1) soil, respectively. H(+) can protonate the hydroxyl groups and oxygen atoms at the broken edges or surfaces of the minerals, thereby weakening Fe-O and Al-O bonds. After protonation of H(+), organic ligands can attack the OH and OH(2) groups in the minerals easily, to form complexes with surface structure cations, such as Al and Fe. The amounts of (137)Cs released from contaminated soil treated with LMWOAs were substantially increased, indicating that the LMWOAs excreted by the roots of plants play a critical role in (137)Cs release. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Effects of N-vinylcaprolactam containing polyelectrolytes on hardness, fluoride release and water sorption of conventional glass ionomers.

    PubMed

    Moshaverinia, Alireza; Ansari, Sahar; Roohpour, Nima; Reshad, Mamaly; Schricker, Scott R; Chee, Winston Wl

    2011-05-01

    N-vinylcaprolactam (NVC) containing glass ionomers are promising dental restorative materials with improved mechanical properties; however, little information is available on other physical properties of this type of modified glass ionomer, especially their water sorption, fluoride releasing properties and microhardness. The purpose of this study was to investigate the effects of NVC-containing polyelectrolytes on microhardness, fluoride release and water sorption of conventional glass ionomer cements (GIC). The terpolymer of acrylic acid (AA), itaconic acid (IA) and N-vinylcaprolactam (NVC) with 8:1:1 and 7:1:2 (AA: IA: NVC) molar ratios was synthesized by free radical polymerization and characterized using 1H-NMR and FTIR. Experimental GIC specimens were made from a 50% solution of the synthesized terpolymer with Fuji IX powder in a 3.6:1 P/L ratio. Specimens were mixed and fabricated at room temperature. Vickers hardness was determined using a microhardness tester. Water sorption and fluoride releasing properties were also investigated. Commercial Fuji IX was used as the control group. All specimens were first conditioned in distilled water at 37°C for 1 day up to 1 month. Results for the experimental GIC were compared with the control group, using 1-way and 2-way ANOVA and the Tukey multiple range test (α=.05). The NVC-modified GIC exhibited higher mean values of Vickers hardness numbers (VHN). However, the data exhibited no statistically significant differences between the experimental and control groups. The experimental cement (TP2) absorbed significantly more water than the control group (P<.034). Additionally, NVC-containing specimens showed comparable fluoride releasing properties with almost the same fluoride burst and continued fluoride release from the bulk of the material. It was concluded that a hydrophilic monomer such as NVC might be able to increase the water sorption and decrease the amount of initial fluoride release of the glass ionomers

  9. The ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cancer death in a Japanese community: The Hisayama Study.

    PubMed

    Nagata, Masaharu; Hata, Jun; Hirakawa, Yoichiro; Mukai, Naoko; Yoshida, Daigo; Ohara, Tomoyuki; Kishimoto, Hiro; Kawano, Hiroyuki; Kitazono, Takanari; Kiyohara, Yutaka; Ninomiya, Toshiharu

    2017-12-01

    Whether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations. A total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002-2012). The levels of the serum EPA:AA ratio were categorized into quartiles (<0.29, 0.29-0.41, 0.42-0.60, and >0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations. During the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend<0.05). In the multivariable-adjusted analysis, the subjects in the first quartile of the serum EPA:AA ratio had a 1.93-fold (95% confidence interval, 1.15-3.22) greater risk of cancer death than those in the fourth quartile. Lower serum EPA concentrations were marginally associated with higher cancer mortality (P trend<0.11), but the serum DHA or AA concentrations and the serum DHA:AA ratio were not (all P trend>0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers. These findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population. Copyright © 2017. Production and hosting by Elsevier B.V.

  10. Further characterization of [3H]gamma-aminobutyric acid release from isolated neuronal growth cones: role of intracellular Ca2+ stores.

    PubMed

    Lockerbie, R O; Gordon-Weeks, P R

    1986-04-01

    We have recently shown that growth cones isolated from neonatal rat forebrain possess uptake and release mechanisms for the neurotransmitter gamma-aminobutyric acid. About half of the K+-induced release of [3H]gamma-aminobutyric acid from isolated growth cones is dependent on extracellular Ca2+. The remaining component of the [3H]gamma-aminobutyric acid release is unaffected by removal of extracellular Ca2+ and is resistant to blockade by the voltage-sensitive Ca2+-channel blocker methoxyverapamil. In the present series of experiments we have used caffeine to assess the possible role of intracellular stores of Ca2+ in supporting that component of the K+-induced release of [3H]gamma-aminobutyric acid from isolated growth cones that is independent of extracellular Ca2+. We have chosen caffeine because of its well established effect of releasing Ca2+ from smooth endoplasmic reticulum in muscle. We found that caffeine can release [3H]gamma-aminobutyric acid from isolated growth cones. This effect persists in Ca2+-free medium, in the presence of methoxyverapamil and in the absence of Na+. Furthermore, isobutylmethylxanthine could not substitute for caffeine suggesting that the caffeine effect is not due to phosphodiesterase inhibition and the subsequent rise in intracellular cyclic nucleotides. A combination of the mitochondrial poisons, Antimycin A and sodium azide had no effect on the release of [3H]gamma-aminobutyric acid induced either by caffeine or by high K+. We conclude that caffeine causes the release of Ca2+ from a non-mitochondrial store within the growth cone and that this Ca2+ store supports that component of the K+-induced release of [3H]gamma-aminobutyric acid that is independent of extracellular Ca2+.

  11. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity

    PubMed Central

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  12. Preparation and Properties of a Novel Semi-IPN Slow-Release Fertilizer with the Function of Water Retention.

    PubMed

    Xiang, Yang; Ru, Xudong; Shi, Jinguo; Song, Jiang; Zhao, Haidong; Liu, Yaqing; Guo, Dongdong; Lu, Xin

    2017-12-20

    A new semi-interpenetrating polymer network (semi-IPN) slow-release fertilizer (SISRF) with water absorbency, based on the kaolin-g-poly(acrylic acid-co-acrylic amide) (kaolin-g-P(AA-co-AM)) network and linear urea-formaldehyde oligomers (UF), was prepared by solution polymerization. Nutrients phosphorus and potassium were supplied by adding dipotassium hydrogen phosphate during the preparation process. The structure and properties of SISRF were characterized by various characterization methods. SISRF showed excellent water absorbency of 68 g g -1 in tap water. The slow-release behavior of nutrients and water-retention capacity of SISRF were also measured. Meanwhile, the swelling kinetics was well described by a pseudo-second-order kinetics model. Results suggested the formation of SISRF with simultaneously good slow-release and water-retention capacity, which was expected to apply in modern agriculture and horticulture.

  13. Adsorption and release of amino acids mixture onto apatitic calcium phosphates analogous to bone mineral

    NASA Astrophysics Data System (ADS)

    El Rhilassi, A.; Mourabet, M.; El Boujaady, H.; Bennani-Ziatni, M.; Hamri, R. El; Taitai, A.

    2012-10-01

    Study focused on the interaction of adsorbate with poorly crystalline apatitic calcium phosphates analogous to bone mineral. Calcium phosphates prepared in water-ethanol medium at physiological temperature (37 °C) and neutral pH, their Ca/P ratio was between 1.33 and 1.67. Adsorbate used in this paper takes the mixture form of two essential amino acids L-lysine and DL-leucine which have respectively a character hydrophilic and hydrophobic. Adsorption and release are investigated experimentally; they are dependent on the phosphate type and on the nature of adsorbate L-lysine, DL-leucine and their mixture. Adsorption of mixture of amino acids on the apatitic calcium phosphates is influenced by the competition between the two amino acids: L-lysine and DL-leucine which exist in the medium reaction. The adsorption kinetics is very fast while the release kinetics is slow. The chemical composition of apatite has an influence on both adsorption and release. The interactions adsorbate-adsorbent are electrostatic type. Adsorption and release reactions of the amino acid mixture are explained by the existence of the hydrated surface layer of calcium phosphate apatite. The charged sbnd COOsbnd and sbnd NH3+ of adsorbates are the strongest groups that interact with the surface of apatites, the adsorption is mainly due to the electrostatic interaction between the groups sbnd COOsbnd of amino acids and calcium Ca2+ ions of the apatite. Comparative study of interactions between adsorbates (L-lysine, DL-leucine and their mixture) and apatitic calcium phosphates is carried out in vitro by using UV-vis and infrared spectroscopy IR techniques.

  14. Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

    PubMed

    Duque, Luisa; Körber, Martin; Bodmeier, Roland

    2018-03-01

    The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Release of endogenous amino acids from the hippocampus and brain stem from developing and adult mice in ischemia.

    PubMed

    Oja, Simo S; Saransaari, Pirjo

    2009-09-01

    The release of neurotransmitters and modulators has been studied mostly using labeled preloaded compounds. For several reasons, however, the estimated release may not reliably reflect the release of endogenous compounds. The basal and K(+)-evoked release of the neuroactive endogenous amino acids GABA, glycine, taurine, L-glutamate and L-aspartate was now studied in slices from the hippocampus and brain stem from 7-day-old and 3-month-old mice under control and ischemic conditions. The release of synaptically not active L-glutamine, L-alanine, L-threonine and L-serine was assessed for comparison. The estimates for the hippocampus and brainstem were markedly different and also different in developing and adult mice. GABA release was much greater in 3-month-old than in 7-day-old mice, whereas with taurine the situation was the opposite, in the hippocampus in particular. K(+) stimulation enhanced glycine release more in the mature than immature brain stem while in the hippocampus the converse was observed. Ischemia enhanced the release of all neuroactive amino acids in both brain regions, the effects being relatively most pronounced in the case of GABA, aspartate and glutamate in the hippocampus in 3-month-old mice, and taurine in 7-day-old and glycine in 3-month-old mice in the brain stem. These results are qualitatively similar to those obtained on earlier experiments with labeled preloaded amino acids. However, the magnitudes of the release cannot be quite correctly estimated using radioactive labels. In developing mice only taurine release may counteract the harmful effects of excitatory amino acids in ischemia in both hippocampus and brain stem.

  16. Incorporating zosteric acid into silicone coatings to achieve its slow release while reducing fresh water bacterial attachment.

    PubMed

    Barrios, Carlos A; Xu, Qingwei; Cutright, Teresa; Newby, Bi-min Zhang

    2005-03-25

    Biofouling has posed serious problems in maritime industry including increased fuel consumptions, economic loss from ship-hull maintenances, contamination of drinking water, and serious corrosion for mechanical instruments. Minimizing the attachment of bacteria and formation of biofilm could be advantageous in reducing the early stages of biofouling. Zosteric acid, a natural product present in eelgrass, was found to have ability for preventing the attachment of some bacteria and barnacles. In this study, the antifouling ability of zosteric acid during the early stages of fouling was evaluated using attachment studies of fresh water bacteria. Simultaneously, various methods were sought for incorporating zosteric acid into silicone to prolong the release of the compound. The main results from this study were that zosteric acid exhibited anti-bacterial attachment regardless of whether it dispersed in water or incorporated into a coating. In addition, the release rate of zosteric acid from the incorporated coatings, particularly those where zosteric acid was uniformly dispersed with aggregates size of 4 microm or less, was orders of magnitude slower than those of previous reports. The release results indicate that the service life of our coatings could be far extended even with a small amount of zosteric acid incorporated.

  17. Sediment amino acids as indicators of anthropogenic activities and potential environmental risk in Erhai Lake, Southwest China.

    PubMed

    Ni, Zhaokui; Wang, Shengrui; Zhang, Mianmian

    2016-05-01

    Total hydrolysable amino acids (THAAs) constitute the most important fraction of labile nitrogen. Anthropogenic activities directly influence various biogeochemical cycles and then accelerate lake ecosystem deterioration. This is the first study that has established the relationship between sediment THAAs and anthropogenic activities using dated sediment cores, and evaluated the possibility of THAAs release at the sediment interface based on changes in environmental conditions in Erhai Lake. The results showed that historical distribution and fractions of THAAs could be divided into three stages: a stable period before the 1970s, a clear increasing period from the 1970s to 1990s, and a gradually steady period that started after the 1990s. The chemical fraction, aromatic and sulfur amino acids (AAs) accounted for only ≤3% of THAAs. Basic AAs accounted for 5-17% of THAAs, and remained at a relatively stable level. However, acidic and neutral AAs, which accounted for 19-44% and 35-69% of THAAs, respectively, were the predominant factors causing THAAs to increase due to rapid agricultural intensification and intensification of contemporary sedimentation of phytoplankton or macrophytes since the 1970s. These trends were closely related to both anthropogenic activities and natural processes, which implied that sediment THAAs could act as an effective indicator that reflects anthropogenic activities and aquatic environmental characteristics. The current contributions of sediment THAAs on TN and TOC were <5% and 1.5%, respectively. However, the dramatic increase in THAAs in the sediment cores indicated that there was a huge potential source of labile nitrogen for the overlying water under certain environmental conditions. Correlation analysis suggested that the release of THAAs was negatively correlated with pH, whereas positively correlated with bacterial number and degree of OM mineralization, which particularly depend on the stability of HFOM. Therefore, the risk of

  18. Injectable and body temperature sensitive hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release.

    PubMed

    Zhang, Wei; Jin, Xin; Li, Heng; Zhang, Run-Run; Wu, Cheng-Wei

    2018-04-15

    Hydrogels based on chitosan/hyaluronic acid/β-sodium glycerophosphate demonstrate injectability, body temperature sensitivity, pH sensitive drug release and adhesion to cancer cell. The drug (doxorubicin) loaded hydrogel precursor solutions are injectable and turn to hydrogels when the temperature is increased to body temperature. The acidic condition (pH 4.00) can trigger the release of drug and the cancer cell (Hela) can adhere to the surface of the hydrogels, which will be beneficial for tumor site-specific administration of drug. The mechanical strength, the gelation temperature, and the drug release behavior can be tuned by varying hyaluronic acid content. The mechanisms were characterized using dynamic mechanical analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and fluorescence microscopy. The carboxyl group in hyaluronic acid can form the hydrogen bondings with the protonated amine in chitosan, which promotes the increase of mechanical strength of the hydrogels and depresses the initial burst release of drug from the hydrogel. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Constitutive behavior of as-cast AA1050, AA3104, and AA5182

    NASA Astrophysics Data System (ADS)

    van Haaften, W. M.; Magnin, B.; Kool, W. H.; Katgerman, L.

    2002-07-01

    Recent thermomechanical modeling to calculate the stress field in industrially direct-chill (DC) cast-aluminum slabs has been successful, but lack of material data limits the accuracy of these calculations. Therefore, the constitutive behavior of three aluminum alloys (AA1050, AA3104, and AA5182) was determined in the as-cast condition using tensile tests at low strain rates and from room temperature to solidus temperature. The parameters of two constitutive equations, the extended Ludwik equation and a combination of the Sellars-Tegart equation with a hardening law, were determined. In order to study the effect of recovery, the constitutive behavior after prestraining at higher temperatures was also investigated. To evaluate the quantified constitutive equations, tensile tests were performed simulating the deformation and cooling history experienced by the material during casting. It is concluded that both constitutive equations perform well, but the combined hardening-Sellars-Tegart (HST) equation has temperature-independent parameters, which makes it easier to implement in a DC casting model. Further, the deformation history of the ingot should be taken into account for accurate stress calculations.

  20. Negative Affect, Relapse, and Alcoholics Anonymous (AA): Does AA Work by Reducing Anger?*

    PubMed Central

    Kelly, John F.; Stout, Robert L.; Tonigan, J. Scott; Magill, Molly; Pagano, Maria E.

    2010-01-01

    Objective: Anger and other indices of negative affect have been implicated in a stress-induced pathway to relapse. The Alcoholics Anonymous (AA) literature states that reduction of anger is critical to recovery, yet this proposed mechanism has rarely been investigated. Using lagged, controlled hierarchical linear modeling analyses, this study investigated whether AA attendance mobilized changes in anger and whether such changes explained AA-related benefit. Method: Alcohol-dependent adults (N = 1,706) receiving treatment as part of a clinical trial were assessed at intake and at 3, 6, 9, 12, and 15 months. Results: Findings revealed substantially elevated levels of anger compared with the general population (98th percentile) that decreased over 15-month follow-up but remained high (89th percentile). AA attendance was associated with better drinking outcomes, and higher levels of anger were associated with heavier drinking. However, AA attendance was unrelated to changes in anger. Conclusions: Although support was not found for anger as a mediator, there was strong convergence between AA's explicit emphasis on anger and the present findings: Anger appears to be a serious, enduring problem related to relapse and heavy alcohol consumption. Methodological factors may have contributed to the lack of association between AA and anger, but results suggest that AA attendance alone may be insufficient to alleviate the suffering and alcohol-related risks specifically associated with anger. PMID:20409438

  1. Ibuprofen-loaded poly(lactic-co-glycolic acid) films for controlled drug release.

    PubMed

    Pang, Jianmei; Luan, Yuxia; Li, Feifei; Cai, Xiaoqing; Du, Jimin; Li, Zhonghao

    2011-01-01

    Ibuprofen- (IBU) loaded biocompatible poly(lactic-co-glycolic acid) (PLGA) films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.

  2. Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus.

    PubMed

    Ghebremeskel, K; Min, Y; Crawford, M A; Nam, J H; Kim, A; Koo, J N; Suzuki, H

    2000-05-01

    Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n = 40) and nonpregnant, nonlactating (n = 40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P < 0.05) and palmitic and oleic acids higher (P < 0.0001) in plasma CPG of the pregnant women. Similarly, the RBC CPG and EPG of the pregnant women had lower AA and DHA (P < 0.05) and higher palmitic and oleic acids (P < 0.01). The reduction in DHA and total n-3 fatty acids in plasma CPG of the pregnant women was paralleled by an increase in docosatetraenoic (DTA) and docosapentaenoic (DPA) acids of the n-6 series and in DPA/DTA ratio. In the RBC phospholipids (CPG and EPG) of the pregnant women, DTA and DPA acids of the n-6 series and DPA/DTA ratio did not increase with the decrease of the n-3 metabolites (eicosapentaenoic acid, DPA, and DHA) and total n-3. Since pregnancy was the main identifiable variable between the two groups, the lower levels of AA and DHA in RBC CPG and EPG of the pregnant women suggest that the mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.

  3. Reductive dechlorination of carbon tetrachloride using buffered alkaline ascorbic acid.

    PubMed

    Lin, Ya-Ting; Liang, Chenju

    2015-10-01

    Alkaline ascorbic acid (AA) was recently discovered as a novel in-situ chemical reduction (ISCR) reagent for remediating chlorinated solvents in the subsurface. For this ISCR process, the maintenance of an alkaline pH is essential. This study investigated the possibility of the reduction of carbon tetrachloride (CT) using alkaline AA solution buffered by phosphate and by NaOH. The results indicated that CT was reduced by AA, and chloroform (CF) was a major byproduct at a phosphate buffered pH of 12. However, CT was completely reduced by AA in 2M NaOH without CF formation. In the presence of iron/soil minerals, iron could be reduced by AA and Fe(2+) tends to precipitate on the mineral surface to accelerate CT degradation. A simultaneous transfer of hydrogenolysis and dichloroelimination would occur under phosphate buffered pH 12. This implies that a high alkaline environment is a crucial factor for maintaining the dominant pathway of two electron transfer from dianionic AA to dehydroascorbic acid, and to undergo dichloroelimination of CT. Moreover, threonic acid and oxalic acid were identified to be the major AA decomposition products in alkaline solutions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Nicotinic Acid Adenine Dinucleotide Phosphate Analogs Substituted on the Nicotinic Acid and Adenine Ribosides. Effects on Receptor-Mediated Ca2+ release

    PubMed Central

    Trabbic, Christopher J.; Zhang, Fan; Walseth, Timothy F.; Slama, James T.

    2015-01-01

    Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca2+ releasing intracellular second messenger in both mammals and echinoderms. We report that large functionalized substituents introduced at the nicotinic acid 5-position are recognized by the sea urchin receptor, albeit with a 20–500 fold loss in agonist potency. 5-(3-Azidopropyl)-NAADP was shown to release Ca2+ with an EC50 of 31 µM and to compete with NAADP for receptor binding with an IC50 of 56 nM. Attachment of charged groups to the nicotinic acid of NAADP is associated with loss of activity, suggesting that the nicotinate riboside moiety is recognized as a neutral zwitterion. Substituents (Br- and N3-) can be introduced at the 8-adenosyl position of NAADP while preserving high potency and agonist efficacy and an NAADP derivative substituted at both the 5-position of the nicotinic acid and at the 8-adenosyl position was also recognized although the agonist potency was significantly reduced. PMID:25826221

  5. Some distinguishable properties between acid-stable and neutral types of alpha-amylases from acid-producing koji.

    PubMed

    Suganuma, Toshihiko; Fujita, Kiyotaka; Kitahara, Kanefumi

    2007-11-01

    The highly humid climate of Japan facilitates the growth of various molds. Among these molds, Aspergillus oryzae is the most important and popular in Japan, and has been used as yellow-koji in producing many traditional fermented beverages and foods, such as Japanese sake, and soy sauce. Taka-amylase A (TAA), a major enzyme produced by the mold, is well known worldwide to be a leading enzyme for industrial utilization and academic study, since many extensive studies have been carried out with TAA. In southern Kyushu, the other koji's of citric acid-producing molds have often been used, such as in the production of a traditional distilled liquor of shochu. The koji molds black-koji and white-koji produce two types of alpha-amylase, namely, acid-stable (AA) and common neutral (NA). The latter enzyme is enzymatically and genetically similar to TAA. In this review, we investigate AA from three molds, Aspergillus niger, A. kawachii and A. awamori, and the yeast Cryptococcus sp. regarding the distinguishable properties between AA and NA. (i) The N-terminus amino acid sequences of AA determined by molecular cloning started with the sequence of L-S-A-, whereas those of NA started with A-T-P-. (ii) Most of the full sequences of AA were composed of, besides a core catalytic domain, an extra domain of a hinge region and a carbohydrate binding domain, which could be responsible for raw-starch-digestibility. The AA from A. niger has no exceptionally extra domain, similarly to NA. (iii) Simple methods for distinguishing AA from NA using CNP-alpha-G3 and G5 as substrates were developed by our group. (iv) The number of subsite in AA on the basis of its cleavage pattern of maltooligosaccharides was estimated to be five, which differs from that of TAA, 7-9. AA has many advantages in industrial applications, such as its acid-stability, thermostability, and raw-starch digesting properties.

  6. The use of the 2-aminobenzoic acid tag for oligosaccharide gel electrophoresis.

    PubMed

    Huang, Z; Prickett, T; Potts, M; Helm, R F

    2000-08-18

    Gel electrophoresis of fluorophore labeled saccharides provides a rapid and reliable method to screen enzymatic and/or chemical treatments of polysaccharides and glycoconjugates, as well as a sensitive and efficient microscale method to separate and purify oligosaccharides for further analysis. A simple and inexpensive method of derivatization and analysis using 2-aminobenzoic acid (anthranilic acid, AA) is described and applied to the extracellular polysaccharide released by the desiccation tolerant cyanobacterium Nostoc commune DRH-1. The results of these analyses suggest a possible protective functionality of two pendent groups, as well as a potential relationship between these groups and the desiccation tolerance of the organism.

  7. PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASIC sensitization in human esophageal epithelial cells.

    PubMed

    Wu, Liping; Oshima, Tadayuki; Shan, Jing; Sei, Hiroo; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

    2015-10-15

    Esophageal visceral hypersensitivity has been proposed to be the pathogenesis of heartburn sensation in nonerosive reflux disease. Protease-activated receptor-2 (PAR-2) is expressed in human esophageal epithelial cells and is believed to play a role in inflammation and sensation. PAR-2 activation may modulate these responses through adenosine triphosphate (ATP) release, which is involved in transduction of sensation and pain. The transient receptor potential vanilloid receptor 1 (TRPV1) and acid-sensing ion channels (ASICs) are both acid-sensitive nociceptors. However, the interaction among these molecules and the mechanisms of heartburn sensation are still not clear. We therefore examined whether ATP release in human esophageal epithelial cells in response to acid is modulated by TRPV1 and ASICs and whether PAR-2 activation influences the sensitivity of TRPV1 and ASICs. Weak acid (pH 5) stimulated the release of ATP from primary human esophageal epithelial cells (HEECs). This effect was significantly reduced after pretreatment with 5-iodoresiniferatoxin (IRTX), a TRPV1-specific antagonist, or with amiloride, a nonselective ASIC blocker. TRPV1 and ASIC3 small interfering RNA (siRNA) transfection also decreased weak acid-induced ATP release. Pretreatment of HEECs with trypsin, tryptase, or a PAR-2 agonist enhanced weak acid-induced ATP release. Trypsin treatment led to the phosphorylation of TRPV1. Acid-induced ATP release enhancement by trypsin was partially blocked by IRTX, amiloride, or a PAR-2 antagonist. Conversely, acid-induced ATP release was augmented by PAR-2 activation through TRPV1 and ASICs. These findings suggested that the pathophysiology of heartburn sensation or esophageal hypersensitivity may be associated with the activation of PAR-2, TRPV1, and ASICs. Copyright © 2015 the American Physiological Society.

  8. Renal Liver-Type Fatty Acid Binding Protein (L-FABP) Attenuates Acute Kidney Injury in Aristolochic Acid Nephrotoxicity

    PubMed Central

    Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro

    2011-01-01

    Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of Nε-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of Nε-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID. PMID:21356355

  9. Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels.

    PubMed

    Abinusawa, Adeyinka; Tenjarla, Srini

    2015-05-01

    Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions. Release of 5-ASA from 6 mesalamine formulations (APRISO®, Salix Pharmaceuticals, Inc., USA; ASACOL® MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL® HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL®, Shire US Inc.; PENTASA®, Ferring Pharmaceuticals, Ltd., UK; SALOFALK®, Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively. Of the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6-8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6-7 h. 5-Aminosalicylic acid release profiles were variable among various commercially available formulations. Shire Development LLC.

  10. Ultrasound stimulated release of gallic acid from chitin hydrogel matrix.

    PubMed

    Jiang, Huixin; Kobayashi, Takaomi

    2017-06-01

    Ultrasound (US) stimulated drug release was examined in this study using a chitin hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin-dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA, with 24h exposure of the solution to water vapor. The GA release from the GA-chitin hydrogel was examined under different US powers of 0-30W at 43kHz. The effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25mg/cm 3 ) and chitin concentrations (0.1, 0.5, and 1wt%) on the release behaviors were recorded under 43kHz US exposure at 30W. Results show that US accelerated the release efficiencies for all samples. Furthermore, the release efficiency increased concomitantly with increasing US power, GA loading amount, and decrease of the chitin concentration. The highest release rate of 0.74μg/mL·min was obtained from 0.54mg/cm 3 of GA-loaded hydrogel fabricated from a 0.1wt% chitin mixture solution under 43kHz US exposure at 30W: nine times higher than that of the sample without US exposure. The hydrogel viscoelasticity demonstrated that the US irradiation rigidified the material. FT-IR showed that US can break the hydrogen bonds in the GA-chitin hydrogels. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Dual inhibitory action of enadoline (CI977) on release of amino acids in the rat hippocampus.

    PubMed

    Millan, M H; Chapman, A G; Meldrum, B S

    1995-06-06

    The effect of the kappa-opioid receptor agonist enadoline (CI977, (5R)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrilidinyl)-1-oxaspiro [4,5]dec-8-yl-4-benzofuranacetamide monohydrochloride), on the release of amino acids was studied in the hippocampus of freely moving rats. K+, 100 mM, or veratrine, 100 microM, were applied for 10 min via the dialysis probe, either alone (control groups) or together with CI977 (after a 10 min pretreatment with CI977 in the perfusion medium). To test the specificity of the response to CI977, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, was delivered together with CI977 in two groups of animals. To test the effect of systemic injection, CI977 was given subcutaneously 30 min prior to either stimulus. K(+)-induced release of glutamate and aspartate was significantly reduced by CI977, 2.5 mM; release of gamma-aminobutyric acid (GABA) was reduced by 250 microM CI977 in the probe. The effect of CI977 on release of glutamate and aspartate, but not of GABA, was reversed by nor-binaltorphimine (45 microM). Systemic treatment with CI977, 1 or 10 mg/kg, did not reduce K(+)-induced release of glutamate. Veratrine-induced release of aspartate and glutamate was significantly inhibited by 25 microM and release of GABA by 250 microM CI977 in the probe, and this effect was not modified by nor-binaltorphimine (58 microM). Systemic injection of CI977 1 mg/kg significantly reduced veratrine-induced release of glutamate. These results indicate that CI977 regulates release of amino acids by two independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis.

    PubMed

    Clara, Rosmarie; Langhans, Wolfgang; Mansouri, Abdelhak

    2016-03-01

    Glucagon-like peptide-1 (GLP-1) is a potent satiating and incretin hormone released by enteroendocrine L-cells in response to eating. Dietary fat, in particular monounsaturated fatty acids, such as oleic acid (OA), potently stimulates GLP-1 secretion from L-cells. It is, however, unclear whether the intracellular metabolic handling of OA is involved in this effect. First we determined the optimal medium for the bioenergetics measurements. Then we examined the effect of OA on the metabolism of the immortalized enteroendocrine GLUTag cell model and assessed GLP-1 release in parallel. We measured oxygen consumption rate and extracellular acidification rate in response to OA and to different metabolic inhibitors with the Seahorse extracellular flux analyzer. OA increased cellular respiration and potently stimulated GLP-1 release. The fatty acid oxidation inhibitor etomoxir did neither reduce OA-induced respiration nor affect the OA-induced GLP-1 release. In contrast, inhibition of the respiratory chain or of downstream steps of aerobic glycolysis reduced the OA-induced GLP-1 release, and an inhibition of the first step of glycolysis by addition of 2-deoxy-d-glucose even abolished it. These findings indicate that an indirect stimulation of glycolysis is crucial for the OA-induced release of GLP-1. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Release of Si from Silicon, a Ferrosilicon (FeSi) Alloy and a Synthetic Silicate Mineral in Simulated Biological Media

    PubMed Central

    Herting, Gunilla; Jiang, Tao; Sjöstedt, Carin; Odnevall Wallinder, Inger

    2014-01-01

    Unique quantitative bioaccessibility data has been generated, and the influence of surface/material and test media characteristics on the elemental release process were assessed for silicon containing materials in specific synthetic body fluids at certain time periods at a fixed loading. The metal release test protocol, elaborated by the KTH team, has previously been used for classification, ranking, and screening of different alloys and metals. Time resolved elemental release of Si, Fe and Al from particles, sized less than 50 µm, of two grades of metallurgical silicon (high purity silicon, SiHG, low purity silicon, SiLG), an alloy (ferrosilicon, FeSi) and a mineral (aluminium silicate, AlSi) has been investigated in synthetic body fluids of varying pH, composition and complexation capacity, simple models of for example dermal contact and digestion scenarios. Individual methods for analysis of released Si (as silicic acid, Si(OH)4) in synthetic body fluids using GF-AAS were developed for each fluid including optimisation of solution pH and graphite furnace parameters. The release of Si from the two metallurgical silicon grades was strongly dependent on both pH and media composition with the highest release in pH neutral media. No similar effect was observed for the FeSi alloy or the aluminium silicate mineral. Surface adsorption of phosphate and lactic acid were believed to hinder the release of Si whereas the presence of citric acid enhanced the release as a result of surface complexation. An increased presence of Al and Fe in the material (low purity metalloid, alloy or mineral) resulted in a reduced release of Si in pH neutral media. The release of Si was enhanced for all materials with Al at their outermost surface in acetic media. PMID:25225879

  14. Synthesis and colon-specific drug delivery of a poly(acrylic acid-co-acrylamide)/MBA nanosized hydrogel.

    PubMed

    Ray, Debajyoti; Mohapatra, Dillip K; Mohapatra, Ranjit K; Mohanta, Guru P; Sahoo, Prafulla K

    2008-01-01

    Intravenous administration of 5-fluorouracil (5-FU) for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The main objective of the present study was to develop novel oral site-specific delivery of 5-FU to the colon with less drug being released in the stomach or small intestine using biodegradable hydrogel, hydrogel nanoparticles and comparing the targeting efficiency of 5-FU to colon from both. Poly(acrylic acid-co-acrylamide) (P(AA-co-Am)) normal hydrogel and hydrogel nanoparticles (HN) were synthesized by free radical polymerization using N,N-methylene-bis-acrylamide (MBA) as cross-linker, potassium persulfate as reaction initiator and 5-FU was loaded. HN were found to be degradable in physiological medium and showed comparatively higher swelling in rat caecal medium (RCM). 5-FU entrapment was increased by increasing Am (wt%) monomer feed. In vitro release of 5-FU from normal hydrogel and HN in pH progressive medium, it was found that a AA/Am ratio of 25:75 showed higher release in RCM. The Higuchi model yielded good adjustment of in vitro release kinetics. A higher amount of 5-FU reached the colon in HN (61 +/- 2.1%) than normal hydrogel (40 +/- 3.6%) by organ biodistribution studies in albino rats.

  15. Longitudinal study of experimental induction of AA amyloidosis in mice seeded with homologous and heterologous AA fibrils.

    PubMed

    Muhammad, Naeem; Murakami, Tomoaki; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-09-01

    To investigate pathogenesis and kinetics of experimentally induced murine AA amyloidosis seeded with homologous (murine) and heterologous (bovine) AA fibrils. Experimental AA amyloidosis was induced by administration of inflammatory stimulus and preformed AA fibrils to a total of 111 female C57/Black mice. In this longitudinal study, heterologous (bovine) as well as homologous (murine) AA fibrils were injected intraperitoneally to mice in various combinations. Re-stimulation was done at 120 or 300 days post first inoculation. To analyze the intensity of amyloid depositions in mice organs, immunohistochemical techniques and image J software were used. Assessment of cytokines level in sera was done using a Mouse Th1/Th2/Th17 Cytokine CBA Kit. Incidence and severity of AA amyloidosis were quite low in mice inoculated with heterologous bovine AA fibrils than homologous murine one. Homologous AA fibrils administration at first and second inoculation caused maximum amount of amyloid depositions and severe systemic form of amyloidosis. Increase in the level of pro-inflammatory cytokine IL-6 was observed after first inoculation, while second inoculation caused a further increase in the level of anti-inflammatory cytokine IL-10. AA amyloidosis can be induced by heterologous as well as homologous AA fibrils. Severity of AA amyloidosis induced with homologous AA fibrils is higher compared to heterologous AA fibrils.

  16. The effect of methylcellulose on metronidazole release from polyacrylic acid hydrogels.

    PubMed

    Musial, Witold

    2007-08-01

    Topical treatment of acne rosacea, a chronic condition characterized by recurrent course for many years, is primarily based on metronidazole preparations. The aim of this study was to evaluate the effect of various acrylic acid polymers, in composition with methylcellulose on metronidazole release rate from hydrogels proposed for the treatment of acne rosacea. Viscosity and release studies using "Paddle over Disk" system with semipermeable membrane of MWCO 3500 were performed. Compositions of Carbopol 971P and methylcellulose revealed an increase in viscosity with increasing concentration of methylcellulose in the range of 17200-26166 mPa.s. In all the examined formulations, the release process was characterized by a two-stage course. Among bipolymeric formulations, the highest first-stage release rate of 9.18 x 10(-3) min(-1) was determined for the gel consisting of 2.00% Carbopol 980NF with 1.00% methylcellulose. The second-stage release rates ranged between 2.88 x 10(-3) and 8.00 x 10(-3) min(-1). Two-stage release course can thus be attributed to metronidazole distribution into two compartments of hydrogel matrix. Proposed gels, with similar rheological properties, may be used for ex vivo and in vivo studies to obtain a suitable drug activity of metronidazole in the treatment of acne rosacea.

  17. Impact of arachidonic versus eicosapentaenoic acid on exotonin-induced lung vascular leakage: relation to 4-series versus 5-series leukotriene generation.

    PubMed

    Grimminger, F; Wahn, H; Mayer, K; Kiss, L; Walmrath, D; Seeger, W

    1997-02-01

    Escherichia coli hemolysin (HlyA) is a proteinaceous pore-forming exotoxin that is implicated as a significant pathogenicity factor in extraintestinal E. coli infections including sepsis. In perfused rabbit lungs, subcytolytic concentrations of the toxin evoke thromboxane-mediated vasoconstriction and prostanoid-independent protracted vascular permeability increase (11). In the present study, the influence of submicromolar concentrations of free arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the HlyA-induced leakage response was investigated. HlyA at concentration from 0.02 to 0.06 hemolytic units/ml provoked a dose-dependent, severalfold increase in the capillary filtration coefficient (Kfc), accompanied by the release of leukotriene(LT)B4, LTC4, and LTE4 into the recirculating buffer fluid. Simultaneous application of 100 nmol/L AA markedly augmented the HlyA-elicited leakage response, concomitant with an amplification of LTB4 release and a change in the kinetics of cysteinyl-LT generation. In contrast, 50 to 200 nmol/L EPA suppressed in a dose-dependent manner the HlyA-induced increase in Kfc values. This was accompanied by a blockage of 4-series LT generation and a dose-dependent appearance of LTB5, LTC5, and LTE5. In addition, EPA fully antagonized the AA-induced amplification of the HlyA-provoked Kfc increase, again accompanied by a shift from 4-series to 5-series LT generation. We conclude that the vascular leakage provoked by HlyA in rabbit lungs is differentially influenced by free AA versus free EPA, related to the generation of 4- versus 5-series leukotrienes. The composition of lipid emulsions used for parenteral nutrition may thus influence inflammatory capillary leakage.

  18. Site-saturation engineering of lysine 47 in cyclodextrin glycosyltransferase from Paenibacillus macerans to enhance substrate specificity towards maltodextrin for enzymatic synthesis of 2-O-D-glucopyranosyl-L-ascorbic acid (AA-2G).

    PubMed

    Han, Ruizhi; Liu, Long; Shin, Hyun-dong; Chen, Rachel R; Du, Guocheng; Chen, Jian

    2013-07-01

    In this work, the site-saturation engineering of lysine 47 in cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans was conducted to improve the specificity of CGTase towards maltodextrin, which can be used as a cheap and easily soluble glycosyl donor for the enzymatic synthesis of 2-O-D-glucopyranosyl-L-ascorbic acid (AA-2G) by CGTase. When using maltodextrin as glycosyl donor, four mutants K47F (lysine→ phenylalanine), K47L (lysine→ leucine), K47V (lysine→ valine) and K47W (lysine→ tryptophan) showed higher AA-2G yield as compared with that produced by the wild-type CGTase. The transformation conditions (temperature, pH and the mass ratio of L-ascorbic acid to maltodextrin) were optimized and the highest titer of AA-2G produced by the mutant K47L could reach 1.97 g/l, which was 64.2% higher than that (1.20 g/l) produced by the wild-type CGTase. The reaction kinetics analysis confirmed the enhanced maltodextrin specificity, and it was also found that compared with the wild-type CGTase, the four mutants had relatively lower cyclization activities and higher disproportionation activities, which was favorable for AA-2G synthesis. The mechanism responsible for the enhanced substrate specificity was further explored by structure modeling and it was indicated that the enhancement of maltodextrin specificity may be due to the short residue chain and the removal of hydrogen bonding interactions between the side chain of residue 47 and the sugar at -3 subsite. Here the obtained mutant CGTases, especially the K47L, has a great potential in the production of AA-2G with maltodextrin as a cheap and easily soluble substrate.

  19. Influence of organic acids on kinetic release of chromium in soil contaminated with leather factory waste in the presence of some adsorbents.

    PubMed

    Taghipour, Marzieh; Jalali, Mohsen

    2016-07-01

    In this study, batch experiments were conducted to investigate the effects of nanoparticles (NPs) (MgO, ZnO, TiO2) and clay minerals (bentonite, zeolite) on the release of chromium (Cr) from leather factory waste (LFW) and LFW treated soil using organic acids. Chromium release from all treatments was studied in the presence of citric acid, oxalic acid and CaCl2 solutions. The results showed that, in all treatments, organic acids released more Cr than inorganic salt (CaCl2). The release of Cr by citric acid was higher than that by oxalic acid. In LFW treated soil and LFW, the release of Cr from the all treatments with NPs was less than that from the clay mineral treatments. On the other hand, in the presence of organic acids, Cr release by NPs and clay minerals decreased. Two kinetic models including pseudo-first- and pseudo-second-order model were tested to describe the time dependent Cr release data. Among the kinetic models used, the pseudo-second-order model generally gave the best fits to experimental data. Before and after release experiments, Cr in LFW, treated LFW, control soil and LFW treated soils were fractionated. In all treatments, the greatest amounts of Cr were found in the residual fraction (RES). The organic acids were effective in reducing the exchangeable (EXC), bound to organic matter (OM) and bound to carbonate (CAR) fractions of Cr in all treatments, whereas, after release of Cr from treated soils, Cr remained mainly in the RES fraction. The application of NPs and clay minerals in soil led to a significant transformation of Cr from mobile fractions to the RES fraction. Therefore, organic ligands played a dominant role in mobility and bioavailability of Cr and the removal of Cr by adsorbents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Synthesis and characterization of agricultural controllable humic acid superabsorbent.

    PubMed

    Gao, Lijuan; Wang, Shiqiang; Zhao, Xuefei

    2013-12-01

    Humic acid superabsorbent polymer (P(AA/AM-HA)) and superabsorbent polymer (P(AA/AM)) were synthesized by aqueous solution polymerization method using acrylic acid (AA), acrylamide (AM) and humic acid (HA) as raw material. The effects of N,N'-methylenebisacrylamide (MBA) crosslinking agent, potassium peroxydisulfate (KPS) initiator, reaction temperature, HA content, ratio of AA to AM, concentration of monomer and neutralization of AA on water absorption were investigated. Absorption and desorption ratios of nitrogen fertilizer and phosphate fertilizer were also investigated by determination of absorption and desorption ratio of NH4(+), PO4(3-) on P(AA/AM-HA) and P(AA/AM). The P(AA/AM-HA) and P(AA/AM) were characterized by Fourier translation infrared spectroscopy, biological photomicroscope and scanning electron microscopy (SEM). The optimal conditions obtained were as follows: the weight ratio of MBA to AA and AM was 0.003; the weight ratio of KPS to AA and AM was 0.008; the weight ratio of HA to AA was 0.1; the mole ratio of AM to AA is 0.1; the mole ratio of NaOH to AA is 0.9; the reaction temperature was 60°C. P(AA/AM-HA) synthesized under optimal conditions, has a good saline tolerance, its water absorbency in distilled water and 0.9 wt.% saline solution is 1180 g/g and 110 g/g, respectively. P(AA/AM-HA) achieves half saturation in 6.5 min. P(AA/AM-HA) is superior to P(AA/AM) on absorption of NH4(+), PO4(3-). The SEM micrograph of P(AA/AM-HA) shows a fine alveolate structure. The biological optical microscope micrograph of P(AA/AM-HA) shows a network structure. Graft polymerization between P(AA/AM) and HA was demonstrated by infrared spectrum. The P(AA/AM-HA) superabsorbent has better absorbing ability of water and fertilizer, electrolytic tolerance and fewer cost than P(AA/AM) superabsorbent. Copyright © 2013 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  1. Amino acid supplementation alters bone metabolism during simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

    2005-01-01

    High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

  2. Uptake and conversion of D-amino acids in Arabidopsis thaliana.

    PubMed

    Gördes, Dirk; Kolukisaoglu, Üner; Thurow, Kerstin

    2011-02-01

    The D-enantiomers of proteinogenic amino acids fulfill essential functions in bacteria, fungi and animals. Just in the plant kingdom, the metabolism and role of D-amino acids (D-AAs) still remains unclear, although plants have to cope with significant amounts of these compounds from microbial decay in the rhizosphere. To fill this gap of knowledge, we tested the inhibitory effects of D-AAs on plant growth and established a method to quantitate 16 out of 19 proteinogenic amino acids and their D-enantiomers in plant tissue extracts. Therefore, the amino acids in the extracts were derivatized with Marfey's reagent and separated by HPLC-MS. We used two ecotypes (Col-0 and C24) and a mutant (lht1) of the model plant Arabidopsis thaliana to determine the influence and fate of exogenously applied D-AAs. All of them were found in high concentrations in the plant extracts after application, even in lht1, which points to additional transporters facilitating the import of D-AAs. The addition of particular amino acids (D-Trp, D-Phe, D-Met and D-His) led to the accumulation of the corresponding L-amino acid. In almost all cases, the application of a D-AA resulted in the accumulation of D-Ala and D-Glu. The presented results indicate that soil borne D-AAs can actively be taken up and metabolized via central metabolic routes.

  3. Detection of AA76, a Common Form of Amyloid A Protein, as a Way of Diagnosing AA Amyloidosis.

    PubMed

    Sato, Junji; Okuda, Yasuaki; Kuroda, Takeshi; Yamada, Toshiyuki

    2016-01-01

    Reactive amyloid deposits consist of amyloid A (AA) proteins, the degradation products of serum amyloid A (SAA). Since the most common species of AA is the amino terminal portion produced by cleavage between residues 76 and 77 of SAA (AA76), the presence of AA76 in tissues could be a consequence of AA amyloid deposition. This study assessed the diagnostic significance of the detection of AA76 for AA amyloidosis using two different approaches. Biopsy specimens (n=130 from 54 subjects) from gastroduodenal mucosa or abdominal fat (n=9 from 9 subjects) of patients who had already been diagnosed with or were suspected of having AA amyloidosis were used. Fixed mucosal sections were subjected to immunohistochemistry using a newly developed antibody recognizing the carboxyl terminal end of AA76 (anti-AA76). The non-fixed materials from gastroduodenal mucosa or abdominal fat were subjected to immunoblotting for detection of the size of AA76. Among the gastroduodenal specimens (n=115) from already diagnosed patients, the positive rates of Congo red staining, immunohistochemistry using anti-AA76, and immunoblotting were 68.4%, 73.0%, and 92.2%, respectively. The anti-AA76 did not stain the supposed SAA in the blood or leakage, which was stained by anti-SAA antibody. AA76 was not detected either by immunohistochemistry or by immunoblot in the materials from patients in whom AA amyloidosis had been ruled out. In the abdominal fat, the immunoblot detected AA76 in 8 materials from 8 already diagnosed patients and did not in 1 patient whose gastroduodenal mucosa was negative. In conclusion, the detection of AA76 may alter the ability to diagnose AA amyloidosis. In immunohistochemistry for fixed specimens, the new anti-AA76 antibody can improve the specificity. Immunoblot for non-fixed materials, which can considerably improve the sensitivity, should be beneficial for small materials like abdominal fat. © 2016 by the Association of Clinical Scientists, Inc.

  4. Dietary arachidonic acid in perinatal nutrition: a commentary.

    PubMed

    Lauritzen, Lotte; Fewtrell, Mary; Agostoni, Carlo

    2015-01-01

    Arachidonic acid (AA) is supplied together with docosahexaenoic acid (DHA) in infant formulas, but we have limited knowledge about the effects of supplementation with either of these long-chain polyunsaturated fatty acids (LCPUFA) on growth and developmental outcomes. AA is present in similar levels in breast milk throughout the world, whereas the level of DHA is highly diet dependent. Autopsy studies show similar diet-dependent variation in brain DHA, whereas AA is little affected by intake. Early intake of DHA has been shown to affect visual development, but the effect of LCPUFA on neurodevelopment remains to be established. Few studies have found any functional difference between infants supplemented with DHA alone compared to DHA+AA, but some studies show neurodevelopmental advantages in breast-fed infants of mothers supplemented with n-3 LCPUFA alone. It also remains to be established whether the AA/DHA balance could affect allergic and inflammatory outcomes later in life. Disentangling effects of genetic variability and dietary intake on AA and DHA-status and on functional outcomes may be an important step in the process of determining whether AA-intake is of any physiological or clinical importance. However, based on the current evidence we hypothesize that dietary AA plays a minor role on growth and development relative to the impact of dietary DHA.

  5. Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

    PubMed

    Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2017-04-01

    Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

  6. Low molecular weight polylactic acid as a matrix for the delayed release of pesticides.

    PubMed

    Zhao, Jing; Wilkins, Richard M

    2005-05-18

    Low molecular weight polylactic acid (LMW PLA) was used as a matrix to formulate biodegradable matrix granules and films with bromacil using a melt process. The compatibility of the PLA with bromacil was evaluated. The release characteristics of the formulations were investigated in vitro. The degradation and erosion of the formulations were monitored by pH and gravimetric analysis during the course of release. Various granules and films had similar biphasic release patterns, a delayed release followed by an explosive release. The release rates were independent of bromacil content in the matrix, but varied with the geometry of matrices. The mechanisms of diffusion and erosion were involved in the release. The delayed release of the formulations was dominantly governed by the degradation and erosion of PLA. LMW PLA underwent bulk erosion. LMW PLA-based matrix formulations could thus be useful for the application of pesticides to sensitive targets such as seed treatment.

  7. Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life.

    PubMed

    Alessandri, Jean-Marc; Guesnet, Philippe; Vancassel, Sylvie; Astorg, Pierre; Denis, Isabelle; Langelier, Bénédicte; Aïd, Sabah; Poumès-Ballihaut, Carine; Champeil-Potokar, Gaëlle; Lavialle, Monique

    2004-01-01

    Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are the major polyunsaturated fatty acids in the membranes of brain and retinal cells. Animals specifically deficient in dietary n-3 fatty acids have low DHA content in their membranes, reduced visual acuity and impaired learning ability. Studies on bottle-fed human infants have shown that adding DHA and AA to milk replacer-formulas can bring their concentrations in the infant blood lipids to values as high as those produced by breast-feeding and significantly improves mental development and maturation of visual function. In older subjects, diverse neuropsychiatric and neurodegenerative diseases have been associated to decreased blood levels of n-3 PUFA. Low intakes of fish or of n-3 PUFA in populations have been associated with increased risks of depression and Alzheimer disease, and n-3 PUFA, especially eicosapentaenoic acid (EPA, 20:5n-3), have shown efficacy as adjunctive treatment - and in some cases as the only treatment--in several psychiatric disorders. The mechanisms by which polyunsaturated fatty acids have an impact on neuronal functions will be reviewed: the modulation of membrane biophysical properties, regulation of neurotransmitter release, synthesis of biologically active oxygenated derivatives, and nuclear receptor-mediated transcription of genes responsive to fatty acids or to their derivatives.

  8. Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols

    PubMed Central

    Bomar, Lindsey; Brugger, Silvio D.; Yost, Brian H.; Davies, Sean S.

    2016-01-01

    ABSTRACT Bacterial interspecies interactions play clinically important roles in shaping microbial community composition. We observed that Corynebacterium spp. are overrepresented in children free of Streptococcus pneumoniae (pneumococcus), a common pediatric nasal colonizer and an important infectious agent. Corynebacterium accolens, a benign lipid-requiring species, inhibits pneumococcal growth during in vitro cocultivation on medium supplemented with human skin surface triacylglycerols (TAGs) that are likely present in the nostrils. This inhibition depends on LipS1, a TAG lipase necessary for C. accolens growth on TAGs such as triolein. We determined that C. accolens hydrolysis of triolein releases oleic acid, which inhibits pneumococcus, as do other free fatty acids (FFAs) that might be released by LipS1 from human skin surface TAGs. Our results support a model in which C. accolens hydrolyzes skin surface TAGS in vivo releasing antipneumococcal FFAs. These data indicate that C. accolens may play a beneficial role in sculpting the human microbiome. PMID:26733066

  9. Adipic acid production catalyzed by a combination of a solid acid and an iodide salt from biomass-derived tetrahydrofuran-2,5-dicarboxylic acid

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gilkey, Matthew J.; Balakumar, Rachana; Vlachos, Dionisios G.

    We recently reported biomass-derived tetrahydrofuran-2,5-dicarboxylic acid (THFDCA) as a potential renewable feedstock for adipic acid (AA) production by combining HI and molecular H 2 in organic acid solvents.

  10. Adipic acid production catalyzed by a combination of a solid acid and an iodide salt from biomass-derived tetrahydrofuran-2,5-dicarboxylic acid

    DOE PAGES

    Gilkey, Matthew J.; Balakumar, Rachana; Vlachos, Dionisios G.; ...

    2018-01-01

    We recently reported biomass-derived tetrahydrofuran-2,5-dicarboxylic acid (THFDCA) as a potential renewable feedstock for adipic acid (AA) production by combining HI and molecular H 2 in organic acid solvents.

  11. Multifunctional hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release for enhanced tumor suppression.

    PubMed

    Liu, Xuhan; Li, Yinghuan; Tan, Xi; Rao, Rong; Ren, Yuanyuan; Liu, Lingyan; Yang, Xiangliang; Liu, Wei

    2018-03-01

    Therapeutic efficacy of conventional single PEGylated polymeric micelles is significantly reduced by limited endocytosis and intracellular drug release. To improve drug delivery efficiency, poly (ethylene glycol)-block-poly (l-lactic acid)/(Arg-Gly-Asp-Phe)-poly (aminoethyl ethylene phosphate)-block-poly (l-lactic acid) (PEG-PLLA/RGDF-PAEEP-PLLA) hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release are developed. The optimized hybrid micelles with 6 wt % of RGDF have favorable in vitro and in vivo activities. The hybrid micelles could temporarily shield the targeting efficacy of RGDF at pH 7.4 due to the steric effect exerted by concealment of RGDF peptides in the PEG corona, which strongly decreases the clearance by mononuclear phagocyte system and consequently improves the tumor accumulation. Inside the solid tumor with a lower acidic pH, the hybrid micelles restore the active tumor targeting property with exposed RGDF on the surface of the micelles because of the increased protonation and stretching degree of PAEEP blocks. RGDF-mediated endocytosis improves the tumor cell uptake. The hybrid micelles would also enhance intracellular drug release because of the hydrolysis of the acid/phosphatase-sensitivity of PAEEP blocks in endo/lysosome. Systemic administration of the hybrid micelles significantly inhibits tumor growth by 96% due to the integration of enhanced circulation time, tumor accumulation, cell uptake and intracellular drug release. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Transcriptome profiling of the intoxication response of Tenebrio molitor larvae to Bacillus thuringiensis Cry3Aa protoxin.

    PubMed

    Oppert, Brenda; Dowd, Scot E; Bouffard, Pascal; Li, Lewyn; Conesa, Ana; Lorenzen, Marcé D; Toutges, Michelle; Marshall, Jeremy; Huestis, Diana L; Fabrick, Jeff; Oppert, Cris; Jurat-Fuentes, Juan Luis

    2012-01-01

    Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against a select number of insect pests, but improvements are needed to increase efficacy and decrease time to mortality for coleopteran pests. To gain insight into the Bt intoxication process in Coleoptera, we performed RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that consumed either a control diet or a diet containing Cry3Aa protoxin. Approximately 134,090 and 124,287 sequence reads from the control and Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated with mitochondrial respiration, signalling, maintenance of cell structure, membrane integrity, protein recycling/synthesis, and glycosyl hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid synthesis. Microarray analysis was used to evaluate temporal changes in gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of the RNA-Seq data. Of the three intoxication intervals, larvae demonstrated more differential expression of transcripts after 12 h exposure to Cry3Aa. Gene expression examined by three different methods in control vs. Cry3Aa-treated larvae at the 24 h time point indicated that transcripts encoding proteins with chitin-binding domain 3 were the most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the data suggest that T. molitor larvae mount a complex response to Cry3Aa during the initial 24 h of intoxication. Data from this study represent the largest genetic sequence dataset for T. molitor

  13. Transcriptome Profiling of the Intoxication Response of Tenebrio molitor Larvae to Bacillus thuringiensis Cry3Aa Protoxin

    PubMed Central

    Oppert, Brenda; Dowd, Scot E.; Bouffard, Pascal; Li, Lewyn; Conesa, Ana; Lorenzen, Marcé D.; Toutges, Michelle; Marshall, Jeremy; Huestis, Diana L.; Fabrick, Jeff; Oppert, Cris; Jurat-Fuentes, Juan Luis

    2012-01-01

    Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against a select number of insect pests, but improvements are needed to increase efficacy and decrease time to mortality for coleopteran pests. To gain insight into the Bt intoxication process in Coleoptera, we performed RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that consumed either a control diet or a diet containing Cry3Aa protoxin. Approximately 134,090 and 124,287 sequence reads from the control and Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated with mitochondrial respiration, signalling, maintenance of cell structure, membrane integrity, protein recycling/synthesis, and glycosyl hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid synthesis. Microarray analysis was used to evaluate temporal changes in gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of the RNA-Seq data. Of the three intoxication intervals, larvae demonstrated more differential expression of transcripts after 12 h exposure to Cry3Aa. Gene expression examined by three different methods in control vs. Cry3Aa-treated larvae at the 24 h time point indicated that transcripts encoding proteins with chitin-binding domain 3 were the most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the data suggest that T. molitor larvae mount a complex response to Cry3Aa during the initial 24 h of intoxication. Data from this study represent the largest genetic sequence dataset for T. molitor

  14. The selective conversion of glutamic acid in amino acid mixtures using glutamate decarboxylase--a means of separating amino acids for synthesizing biobased chemicals.

    PubMed

    Teng, Yinglai; Scott, Elinor L; Sanders, Johan P M

    2014-01-01

    Amino acids (AAs) derived from hydrolysis of protein rest streams are interesting feedstocks for the chemical industry due to their functionality. However, separation of AAs is required before they can be used for further applications. Electrodialysis may be applied to separate AAs, but its efficiency is limited when separating AAs with similar isoelectric points. To aid the separation, specific conversion of an AA to a useful product with different charge behavior to the remaining compounds is desired. Here the separation of L-aspartic acid (Asp) and L-glutamic acid (Glu) was studied. L-Glutamate α-decarboxylase (GAD, Type I, EC 4.1.1.15) was applied to specifically convert Glu into γ-aminobutyric acid (GABA). GABA has a different charge behavior from Asp therefore allowing a potential separation by electrodialysis. Competitive inhibition and reduced operational stability caused by Asp could be eliminated by maintaining a sufficiently high concentration of Glu. Immobilization of GAD does not reduce the enzyme's initial activity. However, the operational stability was slightly reduced. An initial study on the reaction operating in a continuous mode was performed using a column reactor packed with immobilized GAD. As the reaction mixture was only passed once through the reactor, the conversion of Glu was lower than expected. To complete the conversion of Glu, the stream containing Asp and unreacted Glu might be recirculated back to the reactor after GABA has been removed. Overall, the reaction by GAD is specific to Glu and can be applied to aid the electrodialysis separation of Asp and Glu. © 2014 American Institute of Chemical Engineers.

  15. Acetic Acid Can Catalyze Succinimide Formation from Aspartic Acid Residues by a Concerted Bond Reorganization Mechanism: A Computational Study

    PubMed Central

    Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

    2015-01-01

    Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism. PMID:25588215

  16. Acetic acid can catalyze succinimide formation from aspartic acid residues by a concerted bond reorganization mechanism: a computational study.

    PubMed

    Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

    2015-01-12

    Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism.

  17. p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts

    PubMed Central

    Seok, Jin Kyung

    2015-01-01

    Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is associated with skin photoaging. Recent studies demonstrated that keratinocyte-releasable stratifin (SFN) plays a critical role in skin collagen metabolism by inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In the present study, we examined whether SFN released from UVB-irradiated epidermal keratinocytes increases MMP1 release from dermal fibroblasts, and whether these events are affected by p-coumaric acid (p-CA), a natural phenolic compound with UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the absence and presence of p-CA, and the conditioned medium was used to stimulate fibroblasts in medium transfer experiments. The cells and media were analyzed to determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN release from keratinocytes into the medium. The conditioned medium of UVB-irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion of SFN using a siRNA rendered the conditioned medium of UVB-irradiated keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1 release by fibroblasts in medium transfer experiments. In conclusion, the present study demonstrated that the use of UV absorbers such as p-CA would reduce UV-induced SFN-centered signaling events involved in skin photoaging. PMID:25954129

  18. p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts.

    PubMed

    Seok, Jin Kyung; Boo, Yong Chool

    2015-05-01

    Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is associated with skin photoaging. Recent studies demonstrated that keratinocyte-releasable stratifin (SFN) plays a critical role in skin collagen metabolism by inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In the present study, we examined whether SFN released from UVB-irradiated epidermal keratinocytes increases MMP1 release from dermal fibroblasts, and whether these events are affected by p-coumaric acid (p-CA), a natural phenolic compound with UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the absence and presence of p-CA, and the conditioned medium was used to stimulate fibroblasts in medium transfer experiments. The cells and media were analyzed to determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN release from keratinocytes into the medium. The conditioned medium of UVB-irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion of SFN using a siRNA rendered the conditioned medium of UVB-irradiated keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1 release by fibroblasts in medium transfer experiments. In conclusion, the present study demonstrated that the use of UV absorbers such as p-CA would reduce UV-induced SFN-centered signaling events involved in skin photoaging.

  19. Unique anthranilic acid chemistry facilitates profiling and characterization of Ser/Thr-linked sugar chains following hydrazinolysis.

    PubMed

    Anumula, Kalyan Rao

    2008-02-01

    A novel method for the analysis of Ser/Thr-linked sugar chains was made possible by the virtue of unique anthranilic acid (AA, 2-aminobenzoic acid [2AA]) chemistry for labeling carbohydrates in aqueous salt solutions (K. R. Anumula, Anal. Biochem. 350 (2006) 1-23). The protocol for profiling of Ser/Thr carbohydrates by hydrazinolysis was made simple by eliminating intermediary isolation steps involved in a sample preparation such as desalting and various chromatographic purification schemes. A 6-h hydrazinolysis was carried out at 60 degrees C for O-linked oligosaccharides and at 95 degrees C for total oligosaccharides (N-linked with some O-linked). Following evaporation of hydrazine (<10 min), the oligosaccharides were N-acetylated and derivatized with AA in the same reaction mixture containing salts. Presumably, the glycosyl-hydrazines/hydrazones present in the mixture did not interfere with AA labeling. Because AA is the most fluorescent and highly reactive tag for labeling carbohydrates, the procedures described are suitable for the analysis of a limited amount of samples ( approximately 5 microg) by the current high-resolution high-performance liquid chromatography (HPLC) methods. HPLC conditions developed for the separation of O-linked sugar chains based on size on an amide column were satisfactory for quantitative profiling and characterization. Common O-linked sugar chains found in fetuin, equine chorionic gonadotropin, and glycophorin can be analyzed in less than 50 min. In addition, these fast profiling methods were comparable to profiling by PNGase F (peptide N-glycosidase from Flavobacterium meningosepticum) digestion in terms of time, effort, and simplicity and also were highly reproducible for routine testing. The procedures for the release of sugar chains by hydrazinolysis at the microgram level, labeling with fluorescent tag AA, and profiling by HPLC should be useful in characterization of carbohydrates found in glycoproteins.

  20. Docosahexaenoic acid affects arachidonic acid uptake in megakaryocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schick, P.K.; Webster, P.

    1987-05-01

    Dietary omega 3 fatty acids are thought to prevent atherosclerosis, possibly by modifying platelet (PT) function and arachidonic acid (20:4) metabolism. The study was designed to determine whether omega 3 fatty acids primarily affect 20:4 metabolism in megakaryocytes (MK), bone marrow precursors of PT, rather than in circulating PT. MK and PT were isolated from guinea pigs and incubated with (/sup 14/C)-20:4 (0.13uM). Docosahexaenoic acid (22:6) is a major omega 3 fatty acid in marine oils. The incubation of MK with 22:6 (0.1, 1.0 uM) resulted in the decrease of incorporation of (/sup 14/C)-20:4 into total MK phospholipids, 16% andmore » 41% respectively. Alpha-linolenic acid (18:3), a major omega 3 fatty acid present in American diets, had no effect on 20:4 uptake in MK. 22:6 primarily affected the uptake of (/sup 14/C)-20:4 into phosphatidylethanolamine (PE) and phosphatidylserine (PS) in MK. In MK, 22:6 (0.1, 1.0 uM) caused a decrease of incorporation of (/sup 14/C)-20:4 into PE, 21% and 55% respectively; a decrease into PS, 16% and 48% respectively; but only a decrease of 4% and 18%, respectively, into phosphatidylcholine; and a decrease of 3% and 21% into phosphatidylinositol 22:6 (3.0 uM) had no effect on the uptake of AA into PT phospholipids. The study shows that 22:6 has a selective effect on AA uptake in MK and that the acylation or transacylation of PE and PS are primarily affected. 22:6 and other marine omega 3 fatty acids appear to primarily affect megakaryocytes which may result in the production of platelets with abnormal content and compartmentalization of AA.« less

  1. On the cellular metabolism of the click chemistry probe 19-alkyne arachidonic acid[S

    PubMed Central

    Robichaud, Philippe Pierre; Poirier, Samuel J.; Boudreau, Luc H.; Doiron, Jérémie A.; Barnett, David A.; Boilard, Eric; Surette, Marc E.

    2016-01-01

    Alkyne and azide analogs of natural compounds that can be coupled to sensitive tags by click chemistry are powerful tools to study biological processes. Arachidonic acid (AA) is a FA precursor to biologically active compounds. 19-Alkyne-AA (AA-alk) is a sensitive clickable AA analog; however, its use as a surrogate to study AA metabolism requires further evaluation. In this study, AA-alk metabolism was compared with that of AA in human cells. Jurkat cell uptake of AA was 2-fold greater than that of AA-alk, but significantly more AA-Alk was elongated to 22:4. AA and AA-alk incorporation into and remodeling between phospholipid (PL) classes was identical indicating equivalent CoA-independent AA-PL remodeling. Platelets stimulated in the pre­sence of AA-alk synthesized significantly less 12-lipoxygenase (12-LOX) and cyclooxygenase products than in the presence of AA. Ionophore-stimulated neutrophils produced significantly more 5-LOX products in the presence of AA-alk than AA. Neutrophils stimulated with only exogenous AA-alk produced significantly less 5-LOX products compared with AA, and leukotriene B4 (LTB4)-alk was 12-fold less potent at stimulating neutrophil migration than LTB4, collectively indicative of weaker leukotriene B4 receptor 1 agonist activity of LTB4-alk. Overall, these results suggest that the use of AA-alk as a surrogate for the study of AA metabolism should be carried out with caution. PMID:27538823

  2. Nitrous-acid-mediated synthesis of iron-nitrosyl-porphyrin: pH-dependent release of nitric oxide.

    PubMed

    Bhuyan, Jagannath; Sarkar, Sabyasachi

    2012-11-01

    Two iron-nitrosyl-porphyrins, nitrosyl[meso-tetrakis(3,4,5-trimethoxyphenylporphyrin]iron(II) acetic acid solvate (3) and nitrosyl[meso-tetrakis(4-methoxyphenylporphyrin]iron(II) CH(2)Cl(2) solvate (4), were synthesized in quantitative yield by using a modified procedure with nitrous acid, followed by oxygen-atom abstraction by triphenylphosphine under an argon atmosphere. These nitrosyl porphyrins are in the {FeNO}(7) class. Under an argon atmosphere, these compounds are relatively stable over a broad range of pH values (4-8) but, under aerobic conditions, they release nitric oxide faster at high pH values than that at low pH values. The generated nitric-oxide-free iron(III)-porphyrin can be re-nitrosylated by using nitrous acid and triphenylphosphine. The rapid release of NO from these Fe(II) complexes at high pH values seems to be similar to that in nitrophorin, a nitric-oxide-transport protein, which formally possesses Fe(III). However, because the release of NO occurs from ferrous-nitrosyl-porphyrin under aerobic conditions, these compounds are more closely related to nitrobindin, a recently discovered heme protein. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Characterization of carbohydrates using highly fluorescent 2-aminobenzoic acid tag following gel electrophoresis of glycoproteins.

    PubMed

    Anumula, K R; Du, P

    1999-11-15

    Application of the most sensitive fluorescent label 2-aminobenzoic acid (anthranilic acid, AA) for characterization of carbohydrates from the glycoproteins ( approximately 15 pmol) separated by polyacrylamide gel electrophoresis is described. AA label is used for the determination of both monosaccharide composition and oligosaccharide map. For the monosaccharide determination, bands containing the glycoprotein of interest are excised from the polyvinylidene fluoride (PVDF) membrane blots, hydrolyzed in 20% trifluoroacetic acid, derivatized, and analyzed by C-18 reversed-phase high-performance liquid chromatography. For the oligosaccharide mapping, bands were digested with peptide N-glycosidase F (PNGase F) in order to release the N-linked oligosaccharides, derivatized, and analyzed by normal-phase anion-exchange chromatography. For convenience, the PNGase F digestion was performed in 1:100 diluted ammonium hydroxide overnight. The oligosaccharide yield from ammonium hydroxide-PNGase F digestion was better or equal to all the other reported procedures, and the presumed "oligosaccharide-amine" product formed in the reaction mixture did not interfere with labeling of the oligosaccharides under the conditions used for derivatization. Sequencing of oligosaccharides can be performed using the same mapping method following treatment with an array of glycosidases. In addition, the mapping method is useful for determining the relative and simultaneous distribution of sialic acid and fucose. Copyright 1999 Academic Press.

  4. Engineering posttranslational proofreading to discriminate nonstandard amino acids

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kunjapur, Aditya M.; Stork, Devon A.; Kuru, Erkin

    Accurate incorporation of nonstandard amino acids (nsAAs) is central for genetic code expansion to increase the chemical diversity of proteins. However, aminoacyl-tRNA synthetases are polyspecific and facilitate incorporation of multiple nsAAs. We investigated and repurposed a natural protein degradation pathway, the N-end rule pathway, to devise an innovative system for rapid assessment of the accuracy of nsAA incorporation. Using this tool to monitor incorporation of the nsAA biphenylalanine allowed the identification of tyrosyl-tRNA synthetase (TyrRS) variants with improved amino acid specificity. The evolved TyrRS variants enhanced our ability to contain unwanted proliferation of genetically modified organisms. In conclusion, this posttranslationalmore » proofreading system will aid the evolution of orthogonal translation systems for specific incorporation of diverse nsAAs.« less

  5. Engineering posttranslational proofreading to discriminate nonstandard amino acids

    DOE PAGES

    Kunjapur, Aditya M.; Stork, Devon A.; Kuru, Erkin; ...

    2018-01-04

    Accurate incorporation of nonstandard amino acids (nsAAs) is central for genetic code expansion to increase the chemical diversity of proteins. However, aminoacyl-tRNA synthetases are polyspecific and facilitate incorporation of multiple nsAAs. We investigated and repurposed a natural protein degradation pathway, the N-end rule pathway, to devise an innovative system for rapid assessment of the accuracy of nsAA incorporation. Using this tool to monitor incorporation of the nsAA biphenylalanine allowed the identification of tyrosyl-tRNA synthetase (TyrRS) variants with improved amino acid specificity. The evolved TyrRS variants enhanced our ability to contain unwanted proliferation of genetically modified organisms. In conclusion, this posttranslationalmore » proofreading system will aid the evolution of orthogonal translation systems for specific incorporation of diverse nsAAs.« less

  6. Release of Water Soluble Drugs from Dynamically Swelling POLY(2-HYDROXYETHYL Methacrylate - CO - Methacrylic Acid) Hydrogels.

    NASA Astrophysics Data System (ADS)

    Kou, Jim Hwai-Cher

    In this study, ionizable copolymers of HEMA and methacrylic acid (MA) are investigated for their potential use in developing pH dependent oral delivery systems. Because of the MA units, these gels swell extensively at high pH. Since solute diffusion in the hydrophilic polymers depends highly on the water content of the matrix, it is anticipated that the release rate will be modulated by this pH induced swelling. From a practical point of view, the advantage of the present system is that one can minimize drug loss in the stomach and achieve a programmed release in intestine. This approach is expected to improve delivery of acid labile drugs or drugs that cause severe gastrointestinal side effects. This work mainly focuses on the basic understanding of the mechanism involved in drug release from the poly(HEMA -co- MA) gels, especially under dynamic swelling conditions. Equilibrium swelling is first characterized since water content is the major determinant of transport properties in these gels. Phenylpropanolamine (PPA) is chosen as the model drug for the release study and its diffusion characteristics in the gel matrix determined. The data obtained show that the PPA diffusivity follows the free volume theory of Yasuda, which explains the accelerating effect of swelling on drug release. A mathematical model based on a diffusion mechanism has been developed to describe PPA release from the swelling gels. Based on this model, several significant conclusions can be drawn. First, the release rate can be modulated by the aspect ratio of the cylindrical geometry, and this has a practical implication in dosage form design. Second, the release rate can be lowered quite considerably if the dimensional increase due to swelling is significant. Consequently, it is the balance between the drug diffusivity increase and the gel dimensional growth that determines the release rate from the swelling matrix. Third, quasi-steady release kinetics, which are characteristic of swelling

  7. Host cell recruitment patterns by bone morphogenetic protein-2 releasing hyaluronic acid hydrogels in a mouse subcutaneous environment.

    PubMed

    Todeschi, Maria R; El Backly, Rania M; Varghese, Oommen P; Hilborn, Jöns; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2017-07-01

    This study aimed to identify host cell recruitment patterns in a mouse model in response to rhBMP-2 releasing hyaluronic acid hydrogels and influence of added nano-hydroxyapatite particles on rhBMP-2 release and pattern of bone formation. Implanted gels were retrieved after implantation and cells were enzymatically dissociated for flow cytometric analysis. Percentages of macrophages, progenitor endothelial cells and putative mesenchymal stem cells were measured. Implants were evaluated for BMP-2 release by ELISA and by histology to monitor tissue formation. Hyaluronic acid+BMP-2 gels influenced the inflammatory response in the bone healing microenvironment. Host-derived putative mesenchymal stem cells were major contributors. Addition of hydroxyapatite nanoparticles modified the release pattern of rhBMP-2, resulting in enhanced bone formation.

  8. Anti-lipoteichoic acid antibodies enhance release of cytokines by monocytes sensitized with lipoteichoic acid.

    PubMed Central

    Mancuso, G; Tomasello, F; Ofek, I; Teti, G

    1994-01-01

    Lipoteichoic acid (LTA) from gram-positive bacteria can stimulate monocytes to produce cytokines. To ascertain whether aggregation of LTA receptors can contribute to this effect, human monocytes were sensitized with LTA from Streptococcus pyogenes, washed, and treated with anti-LTA antibodies. The addition of anti-LTA antibodies or F(ab')2 fragments markedly enhanced the aggregation of LTA receptors, as evidenced by indirect immunofluorescence and the release of tumor necrosis factor alpha and interleukin-1 beta. These findings suggest that aggregation of LTA receptors of monocytes is required for triggering marked cytokine responses. PMID:8132355

  9. Dynamic in vivo imaging of dual-triggered microspheres for sustained release applications: synthesis, characterization and cytotoxicity study.

    PubMed

    Efthimiadou, Eleni K; Tapeinos, Christos; Chatzipavlidis, Alexandros; Boukos, Nikos; Fragogeorgi, Eirini; Palamaris, Lazaros; Loudos, George; Kordas, George

    2014-01-30

    This paper deals with the synthesis, characterization and property evaluation of drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell. The synthetic procedure consists of 3 steps, of which the first two comprise the synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to the formation of magnetic nanoparticles on the microsphere's surface. AA that attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the inner and the outer surface of the microspheres, enhance the efficacy of this intelligent drug delivery system (DDS), which constitutes a promising approach toward cancer therapy. A number of experimental techniques were used to characterize the resulting microspheres. In order to investigate the in vitro controlled release behavior of the synthesized microspheres, we studied the Dox release percentage under different pH conditions and under external magnetic field. Hyperthermia caused by an alternating magnetic field (AFM) is used in order to study the doxorubicin (Dox) release behavior from microspheres with pH functionality. The in vivo fate of these hybrid-microspheres was tracked by labeling them with the γ-emitting radioisotope (99m)Tc after being intravenously injected in normal mice. According to our results, microsphere present a pH depending and a magnetic heating, release behavior. As expected, labeled microspheres were mainly found in the mononuclear phagocyte system (MPS). The highlights of the current research are: (i) to illustrate the advantages of controlled release by combining hyperthermia and pH-sensitivity and (ii) to provide noninvasive, in vivo information on the spatiotemporal biodistribution of these microsphere by dynamic γ-imaging. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Arachidonic and oleic acid exert distinct effects on the DNA methylome

    PubMed Central

    Silva-Martínez, Guillermo A.; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda; Vaquero, Alejandro; Esteller, Manel; Carmona, F. Javier; Moran, Sebastian; Nielsen, Finn C.; Wickström-Lindholm, Marie; Wrobel, Katarzyna; Wrobel, Kazimierz; Barbosa-Sabanero, Gloria; Zaina, Silvio; Lund, Gertrud

    2016-01-01

    ABSTRACT Abnormal fatty acid metabolism and availability are landmarks of metabolic diseases, which in turn are associated with aberrant DNA methylation profiles. To understand the role of fatty acids in disease epigenetics, we sought DNA methylation profiles specifically induced by arachidonic (AA) or oleic acid (OA) in cultured cells and compared those with published profiles of normal and diseased tissues. THP-1 monocytes were stimulated with AA or OA and analyzed using Infinium HumanMethylation450 BeadChip (Illumina) and Human Exon 1.0 ST array (Affymetrix). Data were corroborated in mouse embryonic fibroblasts. Comparisons with publicly available data were conducted by standard bioinformatics. AA and OA elicited a complex response marked by a general DNA hypermethylation and hypomethylation in the 1–200 μM range, respectively, with a maximal differential response at the 100 μM dose. The divergent response to AA and OA was prominent within the gene body of target genes, where it correlated positively with transcription. AA-induced DNA methylation profiles were similar to the corresponding profiles described for palmitic acid, atherosclerosis, diabetes, obesity, and autism, but relatively dissimilar from OA-induced profiles. Furthermore, human atherosclerosis grade-associated DNA methylation profiles were significantly enriched in AA-induced profiles. Biochemical evidence pointed to β-oxidation, PPAR-α, and sirtuin 1 as important mediators of AA-induced DNA methylation changes. In conclusion, AA and OA exert distinct effects on the DNA methylome. The observation that AA may contribute to shape the epigenome of important metabolic diseases, supports and expands current diet-based therapeutic and preventive efforts. PMID:27088456

  11. Effects of aromatic amino acids, phenylacetate and phenylpropionate on fermentation of xylan by the rumen anaerobic fungi, Neocallimastix frontalis and Piromyces communis.

    PubMed

    Guliye, A Y; Wallace, R J

    2007-10-01

    Anaerobic fungi are important members of the fibrolytic community of the rumen. The aim of this study was to study their requirement for aromatic amino acids (AA) and related phenyl acids (phenylpropionic and phenylacetic acids) for optimal xylan fermentation. Neocallimastix frontalis RE1 and Piromyces communis P were grown in a defined medium containing oat spelts xylan as the sole energy source, plus one of the following N sources: ammonia; ammonia plus a complete mixture of 20 AA commonly found in protein; ammonia plus complete AA mixture minus aromatic AA; ammonia plus phenyl acids; ammonia plus complete AA mixture without aromatic AA plus phenyl acids. Both species grew in all the media, indicating no absolute requirement for AA. The complete AA mixture increased (P<0.05) acetate concentration by 18% and 15%, sugar utilization by 33% and 22% and microbial yield by about 22% and 15% in N. frontalis and P. communis, respectively, in comparison with the treatments that had ammonia as the only N source. Neither the supply of aromatic AA or phenol acids, nor their deletion from the complete AA mixture, affected the fermentation rate, products or yield of either species. AA were not essential for N. frontalis and P. communis, but their growth on xylan was stimulated. The effects could not be explained in terms of aromatic AA alone. Ruminant diets should contain sufficient protein to sustain optimal fibre digestion by ruminal fungi. Aromatic AA or phenyl acids alone cannot replace the complete AA mixture.

  12. Infusions of ascorbic acid into the medial preoptic area facilitate appetitive sexual behavior in the female rat.

    PubMed

    Graham, M Dean; Pfaus, James G

    2013-10-02

    Ascorbic acid (AA), also known as Vitamin C, enhances dopamine (DA) transmission in mesolimbic and nigrostriatal terminals and augments DA-mediated behaviors. It is not yet known whether AA has a similar influence in other DA terminals, in particular terminals of the incertohypothalamic system that modulate the function of the medial preoptic area (mPOA). In female rats, DA in the mPOA plays a critical role in the generation of appetitive sexual responses, notably solicitations, hops, and darts, and we have shown previously that the role of DA in this region on female sexual behavior changes depending on the hormonal profile of the female. Since AA has often been used as a vehicle control in the examination of rat sexual behavior, the present study examined the effect of infusions of AA to the mPOA of sexual experienced ovariectomized rats under two hormonal conditions: partially-primed with estradiol benzoate (EB) alone or fully-primed with EB and progesterone. Relative to saline baselines, females under both hormonal conditions displayed a significant increase in appetitive sexual behaviors following infusions of AA. No difference in lordosis behavior was observed following AA infusions relative to saline baselines. We suggest that the mechanism by which AA infusions to the mPOA increase appetitive sexual behaviors in female rats may be through dose-dependent DA receptor interactions, possibly through both presynaptic release mechanisms and postsynaptic DA D1-related messenger systems. © 2013.

  13. Effects of a garlic-derived principle (ajoene) on aggregation and arachidonic acid metabolism in human blood platelets.

    PubMed

    Srivastava, K C; Tyagi, O D

    1993-08-01

    When garlic cloves are chopped or crushed several dialkyl thiosulfinates are rapidly formed by the action of the enzyme alliin lyase or alliinase (EC 4.4.1.4) on S(+)-alkyl-L-cysteine sulfoxides. Allicin (diallyl thiosulfinate or allyl 2-propene thiosulfinate) is the dominant thiosulfinate released. A variety of sulfur containing compounds are formed from allicin and other thiosulfinates depending on the way in which garlic is handled. One such compound identified recently is ajoene which has been reported to possess antithrombotic properties. We present here data on the antiplatelet properties of ajoene together with its effects on the metabolism of arachidonic acid (AA) in intact platelets. Thus, ajoene was found to inhibit platelet aggregation induced by AA, adrenaline, collagen, adenosine diphosphate (ADP) and calcium ionophore A23187; the nature of the inhibition was irreversible. In washed platelets stimulated by labelled arachidonate, ajoene inhibited the formation of thromboxane A2; 12-lipoxygenase product(s) were reduced at higher ajoene concentrations. This garlic-derived substance inhibited the incorporation of labelled AA into platelet phospholipids at higher concentration. In labelled platelets, on stimulation with either calcium ionophore A23187 or collagen, reduced amounts of thromboxane and 12-HETE (12-hydroxyeicosatetraenoic acid) were produced in ajoene-treated platelets compared to control platelets. This substance had no effect on the deacylation of platelet phospholipids. The results suggest that at least one of the mechanisms by which ajoene shows antiplatelet effects could be related to altered metabolism of AA.

  14. Non-Neuronal Release of Gamma-Aminobutyric Acid by Embryonic Pluripotent Stem Cells

    PubMed Central

    Teng, Lin; Tang, Ya-Bin; Sun, Fan; An, Shi-Min; Zhang, Chun; Yang, Xin-Jie; Lv, Hao-Yu; Lu, Qin; Cui, Yong-Yao; Hu, Jin-Jia

    2013-01-01

    γ-Aminobutyric acid (GABA), the principle inhibitory transmitter in the mature central nervous system, is also involved in activities outside the nervous system. Recent studies have shown that functional GABA receptors are expressed in embryonic stem (ES) cells and these receptors control ES cell proliferation. However, it is not clear whether ES cells have their own GABAergic transmission output machinery that can fulfill GABA release or whether the cells merely process the GABA receptors by receiving and responding to the diffused GABA released elsewhere. To get further insight into this unresolved problem, we detected the repertoire of components for GABA synthesis, storage, reaction, and termination in ES and embryonal carcinoma stem cells by biological assays, and then directly quantified released GABA in the intercellular milieu from these pluripotent stem (PS) cells by an analytical chemical assay based on high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). We found that embryonic PS cells processed a GABAergic circuit machinery and spontaneously released GABA, which suggests the potential that embryonic PS cells could autonomously establish a GABA niche via release of the transmitter. PMID:23799822

  15. IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids

    USDA-ARS?s Scientific Manuscript database

    D-amino acids (D-aas) are reported to bind to IgE antibodies from people with allergy and asthma. The objectives of this study were to determine if D-aas bind or inhibit IgE binding to peanut allergens, and if they are more effective than L-amino acids (L-aas) in this respect. Several D-aa cocktails...

  16. PEG-poly(amino acid) block copolymer micelles for tunable drug release.

    PubMed

    Ponta, Andrei; Bae, Younsoo

    2010-11-01

    To achieve tunable pH-dependent drug release in tumor tissues. Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37°C, for 48 h. A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed <50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 ± 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths. A drug delivery platform for tunable drug release was successfully developed with polymer micelles possessing spacer-modified hydrazone drug-binding linkers.

  17. Repletion of branched chain amino acids reverses mTORC1 signaling but not improved metabolism during dietary protein dilution.

    PubMed

    Maida, Adriano; Chan, Jessica S K; Sjøberg, Kim A; Zota, Annika; Schmoll, Dieter; Kiens, Bente; Herzig, Stephan; Rose, Adam J

    2017-08-01

    Dietary protein dilution (PD) has been associated with metabolic advantages such as improved glucose homeostasis and increased energy expenditure. This phenotype involves liver-induced release of FGF21 in response to amino acid insufficiency; however, it has remained unclear whether dietary dilution of specific amino acids (AAs) is also required. Circulating branched chain amino acids (BCAAs) are sensitive to protein intake, elevated in the serum of obese humans and mice and thought to promote insulin resistance. We tested whether replenishment of dietary BCAAs to an AA-diluted (AAD) diet is sufficient to reverse the glucoregulatory benefits of dietary PD. We conducted AA profiling of serum from healthy humans and lean and high fat-fed or New Zealand obese (NZO) mice following dietary PD. We fed wildtype and NZO mice one of three amino acid defined diets: control, total AAD, or the same diet with complete levels of BCAAs (AAD + BCAA). We quantified serum AAs and characterized mice in terms of metabolic efficiency, body composition, glucose homeostasis, serum FGF21, and tissue markers of the integrated stress response (ISR) and mTORC1 signaling. Serum BCAAs, while elevated in serum from hyperphagic NZO, were consistently reduced by dietary PD in humans and murine models. Repletion of dietary BCAAs modestly attenuated insulin sensitivity and metabolic efficiency in wildtype mice but did not restore hyperglycemia in NZO mice. While hepatic markers of the ISR such as P-eIF2α and FGF21 were unabated by dietary BCAA repletion, hepatic and peripheral mTORC1 signaling were fully or partially restored, independent of changes in circulating glucose or insulin. Repletion of BCAAs in dietary PD is sufficient to oppose changes in somatic mTORC1 signaling but does not reverse the hepatic ISR nor induce insulin resistance in type 2 diabetes during dietary PD.

  18. Slow-release NPK fertilizer encapsulated by carboxymethyl cellulose-based nanocomposite with the function of water retention in soil.

    PubMed

    Olad, Ali; Zebhi, Hamid; Salari, Dariush; Mirmohseni, Abdolreza; Reyhani Tabar, Adel

    2018-09-01

    In this study, new slow release fertilizer encapsulated by superabsorbent nanocomposite was prepared by in-situ graft polymerization of sulfonated-carboxymethyl cellulose (SCMC) with acrylic acid (AA) in the presence of polyvinylpyrrolidone (PVP), silica nanoparticles and nitrogen (N), phosphorous (P), and potassium (K) (NPK) fertilizer compound. The prepared materials were characterized by FT-IR, XRD and scanning electron microscopy (SEM) techniques. The incorporation of NPK fertilizer into hydrogel nanocomposite network was verified by results of these analyses. Also, the swelling behavior in various pH and saline solutions as well as water retention capability of the prepared hydrogel nanocomposite was evaluated. The fertilizer release behavior of the NPK loaded hydrogel nanocomposite was in good agreement with the standard of Committee of European Normalization (CEN), indicating its excellent slow release property. These good characteristics revealed that the hydrogel nanocomposite fertilizer formulation can be practically used in agricultural and horticultural applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Data Fusion Analysis For Test Validation System

    DTIC Science & Technology

    2009-11-16

    triethyl phosphate (TEP), methyl salicylate (MeS), and acetic acid (AA). A total of 29 release scenarios were conducted: fifteen TEP releases of 30...N2 - north second. bA - 2, 3, 6, 7, 10, and 11; B - 1 through 12; NA - not available. cTEP - triethyl phosphate; MeS - methyl salicylate ; AA

  20. Design and Evaluation of Hydrophilic Matrix System for pH-Independent Sustained Release of Weakly Acidic Poorly Soluble Drug.

    PubMed

    Huang, Jinheng; Lin, Huaqing; Peng, Bingxin; Huang, Qianfeng; Shuai, Fangzhou; Xie, Yanxian

    2018-04-30

    The aim of this research was to design and evaluate a hydrophilic matrix system for sustained release of glipizide, a weakly acidic poor soluble drug. A combination of inclusion complexation and microenvironmental pH modification techniques was utilized to improve the dissolution and pH-independent release of glipizide. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as the complexation agent while sodium citrate and magnesium oxide (MgO) were used as model pH modifiers. The hydrophilic matrix tablets were prepared by powder direct compression and evaluated by in vitro dissolution study respectively in pH 6.8 and pH 1.2 dissolution media. The formulations containing MgO exhibited increased cumulative drug release from less than 40% in the reference formulation to 90% within 24 h in acidic media (pH 1.2). The release profile in acidic media was similar to the alkaline media (pH 6.8) with a similarity factor (f 2 ) of 55.0, suggesting the weakening of the effect of pH on the dissolution efficiency of glipizide. The release profile fitted well into the Higuchi model and the dominant mechanism of drug release was Fickian diffusion while case II transport/polymer relaxation occurred. In conclusion, combining inclusion complexation agents and pH modifiers had improved the dissolution of glipizide as well as achieved the pH-independent release profile.

  1. Differences in Arachidonic Acid Levels and Fatty Acid Desaturase (FADS) Gene Variants in African Americans and European Americans with Diabetes/Metabolic Syndrome

    PubMed Central

    Sergeant, Susan; Hugenschmidt, Christina E.; Rudock, Megan E.; Ziegler, Julie T.; Ivester, Priscilla; Ainsworth, Hannah C.; Vaidya, Dhananjay; Case, L. Douglas; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.; Mathias, Rasika A.; Chilton, Floyd H.

    2012-01-01

    Over the past 50 years, increases in dietary n-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid, have been hypothesized to cause or exacerbate chronic inflammatory diseases. This study examines an individual’s innate capacity to synthesize n-6-long chain PUFAs (LC-PUFAs), with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes/metabolic syndrome. Compared to European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7.9±2.1; AfAm 9.8±1.9 % of total fatty acids, mean ± sd; p<2.29×10−9) and the AA to n-6-precursor fatty acid ratio, which estimates FADS1 activity (EAm 5.4±2.2, AfAm 6.9±2.2; p=1.44×10−5). Seven single nucleotide polymorphisms (SNP) mapping to the FADS locus revealed strong association with AA, eicosapentaenoic acid (EPA) and dihomogamma-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT: 6.3±1.0; GG: 8.5±2.1; p=3.0×10−5) and AA/DGLA ratios (TT: 3.4±0.8; GG: 6.5±2.3; p=2.2×10−7) but higher DGLA levels (TT: 1.9±0.4; GG: 1.4±0.4; p=3.3×10−7) compared to those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0.81) compared to EAm (0.46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are likely important differences in the capacity of different populations to synthesize LC-PUFAs. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent. PMID:21733300

  2. Risk of hydrocyanic acid release in the electroplating industry.

    PubMed

    Piccinini, N; Ruggiero, G N; Baldi, G; Robotto, A

    2000-01-07

    This paper suggests assessing the consequences of hydrocyanic acid (HCN) release into the air by aqueous cyanide solutions in abnormal situations such as the accidental introduction of an acid, or the insertion of a cyanide in a pickling bath. It provides a well-defined source model and its resolution by methods peculiar to mass transport phenomena. The procedure consists of four stages: calculation of the liquid phase concentration, estimate of the HCN liquid-vapour equilibrium, determination of the mass transfer coefficient at the liquid-vapour interface, evaluation of the air concentration of HCN and of the damage distances. The results show that small baths operating at high temperatures are the major sources of risk. The building up of lethal air concentrations, on the other hand, is governed by the values of the mass transfer coefficient, which is itself determined by the flow dynamics and bath geometry. Concerning the magnitude of the risk, the fallout for external emergency planning is slight in all the cases investigated.

  3. Association of polyunsaturated fatty acids in breast milk with fatty acid desaturase gene polymorphisms among Chinese lactating mothers.

    PubMed

    Ding, Zhen; Liu, Guo-Liang; Li, Xiang; Chen, Xue-Yan; Wu, Yi-Xia; Cui, Can-Can; Zhang, Xi; Yang, Guang; Xie, Lin

    2016-06-01

    The fatty acid desaturase (FADS) controls polyunsaturated fatty acid (PUFA) synthesis in human tissues and breast milk. Evaluate the influence of 10 single nucleotide polymorphisms (SNPs) and various haplotypes in the FADS gene cluster (FADS1, FADS2, FADS3) on PUFA concentration in the breast milk of 209 healthy Chinese women. PUFA concentrations were measured in breast milk using gas chromatography and genotyping was performed using the Sequenom Mass Array system. A SNP (rs1535) and 2-locus haplotypes (rs3834458-rs1535, rs1535-rs174575) in the FADS2 gene were associated with concentrations of γ-linoleic acid (GLA) and arachidonic acid (AA) in breast milk. Likewise, in the FADS1 gene, a 2-locus constructed haplotype (rs174547-rs174553) also affected GLA and AA concentration (P<0.05 for all). Minor allele carriers of the SNP and haplotypes described above had lower concentrations of GLA and AA. In the FADS2 gene, the 3-locus haplotype rs3834458-rs1535-rs174575, significantly affected concentrations of GLA but not AA. Pairwise comparison showed that individuals major homozygous for the SNP rs1000778 in the FADS3 gene had lower concentrations of ALA and linoleic acid (LA) in their breast milk. Polymorphisms in the FADS gene cluster influence PUFA concentrations in the breast milk of Chinese Han lactating women. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. [Preparation of coated tablets of glycyrrhetic acid-HP-beta-cyclodextrin tablets for colon-specific release].

    PubMed

    Cui, Qi-Hua; Cui, Jing-Hao; Zhang, Jin-Jin

    2008-10-01

    To prepare coated tablets of glycyrrhetinic acid and hydroxypropyl-beta-cyclodextrin (GTA-HP-beta-CYD) inclusion complex tablets for colon-specific release. In order to improve the solubility of GTA, the GTA-HP-beta-CYD inclusion complex was prepared by ultrasonic-lyophilization technique and its formation were characterized by X-ray powder diffraction profiles and infrared spectrometry. The effects of inclusion condition on the inclusion efficiency and stability coefficient of inclusion complex were investigated, respectively. After prepared GTA-HP-beta-CYD tablets by powder direct compression, the pH dependant polymer Eudragit III and/or mixed with Eudragit II were used for further coating materials in fluid-bed coater. The influences of coating weight on the GTA release in different pH conditions were evaluated to establish the method for prepering colon specific delivery tablets with pulsed release properties. The formation of inclusion complexes were proved by X-ray powder diffraction profile and phase solubility curve. The effect of pH value of solvent was played critical role on the preparation of GTA- HP-beta-CYD inclusion complex. And the inclusion efficiency of GTA was 9. 3% and the solubility was increased to 54. 6 times at optimized method. The Eudragit III coated GTA- HP-beta-CYD tablets with coating weight 10% and 16% were showed pH dependant colon specific release profiles with slow release rate. The release profile of tablets coated with the mixture of Eudragit II and Eudragit III (1:2) were indicated typical pH dependant colon specific and pulsed release properties while the coating weight was 17%. The preliminary method for preparation of colon specific release tablets containing glycyrrhetinic acid with improved solubility was established for further in vivo therapeutic experiment.

  5. Simultaneous determination of ascorbic acid, dopamine and uric acid based on tryptophan functionalized graphene.

    PubMed

    Lian, Qianwen; He, Zhifang; He, Qian; Luo, Ai; Yan, Kaiwang; Zhang, Dongxia; Lu, Xiaoquan; Zhou, Xibin

    2014-05-01

    A new type of tryptophan-functionalized graphene nanocomposite (Trp-GR) was synthesized by utilizing a facile ultrasonic method via π-π conjugate action between graphene (GR) and tryptophan (Trp) molecule. The material as prepared had well dispersivity in water and better conductivity than pure GR. The surface morphology of Trp-GR was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The electrochemical behaviors of ascorbic acid (AA), dopamine (DA), and uric acid (UA) were investigated by cyclic voltammetry (CV) on the surface of Trp-GR. The separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA was about 182 mV, 125 mV and 307 mV, which allowed simultaneously determining AA, DA, and UA. Differential pulse voltammetery (DPV) was used for the determination of AA, DA, and UA in their mixture. Under optimum conditions, the linear response ranges for the determination of AA, DA, and UA were 0.2-12.9 mM, 0.5-110 μM, and 10-1000 μM, with the detection limits (S/N=3) of 10.09 μM, 0.29 μM and 1.24 μM, respectively. Furthermore, the modified electrode was investigated for real sample analysis. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  6. Combining eicosapentaenoic acid, decosahexaenoic acid and arachidonic acid, using a fully crossed design, affect gene expression and eicosanoid secretion in salmon head kidney cells in vitro.

    PubMed

    Holen, Elisabeth; He, Juyun; Espe, Marit; Chen, Liqiou; Araujo, Pedro

    2015-08-01

    Future feed for farmed fish are based on untraditional feed ingredients, which will change nutrient profiles compared to traditional feed based on marine ingredients. To understand the impact of oils from different sources on fish health, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were added to salmon head kidney cells, in a fully crossed design, to monitor their individual and combined effects on gene expression. Exposing salmon head kidney cells to single fatty acids, arachidonic acid (AA) or decosahexaenoic acid (DHA), resulted in down-regulation of cell signaling pathway genes and specific fatty acid metabolism genes as well as reduced prostaglandin E2 (PGE2) secretion. Eicosapentaenoic acid (EPA) had no impact on gene transcription in this study, but reduced the cell secretion of PGE2. The combined effect of AA + EPA resulted in up-regulation of eicosanoid pathway genes and the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α), Bclx (an inducer of apoptosis) and fatty acid translocase (CD36) as well as increased cell secretion of PGE2 into the media. Adding single fatty acids to salmon head kidney cells decreased inflammation markers in this model. The combination AA + EPA acted differently than the rest of the fatty acid combinations by increasing the inflammation markers in these cells. The concentration of fatty acid used in this experiment did not induce any lipid peroxidation responses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Laboratory Astrophysics Division of The AAS (LAD)

    NASA Astrophysics Data System (ADS)

    Salama, Farid; Drake, R. P.; Federman, S. R.; Haxton, W. C.; Savin, D. W.

    2012-10-01

    The purpose of the Laboratory Astrophysics Division (LAD) is to advance our understanding of the Universe through the promotion of fundamental theoretical and experimental research into the underlying processes that drive the Cosmos. LAD represents all areas of astrophysics and planetary sciences. The first new AAS Division in more than 30 years, the LAD traces its history back to the recommendation from the scientific community via the White Paper from the 2006 NASA-sponsored Laboratory Astrophysics Workshop. This recommendation was endorsed by the Astronomy and Astrophysics Advisory Committee (AAAC), which advises the National Science Foundation (NSF), the National Aeronautics and Space Administration (NASA), and the U.S. Department of Energy (DOE) on selected issues within the fields of astronomy and astrophysics that are of mutual interest and concern to the agencies. In January 2007, at the 209th AAS meeting, the AAS Council set up a Steering Committee to formulate Bylaws for a Working Group on Laboratory Astrophysics (WGLA). The AAS Council formally established the WGLA with a five-year mandate in May 2007, at the 210th AAS meeting. From 2008 through 2012, the WGLA annually sponsored Meetings in-a-Meeting at the AAS Summer Meetings. In May 2011, at the 218th AAS meeting, the AAS Council voted to convert the WGLA, at the end of its mandate, into a Division of the AAS and requested draft Bylaws from the Steering Committee. In January 2012, at the 219th AAS Meeting, the AAS Council formally approved the Bylaws and the creation of the LAD. The inaugural gathering and the first business meeting of the LAD were held at the 220th AAS meeting in Anchorage in June 2012. You can learn more about LAD by visiting its website at http://lad.aas.org/ and by subscribing to its mailing list.

  8. Laboratory Astrophysics Division of the AAS (LAD)

    NASA Technical Reports Server (NTRS)

    Salama, Farid; Drake, R. P.; Federman, S. R.; Haxton, W. C.; Savin, D. W.

    2012-01-01

    The purpose of the Laboratory Astrophysics Division (LAD) is to advance our understanding of the Universe through the promotion of fundamental theoretical and experimental research into the underlying processes that drive the Cosmos. LAD represents all areas of astrophysics and planetary sciences. The first new AAS Division in more than 30 years, the LAD traces its history back to the recommendation from the scientific community via the White Paper from the 2006 NASA-sponsored Laboratory Astrophysics Workshop. This recommendation was endorsed by the Astronomy and Astrophysics Advisory Committee (AAAC), which advises the National Science Foundation (NSF), the National Aeronautics and Space Administration (NASA), and the U.S. Department of Energy (DOE) on selected issues within the fields of astronomy and astrophysics that are of mutual interest and concern to the agencies. In January 2007, at the 209th AAS meeting, the AAS Council set up a Steering Committee to formulate Bylaws for a Working Group on Laboratory Astrophysics (WGLA). The AAS Council formally established the WGLA with a five-year mandate in May 2007, at the 210th AAS meeting. From 2008 through 2012, the WGLA annually sponsored Meetings in-a-Meeting at the AAS Summer Meetings. In May 2011, at the 218th AAS meeting, the AAS Council voted to convert the WGLA, at the end of its mandate, into a Division of the AAS and requested draft Bylaws from the Steering Committee. In January 2012, at the 219th AAS Meeting, the AAS Council formally approved the Bylaws and the creation of the LAD. The inaugural gathering and the first business meeting of the LAD were held at the 220th AAS meeting in Anchorage in June 2012. You can learn more about LAD by visiting its website at http://lad.aas.org/ and by subscribing to its mailing list.

  9. Uptake and release of amino acids in the fetal-placental unit in human pregnancies.

    PubMed

    Holm, Maia Blomhoff; Bastani, Nasser Ezzatkhah; Holme, Ane Moe; Zucknick, Manuela; Jansson, Thomas; Refsum, Helga; Mørkrid, Lars; Blomhoff, Rune; Henriksen, Tore; Michelsen, Trond Melbye

    2017-01-01

    The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample. This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein) and fetal (umbilical vein and artery) sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations. In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake) for 14 amino acids and a negative venoarterial difference (fetal release) for glutamic acid (p<0.001). In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake) for leucine (p = 0.005), isoleucine (p = 0.01), glutamic acid (p<0.001) and arginine (p = 0.04) and a negative arteriovenous difference (uteroplacental release) for tyrosine (p = 0.002), glycine (p = 0.01) and glutamine (p = 0.02). The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake. Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is the

  10. Effects of seasonings on the stability of ascorbic acid in a cooking model system.

    PubMed

    Kishida, Etsu; Maeda, Tomoko; Nishihama, Akiko; Kojo, Shosuke; Masuzawa, Yasuo

    2004-12-01

    The thermolability of ascorbic acid (AA) in aqueous solution at 100 degrees C was assessed in the presence of various seasonings commonly used in Japanese-style cooking. A model system approximated Japanese cooking with regard to the concentrations of AA and seasonings and the heating time. The decrease of AA in the reaction system of this experiment was a first-order reaction with respect to the concentration of AA loss. Although kinetic constants for AA loss decreased with increasing concentrations of AA (25-400 microg/mL), the absolute amounts degraded were almost the same for all AA concentrations, suggesting that dissolved oxygen is one of main factors affecting the stability of AA solutions during heating at 100 degrees C. When each seasoning was added to AA solution, salt stabilized AA and Japanese alcohol-containing admixtures, such as sake and sweet sake (mirin), did not have a significant effect on the stability. Conversely, soy sauce, miso (fermented soybean paste) and broth powder from skipjack accelerated the decrease of AA in a concentration-dependent manner. The kinetic study suggested that oxygen was rapidly consumed and AA loss accelerated by addition of soy sauce or miso to AA solution. Consequently it is likely that a reaction mechanism shifts from aerobic to anaerobic and the forward reactions proceed. Of the constituents of Japanese seasonings, not only iron but also amino acids are involved in the acceleration of AA degradation. The presence of amino acids should be taken into account when considering the levels of AA in soups.

  11. All-atomistic molecular dynamics (AA-MD) studies and pharmacokinetic performance of PAMAM-dendrimer-furosemide delivery systems.

    PubMed

    Otto, Daniel P; de Villiers, Melgardt M

    2018-06-13

    Improvement of problematic dissolution and solubility properties of a model drug, furosemide, was investigated for poly(amidoamine) (PAMAM) dendrimer complexes of the drug. Full and half generation dendrimers with amino and ester terminals respectively, were studied. In vitro release performance of these complexes was investigated at drug loads ranging 5-60% using simulated gastric fluids. Full generation dendrimers accommodated higher drug loads, outperformed half-generation complexes, and free drug. Pharmacokinetic studies in rats indicated that the dendrimer complexes markedly improved in the bioavailability of the drug compared to the unformulated drug. The G3.0-PAMAM dendrimer complex showed a two-fold increase in C max and a 1.75-fold increase in AUC over the free drug. Additionally, T max was shortened from approximately 25 to 20 min. One of the first all-atomistic molecular dynamics (AA-MD) simulation studies was performed to evaluate low-generation dendrimer-drug complexes as well as its pharmacokinetic performance. AA-MD provided insight into the intermolecular interactions that take place between the dendrimer and drug. It is suggested that the dendrimer not only encapsulates the drug, but can also orientate the drug in stabilized dispersion to prevent drug clustering which could impact release and bioavailability negatively. AA-MD can be a useful tool to develop dendrimer-based drug delivery systems. Copyright © 2018. Published by Elsevier B.V.

  12. Corrosion Susceptibility of AA5083-H116 in Biologically Active Atmospheric Marine Environments

    DTIC Science & Technology

    2014-03-01

    by the standardized nitric acid test ASTM G67." Fatigue and stress corrosion cracking behaviors of sensitized AA5083 have also been evaluated.1213... acid (NAMLT Test)," ASTM Hanbook 3.02 Corrosion of Metals; Wear and Erosion. ASTM Hanbook 3.02 Corrosion of Metals; Wear and Erosion (ASTM...DATE (DD-MM-YYYY) 12-05-2014 REPORT TYPE Conference Proceeding (refereed) 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Corrosion

  13. Release study of diclofenac from new carbomer gels.

    PubMed

    Bregni, Carlos; Chiappetta, Diego; Faiden, Natalia; Carlucci, Adriana; García, Roberto; Pasquali, Ricardoc

    2008-01-01

    Carbopol gels were prepared using a traditional polymer with mucoadhesive properties (974P). A new Carbomer derivative Ultrez 21 was also evaluated. Mineral oil, as occlusive ingredient, glycerol as humectant and ethanol were included in all the compositions. The feasibility of preparing these formulations with or without a bioadhesive polymer (Polycarbophil AA-1) and a second oil phase with enhancer activity (Miglyol 840) was evaluated. Further characterization including physical stability during a year was carried out. In vitro release behaviour of diclofenac sodium in Franz diffusion cell was evaluated with some selected formulations using an ethanol-water (50% w/w) solution as receptor medium. Addition of Polycarbophil AA-1 increased formulation viscosity and decreased drug release. These types of topical dosage forms could give sustained delivery of drug onto the skin, could tolerate the incorporation of an enhancer, a humectant and an occlusive phase, so they are interesting promises to improve skin absorption of nonsteroidal anti-inflammatory drugs and to prevent side effects associated.

  14. Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, M.; Chen, Y.; Tjandrawinata, R. R.

    2001-01-01

    It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

  15. Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells.

    PubMed

    Hughes-Fulford, M; Chen, Y; Tjandrawinata, R R

    2001-05-01

    It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

  16. AAS 227: Day 1

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or at astrobites.com, or catch ourlive-tweeted updates from the @astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Things kicked off last night at our undergraduate reception booth. Thanks to all of you who stopped by we were delightedto have so many people tell us that they already know about and useastrobites, and we were excited to introduce a new cohort of students at AAS to astrobites for the first time.Tuesday morning was the official start of the meeting. Here are just a few of the talks and workshops astrobiters attended today.Opening Address (by Becky Smethurst)The President of the AAS, aka our fearless leader Meg Urry kicked off the meeting this morning at the purely coffee powered hour of 8am this morning. She spoke about the importance of young astronomers at the meeting (heres looking at you reader!) and also the importance of the new Working Group for Accessibility and Disabilities (aka WGAD pronounced like wicked) at the AAS. The Society has made extra effort this year to make the conference accessible to all,a message which was very well received by everyone in attendance.Kavli Lecture: New Horizons Alan Stern (by Becky Smethurst)We were definitely spoilt with the first Plenary lecture at this years conference Alan Stern gave us a a review of the New Horizons mission of the Pluto Fly By (astrobites covered the mission back in July with this post). We were treated to beautiful images, wonderful results and a foray into geology.Before (Hubble) and after #NewHorizons. #thatisall #science #astro alanstern #aas227 pic.twitter.com/kkMt6RsSIR Science News (@topsciencething) January 5, 2016Some awesome facts from the lecture that blew my mind:New Horizons is now 2AU (!) beyond Pluto

  17. Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids.

    PubMed

    Nickling, Jessica H; Baumann, Tobias; Schmitt, Franz-Josef; Bartholomae, Maike; Kuipers, Oscar P; Friedrich, Thomas; Budisa, Nediljko

    2018-05-04

    Nature has a variety of possibilities to create new protein functions by modifying the sequence of the individual amino acid building blocks. However, all variations are based on the 20 canonical amino acids (cAAs). As a way to introduce additional physicochemical properties into polypeptides, the incorporation of non-canonical amino acids (ncAAs) is increasingly used in protein engineering. Due to their relatively short length, the modification of ribosomally synthesized and post-translationally modified peptides by ncAAs is particularly attractive. New functionalities and chemical handles can be generated by specific modifications of individual residues. The selective pressure incorporation (SPI) method utilizes auxotrophic host strains that are deprived of an essential amino acid in chemically defined growth media. Several structurally and chemically similar amino acid analogs can then be activated by the corresponding aminoacyl-tRNA synthetase and provide residue-specific cAA(s) → ncAA(s) substitutions in the target peptide or protein sequence. Although, in the context of the SPI method, ncAAs are also incorporated into the host proteome during the phase of recombinant gene expression, the majority of the cell's resources are assigned to the expression of the target gene. This enables efficient residue-specific incorporation of ncAAs often accompanied with high amounts of modified target. The presented work describes the in vivo incorporation of six proline analogs into the antimicrobial peptide nisin, a lantibiotic naturally produced by Lactococcus lactis. Antimicrobial properties of nisin can be changed and further expanded during its fermentation and expression in auxotrophic Escherichia coli strains in defined growth media. Thereby, the effects of residue-specific replacement of cAAs with ncAAs can deliver changes in antimicrobial activity and specificity. Antimicrobial activity assays and fluorescence microscopy are used to test the new nisin variants

  18. Single amino acid insertions in extracellular loop 2 of Bombyx mori ABCC2 disrupt its receptor function for Bacillus thuringiensis Cry1Ab and Cry1Ac but not Cry1Aa toxins.

    PubMed

    Tanaka, Shiho; Miyamoto, Kazuhisa; Noda, Hiroaki; Endo, Haruka; Kikuta, Shingo; Sato, Ryoichi

    2016-04-01

    In a previous report, seven Cry1Ab-resistant strains were identified in the silkworm, Bombyx mori; these strains were shown to have a tyrosine insertion at position 234 in extracellular loop 2 of the ABC transporter C2 (BmABCC2). This insertion was confirmed to destroy the receptor function of BmABCC2 and confer the strains resistance against Cry1Ab and Cry1Ac. However, these strains were susceptible to Cry1Aa. In this report, we examined the mechanisms of the loss of receptor function of the transporter by expressing mutations in Sf9 cells. After replacement of one or two of the five amino acid residues in loop 2 of the susceptible BmABCC2 gene [BmABCC2_S] with alanine, cells still showed susceptibility, retaining the receptor function. Five mutants with single amino acid insertions at position 234 in BmABCC2 were also generated, resulting in loop 2 having six amino acids, which corresponds to replacing the tyrosine insertion in the resistant BmABCC2 gene [BmABCC2_R(+(234)Y)] with another amino acid. All five mutants exhibited loss of function against Cry1Ab and Cry1Ac. These results suggest that the amino acid sequence in loop 2 is less important than the loop size (five vs. six amino acids) or loop structure for Cry1Ab and Cry1Ac activity. Several domain-swapped mutant toxins were then generated among Cry1Aa, Cry1Ab, and Cry1Ac, which are composed of three domains. Swapped mutants containing domain II of Cry1Ab or Cry1Ac did not kill Sf9 cells expressing BmABCC2_R(+(234)Y), suggesting that domain II of the Cry toxin is related to the interaction with the receptor function of BmABCC2. This also suggests that different reactions against Bt-toxins in some B. mori strains, that is, Cry1Ab resistance or Cry1Aa susceptibility, are attributable to structural differences in domain II of Cry1A toxins. Copyright © 2016. Published by Elsevier Inc.

  19. Photolabile protection for amino acids: studies on the release from novel benzoquinolone cages.

    PubMed

    Fonseca, Andrea S C; Soares, Ana M S; Gonçalves, M Sameiro T; Costa, Susana P G

    2015-12-01

    The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for evaluation as a photocleavable protecting group is described for the first time by coupling to model amino acids (alanine, phenylalanine and glutamic acid). Conversion of the phenylalanine ester conjugate to the thionated derivative was accomplished by reaction with Lawesson's reagent. Photocleavage studies of the carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at different wavelengths (300, 350 and 419 nm) showed that the most interesting result was obtained at 419 nm for the thioconjugate, revealing that the presence of the thiocarbonyl group clearly improved the photolysis rates, giving practicable irradiations times for the release of the amino acids (less than 1 min).

  20. The role of amino acids in hydroxyapatite mineralization

    PubMed Central

    2016-01-01

    Polar and charged amino acids (AAs) are heavily expressed in non-collagenous proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone. Here, we review what is known on the effect of single AAs on HA precipitation. Negatively charged AAs, such as aspartic acid, glutamic acid (Glu) and phosphoserine are largely expressed in NCPs and play a critical role in controlling HA nucleation and growth. Positively charged ones such as arginine (Arg) or lysine (Lys) are heavily involved in HA nucleation within extracellular matrix proteins such as collagen. Glu, Arg and Lys intake can also increase bone mineral density by stimulating growth hormone production. In vitro studies suggest that the role of AAs in controlling HA precipitation is affected by their mobility. While dissolved AAs are able to inhibit HA precipitation and growth by chelating Ca2+ and PO43− ions or binding to nuclei of calcium phosphate and preventing their further growth, AAs bound to surfaces can promote HA precipitation by attracting Ca2+ and PO43− ions and increasing the local supersaturation. Overall, the effect of AAs on HA precipitation is worth being investigated more, especially under conditions closer to the physiological ones, where the presence of other factors such as collagen, mineralization inhibitors, and cells heavily influences HA precipitation. A deeper understanding of the role of AAs in HA mineralization will increase our fundamental knowledge related to bone formation, and could lead to new therapies to improve bone regeneration in damaged tissues or cure pathological diseases caused by excessive mineralization in tissues such as cartilage, blood vessels and cardiac valves. PMID:27707904

  1. Anti-glioma activity and the mechanism of cellular uptake of asiatic acid-loaded solid lipid nanoparticles.

    PubMed

    Garanti, Tanem; Stasik, Aneta; Burrow, Andrea Julie; Alhnan, Mohamed A; Wan, Ka-Wai

    2016-03-16

    Asiatic acid (AA), a pentacyclic triterpene found in Centella Asiatica, has shown neuroprotective and anti-cancer activity against glioma. However, owing to its poor aqueous solubility, effective delivery and absorption across biological barriers, in particular the blood brain barrier (BBB), are challenging. Solid lipid nanoparticles (SLNs) have shown a promising potential as a drug delivery system to carry lipophilic drugs across the BBB, a major obstacle in brain cancer therapy. Nevertheless, limited information is available about the cytotoxic mechanisms of nano-lipidic carriers with AA on normal and glioma cells. This study assessed the anti-cancer efficacy of AA-loaded SLNs against glioblastoma and their cellular uptake mechanism in comparison with SVG P12 (human foetal glial) cells. SLNs were systematically investigated for three different solid lipids; glyceryl monostearate (MS), glyceryl distearate (DS) and glyceryl tristearate (TS). The non-drug containing MS-SLNs (E-MS-SLNs) did not show any apparent toxicity towards normal SVG P12 cells, whilst the AA-loaded MS-SLNs (AA-MS-SLNs) displayed a more favourable drug release profile and higher cytotoxicity towards U87 MG cells. Therefore, MS-SLNs were chosen for further in vitro studies. Cytotoxicity studies of SLNs (± AA) were performed using MTT assay where AA-SLNs showed significantly higher cytotoxicity towards U87 MG cells than SVG P12 normal cells, as confirmed by flow cell cytometry. Cellular uptake of SLNs also appeared to be preferentially facilitated by energy-dependent endocytosis as evidenced by fluorescence imaging and flow cell cytometry. Using the Annexin V-PI double staining technique, it was found that these AA-MS-SLNs displayed concentration-dependent apoptotic activity on glioma cells, which further confirms the potential of exploiting these AA-loaded MS-SLNs for brain cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells.

    PubMed

    Kulikova, Veronika; Shabalin, Konstantin; Nerinovski, Kirill; Dölle, Christian; Niere, Marc; Yakimov, Alexander; Redpath, Philip; Khodorkovskiy, Mikhail; Migaud, Marie E; Ziegler, Mathias; Nikiforov, Andrey

    2015-11-06

    NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells*

    PubMed Central

    Kulikova, Veronika; Shabalin, Konstantin; Nerinovski, Kirill; Dölle, Christian; Niere, Marc; Yakimov, Alexander; Redpath, Philip; Khodorkovskiy, Mikhail; Migaud, Marie E.; Ziegler, Mathias; Nikiforov, Andrey

    2015-01-01

    NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5′-nucleotidases (5′-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5′-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5′-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors. PMID:26385918

  4. Functionalized-graphene modified graphite electrode for the selective determination of dopamine in presence of uric acid and ascorbic acid.

    PubMed

    Mallesha, Malledevaru; Manjunatha, Revanasiddappa; Nethravathi, C; Suresh, Gurukar Shivappa; Rajamathi, Michael; Melo, Jose Savio; Venkatesha, Thimmappa Venkatarangaiah

    2011-06-01

    Graphene is chemically synthesized by solvothermal reduction of colloidal dispersions of graphite oxide. Graphite electrode is modified with functionalized-graphene for electrochemical applications. Electrochemical characterization of functionalized-graphene modified graphite electrode (FGGE) is carried out by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The behavior of FGGE towards ascorbic acid (AA), dopamine (DA) and uric acid (UA) has been investigated by CV, differential pulse voltammetry (DPV) and chronoamperommetry (CA). The FGGE showed excellent catalytic activity towards electrochemical oxidation of AA, DA and UA compared to that of the bare graphite electrode. The electrochemical oxidation signals of AA, DA and UA are well separated into three distinct peaks with peak potential separation of 193mv, 172mv and 264mV between AA-DA, DA-UA and AA-UA respectively in CV studies and the corresponding peak potential separations in DPV mode are 204mv, 141mv and 345mv. The FGGE is successfully used for the simultaneous detection of AA, DA and UA in their ternary mixture and DA in serum and pharmaceutical samples. The excellent electrocatalytic behavior of FGGE may lead to new applications in electrochemical analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. AAS 227: Day 3

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    , think-pair-share style clicker questions, and comparing excerpts from scientific articles and the media. Eventually, students discover that the Earths overall temperature is going up, but observations can vary from year to year because heat is moving between the atmosphere and the oceans.Press Conference: Fermis Vision, First Stars, Massive Galaxy Cluster, and Dark Energy (by Susanna Kohler)Todays afternoon press conference was an exciting assortment of results, difficult to categorize under a single umbrella.First up was Marco Ajello (Clemson University), who spoke about 2FHL, the second Fermi-LAT catalog of high-energy sources. LAT stands for Large Area Telescope, an instrument on board the Fermi gamma-ray space observatory that scans the entire sky every three hours. Ajello described the contents of the 2FHL catalog: 360 gamma-ray sources, of which 75% are blazars (distant galactic nuclei with jets pointed toward us), 11% are sources within the galaxy, and the remaining 14% are unknown. With this catalog, Fermi has expanded into higher energies than ever before, providing the first map of the 50 GeV 2 TeV sky. Heres the press release.OMeara: Im a lowly spectroscopist so I dont have fun pictures to show you, just squiggly lines. #aas227 astrobites (@astrobites) January 7, 2016Next to speak, John OMeara (St. Michaels College) told us about the discovery of a gas cloud that may be a remnant from the first population of stars. OMeara showed us the emission spectrum from a distant quasar, which displays abrupt absorption by a cloud of gas located at a redshift of z~3.5. Absorption by gas clouds is not unusual but what is unusual is that this cloud is extremely metal-poor, with only 1/2500th solar metallicity. This is the lowest heavy-element content ever measured, and a sign that the cloud might have been enriched by Population III stars the theoretical first population of stars, which were born when gas in the universe was still pristine. Heres the press release

  6. A 100-Year Review: Protein and amino acid nutrition in dairy cows.

    PubMed

    Schwab, Charles G; Broderick, Glen A

    2017-12-01

    Considerable progress has been made in understanding the protein and amino acid (AA) nutrition of dairy cows. The chemistry of feed crude protein (CP) appears to be well understood, as is the mechanism of ruminal protein degradation by rumen bacteria and protozoa. It has been shown that ammonia released from AA degradation in the rumen is used for bacterial protein formation and that urea can be a useful N supplement when lower protein diets are fed. It is now well documented that adequate rumen ammonia levels must be maintained for maximal synthesis of microbial protein and that a deficiency of rumen-degradable protein can decrease microbial protein synthesis, fiber digestibility, and feed intake. Rumen-synthesized microbial protein accounts for most of the CP flowing to the small intestine and is considered a high-quality protein for dairy cows because of apparent high digestibility and good AA composition. Much attention has been given to evaluating different methods to quantify ruminal protein degradation and escape and for measuring ruminal outflows of microbial protein and rumen-undegraded feed protein. The methods and accompanying results are used to determine the nutritional value of protein supplements and to develop nutritional models and evaluate their predictive ability. Lysine, methionine, and histidine have been identified most often as the most-limiting amino acids, with rumen-protected forms of lysine and methionine available for ration supplementation. Guidelines for protein feeding have evolved from simple feeding standards for dietary CP to more complex nutrition models that are designed to predict supplies and requirements for rumen ammonia and peptides and intestinally absorbable AA. The industry awaits more robust and mechanistic models for predicting supplies and requirements of rumen-available N and absorbed AA. Such models will be useful in allowing for feeding lower protein diets and increased efficiency of microbial protein synthesis

  7. Acid-Group-Content-Dependent Proton Conductivity Mechanisms at the Interlayer of Poly(N-dodecylacrylamide-co-acrylic acid) Copolymer Multilayer Nanosheet Films.

    PubMed

    Sato, Takuma; Tsukamoto, Mayu; Yamamoto, Shunsuke; Mitsuishi, Masaya; Miyashita, Tokuji; Nagano, Shusaku; Matsui, Jun

    2017-11-14

    The effect of the content of acid groups on the proton conductivity at the interlayer of polymer-nanosheet assemblies was investigated. For that purpose, amphiphilic poly(N-dodecylacrylamide-co-acrylic acid) copolymers [p(DDA/AA)] with varying contents of AA were synthesized by free radical polymerization. Surface pressure (π)-area (A) isotherms of these copolymers indicated that stable polymer monolayers are formed at the air/water interface for AA mole fraction (n) ≤ 0.49. In all cases, a uniform dispersion of the AA groups in the polymer monolayer was observed. Subsequently, polymer monolayers were transferred onto solid substrates using the Langmuir-Blodgett (LB) technique. X-ray diffraction (XRD) analyses of the multilayer films showed strong Bragg diffraction peaks, suggesting a highly uniform lamellar structure for the multilayer films. The proton conductivity of the multilayer films parallel to the direction of the layer planes were measured by impedance spectroscopy, which revealed that the conductivity increased with increasing values of n. Activation energies for proton conduction of ∼0.3 and 0.42 eV were observed for n ≥ 0.32 and n = 0.07, respectively. Interestingly, the proton conductivity of a multilayer film with n = 0.19 did not follow the Arrhenius equation. These results were interpreted in terms of the average distance between the AA groups (l AA ), and it was concluded that, for n ≥ 0.32, an advanced 2D hydrogen bonding network was formed, while for n = 0.07, l AA is too long to form such hydrogen bonding networks. The l AA for n = 0.19 is intermediate to these extremes, resulting in the formation of hydrogen bonding networks at low temperatures, and disruption of these networks at high temperatures due to thermally induced motion. These results indicate that a high proton conductivity with low activation energy can be achieved, even under weakly acidic conditions, by arranging the acid groups at an optimal distance.

  8. Ferulic acid with ascorbic acid synergistically extenuates the mitochondrial dysfunction during beta-adrenergic catecholamine induced cardiotoxicity in rats.

    PubMed

    Yogeeta, Surinder Kumar; Raghavendran, Hanumantha Rao Balaji; Gnanapragasam, Arunachalam; Subhashini, Rajakannu; Devaki, Thiruvengadam

    2006-10-27

    Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.

  9. Quantum chemical density functional theory studies on the molecular structure and vibrational spectra of Gallic acid imprinted polymers

    NASA Astrophysics Data System (ADS)

    Pardeshi, Sushma; Dhodapkar, Rita; Kumar, Anupama

    2013-12-01

    Gallic acid (GA) is known by its antioxidant, anticarcinogenic properties and scavenger activity against several types of harmful free radicals. Molecularly imprinted polymers (MIPs) are used in separation of a pure compound from complex matrices. A stable template-monomer complex generates the MIPs with the highest affinity and selectivity for the template. The quantum chemical computations based on density functional theory (DFT) was used on the template Gallic acid (GA), monomer acrylic acid (AA) and GA-AA complex to study the nature of interactions involved in the GA-AA complex. B3LYP/6-31+G(2d,2p) model chemistry was used to optimize their structures and frequency calculations. The effect of porogen acetonitrile (ACN) on complex formation was included by using polarizable continuum model (PCM). The results demonstrated the formation of a stable GA-AA complex through the intermolecular hydrogen bonding between carboxylic acid groups of GA and AA. The Mulliken atomic charge analysis and simulated vibrational spectra also supported the stable hydrogen bonding interaction between the carboxylic acid groups of GA and AA with minimal interference of porogen ACN. Further, simulations on GA-AA mole ratio revealed that 1:4 GA-AA was optimum for synthesis of MIP for GA.

  10. Acid volatile sulfides oxidation and metals (Mn, Zn) release upon sediment resuspension: laboratory experiment and model development.

    PubMed

    Hong, Yong Seok; Kinney, Kerry A; Reible, Danny D

    2011-03-01

    Sediment from the Anacostia River (Washington, DC, USA) was suspended in aerobic artificial river water for 14 d to investigate the dynamics of dissolved metals release and related parameters including pH, acid volatile sulfides (AVS), and dissolved/solid phase Fe(2+). To better understand and predict the underlying processes, a mathematical model is developed considering oxidation of reduced species, dissolution of minerals, pH changes, and pH-dependent metals' sorption to sediment. Oxidation rate constants of elemental sulfur and zinc sulfide, and a dissolution rate constant of carbonate minerals, were adjusted to fit observations. The proposed model and parameters were then applied, without further calibration, to literature-reported experimental observations of resuspension in an acid sulfate soil collected in a coastal flood plain. The model provided a good description of the dynamics of AVS, Fe(2+), S(0)((s)), pH, dissolved carbonates concentrations, and the release of Ca((aq)), Mg((aq)), and Zn((aq)) in both sediments. Accurate predictions of Mn((aq)) release required adjustment of sorption partitioning coefficient, presumably due to the presence of Mn scavenging by phases not accounted for in the model. The oxidation of AVS (and the resulting release of sulfide-bound metals) was consistent with a two-step process, a relatively rapid AVS oxidation to elemental sulfur (S(0)((s))) and a slow oxidation of S(0)((s)) to SO(4)(2-)((aq)), with an associated decrease in pH from neutral to acidic conditions. This acidification was the dominant factor for the release of metals into the aqueous phase. Copyright © 2010 SETAC.

  11. [Research of preparation craft of Danshen phenolic acid fast release unit in multi-drug delivery system of Tongmai micro-pellets].

    PubMed

    Chen, Bin; Xiao, Wei; Jia, Xiao-Bin; Huang, Yang

    2012-07-01

    To prepare Danshen phenolic acid fast release micro-pellets and study its preparation craft. The factors which could impact yield, extrude shaping, dissolution of Danshen phenolic acid micro-pellets such as wetting agent, drug loading dose, adjuvant, lactose dose, disintegrant, CMS-Na dose and wetting agent dose was investigated. The optimum preparation craft of Danshen phenolic acid fast release micro-pellets was screened out by orhogonal design. Formula of Danshen phenolic acid fast release micro-pellets was calculated as volume dose 50 g. The formula was as follows: principal agent 22.5 g, lactose 5 g, CMS-Na 2 g, MCC 20.5 g, 27 mL 30% ethanol as wetting agent. Extrusion-spheronization was applied. The optimum conditions were screened out as follows: extrusion frequency (25 Hz), spheronization machine frequency (50 Hz), spheronization time (4 min). The process was scientific and rational. The preparation is stable settles basis for multi-drug delivery system of Tongmai micro-pellets.

  12. The oxygen isotope composition of phosphate released from phytic acid by the activity of wheat and Aspergillus niger phytase

    NASA Astrophysics Data System (ADS)

    von Sperber, C.; Tamburini, F.; Brunner, B.; Bernasconi, S. M.; Frossard, E.

    2015-07-01

    Phosphorus (P) is an essential nutrient for living organisms. Under P-limiting conditions plants and microorganisms can exude extracellular phosphatases that release inorganic phosphate (Pi) from organic phosphorus compounds (Porg). Phytic acid (myo-inositol hexakisphosphate, IP6) is an important form of Porg in many soils. The enzymatic hydrolysis of IP6 by phytase yields available Pi and less phosphorylated inositol derivates as products. The hydrolysis of organic P compounds by phosphatases leaves an isotopic imprint on the oxygen isotope composition (δ18O) of released Pi, which might be used to trace P in the environment. This study aims at determining the effect of phytase on the oxygen isotope composition of released Pi. For this purpose, enzymatic assays with histidine acid phytases from wheat and Aspergillus niger were prepared using IP6, adenosine 5'-monophosphate (AMP) and glycerophosphate (GPO4) as substrates. For a comparison to the δ18O of Pi released by other extracellular enzymes, enzymatic assays with acid phosphatases from potato and wheat germ with IP6 as a substrate were prepared. During the hydrolysis of IP6 by phytase, four of the six Pi were released, and one oxygen atom from water was incorporated into each Pi. This incorporation of oxygen from water into Pi was subject to an apparent inverse isotopic fractionation (ϵ ~ 6 to 10 ‰), which was similar to that imparted by acid phosphatase from potato during the hydrolysis of IP6 (ϵ ~ 7 ‰), where less than three Pi were released. The incorporation of oxygen from water into Pi during the hydrolysis of AMP and GPO4 by phytase yielded a normal isotopic fractionation (ϵ ~ -12 ‰), similar to values reported for acid phosphatases from potato and wheat germ. We attribute this similarity in ϵ to the same amino acid sequence motif (RHGXRXP) at the active site of these enzymes, which leads to similar reaction mechanisms. We suggest that the striking

  13. The oxygen isotope composition of phosphate released from phytic acid by the activity of wheat and Aspergillus niger phytase

    NASA Astrophysics Data System (ADS)

    Sperber, C. v.; Tamburini, F.; Brunner, B.; Bernasconi, S. M.; Frossard, E.

    2015-03-01

    Phosphorus (P) is an essential nutrient for living organisms. Under P-limiting conditions plants and microorganisms can exude extracellular phosphatases that release inorganic phosphate (Pi) from organic phosphorus compounds (Porg). Phytic acid (IP6) is an important form of Porg in many soils. The enzymatic hydrolysis of IP6 by phytase yields plant available inorganic phosphate (Pi) and less phosphorylated inositol derivates as products. The hydrolysis of organic P-compounds by phosphatases leaves an isotopic imprint on the oxygen isotope composition (δ18O) of released Pi, which might be used to trace P in the environment. This study aims at determining the effect of phytase on the oxygen isotope composition of released Pi. For this purpose, enzymatic assays with histidine acid phytases from wheat and Aspergillus niger were prepared using IP6, adenosine 5'monophosphate (AMP) and glycerophosphate (GPO4) as substrates. For a comparison to the δ18O of Pi released by other extracellular enzymes, enzymatic assays with acid phosphatases from potato and wheat germ with IP6 as substrate were prepared. During the hydrolysis of IP6 by phytase, four Pi are released, and one oxygen atom from water is incorporated into each Pi. This incorporation of oxygen from water into Pi is subject to an apparent inverse isotopic fractionation (ϵ ∼ 6 to 10‰), which is similar to that imparted by acid phosphatase from potato during the hydrolysis of IP6 (ϵ ∼ 7‰) where less than three Pi are released. The incorporation of oxygen from water into Pi during the hydrolysis of AMP and GPO4 by phytase yielded a normal isotopic fractionation (ϵ ∼ -12‰), again similar to values reported for acid phosphatases from potato and wheat germ. We attribute this similarity in ɛ to the same amino acid sequence motif (RHGXRXP) at the active site of these enzymes, which leads to similar reaction mechanisms. We suggest that the striking substrate-dependency of

  14. Developmental nephrotoxicity of aristolochic acid in a zebrafish model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ding, Yu-Ju; Chen, Yau-Hung, E-mail: yauhung@mail.tku.edu.tw

    2012-05-15

    Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ±more » 2.24% vs. 10 ppm AA treatment for 3–5 h: 71.48 ± 18.84% ∼ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury. -- Highlights: ► Zebrafish were used to evaluate aristolochic acid (AA)-induced nephrotoxicity. ► AA-treated zebrafish embryos exhibited deformed heart as well as malformed kidney. ► Kidney is more sensitive to AA injury than the heart.« less

  15. The influence of ochratoxin A on DNA adduct formation by the carcinogen aristolochic acid in rats.

    PubMed

    Stiborová, Marie; Bárta, František; Levová, Kateřina; Hodek, Petr; Frei, Eva; Arlt, Volker M; Schmeiser, Heinz H

    2015-11-01

    Exposure to the plant nephrotoxin and carcinogen aristolochic acid (AA) leads to the development of AA nephropathy, Balkan endemic nephropathy (BEN) and upper urothelial carcinoma (UUC) in humans. Beside AA, exposure to ochratoxin A (OTA) was linked to BEN. Although OTA was rejected as a factor for BEN/UUC, there is still no information whether the development of AA-induced BEN/UUC is influenced by OTA exposure. Therefore, we studied the influence of OTA on the genotoxicity of AA (AA-DNA adduct formation) in vivo. AA-DNA adducts were formed in liver and kidney of rats treated with AA or AA combined with OTA, but no OTA-related DNA adducts were detectable in rats treated with OTA alone or OTA combined with AA. Compared to rats treated with AA alone, AA-DNA adduct levels were 5.4- and 1.6-fold higher in liver and kidney, respectively, of rats treated with AA combined with OTA. Although AA and OTA induced quinone oxidoreductase (NQO1) activating AA to DNA adducts, their combined treatment did not lead to either higher NQO1 enzyme activity or higher AA-DNA adduct levels in ex vivo incubations. Oxidation of AA I (8-methoxy-6-nitrophenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid) to its detoxification metabolite, 8-hydroxyaristolochic acid, was lower in microsomes from rats treated with AA and OTA, and this was paralleled by lower activities of cytochromes P450 1A1/2 and/or 2C11 in these microsomes. Our results indicate that a decrease in AA detoxification after combined exposure to AA and OTA leads to an increase in AA-DNA adduct formation in liver and kidney of rats.

  16. The Nitric Oxide Donor SNAP-Induced Amino Acid Neurotransmitter Release in Cortical Neurons. Effects of Blockers of Voltage-Dependent Sodium and Calcium Channels

    PubMed Central

    Merino, José Joaquín; Arce, Carmen; Naddaf, Ahmad; Bellver-Landete, Victor; Oset-Gasque, Maria Jesús; González, María Pilar

    2014-01-01

    Background The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. Findings The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Conclusions Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons. PMID:24598811

  17. The nitric oxide donor SNAP-induced amino acid neurotransmitter release in cortical neurons. Effects of blockers of voltage-dependent sodium and calcium channels.

    PubMed

    Merino, José Joaquín; Arce, Carmen; Naddaf, Ahmad; Bellver-Landete, Victor; Oset-Gasque, Maria Jesús; González, María Pilar

    2014-01-01

    The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons.

  18. A facile photoelectrochemical sensor for high sensitive ROS and AA detection based on graphitic carbon nitride nanosheets.

    PubMed

    Motaghed Mazhabi, Robabeh; Ge, Liqin; Jiang, Hui; Wang, Xuemei

    2018-06-01

    Photoactive material is one of the main challenges for fabrication of sensitive and selective photoelectrochemical (PEC) sensor. Herein, a facile PEC sensor is constructed using graphitic carbon nitride nanosheets (g-C 3 N 4 NSs) coated on the surface of ITO electrode, where electron donor properties of potassium ferrocyanide and ascorbic acid is utilized for the tracing of hydrogen peroxide (H 2 O 2 ), hypochlorite (ClO - ), and ascorbic acid (AA). Our designed PEC sensor exhibits a good linear range to H 2 O 2 concentrations from 12.5 to 875 µM in pH = 7.4 and 2.5-400 µM in pH = 10, while that for AA is in the range from 0.25 to 100 µM in pH = 7.4, and with the same pH for ClO - concentrations in the range from 0.5 to 19 × 10 -3 % (V/V) in a bleach sample. Owing to the good responses towards the traces of H 2 O 2 , AA, and ClO - , our designed system may be used as H 2 O 2, ClO - , and AA sensor for outdoor applications with high specificity, long-time stability and good reproducibility. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Impact on sediments and water by release of copper from chalcopyrite bearing rock due to acidic mine drainage

    NASA Astrophysics Data System (ADS)

    Shukla, Anoop Kant; Pradhan, Manoj; Tiwari, Onkar Nath

    2018-04-01

    Mining activity causes transition of rock-mass from its original position in earth into open environment. The action of environmental elements such air, water, microorganisms leads to oxidation of minerals which constitute the rock. The oxidation of sulphide minerals in presence of moisture releases acidic mine discharge (AMD). The acidic nature of AMD causes leaching of metals from rock minerals. Dissolution of other minerals may occur upon reaction with AMD. Chalcopyrite (CuFeS2) undergoes oxidation in acidic condition releasing copper among other products. This study reveals contamination of copper in sediment samples and seepage water from the tailing dam of a large copper project in located in central India. Elevation was studied using GIS to ascertain to the topographic elevation of tailing dam area. It was located at relatively high altitude causing seepage to flow away from tailing dam. The seepage water from tailing dam was found to be acidic with mean pH value of 4.0 and elevated copper content. Similarly, sediments from seepage water flow displayed elevated copper concentration. The copper concentration in seepage water was found with a mean value of 10.73 mg/l. The sediments from seepage water flow also displayed elevated copper concentration with mean value of 26.92 g/kg. This indicates impact on sediments by release of copper due to acidic mine drainage.

  20. 40 CFR Table Aa-2 to Subpart Aa of... - Kraft Lime Kiln and Calciner Emissions Factors for CH4 and N2O

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Kraft Lime Kiln and Calciner Emissions Factors for CH4 and N2O AA Table AA-2 to Subpart AA of Part 98 Protection of Environment ENVIRONMENTAL... Manufacturing Pt. 98, Subpt. AA, Table AA -2 Table AA-2 to Subpart AA of Part 98—Kraft Lime Kiln and Calciner...

  1. Low-visibility light-intensity laser-triggered release of entrapped calcein from 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine liposomes is mediated through a type I photoactivation pathway

    PubMed Central

    Yavlovich, Amichai; Viard, Mathias; Gupta, Kshitij; Sine, Jessica; Vu, Mylinh; Blumenthal, Robert; Tata, Darrell B; Puri, Anu

    2013-01-01

    We recently reported on the physical characteristics of photo-triggerable liposomes containing dipalmitoylphosphatidylcholine (DPPC), and 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) carrying a photo agent as their payload. When exposed to a low-intensity 514 nm wavelength (continuous-wave) laser light, these liposomes were observed to release entrapped calcein green (Cal-G; Ex/Em 490/517 nm) but not calcein blue (Cal-B; Ex/Em 360/460 nm). In this study, we have investigated the mechanism for the 514 nm laser-triggered release of the Cal-G payload using several scavengers that are known specifically to inhibit either type I or type II photoreaction pathways. Liposomes containing DPPC:DC8,9PC: distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol (PEG)-2000 (86:10:04 mole ratio) were loaded either with fluorescent (calcein) or nonfluorescent (3H-inulin) aqueous markers. In addition, a non-photo-triggerable formulation (1-palmitoyl-2-oleoyl phosphatidylcholine [POPC]:DC8,9PC:DSPE-PEG2000) was also studied with the same payloads. The 514 nm wavelength laser exposure on photo-triggerable liposomes resulted in the release of Cal-G but not that of Cal-B or 3H-inulin, suggesting an involvement of a photoactivated state of Cal-G due to the 514 nm laser exposure. Upon 514 nm laser exposures, substantial hydrogen peroxide (H2O2, ≈100 μM) levels were detected from only the Cal-G loaded photo-triggerable liposomes but not from Cal-B-loaded liposomes (≤10 μM H2O2). The Cal-G release from photo-triggerable liposomes was found to be significantly inhibited by ascorbic acid (AA), resulting in a 70%–80% reduction in Cal-G release. The extent of AA-mediated inhibition of Cal-G release from the liposomes also correlated with the consumption of AA. No AA consumption was detected in the 514 nm laserexposed Cal B-loaded liposomes, thus confirming a role of photoactivation of Cal-G in liposome destabilization. Inclusion of 100 mM K3Fe(CN)6 (a

  2. Influences of AMY1 gene copy number and protein expression on salivary alpha-amylase activity before and after citric acid stimulation in splenic asthenia children.

    PubMed

    Yang, Zemin; Lin, Jing; Chen, Longhui; Zhang, Min; Yang, Xiaorong; Chen, Weiwen

    2015-06-01

    To compare the correlations between salivary alpha-amylase (sAA) activity and amylase, alpha 1 (salivary) gene (AMYl) copy number or its gene expression between splenic asthenia and healthy children, and investigate the reasons of attenuated sAA activity ratio before and after citric acid stimulation in splenic asthenia children. Saliva samples from 20 splenic asthenia children and 29 healthy children were collected before and after citric acid stimulation. AMYl copy number, sAA activity, and total sAA and glycosylated sAA contents were determined, and their correlations were analyzed. Although splenic asthenia and healthy children had no differences in AMY1 copy number, splenic asthenia children had positive correlations between AMY1 copy number and sAA activity before or after citric acid stimulation. Splenic asthenia children had a higher sAA glycosylated proportion ratio and glycosylated sAA content ratio, while their total sAA content ratio and sAA activity ratio were lower compared with healthy children. The glycosylated sAA content ratio was higher than the total sAA content ratio in both groups. Splenic asthenia and healthy children had positive correlations between total sAA or glycosylated sAA content and sAA activity. However, the role played by glycosylated sAA content in sAA activity in healthy children increased after citric acid stimulation, while it decreased in splenic asthenia children. Genetic factors like AMY1 copy number variations, and more importantly, sAA glycosylation abnormalities leading to attenuated sAA activity after citric acid stimulation, which were the main reasons of the attenuated sAA activity ratio in splenic asthenia children compared with healthy children.

  3. Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid.

    PubMed

    Duncan, Sylvia H; Russell, Wendy R; Quartieri, Andrea; Rossi, Maddalena; Parkhill, Julian; Walker, Alan W; Flint, Harry J

    2016-07-01

    Cereal fibres such as wheat bran are considered to offer human health benefits via their impact on the intestinal microbiota. We show here by 16S rRNA gene-based community analysis that providing amylase-pretreated wheat bran as the sole added energy source to human intestinal microbial communities in anaerobic fermentors leads to the selective and progressive enrichment of a small number of bacterial species. In particular, OTUs corresponding to uncultured Lachnospiraceae (Firmicutes) related to Eubacterium xylanophilum and Butyrivibrio spp. were strongly enriched (by five to 160 fold) over 48 h in four independent experiments performed with different faecal inocula, while nine other Firmicutes OTUs showed > 5-fold enrichment in at least one experiment. Ferulic acid was released from the wheat bran during degradation but was rapidly converted to phenylpropionic acid derivatives via hydrogenation, demethylation and dehydroxylation to give metabolites that are detected in human faecal samples. Pure culture work using bacterial isolates related to the enriched OTUs, including several butyrate-producers, demonstrated that the strains caused substrate weight loss and released ferulic acid, but with limited further conversion. We conclude that breakdown of wheat bran involves specialist primary degraders while the conversion of released ferulic acid is likely to involve a multi-species pathway. © 2015 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. Antioxidants Modulate the Antiproliferative Effects of Nitric Oxide on Vascular Smooth Muscle Cells and Adventitial Fibroblasts by Regulating Oxidative Stress

    PubMed Central

    Gregory, Elaine K.; Vavra, Ashley K.; Moreira, Edward S.; Havelka, George E.; Jiang, Qun; Lee, Vanessa R.; Van Lith, Robert; Ameer, Guillermo A.; Kibbe, Melina R.

    2011-01-01

    Background S-nitrosothiols (SNO) release nitric oxide (NO) through interaction with ascorbic acid (AA). However, little is known about their combined effect in the vasculature. The aim of this study is to investigate the effect of AA on SNO-mediated NO release, proliferation, cell cycle progression, cell death and oxidative stress in vascular cells. Methods VSMC and adventitial fibroblasts (AF) harvested from the aortae of Sprague Dawley rats were treated with AA, ± S-nitrosoglutathione (GSNO), or ± diethylenetriamine NONOate (DETA/NO). NO release, proliferation, cell cycle progression, cell death, and oxidative stress were determined by the Greiss reaction, [3H]-thymidine incorporation, flow cytometry, trypan blue exclusion, and DCF staining, respectively. Results AA increased NO release from GSNO 3-fold (p<0.001). GSNO and DETA/NO significantly decreased proliferation, but AA abrogated this effect (p<0.05). Mirroring the proliferation data, changes in cell cycle progression induced by GSNO and DETA/NO were reversed by addition of AA. GSNO- and DETA/NO-mediated increases in oxidative stress were significantly decreased by addition of AA (p<0.001). Conclusion Despite causing increased NO release from GSNO, AA reduced the antiproliferative and cell cycle effects of GSNO and DETA/NO through modulation of oxidative stress. PMID:21944289

  5. AAS Statistics and the 60% Cohort

    NASA Astrophysics Data System (ADS)

    Marvel, K. B.

    2004-05-01

    I will present the latest statistics available describing the gender of the AAS membership including an update on the so-called 60% cohort (that group of AAS members from the ages of 18 to 25 who are 60% women and 40% men). The AAS membership has changed significantly in the past 30 years from an overall female membership percentage of about 10% to a level around 30% today. This trend is accelerating and indicates the ongoing inclusion of women in the physical sciences, especially astronomy. By the year 2030, the AAS membership should reach gender parity if the present trend continues.

  6. Effect of insulin sensitizer therapy on amino acids and their metabolites.

    PubMed

    Irving, Brian A; Carter, Rickey E; Soop, Mattias; Weymiller, Audrey; Syed, Husnain; Karakelides, Helen; Bhagra, Sumit; Short, Kevin R; Tatpati, Laura; Barazzoni, Rocco; Nair, K Sreekumaran

    2015-06-01

    Prior studies have reported that elevated concentrations of several plasma amino acids (AA), particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI ~30kg/m(2)) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45mg per day) plus metformin (1000mg twice per day, N=12 participants) or placebo (N=13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Control of Clostridium perfringens-induced necrotic enteritis in broilers by target-released butyric acid, fatty acids and essential oils.

    PubMed

    Timbermont, L; Lanckriet, A; Dewulf, J; Nollet, N; Schwarzer, K; Haesebrouck, F; Ducatelle, R; Van Immerseel, F

    2010-04-01

    The efficacy of target-released butyric acid, medium-chain fatty acids (C(6) to C(12) but mainly lauric acid) and essential oils (thymol, cinnamaldehyde, essential oil of eucalyptus) micro-encapsulated in a poly-sugar matrix to control necrotic enteritis was investigated. The minimal inhibitory concentrations of the different additives were determined in vitro, showing that lauric acid, thymol, and cinnamaldehyde are very effective in inhibiting the growth of Clostridium perfringens. The in vivo effects were studied in two trials in an experimental necrotic enteritis model in broiler chickens. In the first trial, four groups of chickens were fed a diet supplemented with butyric acid, with essential oils, with butyric acid in combination with medium-chain fatty acids, or with butyric acid in combination with medium-chain fatty acids and essential oils. In all groups except for the group receiving only butyric acid, a significant decrease in the number of birds with necrotic lesions was found compared with the infected, untreated control group. In the second trial the same products were tested but at a higher concentration. An additional group was fed a diet supplemented with only medium-chain fatty acids. In all groups except for that receiving butyric acid in combination with medium-chain fatty acids and essential oils, a significant decrease in the number of birds with necrotic lesions was found compared with the infected, untreated control group. These results suggest that butyric acid, medium-chain fatty acids and/or essential oils may contribute to the prevention of necrotic enteritis in broilers.

  8. Controlled release of acidic drugs in compendial and physiological hydrogen carbonate buffer from polymer blend-coated oral solid dosage forms.

    PubMed

    Wulff, R; Rappen, G-M; Koziolek, M; Garbacz, G; Leopold, C S

    2015-09-18

    The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300 min. To simulate drug release from the mini tablets coated with RL/L55 blends in the gastrointestinal (GI) tract, drug release profiles in Hanks buffer pH 6.8 were recorded and compared with drug release profiles in compendial media. RL/L55 blend coatings showed increased drug permeability in Hanks buffer pH 6.8 compared to phosphate buffer pH 6.8 due to its higher ion concentration. However, drug release rates of acidic drugs were lower in Hanks buffer pH 6.8 because of the lower buffer capacity resulting in reduced drug solubility. Further dissolution tests were performed in Hanks buffer using pH sequences simulating the physiological pH conditions in the GI tract. Drug release from mini tablets coated with an RL/L55 blend (8:1) was insensitive to pH changes of the medium within the pH range of 5.8-7.5. It was concluded that coatings of RL/L55 blends show a high potential for application in coated oral drug delivery systems with a special focus on pH-independent release of acidic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

    PubMed

    Taha, Ameer Y; Cheon, Yewon; Faurot, Keturah F; Macintosh, Beth; Majchrzak-Hong, Sharon F; Mann, J Douglas; Hibbeln, Joseph R; Ringel, Amit; Ramsden, Christopher E

    2014-05-01

    Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd.

  10. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools

    PubMed Central

    Taha, Ameer Y.; Cheon, Yewon; Faurot, Keturah F.; MacIntosh, Beth; Majchrzak-Hong, Sharon F.; Mann, J. Douglas; Hibbeln, Joseph R.; Ringel, Amit; Ramsden, Christopher E.

    2014-01-01

    Background Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. Objective To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, change unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Design Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to: (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Results Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Conclusion Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFA for 12 weeks further increases n-3 PUFA plasma concentrations, but also reduces AA. PMID:24675168

  11. Release properties of tannic acid from hydrogen bond driven antioxidative cellulose nanofibrous films.

    PubMed

    Zhou, Bin; Hu, Xiaoqian; Zhu, Jinjin; Wang, Zhenzhen; Wang, Xichang; Wang, Mingfu

    2016-10-01

    Layer-by-layer (LBL) assembled films have been exploited for surface-mediated bioactive compound delivery. Here, an antioxidative hydrogen-bonded multilayer electrospun nanofibrous film was fabricated from tannic acid (TA), acting as a polyphenolic antioxidant, and poly(ethylene glycol) (PEG) via layer-by-layer assembly. It overcame the burst release behavior of nanofibrous carrier, due to the reversible/dynamic nature of hydrogen bond, which was responded to external stimuli. The PEG/TA nanofibrous films disassembled gradually and released TA to the media, when soaked in aqueous solutions. The release rate of TA increased with increasing bilayer number, pH and temperature, but decreased with enhancing ionic strength. The surface morphology of the nanofibrous mats was observed by scanning electron microscopy (SEM). The following antioxidant activity assay revealed that it could scavenge DPPH free radicals and ABTS(+) cation radicals, a major biological activity of polyphenols. This technology can be used to fabricate other phenolic-containing slowly releasing antioxidative nanofibrous films. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Effects of processing on the release profiles of matrix systems containing 5-aminosalicylic acid.

    PubMed

    Korbely, Anita; Kelemen, András; Kása, Péter; Pintye-Hódi, Klára

    2012-12-01

    The aim of this study was to investigate the influence of different processing methods on the profiles of 5-aminosalicylic acid dissolution from controlled-release matrix systems based on Eudragit® RL and Eudragit® RS water-insoluble polymers. The pure polymers and their mixtures were studied as matrix formers using different processing methods, i.e., direct compression, wet granulation of the active ingredient with the addition of polymer(s) to the external phase, wet granulation with water, and wet granulation with aqueous dispersions. In comparison with the directly compressed tablets, tablets made by wet granulation with water demonstrated a 6-19% increase in final drug dissolution, whereas when polymers were applied in the external phase during compression, a 0-13% decrease was observed in the amount of drug released. Wet granulation with aqueous polymer dispersions delayed the release of the drug; this was especially marked (a 54-56% decrease in drug release) in compositions, which contained a high amount of Eudragit RL 30D. The release profiles were mostly described by the Korsmeyer-Peppas model or the Hopfenberg model.

  13. Biodegradable poly(L-lactic acid)-lavender nanocapsules: synthesis, controlled release, and application in remedy of sleep disorder.

    PubMed

    Daoud, Walid A; Ngan, Mandy; Cheuk, Kevin

    2010-02-01

    In this study, nanocapsules of poly(L-lactic acid) (PLLA) containing lavender oil were synthesized by solvent evaporation emulsion. Poly(L-lactic acid) is a biodegradable aliphatic polyester derived from lactic acid formed by bacterial fermentation of glucose-rich substances. Lavender oil is a plant extract that finds uses in phytotherapy. It is reputed as anti-septic, anti-depressant and sleep promoter. Encapsulation is a technique used to encase tiny oil droplets with a thin and permeable coating that allows for a controlled release of the volatile oil. The size and morphology of the nanocapsules were characterized by scanning electron microscope. The particle size and distribution were measured by photon correlation spectroscopy. The time-controlled release of the lavender oil was studied and the use of the lavender capsules in the remedy of sleep disorder was investigated.

  14. Preparation and characterization of poly(acrylic acid)-hydroxyethyl cellulose graft copolymer.

    PubMed

    Abdel-Halim, E S

    2012-10-01

    Poly(acrylic acid) hydroxyethyl cellulose [poly(AA)-HEC] graft copolymer was prepared by polymerizing acrylic acid (AA) with hydroxyethyl cellulose (HEC) using potassium bromate/thiourea dioxide (KBrO(3)/TUD) as redox initiation system. The polymerization reaction was carried out under a variety of conditions including concentrations of AA, KBrO(3) and TUD, material to liquor ratio and polymerization temperature. The polymerization reaction was monitored by withdrawing samples from the reaction medium and measuring the total conversion. The rheological properties of the poly(AA)-HEC graft copolymer were investigated. The total conversion and rheological properties of the graft copolymer depended on the ratio of KBrO(3) to TUD and on acrylic acid concentration as well as temperature and material to liquor ratio. Optimum conditions of the graft copolymer preparation were 30 mmol KBrO(3) and 30 mmol TUD/100g HEC, 100% AA (based on weight of HEC), duration 2h at temperature 50 °C using a material to liquor ratio of 1:10. Copyright © 2012. Published by Elsevier Ltd.

  15. Prediction of protein-protein interactions based on PseAA composition and hybrid feature selection.

    PubMed

    Liu, Liang; Cai, Yudong; Lu, Wencong; Feng, Kaiyan; Peng, Chunrong; Niu, Bing

    2009-03-06

    Based on pseudo amino acid (PseAA) composition and a novel hybrid feature selection frame, this paper presents a computational system to predict the PPIs (protein-protein interactions) using 8796 protein pairs. These pairs are coded by PseAA composition, resulting in 114 features. A hybrid feature selection system, mRMR-KNNs-wrapper, is applied to obtain an optimized feature set by excluding poor-performed and/or redundant features, resulting in 103 remaining features. Using the optimized 103-feature subset, a prediction model is trained and tested in the k-nearest neighbors (KNNs) learning system. This prediction model achieves an overall accurate prediction rate of 76.18%, evaluated by 10-fold cross-validation test, which is 1.46% higher than using the initial 114 features and is 6.51% higher than the 20 features, coded by amino acid compositions. The PPIs predictor, developed for this research, is available for public use at http://chemdata.shu.edu.cn/ppi.

  16. Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

    PubMed

    Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

    2015-09-01

    This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile. © The Author(s) 2015.

  17. Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

    PubMed Central

    Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

    1995-01-01

    Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation. Images Fig. 2 PMID:11607567

  18. Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

    PubMed

    Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

    1995-08-01

    Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation.

  19. Evaluation of AA5052 alloy anode in alkaline electrolyte with organic rare-earth complex additives for aluminium-air batteries

    NASA Astrophysics Data System (ADS)

    Wang, Dapeng; Li, Heshun; Liu, Jie; Zhang, Daquan; Gao, Lixin; Tong, Lin

    2015-10-01

    Behaviours of the AA5052 aluminium alloy anode of the alkaline aluminium-air battery are studied by the hydrogen evolution test, the electrochemical measurements and the surface analysis method. The combination of amino-acid and rare earth as electrolyte additives effectively retards the self-corrosion of AA5052 aluminium alloy in 4 M NaOH solution. It shows that the combination of L-cysteine and cerium nitrate has a synergistic effect owing to the formation of a complex film on AA5052 alloy surface. The organic rare-earth complex can decrease the anodic polarisation, suppress the hydrogen evolution and increase the anodic utilization rate.

  20. Nonreductive chemical release of intact N-glycans for subsequent labeling and analysis by mass spectrometry.

    PubMed

    Yuan, Jiangbei; Wang, Chengjian; Sun, Yujiao; Huang, Linjuan; Wang, Zhongfu

    2014-10-01

    A novel strategy is proposed, using cost-saving chemical reactions to generate intact free reducing N-glycans and their fluorescent derivatives from glycoproteins for subsequent analysis. N-Glycans without core α-1,3-linked fucose are released in reducing form by selective hydrolysis of the N-type carbohydrate-peptide bond of glycoproteins under a set of optimized mild alkaline conditions and are comparable to those released by commonly used peptide-N-glycosidase (PNGase) F in terms of yield without any detectable side reaction (peeling or deacetylation). The obtained reducing glycans can be routinely derivatized with 2-aminobenzoic acid (2-AA), 1-phenyl-3-methyl-5-pyrazolone (PMP), and potentially some other fluorescent reagents for comprehensive analysis. Alternatively, the core α-1,3-fucosylated N-glycans are released in mild alkaline medium and derivatized with PMP in situ, and their yields are comparable to those obtained using commonly used PNGase A without conspicuous peeling reaction or any detectable deacetylation. Using this new technique, the N-glycans of a series of purified glycoproteins and complex biological samples were successfully released and analyzed by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS), demonstrating its general applicability to glycomic studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols.

    PubMed

    Bomar, Lindsey; Brugger, Silvio D; Yost, Brian H; Davies, Sean S; Lemon, Katherine P

    2016-01-05

    Bacterial interspecies interactions play clinically important roles in shaping microbial community composition. We observed that Corynebacterium spp. are overrepresented in children free of Streptococcus pneumoniae (pneumococcus), a common pediatric nasal colonizer and an important infectious agent. Corynebacterium accolens, a benign lipid-requiring species, inhibits pneumococcal growth during in vitro cocultivation on medium supplemented with human skin surface triacylglycerols (TAGs) that are likely present in the nostrils. This inhibition depends on LipS1, a TAG lipase necessary for C. accolens growth on TAGs such as triolein. We determined that C. accolens hydrolysis of triolein releases oleic acid, which inhibits pneumococcus, as do other free fatty acids (FFAs) that might be released by LipS1 from human skin surface TAGs. Our results support a model in which C. accolens hydrolyzes skin surface TAGS in vivo releasing antipneumococcal FFAs. These data indicate that C. accolens may play a beneficial role in sculpting the human microbiome. Little is known about how harmless Corynebacterium species that colonize the human nose and skin might impact pathogen colonization and proliferation at these sites. We show that Corynebacterium accolens, a common benign nasal bacterium, modifies its local habitat in vitro as it inhibits growth of Streptococcus pneumoniae by releasing antibacterial free fatty acids from host skin surface triacylglycerols. We further identify the primary C. accolens lipase required for this activity. We postulate a model in which higher numbers of C. accolens cells deter/limit S. pneumoniae nostril colonization, which might partly explain why children without S. pneumoniae colonization have higher levels of nasal Corynebacterium. This work narrows the gap between descriptive studies and the needed in-depth understanding of the molecular mechanisms of microbe-microbe interactions that help shape the human microbiome. It also lays the

  2. Analysis of fluorescently labeled glycosphingolipid-derived oligosaccharides following ceramide glycanase digestion and anthranilic acid labeling.

    PubMed

    Neville, David C A; Coquard, Virginie; Priestman, David A; te Vruchte, Danielle J M; Sillence, Daniel J; Dwek, Raymond A; Platt, Frances M; Butters, Terry D

    2004-08-15

    Interest in cellular glycosphingolipid (GSL) function has necessitated the development of a rapid and sensitive method to both analyze and characterize the full complement of structures present in various cells and tissues. An optimized method to characterize oligosaccharides released from glycosphingolipids following ceramide glycanase digestion has been developed. The procedure uses the fluorescent compound anthranilic acid (2-aminobenzoic acid; 2-AA) to label oligosaccharides prior to analysis using normal-phase high-performance liquid chromatography. The labeling procedure is rapid, selective, and easy to perform and is based on the published method of Anumula and Dhume [Glycobiology 8 (1998) 685], originally used to analyze N-linked oligosaccharides. It is less time consuming than a previously published 2-aminobenzamide labeling method [Anal. Biochem. 298 (2001) 207] for analyzing GSL-derived oligosaccharides, as the fluorescent labeling is performed on the enzyme reaction mixture. The purification of 2-AA-labeled products has been improved to ensure recovery of oligosaccharides containing one to four monosaccharide units, which was not previously possible using the Anumula and Dhume post-derivatization purification procedure. This new approach may also be used to analyze both N- and O-linked oligosaccharides.

  3. Acetic acid in aged vinegar affects molecular targets for thrombus disease management.

    PubMed

    Jing, Li; Yanyan, Zhang; Junfeng, Fan

    2015-08-01

    To elucidate the mechanism underlying the action of dietary vinegar on antithrombotic activity, acetic acid, the main acidic component of dietary vinegar, was used to determine antiplatelet and fibrinolytic activity. The results revealed that acetic acid significantly inhibits adenosine diphosphate (ADP)-, collagen-, thrombin-, and arachidonic acid (AA)-induced platelet aggregation. Acetic acid (2.00 mM) reduced AA-induced platelet aggregation to approximately 36.82 ± 1.31%, and vinegar (0.12 mL L(-1)) reduced the platelet aggregation induced by AA to 30.25 ± 1.34%. Further studies revealed that acetic acid exerts its effects by inhibiting cyclooxygenase-1 and the formation of thromboxane-A2. Organic acids including acetic acid, formic acid, lactic acid, citric acid, and malic acid also showed fibrinolytic activity; specifically, the fibrinolytic activity of acetic acid amounted to 1.866 IU urokinase per mL. Acetic acid exerted its fibrinolytic activity by activating plasminogen during fibrin crossing, thus leading to crosslinked fibrin degradation by the activated plasmin. These results suggest that organic acids in dietary vinegar play important roles in the prevention and cure of cardiovascular diseases.

  4. Co-expression of AaPMT and AaTRI effectively enhances the yields of tropane alkaloids in Anisodus acutangulus hairy roots

    PubMed Central

    2011-01-01

    Background Tropane alkaloids (TA) including anisodamine, anisodine, hyoscyamine and scopolamine are a group of important anticholinergic drugs with rapidly increasing market demand, so it is significant to improve TA production by biotechnological approaches. Putrescine N-methyltransferase (PMT) was considered as the first rate-limiting upstream enzyme while tropinone reductase I (TRI) was an important branch-controlling enzyme involved in TA biosynthesis. However, there is no report on simultaneous introduction of PMT and TRI genes into any TA-producing plant including Anisodus acutangulus (A. acutangulus), which is a Solanaceous perennial plant that is endemic to China and is an attractive resource plant for production of TA. Results In this study, 21 AaPMT and AaTRI double gene transformed lines (PT lines), 9 AaPMT single gene transformed lines (P lines) and 5 AaTRI single gene transformed lines (T lines) were generated. RT-PCR and real-time fluorescence quantitative analysis results revealed that total AaPMT (AaPMT T) and total AaTRI (AaTRI T) gene transcripts in transgenic PT, P and T lines showed higher expression levels than native AaPMT (AaPMT E) and AaTRI (AaTRI E) gene transcripts. As compared to the control and single gene transformed lines (P or T lines), PT transgenic hairy root lines produced significantly higher levels of TA. The highest yield of TA was detected as 8.104 mg/g dw in line PT18, which was 8.66, 4.04, and 3.11-times higher than those of the control (0.935 mg/g dw), P3 (highest in P lines, 2.004 mg/g dw) and T12 (highest in T lines, 2.604 mg/g dw), respectively. All the tested samples were found to possess strong radical scavenging capacity, which were similar to control. Conclusion In the present study, the co-expression of AaPMT and AaTRI genes in A. acutangulus hairy roots significantly improved the yields of TA and showed higher antioxidant activity than control because of higher total TA content, which is the first report on

  5. Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

    PubMed Central

    Maliszewski, Anne M.; Gadhia, Monika M.; O'Meara, Meghan C.; Thorn, Stephanie R.; Rozance, Paul J.

    2012-01-01

    Maternal high-protein supplements designed to increase birth weight have not been successful. We recently showed that maternal amino acid infusion into pregnant sheep resulted in competitive inhibition of amino acid transport across the placenta and did not increase fetal protein accretion rates. To bypass placental transport, singleton fetal sheep were intravenously infused with an amino acid mixture (AA, n = 8) or saline [control (Con), n = 10] for ∼12 days during late gestation. Fetal leucine oxidation rate increased in the AA group (3.1 ± 0.5 vs. 1.4 ± 0.6 μmol·min−1·kg−1, P < 0.05). Fetal protein accretion (2.6 ± 0.5 and 2.2 ± 0.6 μmol·min−1·kg−1 in AA and Con, respectively), synthesis (6.2 ± 0.8 and 7.0 ± 0.9 μmol·min−1·kg−1 in AA and Con, respectively), and degradation (3.6 ± 0.6 and 4.5 ± 1.0 μmol·min−1·kg−1 in AA and Con, respectively) rates were similar between groups. Net fetal glucose uptake decreased in the AA group (2.8 ± 0.4 vs. 3.9 ± 0.1 mg·kg−1·min−1, P < 0.05). The glucose-O2 quotient also decreased over time in the AA group (P < 0.05). Fetal insulin and IGF-I concentrations did not change. Fetal glucagon increased in the AA group (119 ± 24 vs. 59 ± 9 pg/ml, P < 0.05), and norepinephrine (NE) also tended to increase in the AA group (785 ± 181 vs. 419 ± 76 pg/ml, P = 0.06). Net fetal glucose uptake rates were inversely proportional to fetal glucagon (r2 = 0.38, P < 0.05), cortisol (r2 = 0.31, P < 0.05), and NE (r2 = 0.59, P < 0.05) concentrations. Expressions of components in the mammalian target of rapamycin signaling pathway in fetal skeletal muscle were similar between groups. In summary, prolonged infusion of amino acids directly into normally growing fetal sheep increased leucine oxidation. Amino acid-stimulated increases in fetal glucagon, cortisol, and NE may contribute to a shift in substrate oxidation by the fetus from glucose to amino acids. PMID:22454287

  6. Novel graphene flowers modified carbon fibers for simultaneous determination of ascorbic acid, dopamine and uric acid.

    PubMed

    Du, Jiao; Yue, Ruirui; Ren, Fangfang; Yao, Zhangquan; Jiang, Fengxing; Yang, Ping; Du, Yukou

    2014-03-15

    A novel and sensitive carbon fiber electrode (CFE) modified by graphene flowers was prepared and used to simultaneously determine ascorbic acid (AA), dopamine (DA) and uric acid (UA). SEM images showed that beautiful and layer-petal graphene flowers homogeneously bloomed on the surface of CFE. Moreover, sharp and obvious oxidation peaks were found at the obtained electrode when compared with CFE and glassy carbon electrode (GCE) for the oxidation of AA, DA and UA. Also, the linear calibration plots for AA, DA and UA were observed, respectively, in the ranges of 45.4-1489.23 μM, 0.7-45.21 μM and 3.78-183.87 μM in the individual detection of each component. By simultaneously changing the concentrations of AA, DA and UA, their oxidation peaks appeared at -0.05 V, 0.16 V and 2.6 V, and the good linear responses ranges were 73.52-2305.53 μM, 1.36-125.69 μM and 3.98-371.49 μM, respectively. In addition, the obtained electrode showed satisfactory results when applied to the determination of AA, DA and UA in urine and serum samples. © 2013 Elsevier B.V. All rights reserved.

  7. Effects of ascorbic acid supplementation on male reproductive system during exposure to hypoxia

    NASA Astrophysics Data System (ADS)

    Havazhagan, G.; Riar, S. S.; Kain, A. K.; Bardhan, Jaya; Thomas, Pauline

    1989-09-01

    Two groups of male rats were exposed to simulated altitudes of 6060 m and 7576 m for 6 h/day for 7 days (intermittent exposure). In two additional groups of animals exposed to the same altitude, 100 mg of ascorbic acid (AA) was fed daily for 5 days prior to the exposure period and also during the exposure period. Rats that did not receive AA showed loss of body weight and weight of reproductive organs after exposure. Sex organs showed atrophy on histological examination and there was a deterioration in spermatozoal quality. There was an increase in alkaline and acid phosphatase, and decrease in protein, sialic acid and glyceryl phosphorylcholine content in various reproductive tissues after exposure. All the above changes in histology and biochemical composition could be partially prevented by AA supplementation. AA supplementation can therefore protect the male reproductive system from deleterious effects of hypoxia. The probable mechanism of action of AA is discussed.

  8. A novel and simple strategy for simultaneous determination of dopamine, uric acid and ascorbic acid based on the stacked graphene platelet nanofibers/ionic liquids/chitosan modified electrode.

    PubMed

    Niu, Xiuli; Yang, Wu; Guo, Hao; Ren, Jie; Yang, Fusheng; Gao, Jinzhang

    2012-09-15

    A promising electrochemical sensor for simultaneous determination of dopamine (DA), uric acid (UA) and ascorbic acid (AA) was fabricated based on the stacked graphene platelet nanofibers (SGNF)/ionic liquid (IL)/chitosan (CS) modified electrode. The SGNF/IL/CS modified electrode possessed excellent electrocatalytic activity towards the oxidation of DA, UA and AA with obvious reduction of over-potential and increased peak current, and the separations of oxidation peak potentials of DA-UA, DA-AA, and UA-AA were of 151, 213 and 364 mV, respectively. Under the optimum conditions, the linear range for the detection of DA, UA and AA were 0.05-240, 0.12-260, and 30-350 μM with the lowest detection limits of 0.05, 0.10 and 14.8 μM for DA, UA and AA, respectively. In addition, the electrochemical sensor showed high sensitivity, excellent selectivity, reproducibility and long-term stability. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Amino acid and hexosamine in the equatorial western Pacific: vertical fluxes and individual preservation through water column to surface sediments

    NASA Astrophysics Data System (ADS)

    Kawahata, H.; Gupta, L. P.; Ishizuka, T.

    2002-12-01

    Amino acids (AA) and hexosamines (HA) are major constituents for all living organisms, constituting important fractions of labile organic carbon and nitrogen. They usually decompose rapidly than bulk OM and must be expected to be closely linked to biogeochemical processes. In spite of such importance, our understanding of degradation processes of labile components is still limited. Therefore vertical fluxes and preservation of AA and HA from water column to surface sediments are investigated at the western equatorial Pacific. The settling particles were composed of fairly fresh AA, which could be derived from siliceous diatom with less amount of calcareous plankton. In contrast, AA were degraded in sediments and porewaters. Each AA showed highly variable preservation ratio from settling to sedimentary particles. Compared with glycine, the calculated preservation ratio was the lowest (0%) for cysteine, followed by phenylalanine (6%), tyrosine (17%), methionine (47%), leucine (60%), isoleucine (65%), proline (67%), valine (91%), serine (99%), arginine (107%), threonine (112%), alanine (115%), glutamic acid (114%), aspartic acid (150%), lysine (166%) and histidine (186%). Beta-alanine and gamma-aminobutyric acid were the least labile AA. Probably they are so difficult to degrade for bacteria to get biochemical energy that the degradation proceeds fairly slowly. In contrast, after burial, even most labile, aromatic and sulfur-containing AA, degrade at a rate similar to the other protein AA. In spite of complicated reactions, most of the AA showed first-order reaction kinetics during the degradation in the sediments. The decomposition rate constant k (kyr-1) in this study was 2-3 orders lower than those in coastal marine environments. Better preservation of HA over AA in the sediments was probably due to the general incorporation of HA into structural biopolymer matrices, such as bacterial cell-walls and chitinous material. Abundant glycine in the AA in the sediments is

  10. Dipicolinic Acid Release and the Germination of Alicyclobacillus acidoterrestris Spores under Nutrient Germinants.

    PubMed

    Porębska, Izabela; Sokołowska, Barbara; Woźniak, Łukasz

    2017-03-30

    The presence of Alicyclobacillus, a thermoacidophilic and spore-forming bacterium, in acidic fruit juices poses a serious problem for the processing industry. A typical sign of spoilage in contaminated juices is a characteristic phenolic off-flavour associated with the production of guaiacol. Spores are formed in response to starvation and in a natural environment re-access the nutrients, e.g.: L-alanine and AGFK - a mixture of asparagine, glucose, fructose and potassium, triggers germination. The aim of this study was to estimate the impact of L-alanine and AGFK on the germination of the spores of two Alicyclobacillus acidoterrestris strains and to evaluate the relationship of the germination rate with dipicolinic acid (DPA) release. The spores were suspended in apple juice or in buffers at pH 4 and pH 7, followed by the addition of L-alanine and AGFK. Suspensions were or were not subjected, to a temperature of 80°C/10 min and incubated for various periods of time at 45°C. Optical density (OD660) was used to estimate the number of germinated spores. The amount of DPA released was determined using HPLC. The results indicate that the degree of germination of A. acidoterrestris spores depended on the strain and time of incubation and the nutritious compounds used. The data obtained show that the amount of DPA released correlated to the number of A. acidoterrestris spores germinated.

  11. Role of ion channels and subcellular Ca2+ signaling in arachidonic acid-induced dilation of pressurized retinal arterioles.

    PubMed

    Kur, Joanna; McGahon, Mary K; Fernández, Jose A; Scholfield, C Norman; McGeown, J Graham; Curtis, Tim M

    2014-05-02

    To investigate the mechanisms responsible for the dilatation of rat retinal arterioles in response to arachidonic acid (AA). Changes in the diameter of isolated, pressurized rat retinal arterioles were measured in the presence of AA alone and following pre-incubation with pharmacologic agents inhibiting Ca(2+) sparks and oscillations and K(+) channels. Subcellular Ca(2+) signals were recorded in arteriolar myocytes using Fluo-4-based confocal imaging. The effects of AA on membrane currents of retinal arteriolar myocytes were studied using whole-cell perforated patch clamp recording. Arachidonic acid dilated pressurized retinal arterioles under conditions of myogenic tone. Eicosatetraynoic acid (ETYA) exerted a similar effect, but unlike AA, its effects were rapidly reversible. Arachidonic acid-induced dilation was associated with an inhibition of subcellular Ca(2+) signals. Interventions known to block Ca(2+) sparks and oscillations in retinal arterioles caused dilatation and inhibited AA-induced vasodilator responses. Arachidonic acid accelerated the rate of inactivation of the A-type Kv current and the voltage dependence of inactivation was shifted to more negative membrane potentials. It also enhanced voltage-activated and spontaneous large-conductance calcium-activated K(+) (BK) currents, but only at positive membrane potentials. Pharmacologic inhibition of A-type Kv and BK currents failed to block AA-induced vasodilator responses. Arachidonic acid suppressed L-type Ca(2+) currents. These results suggest that AA induces retinal arteriolar vasodilation by inhibiting subcellular Ca(2+)-signaling activity in retinal arteriolar myocytes, most likely through a mechanism involving the inhibition of L-type Ca(2+)-channel activity. Arachidonic acid actions on K(+) currents are inconsistent with a model in which K(+) channels contribute to the vasodilator effects of AA.

  12. Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets.

    PubMed

    Bassaganya-Riera, Josep; Guri, Amir J; Noble, Alexis M; Reynolds, Kathryn A; King, Jennifer; Wood, Cynthia M; Ashby, Michael; Rai, Deshanie; Hontecillas, Raquel

    2007-03-01

    Whereas the immunomodulatory effects of feeding either arachidonic acid (AA) or docosahexaenoic acid (DHA) separately have been previously investigated, little is known about the immunomodulatory efficacy of AA or DHA when they are fed in combination as infant formula ingredients. The objective of this study was to investigate the ability of AA- and DHA(AA/DHA)-enriched infant formula to modulate immune responses in the neonate in response to an inactivated influenza virus vaccine. Neonatal piglets (n = 48) were weaned on day 2 of age and distributed into 16 blocks of 3 littermate piglets each. Within each block, piglets were randomly assigned to a control formula, AA/DHA-enriched formula (0.63% AA and 0.34% DHA), or sow milk for 30 d. On day 9, 8 blocks of piglets were immunized with an inactivated influenza virus vaccine. On days 0, 9, 16, 23, and 30 after weaning, we measured influenza virus-specific T cell proliferation and phenotype of T subsets in peripheral blood. A delayed-type hypersensitivity reaction test was administered on day 28. Cytokine messenger RNA expression was determined by quantitative real time reverse transcriptase-polymerase chain reaction on day 30. The influenza virus-specific CD4(+) and CD8(+) T cell ex vivo lymphoproliferative responses were significantly lower on day 23 after immunization in piglets receiving dietary AA/DHA supplementation and sow milk than in those receiving the unsupplemented control formula. The immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.

  13. Variation in plasma amino acid concentrations during a cycling competition.

    PubMed

    Medelli, J; Lounana, J; Hill, D

    2003-06-01

    The variations in plasma concentrations of 24 amino acids (AAs) were measured, taking into account modifications in plasma volume, in 7 male subjects, professional cyclists, during the first 2 stages (EI and EII) of the competition "4 Days of Dunkirk 1999". Blood samples were taken before the start and at the end of each stage. At the end of EI a significant reduction (p<0.02) in alpha-aminobutyric acid was observed (-38%) and a significant increase (Wilcoxon 0.01AAs, remained relatively stable at this stage. At the end vs start of EII there was a significant reduction in several AAs, alpha-aminobutyric acid (33%), arginine (-21%), cystine (-15%), glycocholic acid (26%), hydroxyproline (-28%), leucine (-17%), lysine (-26%), methionine (-19%), threonine (-15%) and valine (-16%). The recovery period was characterised by increases in previously reduced AAs and vice versa. These results show that cellular use of plasma AAs in the endurance cyclist could differ between the first hours of competition and the subsequent stages, possibly in relation to the gradual increase in stress level as the stages progress; they also suggest that appropriate consideration should be given to the quality of protein inputs in the nutrition of cyclists involved in a high-level stage competition.

  14. Protein Complexation and pH Dependent Release Using Boronic Acid Containing PEG-Polypeptide Copolymers.

    PubMed

    Negri, Graciela E; Deming, Timothy J

    2017-01-01

    New poly(L-lysine)-b-poly(ethylene glycol) copolypeptides have been prepared, where the side-chain amine groups of lysine residues are modified to contain ortho-amine substituted phenylboronic acid, i.e., Wulff-type phenylboronic acid (WBA), groups to improve their pH responsive, carbohydrate binding properties. These block copolymers form nanoscale complexes with glycosylated proteins that are stable at physiological pH, yet dissociate and release the glycoproteins under acidic conditions, similar to those found in endosomal and lysosomal compartments within cells. These results suggest that WBA modified polypeptide copolymers are promising for further development as degradable carriers for intracellular protein delivery. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Microstructural features of friction stir welded dissimilar Aluminium alloys AA2219-AA7475

    NASA Astrophysics Data System (ADS)

    Zaman Khan, Noor; Ubaid, Mohammed; Siddiquee, Arshad Noor; Khan, Zahid A.; Al-Ahmari, Abdulrahman; Chen, Xizhang; Haider Abidi, Mustufa

    2018-05-01

    High strength, good corrosion resistance, light weight make aluminium alloys a material of choice in many industrial sectors like aerospace, marine etc. Problems associated with welding of these alloys by fusion welding processes restricted their use in various industries. Friction stir welding (FSW), a clean solid-state joining process, easily overcomes various difficulties encountered during conventional fusion welding processes. In the present work, the effect of rotational speed (710 rpm, 900 rpm and 1120 rpm) on micro-hardness distribution and microstructure of FSWed dissimilar aluminium alloy joints were analyzed. Plates of AA7475-T761 and AA2219-O having thickness of 2.5 mm were welded by fixing AA7475 on retreating side (RS) and AA2219 on advancing side (AS). Welded joints were characterized by Vickers micro-hardness testing, scanning electron microscopy (SEM) and optical microscopy (OM). Results revealed that rotational speed significantly affects the micro-hardness due to increase in grain size, coarsening and dissolution of strengthening precipitates and re-precipitation. Higher micro-hardness values were observed in stir zone due to grain refinement and re-precipitation. Minimum micro-hardness value was observed at the TMAZ/HAZ of advancing side due to thermal softening.

  16. Arachidonic acid is involved in the regulation of hCG induced steroidogenesis in rat Leydig cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Didolkar, A.K.; Sundaram, K.

    1987-07-27

    Phospholipase C (PLC), an enzyme involved in the hydrolysis of membrane phospholipid- phosphatidylinositol-bisphosphate to insositol triphosphate and diacylglycerol, and Phorbol 12, myristate 13, acetate (PMA) could significantly stimulate testosterone (T) secretion from Leydig cells. Arachidonic acid (AA) stimulated T secretion by about 2 fold. The steroidogenic effect of PLC and AA was biphasic. At low concentrations both PLC and AA augmented hCG induced T secretion, while at higher concentrations they inhibited steroid production. AA also had a biphasic effect on hCG induced cyclic AMP secretion. 5,8,11,14 Eicosatetrayenoic acid, a general inhibitor of AA metabolism, and Nordihydroguaiaretic acid, an inhibitor ofmore » the lipoxygenase pathway of AA metabolism, inhibited hCG induced T secretion while indomethacin, an inhibitor of cyclo-oxygenase pathway, had no effect on hCG induced T secretion. The authors conclude from these data that AA plays a role in the regulation of hCG induced steroidogenic responses in rat Leydig cells and that the metabolite(s) of AA that are involved are not cyclo-oxygenase products. 28 references, 4 figures, 2 tables.« less

  17. Amino acid-assisted synthesis of zinc oxide nanostructures

    NASA Astrophysics Data System (ADS)

    Singh, Baljinder; Moudgil, Lovika; Singh, Gurinder; Kaura, Aman

    2018-05-01

    In this manuscript we have used experimental approach that can provide a fundamental knowledge about the role played by biomolecules in designing the shape of nanostructure (NS) at a microscopic level. The three different amino acids (AAs) - Arginine (Arg), Aspartic acid (Asp) and Histidine (His) coated Zinc oxide (ZnO) NSs to explain the growth mechanism of nanoparticles of different shapes. Based on the experimental methodology we propose that AA-ZnO (Asp and Arg) nanomaterials could form of rod like configuration and His-ZnO NPs could form tablet like configuration. The synthesized samples are characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). Results reveal that AAs are responsible for formation of different NSs

  18. Post term dietary-induced changes in DHA and AA status relate to gains in weight, length, and head circumference in preterm infants.

    PubMed

    van de Lagemaat, Monique; Rotteveel, Joost; Muskiet, Frits A J; Schaafsma, Anne; Lafeber, Harrie N

    2011-12-01

    Preterms need supplementation with docosahexaenoic (DHA) and arachidonic (AA) acids to prevent steep postnatal declines. Associations between growth and erythrocyte (RBC) DHA and AA were studied in 139 preterms (51% male, gestational age 30.3±1.5 weeks, birth weight 1341±288g) fed human milk with breast milk fortifier or preterm formula until term, followed by postdischarge formula (PDF; n=52, 0.4% DHA, 0.4% AA), term formula (TF; n=41, 0.2% DHA, 0.2% AA), or human milk (HM; n=46). At six months, PDF resulted in higher RBC-DHA than TF and HM, while RBC-AA was higher than TF, but similar to HM. There were no between-group differences in growth between term and six months. RHC-DHA related positively with gain in weight and length and negatively with gain in head circumference. RBC-AA related positively with gain in head circumference and negatively with gain in weight and length. In conclusion, PDF with higher DHA and AA than TF may promote postnatal growth of preterms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Analysis of the Cytotoxic Potential of Anisomelic Acid Isolated from Anisomeles malabarica

    PubMed Central

    Preethy, Christo Paul; Alshatwi, Ali Abdullah; Gunasekaran, Muthukumaran; Akbarsha, Mohammad Abdulkadher

    2013-01-01

    Anisomelic acid (AA), one of the major compounds in Anisomeles malabarica, was tested for its cytotoxicity and apoptosis-inducing potential in breast and cervical cancer cells. The MTT assay for cell viability indicated that AA is cytotoxic to all of the four cell lines tested in a dose- and duration-dependent manner. Acridine Orange & Ethidium Bromide (AO & EB) and Hoechst 33258 staining of AA-treated cells revealed typical apoptotic morphology such as condensed chromatin and formation of apoptotic bodies. The comet assay revealed DNA strand break(s), indicating that AA induces DNA damage which culminates in apoptosis. Thus, the study revealed the anti-proliferative and apoptosis-inducing properties of AA in both breast and cervical cancer cells. Therefore, anisomelic acid offers potential for application in breast and cervical cancer therapy. PMID:23833721

  20. Screening of Catalyst and Important Variable for The Esterification of Acrylic Acid with 2 Ethylhexanol

    NASA Astrophysics Data System (ADS)

    Ahmad, M. A. A.; Chin, S. Y.

    2017-06-01

    The global demand of 2-ethylhexyl acrylate (2EHA) market has witnessed a significant growth in the past few years and this growth is anticipated to increase in the coming years. 2EHA is one of the basic organic building blocks that mainly used in the production of coatings, adhesives, superabsorbents, thickeners and plastic additives. Homogenous acid-catalysed esterification of acrylic acid (AA) with 2-ethylhexanol (2EH) is commonly used for the production of 2EHA. The homogeneous catalysts such as sulfuric and para-toluene sulfonic acid have resulted the costly and complicated downstream process that generates acidic, corrosive and non-environmental friendly waste. Therefore, it is importance to develop a cheaper process that employing heterogeneous catalysts and alternative raw material from wastewater containing acrylic acid. In this research, the study for the esterification of AA with 2EH catalysed by ion-exchange resin was conducted. The best sulfonic acid functional cation-exchange resin among SK104, SK1B, PK208, PK216, PK228, RCP145, and RCP160 was screened. PK208 outperformed the other resins and it was used subsequently in the parametric studies. The effect of important parameters (initial concentration of acrylic acid (AA), temperature, molar ratio of reactant (AA and 2EH), catalyst loading, and polymerisation inhibitor loading) was studied using 2 factorial design to determine the significant parameters to the esterification. It was found that the initial concentration of AA and temperature were most significantly affecting the esterification of AA with 2EH.

  1. Release of Ciprofloxacin-HCl and Dexamethasone Phosphate by Hyaluronic Acid Containing Silicone Polymers.

    PubMed

    Nguyen, Darrene; Hui, Alex; Weeks, Andrea; Heynen, Miriam; Joyce, Elizabeth; Sheardown, Heather; Jones, Lyndon

    2012-04-19

    The purpose of this study was to determine the effect of the covalent incorporation of hyaluronic acid (HA) into conventional hydrogel and hydrogels containing silicone as models for contact lens materials on the uptake and release of the fluoroquinolone antibiotic ciprofloxacin and the anti-inflammatory steroid dexamethasone phosphate. A 3 mg/mL ciprofloxacin solution (0.3% w/v) and a 1 mg/mL dexamethasone phosphate solution (0.1%) was prepared in borate buffered saline. Three hydrogel material samples (pHEMA; pHEMA TRIS; DMAA TRIS) were prepared with and without the covalent incorporation of HA of molecular weight (MW) 35 or 132 kDa. Hydrogel discs were punched from a sheet of material with a uniform diameter of 5 mm. Uptake kinetics were evaluated at room temperature by soaking the discs for 24 h. Release kinetics were evaluated by placing the drug-loaded discs in saline at 34 °C in a shaking water bath. At various time points over 6-7 days, aliquots of the release medium were assayed for drug amounts. The majority of the materials tested released sufficient drug to be clinically relevant in an ophthalmic application, reaching desired concentrations for antibiotic or anti-inflammatory activity in solution. Overall, the silicone-based hydrogels (pHEMA TRIS and DMAA TRIS), released lower amounts of drug than the conventional pHEMA material (p < 0.001). Materials with HA MW132 released more ciprofloxacin compared to materials with HA MW35 and lenses without HA (p < 0.02). Some HA-based materials were still releasing the drug after 6 days.

  2. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Baowei; Shah, Saumil S.; Shin, Yongsoon

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO(3)-Na(2)CO(3) buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH(2)-FMSmore » can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.« less

  3. Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

    PubMed

    Watanabe, K; Uchida, K; Chambers, J K; Tei, M; Shoji, A; Ushio, N; Nakayama, H

    2015-05-01

    The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis. © The Author(s) 2014.

  4. The simultaneous electrochemical detection of ascorbic acid, dopamine, and uric acid using graphene/size-selected Pt nanocomposites.

    PubMed

    Sun, Chia-Liang; Lee, Hsin-Hsien; Yang, Jen-Ming; Wu, Ching-Chou

    2011-04-15

    In this study, a graphene/Pt-modified glassy carbon (GC) electrode was created to simultaneously characterize ascorbic acid (AA), dopamine (DA), and uric acid (UA) levels via cyclic voltammetry (CV) and differential pulse voltammetry (DPV). During the preparation of the nanocomposite, size-selected Pt nanoparticles with a mean diameter of 1.7 nm were self-assembled onto the graphene surface. In the simultaneous detection of the three aforementioned analytes using CV, the electrochemical potential differences among the three detected peaks were 185 mV (AA to DA), 144 mV (DA to UA), and 329 mV (AA and UA), respectively. In comparison to the CV results of bare GC and graphene-modified GC electrodes, the large electrochemical potential difference that is achieved via the use of the graphene/Pt nanocomposites is essential to the distinguishing of these three analytes. An optimized adsorption of size-selected Pt colloidal nanoparticles onto the graphene surface results in a graphene/Pt nanocomposite that can provide a good platform for the routine analysis of AA, DA, and UA. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Effects of different cellulases on the release of phenolic acids from rice straw during saccharification.

    PubMed

    Xue, Yiyun; Wang, Xiahui; Chen, Xingxuan; Hu, Jiajun; Gao, Min-Tian; Li, Jixiang

    2017-06-01

    Effects of different cellulases on the release of phenolic acids from rice straw during saccharification were investigated in this study. All cellulases tested increased the contents of phenolic acids during saccharification. However, few free phenolic acids were detected, as they were present in conjugated form after saccharification when the cellulases from Trichoderma reesei, Trichoderma viride and Aspergillus niger were used. On the other hand, phenolic acids were present in free form when the Acremonium cellulolyticus cellulase was used. Assays of enzyme activity showed that, besides high cellulase activity, the A. cellulolyticus cellulase exhibited high feruloyl esterase (FAE) activity. A synergistic interaction between FAE and cellulase led to the increase in free phenolic acids, and thus an increase in antioxidative and antiradical activities of the phenolic acids. Moreover, a cost estimation demonstrated the feasibility of phenolic acids as value-added products to reduce the total production cost of ethanol. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex.

    PubMed

    Mir, Joan Francesc; Zagmutt, Sebastián; Lichtenstein, Mathieu P; García-Villoria, Judit; Weber, Minéia; Gracia, Ana; Fabriàs, Gemma; Casas, Josefina; López, Miguel; Casals, Núria; Ribes, Antònia; Suñol, Cristina; Herrero, Laura; Serra, Dolors

    2018-02-02

    Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system.

  7. Effects of an acid/alkaline treatment on the release of antioxidants and cellulose from different agro-food wastes.

    PubMed

    Vadivel, Vellingiri; Moncalvo, Alessandro; Dordoni, Roberta; Spigno, Giorgia

    2017-06-01

    The present investigation was aimed to evaluate the release of both antioxidants and cellulosic fibre from different agro-food wastes. Cost-effective and easily available agro-food residues (brewers' spent grains, hazelnut shells, orange peels and wheat straw) were selected and submitted to a double-step acid/alkaline fractionation process. The obtained acid and alkaline liquors were analysed for total phenols content and antioxidant capacity. The final fibre residue was analysed for the cellulose, lignin and hemicellulose content. The total phenols content and antioxidant capacity of the acid liquors were higher than the alkaline hydrolysates. Orange peels and wheat straw gave, respectively, the highest (19.70±0.68mg/g dm ) and the lowest (4.70±0.29mg/g dm ) total phenols release. Correlation between antioxidant capacity of the liquors and their origin depended on the analytical assay used to evaluate it. All the acid liquors were also rich in sugar degradation products (mainly furfural). HPLC analysis revealed that the most abundant phenolic compound in the acid liquors was vanillin for brewers' spent grains, hazelnut shells and wheat straw, and p-hydroxybenzoic acid for orange peels. Wheat straw served as the best raw material for cellulose isolation, providing a final residue with a high cellulose content (84%) which corresponded to 45% of the original cellulose. The applied process removed more than 90% of the hemicellulose fraction in all the samples, while delignification degree ranged from 67% (in hazelnut shells), to 93% (in brewers' spent grains). It was not possible to select a unique raw material for the release of highest levels of both total phenols and cellulose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Bacillus thuringiensis Crystal Protein Cry6Aa Triggers Caenorhabditis elegans Necrosis Pathway Mediated by Aspartic Protease (ASP-1)

    PubMed Central

    Zhang, Fengjuan; Peng, Donghai; Cheng, Chunsheng; Zhou, Wei; Ju, Shouyong; Wan, Danfeng; Yu, Ziquan; Shi, Jianwei; Deng, Yaoyao; Wang, Fenshan; Ye, Xiaobo; Hu, Zhenfei; Lin, Jian; Ruan, Lifang; Sun, Ming

    2016-01-01

    Cell death plays an important role in host-pathogen interactions. Crystal proteins (toxins) are essential components of Bacillus thuringiensis (Bt) biological pesticides because of their specific toxicity against insects and nematodes. However, the mode of action by which crystal toxins to induce cell death is not completely understood. Here we show that crystal toxin triggers cell death by necrosis signaling pathway using crystal toxin Cry6Aa-Caenorhabditis elegans toxin-host interaction system, which involves an increase in concentrations of cytoplasmic calcium, lysosomal lyses, uptake of propidium iodide, and burst of death fluorescence. We find that a deficiency in the necrosis pathway confers tolerance to Cry6Aa toxin. Intriguingly, the necrosis pathway is specifically triggered by Cry6Aa, not by Cry5Ba, whose amino acid sequence is different from that of Cry6Aa. Furthermore, Cry6Aa-induced necrosis pathway requires aspartic protease (ASP-1). In addition, ASP-1 protects Cry6Aa from over-degradation in C. elegans. This is the first demonstration that deficiency in necrosis pathway confers tolerance to Bt crystal protein, and that Cry6A triggers necrosis represents a newly added necrosis paradigm in the C. elegans. Understanding this model could lead to new strategies for nematode control. PMID:26795495

  9. Multifunctional Environmental Smart Fertilizer Based on l-Aspartic Acid for Sustained Nutrient Release.

    PubMed

    Lü, Shaoyu; Feng, Chen; Gao, Chunmei; Wang, Xinggang; Xu, Xiubin; Bai, Xiao; Gao, Nannan; Liu, Mingzhu

    2016-06-22

    Fertilizer is one of the most important elements of modern agriculture. However, conventional fertilizer, when applied to crops, is vulnerable to losses through volatilization, leaching, nitrification, or other means. Such a loss limits crop yields and pollutes the environment. In an effort to enhance nutrient use efficiency and reduce environmental pollution, an environmental smart fertilizer was reported in the current study. Poly(aspartic acid) and a degradable macro-cross-linker based on l-aspartic acid were synthesized and introduced into the fertilizer as a superabsorbent to improve the fertilizer degradability and soil moisture-retention capacity. Sustained release behavior of the fertilizer was achieved in soil. Cumulative release of nitrogen and phosphorus was 79.8% and 64.4% after 30 days, respectively. The water-holding and water-retention capacities of soil with the superabsorbent are obviously higher than those of the control soil without superabsorbent. For the sample of 200 g of soil with 1.5 g of superabsorbent, the water-holding capacity is 81.8%, and the water-retention capacity remains 22.6% after 23 days. All of the current results in this study indicated that the as-prepared fertilizer has a promising application in sustainable modern agriculture.

  10. Purified fish oil eliminating linoleic and alpha linolenic acid meets essential fatty acid requirements in rats.

    PubMed

    Ling, Pei-Ra; Puder, Mark; Bistrian, Bruce R

    2012-10-01

    This study examined whether purified fish oil (PFO) supplemented to an essential fatty acid deficient (EFAD) diet meets EFA needs in rats. The EFAD diet contained 10% hydrogenated coconut oil (HCO). A similar diet contained 7% HCO and 3% PFO which also provided 2.84% arachidonic acid (AA), 52.50% eicosapentaenoic acid (EPA) and 35.73% docosahexaenoic acid (DHA) but no linoleic acid (LA) or alpha linolenic acid (ALA). A 10% soybean oil control diet provided ample LA and ALA. After 4 weeks of feeding, blood glucose, plasma triglyceride and phospholipid fatty acid profiles, C-reactive protein (CRP), TNF and IL-6 were determined after saline or LPS injection. EFAD developed with the HCO diet with triene:tetraene ratios in plasma phospholipids >.20, which remained <.02 with the control and HCO+PFO diets. Mead acid levels significantly increased by a factor of 10 with the HCO diet compared to the AIN and HCO+PFO diets and were significantly lowest with the HCO+PFO diet. 18:1 n9 levels were significantly higher in plasma phospholipids and triglycerides with the HCO diet. CRP levels were significantly highest with the control diet and significantly lowest with the HCO diet. LPS significantly increased 18:1 n9 and cytokines, and decreased AA and plasma glucose in all diets and significantly increased plasma triglycerides and decreased plasma glucose in controls. Providing AA, EPA and DHA in EFAD prevents EFAD over the short-term as reflected in Mead acid production, triene:tetraene ratio, and de novo lipogenesis and may reduce the inflammatory response to LPS. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Bioinformatic flowchart and database to investigate the origins and diversity of Clan AA peptidases

    PubMed Central

    Llorens, Carlos; Futami, Ricardo; Renaud, Gabriel; Moya, Andrés

    2009-01-01

    Background Clan AA of aspartic peptidases relates the family of pepsin monomers evolutionarily with all dimeric peptidases encoded by eukaryotic LTR retroelements. Recent findings describing various pools of single-domain nonviral host peptidases, in prokaryotes and eukaryotes, indicate that the diversity of clan AA is larger than previously thought. The ensuing approach to investigate this enzyme group is by studying its phylogeny. However, clan AA is a difficult case to study due to the low similarity and different rates of evolution. This work is an ongoing attempt to investigate the different clan AA families to understand the cause of their diversity. Results In this paper, we describe in-progress database and bioinformatic flowchart designed to characterize the clan AA protein domain based on all possible protein families through ancestral reconstructions, sequence logos, and hidden markov models (HMMs). The flowchart includes the characterization of a major consensus sequence based on 6 amino acid patterns with correspondence with Andreeva's model, the structural template describing the clan AA peptidase fold. The set of tools is work in progress we have organized in a database within the GyDB project, referred to as Clan AA Reference Database . Conclusion The pre-existing classification combined with the evolutionary history of LTR retroelements permits a consistent taxonomical collection of sequence logos and HMMs. This set is useful for gene annotation but also a reference to evaluate the diversity of, and the relationships among, the different families. Comparisons among HMMs suggest a common ancestor for all dimeric clan AA peptidases that is halfway between single-domain nonviral peptidases and those coded by Ty3/Gypsy LTR retroelements. Sequence logos reveal how all clan AA families follow similar protein domain architecture related to the peptidase fold. In particular, each family nucleates a particular consensus motif in the sequence position

  12. Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

    PubMed Central

    2011-01-01

    The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis. PMID:21375761

  13. Formulation with ascorbic acid and sucrose modulates catechin bioavailability from green tea

    PubMed Central

    Peters, Catrina M.; Green, Rodney J.; Janle, Elsa M.; Ferruzzi, Mario G.

    2009-01-01

    In order to investigate the impact of common food ingredients on catechin absorption, green tea (GT) extract (50 mg) was formulated plain, with sucrose (GT+S), with ascorbic acid (GT+AA) and with sucrose and ascorbic acid (GT+S+AA). Bioavailability and bioaccessibility were assessed in Sprague Dawley rats and an in vitro digestion/Caco-2 cell model respectively. Absorption of epigallocatechin (EGC) and epigallocatechin gallate (EGCG) was significantly (P<0.05) enhanced in GT+S+AA formulations (AUC0-6h= 3237.0 and 181.8 pmol*h/L plasma respectively) relative to GT control (AUC0-6h = 1304.1 and 61.0 pmol*h/L plasma respectively). In vitro digestive recovery was higher for EGC and epicatechin (EC) (∼51-53%) relative to EGCG and epicatechin gallate (ECG) (< 20%) and was modestly enhanced in GT+S and GT+S+AA formulations. Accumulation of EGC, EGCG and ECG by Caco-2 cells was significantly (P<0.05) higher from GT+S+AA compared to other formulations while retention of catechins was enhanced in presence of ascorbic acid. These data suggest that formulation with sucrose and ascorbic acid may improve catechin bioavailability by enhancing bioaccessibility and intestinal uptake from tea. PMID:20161530

  14. Ethylene signaling triggered by low concentrations of ascorbic acid regulates biomass accumulation in Arabidopsis thaliana.

    PubMed

    Caviglia, M; Mazorra Morales, L M; Concellón, A; Gergoff Grozeff, G E; Wilson, M; Foyer, C H; Bartoli, C G

    2018-02-02

    Ascorbic acid (AA) is a major redox buffer in plant cells. The role of ethylene in the redox signaling pathways that influence photosynthesis and growth was explored in two independent AA deficient Arabidopsis thaliana mutants (vtc2-1 and vtc2-4). Both mutants, which are defective in the AA biosynthesis gene GDP-L-galactose phosphorylase, produce higher amounts of ethylene than wt plants. In contrast to the wt, the inhibition of ethylene signaling increased leaf conductance, photosynthesis and dry weight in both vtc2 mutant lines. The AA-deficient mutants showed altered expression of genes encoding proteins involved in the synthesis/responses to phytohormones that control growth, particularly auxin, cytokinins, abscisic acid, brassinosterioids, ethylene and salicylic acid. These results demonstrate that AA deficiency modifies hormone signaling in plants, redox-ethylene interactions providing a regulatory node controlling shoot biomass accumulation. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. 40 CFR Table Aa-1 to Subpart Aa of... - Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O AA Table AA-1 to Subpart AA of Part 98 Protection of Environment... Paper Manufacturing Pt. 98, Subpt. AA, Table AA-1 Table AA-1 to Subpart AA of Part 98—Kraft Pulping...

  16. 40 CFR Table Aa-1 to Subpart Aa of... - Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O AA Table AA-1 to Subpart AA of Part 98 Protection of Environment... Paper Manufacturing Pt. 98, Subpt. AA, Table AA-1 Table AA-1 to Subpart AA of Part 98—Kraft Pulping...

  17. 40 CFR Table Aa-1 to Subpart Aa of... - Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O AA Table AA-1 to Subpart AA of Part 98 Protection of Environment... Paper Manufacturing Pt. 98, Subpt. AA, Table AA-1 Table AA-1 to Subpart AA of Part 98—Kraft Pulping...

  18. 40 CFR Table Aa-1 to Subpart Aa of... - Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Kraft Pulping Liquor Emissions Factors for Biomass-Based CO2, CH4, and N2O AA Table AA-1 to Subpart AA of Part 98 Protection of Environment... Paper Manufacturing Pt. 98, Subpt. AA, Table AA-1 Table AA-1 to Subpart AA of Part 98—Kraft Pulping...

  19. Development of switchable polymers to address the dilemma of stability and cargo release in polycationic nucleic acid carriers.

    PubMed

    Cheng, Yilong; Sellers, Drew L; Tan, James-Kevin Y; Peeler, David J; Horner, Philip J; Pun, Suzie H

    2017-05-01

    Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)-co-poly(2-(dimethylamino)ethyl methacrylate)-block- poly(propargyl methacrylate-graft-propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)-b-(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart. In endosomes, the polymer undergoes an acid-triggered hydrophilic transition through the cleavage of benzoic imines, thus allowing the vector to quickly release nucleic acid cargo due to the loss of hydrophobic functionalization. Compared to a pH-insensitive polymer (IP), SP exhibited more significant luciferase plasmid delivery efficiency with HeLa cells in vitro and with in vivo intraventricular brain injections. Therefore, the polymer designed here is a good solution to address the dilemma of stability and cargo release in gene delivery, and may have broad potential applications in therapeutic agent delivery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs.

    PubMed

    Asha, G S; Indira, M

    2004-02-01

    Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism.

  1. [Effects of several low-molecular-weight organic acids on the release kinetic of endosulfan from red soil].

    PubMed

    Zhao, Zhen-hua; Wu, Yu; Jiang, Xin; Xia, Li-ling; Ni, Li-xiao

    2009-10-15

    The kinetic release behaviors of a-endosulfan from red soil with three kinds of low-molecular-weight organic acids (LMWOA: oxalate, tartrate and citrate) solution and water leaching were investigated by kinetic device designed by ourselves and batch method. The results show that: the release percentage of endosulfan from red soil by tartrate and citrate solution (10 mmol/L) can increase by 7%-18% more than that by distilled water and oxalate solution, especially for tartrate solution. There is no significant difference between distilled water and oxalate solution for the release percentage of endosulfan (p > 0.05). There are two stages of quick and slow for the release of endosulfan from red soil, and the leaching speed is quicker especially for the initial 200 mL leaching solution. When using distilled water or oxalate solution as leaching solution, the best equations that described the kinetic release behavior of endosulfan from red soil were parabola diffuse equation and double constant equation, and weren't the apparent first dynamics equation that represented the simple surface diffusion mechanism. The kinetic release behavior of endosulfan in tartrate or citrate leaching system can be described by Elovich equation (R2 > 0.99, p < 0.0001), it implied that the simple surface diffusion mechanism is not the primary factor that effected the release of endosulfan, which three-dimensional molecule structure is complex, from red soil in aqueous phase leaching systems, and it maybe related to the outward diffuse mechanism from soil particle, activation and deactivation function of soil particles surface, the dissolution of soil mineral surface and structure change of inherent organic matter that coating onto the soil mineral surface induced by LMW organic acid. It suggested that the tartrate and citrate induced the complication of the release mechanisms of the pesticides from red soil.

  2. A near-infrared luminescent Mn2+-doped NaYF4:Yb,Tm/Fe3+ upconversion nanoparticles redox reaction system for the detection of GSH/Cys/AA.

    PubMed

    Zhang, Liping; Ling, Bo; Wang, Lun; Chen, Hongqi

    2017-09-01

    An upconversion luminescence method was developed for the determination of glutathione (GSH), L-cysteine (Cys) or L-ascorbic acid (AA) based on redox reaction. We synthesized poly(acrylic acid) (PAA)-modified Mn 2+ -doped NaYF 4 :Yb,Tm upconversion nanoparticles (UCNPs), and the luminescence of these UCNPs was effectively quenched due to their carboxyl groups coordinating with Fe 3+ to form a UCNPs/Fe 3+ system. GSH, Cys or AA reduced Fe 3+ to Fe 2+ , which induced the luminescence recovery of the UCNPs. Under the optimized conditions, wide linear concentration ranges from 0.25-300μM for GSH, 0.5-875μM for Cys and 0.5-350μM for AA were found, and the detection limits (3S/K) were 0.2μM, 0.5μM and 0.2μM, respectively. Thus, the UCNPs/Fe 3+ system was successfully applied for sensing GSH, Cys or AA. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. PRELIMINARY RESULTS: RELEASE OF METALS FROM ACID-MINE DRAINAGE CONTAMINATED STREAMBED SEDIMENTS UNDER ANOXIC CONDITIONS

    EPA Science Inventory

    Many miles of streams are contaminated with acid-mine drainage (AMD) from abandoned metal mines in the western U.S. Treatment of these streams may include dredging of the existing sediments, with subsequent burial. Burial of previously toxic sediments may result in release of met...

  4. Quantitative Protein Sulfenic Acid Analysis Identifies Platelet Releasate-Induced Activation of Integrin β2 on Monocytes via NADPH Oxidase.

    PubMed

    Li, Ru; Klockenbusch, Cordula; Lin, Liwen; Jiang, Honghui; Lin, Shujun; Kast, Juergen

    2016-12-02

    Physiological stimuli such as thrombin, or pathological stimuli such as lysophosphatidic acid (LPA), activate platelets. The activated platelets bind to monocytes through P-selectin-PSGL-1 interactions but also release the contents of their granules, commonly called "platelet releasate". It is known that monocytes in contact with platelet releasate produce reactive oxygen species (ROS). Reversible cysteine oxidation by ROS is considered to be a potential regulator of protein function. In a previous study, we used THP-1 monocytic cells exposed to LPA- or thrombin-induced platelet releasate and a modified biotin switch assay to unravel the biological processes that are influenced by reversible cysteine oxidation. To gain a better understanding of the redox regulation of monocytes in atherosclerosis, we have now altered the modified biotin switch to selectively quantify protein sulfenic acid, a subpopulation of reversible cysteine oxidation. Using arsenite as reducing agent in the modified biotin switch assay, we were able to quantify 1161 proteins, in which more than 100 sulfenic acid sites were identified. Bioinformatics analysis of the quantified sulfenic acid sites highlighted the relevant, previously missed biological process of monocyte transendothelial migration, which included integrin β 2 . Flow cytometry validated the activation of LFA-1 (α L β 2 ) and Mac-1 (α M β 2 ), two subfamilies of integrin β 2 complexes, on human primary monocytes following platelet releasate treatment. The activation of LFA-1 was mediated by ROS from NADPH oxidase (NOX) activation. Production of ROS and activation of LFA-1 in human primary monocytes were independent of P-selectin-PSGL-1 interaction. Our results proved the modified biotin switch assay to be a powerful tool with the ability to reveal new regulatory mechanisms and identify new therapeutic targets.

  5. [Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].

    PubMed

    Ding, Xiao-shuang; Liang, Ai-hua; Wang, Jin-hua; Xiao, Yong-qing; Wu, Zi-lun; Li, Chun-ying; Li, Li; He, Rong; Hui, Lian-qiang; Liu, Bao-yan

    2005-07-01

    The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined. A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice. LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA. GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.

  6. [Effect of citric acid stimulation on salivary alpha-amylase, total protein, salivary flow rate and pH value in Pi deficiency children].

    PubMed

    Yang, Ze-min; Chen, Long-hui; Lin, Jing; Zhang, Min; Yang, Xiao-rong; Chen, Wei-wen

    2015-02-01

    To compare the effect of citric acid stimulation on salivary alpha-amylase (sAA), total protein (TP), salivary flow rate, and pH value between Pi deficiency (PD) children and healthy children, thereby providing evidence for Pi controlling saliva theory. Twenty PD children were recruited, and 29 healthy children were also recruited at the same time. Saliva samples from all subjects were collected before and after citric acid stimulation. The sAA activity and amount, TP contents, salivary flow rate, and pH value were determined and compared. (1) Citric acid stimulation was able to significantly increase salivary flow rate, pH value, sAA activities, sAA specific activity and sAA amount (including glycosylated and non-glycosylated sAA amount) in healthy children (P<0.05), while it could markedly increase salivary flow rate, pH value, and glycosylated sAA levels in PD children (P<0.05); (2) Although there was no statistical difference in determined salivary indices between the two groups (P>0.05), salivary indices except salivary flow rate and glycosylated sAA levels decreased more in PD children. There was statistical difference in sAA activity ratio, sAA specific activity ratio, and the ratio of glycosylated sAA levels between PD children and healthy children (P<0.05). PD children had decreased response to citric acid stimulation.

  7. Different Fatty Acids Compete with Arachidonic Acid for Binding to the Allosteric or Catalytic Subunits of Cyclooxygenases to Regulate Prostanoid Synthesis*

    PubMed Central

    Dong, Liang; Zou, Hechang; Yuan, Chong; Hong, Yu H.; Kuklev, Dmitry V.; Smith, William L.

    2016-01-01

    Prostaglandin endoperoxide H synthases (PGHSs), also called cyclooxygenases (COXs), convert arachidonic acid (AA) to PGH2. PGHS-1 and PGHS-2 are conformational heterodimers, each composed of an (Eallo) and a catalytic (Ecat) monomer. Previous studies suggested that the binding to Eallo of saturated or monounsaturated fatty acids (FAs) that are not COX substrates differentially regulate PGHS-1 versus PGHS-2. Here, we substantiate and expand this concept to include polyunsaturated FAs known to modulate COX activities. Non-substrate FAs like palmitic acid bind Eallo of PGHSs stimulating human (hu) PGHS-2 but inhibiting huPGHS-1. We find the maximal effects of non-substrate FAs on both huPGHSs occurring at the same physiologically relevant FA/AA ratio of ∼20. This inverse allosteric regulation likely underlies the ability of PGHS-2 to operate at low AA concentrations, when PGHS-1 is effectively latent. Unlike FAs tested previously, we observe that C-22 FAs, including ω-3 fish oil FAs, have higher affinities for Ecat than Eallo subunits of PGHSs. Curiously, C-20 ω-3 eicosapentaenoate preferentially binds Ecat of huPGHS-1 but Eallo of huPGHS-2. PGE2 production decreases 50% when fish oil consumption produces tissue EPA/AA ratios of ≥0.2. However, 50% inhibition of huPGHS-1 itself is only seen with ω-3 FA/AA ratios of ≥5.0. This suggests that fish oil-enriched diets disfavor AA oxygenation by altering the composition of the FA pool in which PGHS-1 functions. The distinctive binding specificities of PGHS subunits permit different combinations of non-esterified FAs, which can be manipulated dietarily, to regulate AA binding to Eallo and/or Ecat thereby controlling COX activities. PMID:26703471

  8. Antioxidants modulate the antiproliferative effects of nitric oxide on vascular smooth muscle cells and adventitial fibroblasts by regulating oxidative stress.

    PubMed

    Gregory, Elaine K; Vavra, Ashley K; Moreira, Edward S; Havelka, George E; Jiang, Qun; Lee, Vanessa R; Van Lith, Robert; Ameer, Guillermo A; Kibbe, Melina R

    2011-11-01

    S-nitrosothiols (SNO) release nitric oxide (NO) through interaction with ascorbic acid (AA). However, little is known about their combined effect in the vasculature. The aim of this study was to investigate the effect of AA on SNO-mediated NO release, proliferation, cell cycle progression, cell death, and oxidative stress in vascular cells. Vascular smooth muscle cells and adventitial fibroblasts harvested from the aortae of Sprague-Dawley rats were treated with AA, ± S-nitrosoglutathione (GSNO), or ± diethylenetriamine NONOate (DETA/NO). NO release, proliferation, cell cycle progression, cell death, and oxidative stress were determined by the Griess reaction, [(3)H]-thymidine incorporation, flow cytometry, trypan blue exclusion, and 5-(and-6)chloromethyl-2',7'dichlorodihydrofluorescein staining, respectively. AA increased NO release from GSNO 3-fold (P < .001). GSNO and DETA/NO significantly decreased proliferation, but AA abrogated this effect (P < .05). Mirroring the proliferation data, changes in cell cycle progression induced by GSNO and DETA/NO were reversed by the addition of AA. GSNO- and DETA/NO-mediated increases in oxidative stress were significantly decreased by the addition of AA (P < .001). Despite causing increased NO release from GSNO, AA reduced the antiproliferative and cell cycle effects of GSNO and DETA/NO through the modulation of oxidative stress. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Determination of aristolochic acids by high-performance liquid chromatography with fluorescence detection.

    PubMed

    Wang, Yinan; Chan, Wan

    2014-06-25

    Nephrotoxic and carcinogenic aristolochic acids (AAs) are naturally occurring nitrophenanthrene carboxylic acids in the herbal genus Aristolochia. The misuse of AA-containing herbs in preparing slimming drugs has caused hundred of cases of kidney disease in Belgium women in a slimming regime in the early 1990s. Accumulating evidence also suggested that prolong dietary intake of AA-contaminated food is one of the major causes to the Balkan endemic nephropathy that was first observed in the late 1950s. Therefore, analytical methods of high sensitivity are extremely important for safeguarding human exposure to AA-containing herbal medicines, herbal remedies, and food composites. In this paper, we describe the development of a new high-performance liquid chromatography coupled fluorescence detector (HPLC-FLD) method for the sensitive determination of AAs. The method makes use of a novel cysteine-induced denitration reaction that "turns on" the fluorescence of AAs for fluorometric detections. Our results showed that the combination of cysteine-induced denitration and HPLC-FLD analysis allows for sensitive quantification of AA-I and AA-II at detection limits of 27.1 and 25.4 ng/g, respectively. The method was validated and has been successfully applied in quantifying AAs in Chinese herbal medicines.

  10. Electrochemical Sensing of Dopamine, Uric Acid and Ascorbic Acid Using tRGO-TiO2 Nanocomposites.

    PubMed

    Rajamani, A R; Kannan, Rajesh; Krishnan, Sruthy; Ramakrishnan, S; Raj, S Mohan; Kumaresan, D; Kothurkar, Nikhil; Rangarajan, Murali

    2015-07-01

    This work reports a graphene-based nonenzymatic electrochemical sensing platform for the detection of dopamine (DA), uric acid (UA), and ascorbic acid (AA). Graphene oxide, synthesized by modified Hummers method, was thermally reduced in an induction furnace at 200 °C in an Ar-H2 atmosphere to obtain thermally reduced graphene oxide (tRGO). Nanocomposites of tRGO-TiO2 were obtained by a hydrothermal method, and were characterized using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). FTIR spectra showed Ti-O-C peaks, indicating covalent linkage between the TiO2 nanoparticles and the reduced graphene oxide sheets. Glassy carbon electrode (GCE) was modified with the nanocomposite (tRGO-TiO2-GCE), and the modified electrode could detect dopamine (DA: 1 to 1000 µM), uric acid (UA: 1 to 900 µM), and ascorbic acid (AA: 10 to 1000 µM) in each other's presence over wide ranges, with adequate separation in peak potentials. Differential pulse voltammetry experiments yielded linear responses with sensitivities of 133.18, 33.96, and 155.59 µA mM(-1) cm(-2) for DA, UA, and AA, respectively.

  11. Effect of thiopental sodium on the release of glutamate and gamma-aminobutyric acid from rats prefrontal cortical synaptosomes.

    PubMed

    Liu, Hongliang; Yao, Shanglong

    2004-01-01

    To investigate the effect of thiopental sodium on the release of glutamate and gamma-aminobutyric acid (GABA) from synaptosomes in the prefrontal cortex, synaptosomes were made, the spontaneous release and the evoked release by 30 mmol/L KCl or 20 micromol/L veratridine of glutamate and GABA were performed under various concentrations of thiopental sodium (10-300 micromol/L), glutamate and GABA concentrations were determined by reversed-phase high-performance liquid chromatography. Our results showed that spontaneous release and evoked release of glutamate were significantly inhibited by 30 micromol/L, 100 micromol/L and 300 micromol/L thiopental sodium, IC50 of thiopental sodium was 25.8 +/- 2.3 micromol/L for the spontaneous release, 23.4 +/- 2.4 micromol/L for KCl-evoked release, and 24.3 +/- 1.8 micromol/L for veratridine-evoked release. But GABA spontaneous release and evoked release were unaffected. The study showed that thiopental sodium with clinically related concentrations could inhibit the release of glutamate, but had no effect on the release of GABA from rats prefrontal cortical synaptosomes.

  12. A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin

    NASA Astrophysics Data System (ADS)

    Khatun, Zehedina; Nurunnabi, Md; Nafiujjaman, Md; Reeck, Gerald R.; Khan, Haseeb A.; Cho, Kwang Jae; Lee, Yong-Kyu

    2015-06-01

    The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid

  13. The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

    PubMed Central

    2011-01-01

    Background Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date. Results In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10-48) and lower DGLA levels (p = 9.80 × 10-11) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10-16 in African Americans, 2.68 × 10-23 in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups. Conclusions We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA. PMID:21599946

  14. Potential of Sulphur-containing Amino Acids in the Prevention of Catecholamine-induced Arrhythmias.

    PubMed

    Adameova, Adriana; Tappia, Paramjit S; Hatala, Robert; Dhalla, Naranjan S

    2018-01-30

    Various physiological and pathological stimuli can hypersensitize the sympathetic nervous system resulting in a substantial release of catecholamines (CA) and consequent alterations in excitation-contraction coupling and excitation-transcription coupling. It has been shown that oxidation products of CA, rather than CA themselves, are responsible for such adaptation to a new equilibrium. While chronic, sustained accumulation of CA and their toxic products are associated with the depression in cardiac contractile force and remodeling, acute excessive release of CA can result in brief oxidative bursts and serious damage leading in lethal arrhythmias. In response to such oxidative stress, dysregulation of ion homeostasis, activation of neurohumoral system, immune and inflammatory responses, are augmented. These events are inter-related, and as a complex promote electrical instability. Likewise, remodeling occurring after the loss of cardiomyocytes, induces the development of a proarrhythmogenic environment. Thus, CA oxidation products may be involved in triggering arrhythmias as a result of both changes in cardiac cell automaticity and conduction velocity. In contrast, sulphur-containing amino acids (S-AA), in particular taurine and its precursor cysteine have been shown to modulate redox state of the heart. However, the multiple anti-oxidant properties of S-AA are unlikely to be exclusively responsible for their anti-arrhythmic action. They also possess additional cytoprotective effects which can stabilize electrical activity of the heart. It is concluded that specific S-AA may attenuate deleterious effects of supraphysiological levels of CA and this could serve as an important mechanism for the treatment and/or prevention of arrhythmogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Affinity resins as new tools for identifying target proteins of ascorbic acid.

    PubMed

    Iwaoka, Yuji; Nishino, Kohei; Ishikawa, Takahiro; Ito, Hideyuki; Sawa, Yoshihiro; Tai, Akihiro

    2018-02-12

    l-Ascorbic acid (AA) has diverse physiological functions, but little is known about the functional mechanisms of AA. In this study, we synthesized two types of affinity resin on which AA is immobilized in a stable form to identify new AA-targeted proteins, which can provide important clues for elucidating unknown functional mechanisms of AA. To our knowledge, an affinity resin on which AA as a ligand is immobilized has not been prepared, because AA is very unstable and rapidly degraded in an aqueous solution. By using the affinity resins, cytochrome c (cyt c) was identified as an AA-targeted protein, and we showed that oxidized cyt c exhibits specific affinity for AA. These results suggest that two kinds of AA-affinity resin can be powerful tools to identify new target proteins of AA.

  16. Concurrent release of admixed antimicrobials and salicylic acid from salicylate-based poly(anhydride-esters)

    PubMed Central

    Johnson, Michelle L.; Uhrich, Kathryn E.

    2008-01-01

    A polymer blend consisting of antimicrobials (chlorhexidine, clindamycin, and minocycline) physically admixed at 10% by weight into a salicylic acid-based poly (anhydride-ester) (SA-based PAE) was developed as an adjunct treatment for periodontal disease. The SA-based PAE/antimicrobial blends were characterized by multiple methods, including contact angle measurements and differential scanning calorimetry. Static contact angle measurements showed no significant differences in hydrophobicity between the polymer and antimicrobial matrix surfaces. Notable decreases in the polymer glass transition temperature (Tg) and the antimicrobials' melting points (Tm) were observed indicating that the antimicrobials act as plasticizers within the polymer matrix. In vitro drug release of salicylic acid from the polymer matrix and for each physically admixed antimicrobial was concurrently monitored by high pressure liquid chromatography during the course of polymer degradation and erosion. Although the polymer/antimicrobial blends were immiscible, the initial 24 h of drug release correlated to the erosion profiles. The SA-based PAE/antimicrobial blends are being investigated as an improvement on current localized drug therapies used to treat periodontal disease. PMID:19180627

  17. Degradation kinetics of chlorogenic acid at various pH values and effects of ascorbic acid and epigallocatechin gallate on its stability under alkaline conditions.

    PubMed

    Narita, Yusaku; Inouye, Kuniyo

    2013-01-30

    5-Caffeoylquinic acid (5-CQA) is generally referred to as chlorogenic acid and exhibits various biological activities such as antioxidant activity and porcine pancreas α-amylase inhibitory activities. 5-CQA may be useful as an antioxidant for food and to prevent diabetes and obesity. The degradation of 5-CQA and caffeic acid (CA) in an aqueous solution at 37 °C and pH 5.0-9.0 was studied. The degradation of 5-CQA and CA, demonstrating time and pH dependence (i.e., the rate constant, k, was higher at higher pH), was satisfactorily described by the Weibull equation. The stability of 5-CQA at pH 7.4 and 9.0 was improved by adding (-)-epigallocatechin gallate (EGCG) and ascorbic acid (AA). Moreover, the degradation of 5-CQA in the presence of EGCG or AA could be described by the Weibull equation. The k value in the presence of EGCG or AA was dependent on their concentration.

  18. Effect of different carboxylic acids in cyclodextrin functionalization of cellulose nanocrystals for prolonged release of carvacrol.

    PubMed

    Castro, D O; Tabary, N; Martel, B; Gandini, A; Belgacem, N; Bras, J

    2016-12-01

    Current investigations deal with new surface functionalization strategy of nanocrystalline cellulose-based substrates to impart active molecule release properties. In this study, cellulose nanocrystals (CNC) were surface-functionalized with β-cyclodextrin (β-CD) using succinic acid (SA) and fumaric acid (FA) as bridging agents. The main objective of this surface modification performed only in aqueous media was to obtain new active materials able to release antibacterial molecules over a prolonged period of time. The reactions were conducted by immersing the CNC film into a solution composed of β-CD, SA and FA, leading to CNC grafting. The materials were characterized by infrared spectroscopy (FT-IR), Quartz crystal microbalance-dissipation (QCM-D), AFM and phenolphthalein (PhP) was used to determine the efficiency of CNC grafting with β-CD. The results indicated that β-CD was successfully attached to the CNC backbone through the formation of ester bonds. Furthermore, carvacrol was entrapped by the attached β-CD and a prolonged release was confirmed. In particular, CNC grafted to β-CD in the presence of FA was selected as the best solution. The antibacterial activity and the controlled release were studied for this sample. Considerably longer bacterial activity against B. subtilis was observed for CNC grafted to β-CD compared to CNC and CNC-FA, confirming the promising impact of the present strategy. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Obesity is a significant susceptibility factor for idiopathic AA amyloidosis.

    PubMed

    Blank, Norbert; Hegenbart, Ute; Dietrich, Sascha; Brune, Maik; Beimler, Jörg; Röcken, Christoph; Müller-Tidow, Carsten; Lorenz, Hanns-Martin; Schönland, Stefan O

    2018-03-01

    To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis. Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease. Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n = 111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30 µg/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease. Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.

  20. AAS Career Services

    NASA Astrophysics Data System (ADS)

    Marvel, Kevin B.

    2012-08-01

    The American Astronomical Society provides substantial programs in the area of Career Services.Motivated by the Society's mission to enhance and share humanity's understanding of the Universe, the AAS provides a central resource for advertising positions, interviewing opportunities at its annual winter meeting and information, workshops and networks to enable astronomers to find employment.The programs of the Society in this area are overseen by an active committee on employment and the AAS Council itself.Additional resources that help characterize the field, its growth and facts about employment such as salaries and type of jobs available are regularly summarized and reported on by the American Institute of Physics.

  1. Arachidonic Acid Enhances Reproduction in Daphnia magna and Mitigates Changes in Sex Ratios Induced by Pyriproxyfen

    PubMed Central

    Ginjupalli, Gautam K.; Gerard, Patrick D.; Baldwin, William S.

    2016-01-01

    Arachidonic acid (AA) is one of only two unsaturated fatty acids retained in the ovaries of crustaceans, and an inhibitor of HR97g, a nuclear receptor expressed in adult ovaries. We hypothesized that as a key fatty acid, AA may be associated with reproduction and potentially environmental sex determination in Daphnia. Reproduction assays with AA indicate that it alters female/male sex ratios by increasing female production. This reproductive effect only occurred during a restricted P. subcapitata diet. Next, we tested whether enriching a poorer algal diet (C. vulgaris) with AA enhances overall reproduction and sex ratios. AA enrichment of a C. vulgaris diet also enhances fecundity at 1.0 and 4.0μM by 30–40% in the presence and absence of pyriproxyfen. This indicates that AA is crucial in reproduction regardless of environmental sex determination. Furthermore, our data indicates that P. subcapitata may provide a threshold concentration of AA needed for reproduction. Diet switch experiments from P. subcapitata to C. vulgaris mitigate some but not all of AA’s effects when compared to a C. vulgaris only diet, suggesting that some AA provided by P. subcapitata is retained. In summary, AA supplementation increases reproduction and represses pyriproxyfen-induced environmental sex determination in D. magna in restricted diets. A diet rich in AA may provide protection from some reproductive toxicants such as the juvenile hormone agonist, pyriproxyfen. PMID:25393616

  2. Preparation and characterization of poly(lactic acid) nanoparticles for sustained release of pyridostigmine bromide.

    PubMed

    Tan, Q Y; Xu, M L; Wu, J Y; Yin, H F; Zhang, J Q

    2012-04-01

    A novel pyridostigmine bromide poly (lactic acid) nanoparticles (PBPNPs) was prepared to obtain sustained release characteristics of PB. A central composite design approach was employed for process optimization. The in vitro release studies were carried out by dialysis method and conducted using four different dissolution media. Similar factor method was investigated for dissolution profile comparison. Multiple linear regression analysis for process optimization revealed that the optimal PBPNPs were obtained where the values of the amount of PB (X1, mg), PLA concentration (X2, % w:v), and PVA concentration (X3, % w:v) were 49.20 mg, 3.31% and 3.41%, respectively. The average particle size and zeta potential of PBPNPs with the optimized formulation were 722.9 +/- 4.3 nm, and -25.12 +/- 1.2 mV, respectively. PBPNPs provided an initial burst of drug release followed by a very slow release over an extended period of time (72 h). Compared with free PB, PBPNPs had a significantly lower release rate of PB in vitro. The in vitro release profile of the PBPNPs could be described by Weibull models, regardless of type of dissolution medium. Statistical significance of similarity between every two dissolution profiles of PBPNPs in different dissolution media was found, and the difference between the curves of PBPNPs and pure PB was statistically significant.

  3. Uncovering the Design Principle of Amino Acid-Derived Photoluminescent Biodots with Tailor-Made Structure-Properties and Applications for Cellular Bioimaging.

    PubMed

    Xu, Hesheng Victor; Zheng, Xin Ting; Zhao, Yanli; Tan, Yen Nee

    2018-06-13

    Natural amino acids possess side chains with different functional groups (R groups), which make them excellent precursors for programmable synthesis of biomolecule-derived nanodots (biodots) with desired properties. Herein, we report the first systematic study to uncover the material design rules of biodot synthesis from 20 natural α-amino acids via a green hydrothermal approach. The as-synthesized amino acid biodots (AA dots) are comprehensively characterized to establish a structure-property relationship between the amino acid precursors and the corresponding photoluminescent properties of AA dots. It was found that the amino acids with reactive R groups, including amine, hydroxyl, and carboxyl functional groups form unique C-O-C/C-OH and N-H bonds in the AA dots which stabilize the surface defects, giving rise to brightly luminescent AA dots. Furthermore, the AA dots were found to be amorphous and the length of the R group was observed to affect the final morphology (e.g., disclike nanostructure, nanowire, or nanomesh) of the AA dots, which in turn influence their photoluminescent properties. It is noteworthy to highlight that the hydroxyl-containing amino acids, that is, Ser and Thr, form the brightest AA dots with a quantum yield of 30.44% and 23.07%, respectively, and possess high photostability with negligible photobleaching upon continuous UV exposure for 3 h. Intriguingly, by selective mixing of Ser or Thr with another amino acid precursor, the resulting mixed AA dots could inherit unique properties such as improved photostability and significant red shift in their emission wavelength, producing enhanced green and red fluorescent intensity. Moreover, our cellular studies demonstrate that the as-synthesized AA dots display outstanding biocompatibility and excellent intracellular uptake, which are highly desirable for imaging applications. We envision that the material design rules discovered in this study will be broadly applicable for the rational

  4. Quantification and Evidence for Mechanically Metered Release of Pygidial Secretions in Formic Acid-Producing Carabid Beetles

    PubMed Central

    Will, Kipling W.; Gill, Aman S.; Lee, Hyeunjoo; Attygalle, Athula B.

    2010-01-01

    This study is the first to measure the quantity of pygidial gland secretions released defensively by carabid beetles (Coleoptera: Carabidae) and to accurately measure the relative quantity of formic acid contained in their pygidial gland reservoirs and spray emissions. Individuals of three typical formic acid producing species were induced to repeatedly spray, ultimately exhausting their chemical compound reserves. Beetles were subjected to faux attacks using forceps and weighed before and after each ejection of chemicals. Platynus brunneomarginatus (Mannerheim) (Platynini), P. ovipennis (Mannerheim) (Platynini) and Calathus ruficollis Dejean (Sphodrini), sprayed average quantities with standard error of 0.313 ± 0.172 mg, 0.337 ± 0.230 mg, and 0.197 ± 0.117 mg per spray event, respectively. The quantity an individual beetle released when induced to spray tended to decrease with each subsequent spray event. The quantity emitted in a single spray was correlated to the quantity held in the reservoirs at the time of spraying for beetles whose reserves are greater than the average amount emitted in a spray event. For beetles with a quantity less than the average amount sprayed in reserve there was no significant correlation. For beetles comparable in terms of size, physiological condition and gland reservoir fullness, the shape of the gland reservoirs and musculature determined that a similar effort at each spray event would mechanically meter out the release so that a greater amount was emitted when more was available in the reservoir. The average percentage of formic acid was established for these species as 34.2%, 73.5% and 34.1% for for P. brunneomarginatus, P. ovipennis and C. ruficollis, respectively. The average quantities of formic acid released by individuals of these species was less than two-thirds the amount shown to be lethal to ants in previously published experiments. However, the total quantity from multiple spray events from a single individual could

  5. Combined α-tocopherol and ascorbic acid protects against smoke-induced lung squamous metaplasia in ferrets.

    PubMed

    Kim, Yuri; Chongviriyaphan, Nalinee; Liu, Chun; Russell, Robert M; Wang, Xiang-Dong

    2012-01-01

    Many epidemiological studies show the benefit of fruits and vegetables on reducing risk of lung cancer, the leading cause of cancer death in the United States. Previously, we demonstrated that cigarette smoke exposure (SM)-induced lung lesions in ferrets were prevented by a combination of low dose of β-carotene, α-tocopherol (AT), and ascorbic acid (AA). However, the role of a combination of AT and AA alone in the protective effect on lung carcinogenesis remains to be examined. In the present study, we investigated whether the combined AT (equivalent to ∼100 mg/day in the human) and AA (equivalent to ∼210 mg/day) supplementation prevents against SM (equivalent to 1.5 packs of cigarettes/day) induced lung squamous metaplasia in ferrets. Ferrets were treated for 6 weeks in the following three groups (9 ferrets/group): (i) Control (no SM, no AT+AA), (ii) SM alone, and (iii) SM+AT+AA. Results showed that SM significantly decreased concentrations of retinoic acid, AT, and reduced form of AA, not total AA, retinol and retinyl palmitate, in the lungs of ferrets. Combined AT+AA treatment partially restored the lowered concentrations of AT, reduced AA and retinoic acid in the lungs of SM-exposed ferrets to the levels in the control group. Furthermore, the combined AT+AA supplementation prevented SM-induced squamous metaplasia [0 positive/9 total ferrets (0%) vs. 5/8 (62%); p<0.05] and cyclin D1 expression (p<0.05) in the ferret lungs, in which both were positively correlated with expression of c-Jun expression. Although there were no significant differences in lung microsomal malondialdehyde (MDA) levels among the three groups, we found a positive correlation between MDA levels and cyclin D1, as well as c-Jun expressions in the lungs of ferrets. These data indicate that the combination of antioxidant AT+AA alone exerts protective effects against SM-induced lung lesions through inhibiting cyclin D1 expression and partially restoring retinoic acid levels to normal

  6. Thermal stability of L-ascorbic acid and ascorbic acid oxidase in broccoli (Brassica oleracea var. italica).

    PubMed

    Munyaka, Ann Wambui; Makule, Edna Edward; Oey, Indrawati; Van Loey, Ann; Hendrickx, Marc

    2010-05-01

    The thermal stability of vitamin C (including l-ascorbic acid [l-AA] and dehydroascorbic acid [DHAA]) in crushed broccoli was evaluated in the temperature range of 30 to 90 degrees C whereas that of ascorbic acid oxidase (AAO) was evaluated in the temperature range of 20 to 95 degrees C. Thermal treatments (for 15 min) of crushed broccoli at 30 to 60 degrees C resulted in conversion of l-AA to DHAA whereas treatments at 70 to 90 degrees C retained vitamin C as l-AA. These observations indicated that enzymes (for example, AAO) could play a major role in the initial phase (that is, oxidation of l-AA to DHAA) of vitamin C degradation in broccoli. Consequently, a study to evaluate the temperature-time conditions that could result in AAO inactivation in broccoli was carried out. In this study, higher AAO activity was observed in broccoli florets than stalks. During thermal treatments for 10 min, AAO in broccoli florets and stalks was stable until around 50 degrees C. A 10-min thermal treatment at 80 degrees C almost completely inactivated AAO in broccoli. AAO inactivation followed 1st order kinetics in the temperature range of 55 to 65 degrees C. Based on this study, a thermal treatment above 70 degrees C is recommended for crushed vegetable products to prevent oxidation of l-AA to DHAA, the onset of vitamin C degradation. The results reported in this study are applicable for both domestic and industrial processing of vegetables into products such as juices, soups, and purees. In this report, we have demonstrated that processing crushed broccoli in a temperature range of 30 to 60 degrees C could result in the conversion of l-ascorbic acid to dehydroascorbic (DHAA), a very important reaction in regard to vitamin C degradation because DHAA could be easily converted to other compounds that do not have the biological activity of vitamin C.

  7. Comparison of soil pollution concentrations determined using AAS and portable XRF techniques.

    PubMed

    Radu, Tanja; Diamond, Dermot

    2009-11-15

    Past mining activities in the area of Silvermines, Ireland, have resulted in heavily polluted soils. The possibility of spreading pollution to the surrounding areas through dust blow-offs poses a potential threat for the local communities. Conventional environmental soil and dust analysis techniques are very slow and laborious and consequently there is a need for fast and accurate analytical methods, which can provide real-time in situ pollution mapping. Laboratory-based aqua regia acid digestion of the soil samples collected in the area followed by the atomic absorption spectrophotometry (AAS) analysis confirmed very high pollution, especially by Pb, As, Cu, and Zn. In parallel, samples were analyzed using portable X-ray fluorescence radioisotope and miniature tube powered (XRF) NITON instruments and their performance was compared. Overall, the portable XRF instrument gave excellent correlation with the laboratory-based reference AAS method.

  8. Effects of conventional and a novel colonic-release bile acid sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea.

    PubMed

    Appleby, R N; Bajor, A; Gillberg, P-G; Graffner, H; Simrén, M; Ung, K A; Walters, Jrf

    2017-04-01

    Primary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency. The purpose of this study was to evaluate the pharmacological effects of conventional sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD. Patients with seven-day 75 selenium-homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double-blind protocol to two weeks treatment with twice-daily A3384 250 mg ( n  = 6), 1 g ( n  = 7) or placebo ( n  = 6). Thirteen patients were taking conventional sequestrants at the start of the study. Symptoms were recorded and serum FGF19 and 7α-hydroxy-4-cholesten-3-one (C4) measured. Median serum FGF19 on conventional sequestrant treatment was 28% lower than baseline values in BAD ( p  < 0.05). C4 on conventional sequestrant treatment was 58% higher in BAD ( p  < 0.001). No changes were seen on starting or withdrawing A3384. A3384 improved diarrhoeal symptoms, with a median reduction of 2.2 points on a 0-10 Likert scale compared to placebo, p  < 0.05. Serum FGF19 was suppressed and bile acid production up-regulated on conventional bile acid sequestrants, but not with A3384. This colonic-release formulation of colestyramine produced symptomatic benefit in patients with BAD.

  9. Effects of conventional and a novel colonic-release bile acid sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea

    PubMed Central

    Bajor, A; Gillberg, P-G; Graffner, H; Simrén, M; Ung, KA; Walters, JRF

    2016-01-01

    Background Primary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency. Aim The purpose of this study was to evaluate the pharmacological effects of conventional sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD. Methods Patients with seven-day 75selenium-homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double-blind protocol to two weeks treatment with twice-daily A3384 250 mg (n = 6), 1 g (n = 7) or placebo (n = 6). Thirteen patients were taking conventional sequestrants at the start of the study. Symptoms were recorded and serum FGF19 and 7α-hydroxy-4-cholesten-3-one (C4) measured. Results Median serum FGF19 on conventional sequestrant treatment was 28% lower than baseline values in BAD (p < 0.05). C4 on conventional sequestrant treatment was 58% higher in BAD (p < 0.001). No changes were seen on starting or withdrawing A3384. A3384 improved diarrhoeal symptoms, with a median reduction of 2.2 points on a 0–10 Likert scale compared to placebo, p < 0.05. Conclusions Serum FGF19 was suppressed and bile acid production up-regulated on conventional bile acid sequestrants, but not with A3384. This colonic-release formulation of colestyramine produced symptomatic benefit in patients with BAD. PMID:28507750

  10. Dietary Intakes of Arachidonic Acid and α-Linolenic Acid Are Associated with Reduced Risk of Hip Fracture in Older Adults12

    PubMed Central

    Farina, Emily K.; Kiel, Douglas P.; Roubenoff, Ronenn; Schaefer, Ernst J.; Cupples, L. Adrienne; Tucker, Katherine L.

    2011-01-01

    PUFA are hypothesized to influence bone health, but longitudinal studies on hip fracture risk are lacking. We examined associations between intakes of PUFA and fish, and hip fracture risk among older adults (n = 904) in the Framingham Osteoporosis Study. Participants (mean age ~75 y at baseline) were followed for incident hip fracture from the time they completed the baseline exam (1988–1989) until December 31, 2005. HR and 95% CI were estimated for energy-adjusted dietary fatty acid exposure variables [(n-3) fatty acids: α-linolenic acid (ALA), EPA, DHA, EPA+DHA; (n-6) fatty acids: linoleic acid, arachidonic acid (AA); and the (n-6):(n-3) ratio] and fish intake categories, adjusting for potential confounders and covariates. Protective associations were observed between intakes of ALA (P-trend = 0.02) and hip fracture risk in a combined sample of women and men and between intakes of AA (P-trend = 0.05) and hip fracture risk in men only. Participants in the highest quartile of ALA intake had a 54% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.46; 95% CI = 0.26–0.83). Men in the highest quartile of AA intake had an 80% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.20; 95% CI = 0.04–0.96). No significant associations were observed among intakes of EPA, DHA, EPA+DHA, or fish. These findings suggest dietary ALA may reduce hip fracture risk in women and men and dietary AA may reduce hip fracture risk in men. PMID:21508210

  11. Modification of rat detrusor muscle contraction by ascorbic acid and citric acid involving enhanced neurotransmitter release and Ca2+ influx.

    PubMed

    Dasgupta, Jaydip; Elliott, Ruth A; Tincello, Douglas G

    2009-01-01

    Consumption of carbonated soft drinks is independently associated with the development of overactive bladder (OR 1.41, 95% Cl 1.02-1.95). We have shown previously that artificial sweeteners, present in carbonated soft drinks, enhanced detrusor muscle contraction. Other constituents of soft drinks are preservatives and antioxidants, we evaluated the effects of two of these, ascorbic acid and citric acid, on the contractile response of isolated rat bladder muscle strips. Detrusor muscle strips were suspended in a perfusion organ bath. We determined the effect of ascorbic acid and citric acid on the contractile responses to electrical field stimulation (EFS) in the absence and presence of atropine, carbachol, alpha, beta methylene ATP, potassium and calcium. Ascorbic acid and citric acid (10(-7) M to 10(-3) M) enhanced the contractile response to 10 Hz EFS compared to control (P < 0.01). The frequency and amplitude of spontaneous bladder contractions were enhanced in the presence of ascorbic acid and citric acid by 14%, 21%, 21%, and 11% respectively. Ascorbic acid 10(-4) M significantly increased the atropine resistant response to EFS 5 Hz by 37% (P < 0.01) and inhibited contraction in response to carbachol 10(-4) M by 24%, (P < 0.05). Both ascorbic acid 10(-4) M and citric acid 10(-5) M significantly enhanced maximum contractile responses to alpha, beta methylene ATP, KCI and calcium compared to control. Ascorbic acid and citric acid augmented bladder muscle contraction possibly by enhanced Ca(2+) influx. Presynaptic neurotransmitter release was enhanced by ascorbic acid. Carbonated beverages containing preservatives may aggravate symptoms of OAB. (c) 2009 Wiley-Liss, Inc.

  12. Attenuated acute salivary α-amylase responses to gustatory stimulation with citric acid in thin children.

    PubMed

    Chen, Long Hui; Yang, Ze Min; Chen, Wei Wen; Lin, Jing; Zhang, Min; Yang, Xiao Rong; Zhao, Ling Bo

    2015-04-14

    Salivary α-amylase (sAA) is responsible for the 'pre-digestion' of starch in the oral cavity and accounts for up to 50 % of salivary protein in human saliva. An accumulating body of literature suggests that sAA is of nutritional importance; however, it is still not clear how sAA is related to individual's nutritional status. Although copy number variations (CNV) of the salivary amylase gene (AMY1) are associated with variation in sAA levels, a significant amount of sAA variation is not explained by AMY1 CNV. To measure sAA responses to gustatory stimulation with citric acid, we used sAA ratio (the ratio of stimulated sAA levels to those of resting sAA) and investigated acute sAA responses to citric acid in children with normal (Normal-BMI, n 22) and low (Low-BMI, n 21) BMI. The AMY1 gene copy number was determined by quantitative PCR. We, for the first time, demonstrated attenuated acute sAA responses (decreased sAA ratio) to gustatory stimulation in Low-BMI (thinness grade 3) children compared with the Normal-BMI children, which suggest that sAA responses to gustatory stimulation may be of nutritional importance. However, child's nutritional status was not directly related to their resting or stimulated sAA levels, and it was not associated with AMY1 gene copy number. Finally, AMY1 CNV might influence, but did not eventually determine, sAA levels in children.

  13. Prebiotic synthesis and degradation of amino acids by UV-irradiation at room temperature and 77K.

    NASA Astrophysics Data System (ADS)

    Mita, H.; Shimoyama, A.

    Amino acids (AAs) were synthesized prebioticaly by UV irradiation to aqueous solution of amines and nitriles, and mixtures of graphite-ammonia-water (GAW mix.) at room temperature (RT, model of the primitive ocean) and 77 K (model of comet ice), using a Xe excimer lamp (max is 172 nm) and a low-pressure mercury lamp (max is 185/254 nm). Degradation of glycine and, degradation and racemization of aspartic acid were carried out by UV irradiation at RT. AAs in the irradiated samples were determined quantitatively by a gas chromatograph combined with a mass spectrometer after derivatized with HCl/2-propanol and trifluoroacetic anhydride. Maximum 16 hydrolyzed AAs from C2 to C6 were detected quantitatively. Amino acids have chiral center were nearly racemic. Therefore, those amino acids were not contaminants. In the most case, glycine was the most abundant AA and its concentration was 4.1 μmol/l from 1mmol/l acetonitrile solu. at RT for 3 h, 1 nmol/l from 100 mmol/l acetonitrile solu. at 77K for 1 h, 3.8?μmol/l from 10 mmol/l methylamine solu. at RT for 15 h, 278 μmol/l from 1 mol/l methylamine solu. At 77K for 4h, and 38.6 pmol/g-Carbon from GAW mix. at RT for 24 h. Maximum producing time of glycine from acetonitrile was 3 h and the shortest, that from GAW mix. was the longest among our experiments. Amount of glycine was decreased in gradually, after maximum producing time. Yields of glycine from acetonitrile and methylamine at 77K were lower than those at RT. Amounts of large AAs were lower than those of small AAs as glycine and alanine. Half-life time of glycine UV irradiation at RT was nearly 30 min. and similar to that of aspartic acid. Half-life time of racemization of aspartic acid was 2.1 h. It was able to confirm that a lot of AAs were synthesized by UV irradiation in the model experiments of primitive environments, even in simulated comet ice, from different starting materials. AA formation from developed material, as acetonitrile was more rapid and higher

  14. Arachidonic acid stimulates DNA synthesis in brown preadipocytes through the activation of protein kinase C and MAPK.

    PubMed

    Garcia, Bibian; Martinez-de-Mena, Raquel; Obregon, Maria-Jesus

    2012-10-01

    Arachidonic acid (AA) is a polyunsaturated fatty acid that stimulates the proliferation of many cellular types. We studied the mitogenic potential of AA in rat brown preadipocytes in culture and the signaling pathways involved. AA is a potent mitogen which induces 4-fold DNA synthesis in brown preadipocytes. The AA mitogenic effect increases by NE addition. AA also increases the mitogenic action of different growth factor combinations. Other unsaturated and saturated fatty acids do not stimulate DNA synthesis to the same extent as AA. We analyzed the role of PKC and MEK/MAPK signaling pathways. PKC inhibition by bisindolilmaleimide I (BIS) abolishes AA and phorbol ester stimulation of DNA synthesis and reduces the mitogenic activity of different growth factors in brown preadipocytes. Brown preadipocytes in culture express PKC α, δ, ε and ζ isoforms. Pretreatment with high doses of the phorbol ester PDBu, induces downregulation of PKCs ε and δ and reproduces the effect of BIS indicating that AA-dependent induction of DNA synthesis requires PKC activity. AA also activates MEK/MAPK pathway and the inhibition of MEK activity inhibits AA stimulation of DNA synthesis and brown adipocyte proliferation. Inhibition of PKC δ by rottlerin abolishes AA-dependent stimulation of DNA synthesis and MAPK activation, whereas PKC ε inhibition does not produce any effect. In conclusion, our results identify AA as a potent mitogen for brown adipocytes and demonstrate the involvement of the PDBu-sensitive PKC δ isoform and MEK/MAPK pathway in AA-induced proliferation of brown adipocytes. Increased proliferative activity might increase the thermogenic capacity of brown fat. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Commensal bacteria and essential amino acids control food choice behavior and reproduction

    PubMed Central

    Fioreze, Gabriela Tondolo; Anjos, Margarida; Baltazar, Célia; Elias, Ana Paula; Itskov, Pavel M.; Piper, Matthew D. W.

    2017-01-01

    Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits. PMID:28441450

  16. Commensal bacteria and essential amino acids control food choice behavior and reproduction.

    PubMed

    Leitão-Gonçalves, Ricardo; Carvalho-Santos, Zita; Francisco, Ana Patrícia; Fioreze, Gabriela Tondolo; Anjos, Margarida; Baltazar, Célia; Elias, Ana Paula; Itskov, Pavel M; Piper, Matthew D W; Ribeiro, Carlos

    2017-04-01

    Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits.

  17. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

    PubMed

    Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

    2016-10-01

    Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Associations of cord blood fatty acids with lymphocyte proliferation, IL-13, and IFN-γ

    PubMed Central

    Gold, Diane R.; Willwerth, Ben M.; Tantisira, Kelan G.; Finn, Patricia W.; Schaub, Bianca; Perkins, David L.; Tzianabos, Arthur; Ly, Ngoc P.; Schroeter, Christian; Gibbons, Fiona; Campos, Hannia; Oken, Emily; Gillman, Matthew W.; Palmer, Lyle J.; Ryan, Louise M.; Weiss, Scott T.

    2006-01-01

    Background. N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been hypothesized to have opposing influences on neonatal immune responses that might influence the risk of allergy or asthma. However, both n-3 eicosapentaenoic acid (EPA) and n-6 arachidonic acid (AA) are required for normal fetal development. Objective. We evaluated whether cord blood fatty acid levels were related to neonatal immune responses and whether n-3 and n-6 PUFA responses differed. Methods. We examined the relation of cord blood plasma n-3 and n-6 PUFAs (n = 192) to antigen- and mitogen-stimulated cord blood lymphocyte proliferation (n = 191) and cytokine (IL-13 and IFN-γ; n = 167) secretion in a US birth cohort. Results. Higher levels of n-6 linoleic acid were correlated with higher IL-13 levels in response to Bla g 2 (cockroach, P = .009) and Der f 1 (dust mite, P = .02). Higher n-3 EPA and n-6 AA levels were each correlated with reduced lymphocyte proliferation and IFN-γ levels in response to Bla g 2 and Der f 1 stimulation. Controlling for potential confounders, EPA and AA had similar independent effects on reduced allergen-stimulated IFN-γ levels. If neonates had either EPA or AA levels in the highest quartile, their Der f 1 IFN-γ levels were 90% lower (P = .0001) than those with both EPA and AA levels in the lowest 3 quartiles. Reduced AA/EPA ratio was associated with reduced allergen-stimulated IFN-γ level. Conclusion. Increased levels of fetal n-3 EPA and n-6 AA might have similar effects on attenuation of cord blood lymphocyte proliferation and IFN-γ secretion. Clinical implications. The implications of these findings for PMID:16630954

  19. Polylactide-based renewable composites from natural products residues by encapsulated film bag: characterization and biodegradability.

    PubMed

    Wu, Chin-San

    2012-09-01

    In the present study, the biodegradability, morphology, and mechanical properties of composite materials consisting of acrylic acid-grafted polylactide (PLA-g-AA) and natural products residues (corn starch, CS) were evaluated. Composites containing acrylic acid-grafted PLA (PLA-g-AA/CS) exhibited noticeably superior mechanical properties due to their greater compatibility with CS compared with PLA/CS. The feasibility of using PLA-g-AA/CS as a film bag material to facilitate the controlled release of an encapsulated phosphate-solubilizing bacterium (PSB) Burkholderia cepacia as a fertilizer use promoter was then evaluated. For purposes of comparison and accurate characterization, a PLA film bag was also assessed. The results showed that the bacterium completely degraded both the PLA and the PLA-g-AA/CS composite film bags, resulting in cell release. The PLA-g-AA/CS (20 wt%) film bags were more biodegradable than those made of PLA, and displayed a higher loss of molecular weight and intrinsic viscosity, indicating a strong connection between these characteristics and biodegradability. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Release of carbon nanoparticles of different size and shape from nanocomposite poly(lactic) acid film into food simulants.

    PubMed

    Velichkova, Hristiana; Kotsilkov, Stanislav; Ivanov, Evgeni; Kotsilkova, Rumiana; Gyoshev, Stanislav; Stoimenov, Nikolay; Vitanov, Nikolay K

    2017-06-01

    Poly(lactic) acid (PLA) film with 2 wt% mixed carbon nanofillers of graphene nanoplates (GNPs) and multiwall carbon nanotubes (MWCNTs) in a weight ratio of 1:1 with impurities of fullerene and carbon black (CB) was produced by layer-to-layer deposition and hot pressing. The release of carbon nanoparticles from the film was studied at varying time-temperature conditions and simulants. Migrants in simulant solvents were examined with laser diffraction analysis and transmission electron microscopy (TEM). Film integrity and the presence of migrants on the film surfaces were visualised by scanning electron microscopy (SEM). The partial dissolution of PLA polymer in the solvents was confirmed by swelling tests and differential scanning calorimetry (DSC). Nanoparticle migrants were not detected in the simulants (at the LOD 0.020 μm of the laser diffraction analysis) after migration testing at 40°C for 10 days. However, high-temperature migration testing at 90°C for 4 h provoked a release of GNPs from the film into ethanol, acetic acid and oil-based food simulants. Short carbon nanotubes were observed rarely to release in the most aggressive acetic acid solvent. Obviously, the enhanced molecular mobility at temperatures above the glass transition and partial dissolution of PLA polymer by the food simulant facilitate the diffusion processes. Moreover, shape, size and concentration of nanoparticles play a significant role. Flexible naked GNPs (lateral size 100-1000 nm) easily migrate when the polymer molecules exhibit enhanced mobility, while fibrous MWCNTs (> 1 μm length) formed entangled networks on the film surfaces as the PLA polymer is partly dissolved, preventing their release into food simulants. The impurities of fullerenes and CB (5-30 nm) were of minor concentration in the polymer, therefore their migration is low or undetectable. The total amount of released migrants is below overall migration limits.

  1. Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

    PubMed

    Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G

    2017-10-01

    Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Sensitive electrochemical sensors for simultaneous determination of ascorbic acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide nanocomposites

    NASA Astrophysics Data System (ADS)

    Jiang, Jingjing; Du, Xuezhong

    2014-09-01

    Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing.Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the

  3. A pH and redox dual stimuli-responsive poly(amino acid) derivative for controlled drug release.

    PubMed

    Gong, Chu; Shan, Meng; Li, Bingqiang; Wu, Guolin

    2016-10-01

    A pH and redox dual stimuli-responsive poly(aspartic acid) derivative for controlled drug release was successfully developed through progressive ring-opening reactions of polysuccinimide (PSI). Polyethylene glycol (PEG) chains were grafted onto the polyaspartamide backbone via redox-responsive disulfide linkages, providing a sheddable shell for the polymeric micelles in a reductive environment. Phenyl groups were introduced into the polyaspartamide backbone via the aminolysis reaction of PSI to serve as the hydrophobic segment of micelles. The polyaspartamide scaffold was also functionalized with N-(3-aminopropyl)-imidazole to obtain the pH-responsiveness manifesting as a swelling of the core of micelles at a low pH. The polymeric micelles with a core-shell nanostructure forming in neutral media exhibited both pH and redox responsive characteristics. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through both hydrophobic and π-π interactions between aromatic rings and the DOX-loaded polymeric micelles exhibited accelerated drug release behaviors in an acidic and reductive environment due to the swelling of hydrophobic cores and the shedding of PEG shells. Furthermore, the cytocompability of the polymer and the cytotoxicity of DOX-loaded micelles towards Hela cells under corresponding conditions were evaluated, and the endocytosis of DOX-loaded polymeric micelles and the intracellular drug release from micelles were observed. All obtained data indicated that the micelle was a promising candidate for controlled drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Determination of furan precursors and some thermal damage markers in baby foods: ascorbic acid, dehydroascorbic acid, hydroxymethylfurfural and furfural.

    PubMed

    Mesías-García, Marta; Guerra-Hernández, Eduardo; García-Villanova, Belén

    2010-05-26

    The presence of ascorbic acid (AA), vitamin C (AA + dehydroascorbic acid (DHAA)) and furfural as potential precursors of furan in commercial fruit and vegetable jarred baby food was studied. Hydroxymethylfurfural (HMF) was also determined and used, together with furfural levels, as markers of thermal damage. AA, calculated DHAA and vitamin C values ranged between 22.4 and 103, 2.9 and 13.8, and 32.1 and 113.2 mg/100 g, respectively, in fruit-based baby food. However, no trace of AA was found in the vegetable-based baby food samples tested, probably because these samples are not enriched in vitamin C and the content of this vitamin in fresh vegetables is destroyed during processing. Furfural values ranged from not detected to 236 microg/100 g, being higher in vegetable samples than in fruit samples possibly because of greater AA degradation favored by a higher pH in the vegetable samples. HMF values (range: not detected-959 microg/100 g), however, were higher in the fruit samples, probably due to greater carbohydrate content degradation and as a consequence of the Maillard reaction, favored by a lower pH in these samples. According to these results, HMF would be the optimum indicator of thermal treatment for fruits, and furfural for vegetables. The higher furfural content of vegetable baby food could be considered an index of greater AA degradation and, therefore, the furan content might be higher in this kind of sample than in fruit-based baby food.

  5. Anacardic acid from brazilian cashew nut trees reduces dentine erosion.

    PubMed

    Silveira, Cintia; Oliveira, Flávia; Dos Santos, Maria Lucilia; de Freitas, Thiago; Imparato, José Carlos; Magalhães, Ana Carolina

    2014-01-01

    The aim of this study was to analyze the effect of solutions containing saturated anacardic acid (AA) on dentine erosion in vitro. AA was chemically isolated from natural cashew nutshell liquid obtained by continuous extraction in a Soxhlet extractor and was fully saturated by catalytic hydrogenation. Matrix metalloproteinase 2 (MMP-2) activity, when exposed to buffers containing 100 µmol/l AA, was analyzed using zymography. Bovine root samples were subjected to erosive demineralization (Sprite Zero™, 4 × 90 s/day) and remineralization with artificial saliva between the erosive cycles for 5 days. The samples were treated as follows, after the first and the last acid exposure (1 min; n = 12/group): (1) 100 µmol/l epigallocatechin-3-gallate (EGCG) (positive control); (2) 0.05% NaF; (3) 100 µmol/l saturated AA; (4) saturated AA and EGCG; (5) saturated AA, EGCG and NaF; (6) untreated (negative control). Dentine erosion was measured using a contact profilometer. Two dentine samples from each group were analyzed using scanning electron microscopy. Saturated AA reduced the activity of MMP-2. ANOVA and Tukey's test revealed that all treatments significantly reduced dentine loss compared to the negative control (6.03 ± 0.98 µm). Solutions containing saturated AA (1.97 ± 1.02 µm) showed the greatest reduction in dentine erosion compared to the NaF (3.93 ± 1.54 µm) and EGCG (3.79 ± 0.83 µm) solutions. Therefore, it may be concluded that AA significantly reduces dentine erosion in vitro, possibly by acting as an MMP-2 inhibitor.

  6. Role of Arachidonic Acid in Promoting Hair Growth

    PubMed Central

    Munkhbayar, Semchin; Jang, Sunhyae; Cho, A-Ri; Choi, Soon-Jin; Shin, Chang Yup; Eun, Hee Chul; Kim, Kyu Han

    2016-01-01

    Background Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid present in all mammalian cell membranes, and involved in the regulation of many cellular processes, including cell survival, angiogenesis, and mitogenesis. The dermal papilla, composed of specialized fibroblasts located in the bulb of the hair follicle, contributes to the control of hair growth and the hair cycle. Objective This study investigated the effect of AA on hair growth by using in vivo and in vitro models. Methods The effect of AA on human dermal papilla cells (hDPCs) and hair shaft elongation was evaluated by MTT assay and hair follicle organ culture, respectively. The expression of various growth and survival factors in hDPCs were investigated by western blot or immunohistochemistry. The ability of AA to induce and prolong anagen phase in C57BL/6 mice was analyzed. Results AA was found to enhance the viability of hDPCs and promote the expression of several factors responsible for hair growth, including fibroblast growth factor-7 (FGF-7) and FGF-10. Western blotting identified the role of AA in the phosphorylation of various transcription factors (ERK, CREB, and AKT) and increased expression of Bcl-2 in hDPCs. In addition, AA significantly promoted hair shaft elongation, with increased proliferation of matrix keratinocytes, during ex vivo hair follicle culture. It was also found to promote hair growth by induction and prolongation of anagen phase in telogen-stage C57BL/6 mice. Conclusion This study concludes that AA plays a role in promoting hair growth by increasing the expression of growth factors in hDPCs and enhancing follicle proliferation and survival. PMID:26848219

  7. Proteolysis of serum amyloid A and AA amyloid proteins by cysteine proteases: cathepsin B generates AA amyloid proteins and cathepsin L may prevent their formation

    PubMed Central

    Rocken, C; Menard, R; Buhling, F; Vockler, S; Raynes, J; Stix, B; Kruger, S; Roessner, A; Kahne, T

    2005-01-01

    Background: AA amyloidosis develops in patients with chronic inflammatory diseases. The AA amyloid proteins are proteolytic fragments obtained from serum amyloid A (SAA). Previous studies have provided evidence that endosomes or lysosomes might be involved in the processing of SAA, and contribute to the pathology of AA amyloidosis. Objective: To investigate the anatomical distribution of cathepsin (Cath) B and CathL in AA amyloidosis and their ability to process SAA and AA amyloid proteins. Methods and results: CathB and CathL were found immunohistochemically in every patient with AA amyloidosis and displayed a spatial relationship with amyloid in all the cases studied. Both degraded SAA and AA amyloid proteins in vitro. With the help of mass spectrometry 27 fragments were identified after incubation of SAA with CathB, nine of which resembled AA amyloid proteins, and seven fragments after incubation with CathL. CathL did not generate AA amyloid-like peptides. When native human AA amyloid proteins were used as a substrate 26 fragments were identified after incubation with CathB and 18 after incubation with CathL. Conclusion: The two most abundant and ubiquitously expressed lysosomal proteases can cleave SAA and AA amyloid proteins. CathB generates nine AA amyloid-like proteins by its carboxypeptidase activity, whereas CathL may prevent the formation of AA amyloid proteins by endoproteolytic activity within the N-terminal region of SAA. This is particularly interesting, because AA amyloidosis is a systemic disease affecting many organs and tissue types, almost all of which express CathB and CathL. PMID:15897303

  8. AAS Oral History Project

    NASA Astrophysics Data System (ADS)

    Buxner, Sanlyn; Holbrook, Jarita; AAS Oral History Team

    2016-06-01

    Now in its fourth year, the AAS Oral History Project has interviewed over 80 astronomers from all over the world. Led by the AAS Historical Astronomy Division (HAD) and partially funded by the American Institute of Physics Niels Bohr Library and ongoing support from the AAS, volunteers have collected oral histories from astronomers at professional meetings starting in 2015, including AAS, DPS, and the IAU general assembly. Each interview lasts one and a half to two hours and focuses on interviewees’ personal and professional lives. Questions include those about one’s family, childhood, strong influences on one’s scientific career, career path, successes and challenges, perspectives on how astronomy is changing as a field, and advice to the next generation. Each interview is audio recorded and transcribed, the content of which is checked with each interviewee. Once complete, interview transcripts are posted online as part of a larger oral history library at https://www.aip.org/history-programs/niels-bohr-library/oral-histories. Future analysis will reveal a rich story of astronomers and will help the community address issues of diversity, controversies, and the changing landscape of science. We are still recruiting individuals to be interviewed from all stages of career from undergraduate students to retired and emeritus astronomers. Contact Jarita Holbrook to schedule an interview or to find out more information about the project (astroholbrook@gmail.com). Also, contact Jarita Holbrook if you would like to become an interviewer for the project.

  9. Morphological assessment of bone mineralization in tibial metaphyses of ascorbic acid-deficient ODS rats.

    PubMed

    Hasegawa, Tomoka; Li, Minqi; Hara, Kuniko; Sasaki, Muneteru; Tabata, Chihiro; de Freitas, Paulo Henrique Luiz; Hongo, Hiromi; Suzuki, Reiko; Kobayashi, Masatoshi; Inoue, Kiichiro; Yamamoto, Tsuneyuki; Oohata, Noboru; Oda, Kimimitsu; Akiyama, Yasuhiro; Amizuka, Norio

    2011-08-01

    Osteogenic disorder shionogi (ODS) rats carry a hereditary defect in ascorbic acid synthesis, mimicking human scurvy when fed with an ascorbic acid-deficient (aa-def) diet. As aa-def ODS rats were shown to feature disordered bone formation, we have examined the bone mineralization in this rat model. A fibrous tissue layer surrounding the trabeculae of tibial metaphyses was found in aa-def ODS rats, and this layer showed intense alkaline phosphatase activity and proliferating cell nuclear antigen-immunopositivity. Many osteoblasts detached from the bone surfaces and were characterized by round-shaped rough endoplasmic reticulum (rER), suggesting accumulation of malformed collagen inside the rER. Accordingly, fine, fragile fibrillar collagenous structures without evident striation were found in aa-def bones, which may result from misassembling of the triple helices of collagenous α-chains. Despite a marked reduction in bone formation, ascorbic acid deprivation seemed to have no effect on mineralization: while reduced in number, normal matrix vesicles and mineralized nodules could be seen in aa-def bones. Fine needle-like mineral crystals extended from these mineralized nodules, and were apparently bound to collagenous fibrillar structures. In summary, collagen mineralization seems unaffected by ascorbic acid deficiency in spite of the fine, fragile collagenous fibrils identified in the bones of our animal model.

  10. Effects of unsaturated fatty acids on the kinetics of voltage‐gated proton channels heterologously expressed in cultured cells

    PubMed Central

    Kawanabe, Akira

    2016-01-01

    Key points Arachidonic acid (AA) greatly enhances the activity of the voltage‐gated proton (Hv) channel, although its mechanism of action and physiological function remain unclear.In the present study, we analysed the effects of AA on proton currents through Hv channels heterologously expressed in HEK293T cells.The dramatic increase in proton current amplitude elicited by AA was accompanied by accelerated activation kinetics and a leftward shift in the voltage‐dependence of activation.Mutagenesis studies suggest the two aforementioned effects of AA reflect two distinct structural mechanisms.Application of phospholipase A2, which liberates AA from phospholipids in the membrane, also enhances Hv channel activity, supporting the idea that AA modulates Hv channel activity within physiological contexts. Abstract Unsaturated fatty acids are key components of the biological membranes of all cells, and precursors of mediators for cell signalling. Arachidonic acid (AA) is an unsaturated fatty acid known to modulate the activities of various ion channels, including the voltage‐gated proton (Hv) channel, which supports the rapid production of reactive oxygen species (ROS) in phagocytes through regulation of pH and membrane potential. However, the molecular mechanisms and physiological functions of the effects of AA on Hv channels remain unclear. In the present study, we report an electrophysiological analysis of the effects of AA on the mouse Hv channel (mHv1) heterologously expressed in HEK293T cells. Application of AA to excised inside‐out patch membranes rapidly induced a robust increase in the amplitude of the proton current through mHv1. The current increase was accompanied by accelerated activation kinetics and a small leftward shift of the current–voltage relationship. In monomeric channels lacking the coiled‐coil region of the channel protein, the shift in the current–voltage relationship was diminished but activation and deactivation remained

  11. Overoxidized polyimidazole/graphene oxide copolymer modified electrode for the simultaneous determination of ascorbic acid, dopamine, uric acid, guanine and adenine.

    PubMed

    Liu, Xiaofang; Zhang, Ling; Wei, Shaping; Chen, Shihong; Ou, Xin; Lu, Qiyi

    2014-07-15

    In the present work, a novel strategy based on overoxidized polyimidazole (PImox) and graphene oxide (GO) copolymer modified electrode was proposed for the simultaneous determination of ascorbic acid (AA), dopamine (DA), uric acid (UA), guanine (G) and adenine (A). The copolymer was characterized by the scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). Due to the synergistic effects between PImox and GO, the proposed electrode exhibited excellent electrochemical catalytic activities and high selectivity and sensitivity toward the oxidation of AA, DA, UA, G and A. The peak separations between AA and DA, AA and UA, UA and G, and G and A were 140 mV, 200 mV, 380 mV and 300 mV, respectively. The linear response ranges for AA, DA, UA, G and A were 75-2275 μM, 12-278 μM, 3.6-249.6 μM, 3.3-103.3 μM and 9.6-215 μM, respectively, and corresponding detection limits were 18 μM, 0.63 μM, 0.59 μM, 0.48 μM and 1.28 μM. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Functional amino acids in nutrition and health.

    PubMed

    Wu, Guoyao

    2013-09-01

    The recent years have witnessed growing interest in biochemistry, physiology and nutrition of amino acids (AA) in growth, health and disease of humans and other animals. This results from the discoveries of AA in cell signaling involving protein kinases, G protein-coupled receptors, and gaseous molecules (i.e., NO, CO and H2S). In addition, nutritional studies have shown that dietary supplementation with several AA (e.g., arginine, glutamine, glutamate, leucine, and proline) modulates gene expression, enhances growth of the small intestine and skeletal muscle, or reduces excessive body fat. These seminal findings led to the new concept of functional AA, which are defined as those AA that participate in and regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of the organisms. Functional AA hold great promise in prevention and treatment of metabolic diseases (e.g., obesity, diabetes, and cardiovascular disorders), intrauterine growth restriction, infertility, intestinal and neurological dysfunction, and infectious disease (including viral infections).

  13. Amino acid adsorption on anatase (101) surface at vacuum and aqueous solution: a density functional study.

    PubMed

    Liu, Liuxie; Li, Kai; Chen, Xiao; Liang, Xiaoqin; Zheng, Yan; Li, Laicai

    2018-03-29

    The adsorption of 20 amino acids (AAs) on the (101) surface of anatase titanium dioxide (TiO 2 ) has been investigated under the scheme of density functional theory. Through the analysis of adsorption geometries, amino group and side chains of AAs have been identified as the major side to adsorb on TiO 2 , while the carboxyl group prefers to stay outside to avoid the repulsion between negatively charged oxygen from TiO 2 and AAs. On the surface, two-coordinated oxygen is the major site to stabilize AAs through O-H interactions. The above conclusion does not change when it is in the aqueous solution based on the calculations with AAs surrounded by explicit water molecules. The above knowledge is helpful in predicting how AAs and even peptides adsorb on inorganic materials. Graphical abstract The adsorption of 20 amino acids (AAs) on the (101) surface of anatase titanium dioxide (TiO 2 ) has been investigated under the scheme of density functional theory.

  14. Ascorbic Acid Intake and Oxalate Synthesis

    PubMed Central

    Knight, John; Madduma-Liyanage, Kumudu; Mobley, James A.; Assimos, Dean G.; Holmes, Ross P.

    2016-01-01

    In humans approximately 60 mg of ascorbic acid (AA) breaks down in the body each day and has to be replaced by a dietary intake of 70 mg in females and 90 mg in males to maintain optimal health and AA homeostasis. The breakdown of AA is non-enzymatic and results in oxalate formation. The exact amount of oxalate formed has been difficult to ascertain primarily due to the limited availability of healthy human tissue for such research and the difficulty in measuring AA and its breakdown products. The breakdown of 60 mg of AA to oxalate could potentially result in the formation of up to 30 mg oxalate per day. This exceeds our estimates of the endogenous production of 10 – 25 mg oxalate per day, indicating that degradative pathways that do not form oxalate exist. In this review we examine what is known about the pathways of AA metabolism and how oxalate forms. We further identify how gaps in our knowledge may be filled to more precisely determine the contribution of AA breakdown to oxalate production in humans. The use of stable isotopes of AA to directly assess the conversion of vitamin to oxalate should help fill this void. PMID:27002809

  15. Whey protein/polysaccharide-stabilized emulsions: Effect of polymer type and pH on release and topical delivery of salicylic acid.

    PubMed

    Combrinck, Johann; Otto, Anja; du Plessis, Jeanetta

    2014-06-01

    Emulsions are widely used as topical formulations in the pharmaceutical and cosmetic industries. They are thermodynamically unstable and require emulsifiers for stabilization. Studies have indicated that emulsifiers could affect topical delivery of actives, and this study was therefore designed to investigate the effects of different polymers, applied as emulsifiers, as well as the effects of pH on the release and topical delivery of the active. O/w emulsions were prepared by the layer-by-layer technique, with whey protein forming the first layer around the oil droplets, while either chitosan or carrageenan was subsequently adsorbed to the protein at the interface. Additionally, the emulsions were prepared at three different pH values to introduce different charges to the polymers. The active ingredient, salicylic acid, was incorporated into the oil phase of the emulsions. Physical characterization of the resulting formulations, i.e., droplet size, zeta potential, stability, and turbidity in the water phase, was performed. Release studies were conducted, after which skin absorption studies were performed on the five most stable emulsions, by using Franz type diffusion cells and utilizing human, abdominal skin membranes. It was found that an increase in emulsion droplet charge could negatively affect the release of salicylic acid from these formulations. Contrary, positively charged emulsion droplets were found to enhance dermal and transdermal delivery of salicylic acid from emulsions. It was hypothesized that electrostatic complex formation between the emulsifier and salicylic acid could affect its release, whereas electrostatic interaction between the emulsion droplets and skin could influence dermal/transdermal delivery of the active.

  16. Influence of 4,4’-azobis (4-cyanopentanoic acid) in Transmission and Reflection Gratings Stored in a PVA/AA Photopolymer

    PubMed Central

    Fernandez, Elena; Fuentes, Rosa; Belendez, Augusto; Pascual, Inmaculada

    2016-01-01

    Holographic transmission gratings with a spatial frequency of 2658 lines/mm and reflection gratings with a spatial frequency of 4553 lines/mm were stored in a polyvinyl alcohol (PVA)/acrylamide (AA) based photopolymer. This material can reach diffraction efficiencies close to 100% for spatial frequencies about 1000 lines/mm. However, for higher spatial frequencies, the diffraction efficiency decreases considerably as the spatial frequency increases. To enhance the material response at high spatial frequencies, a chain transfer agent, the 4,4’-azobis (4-cyanopentanoic acid), ACPA, is added to the composition of the material. Different concentrations of ACPA are incorporated into the main composition of the photopolymer to find the concentration value that provides the highest diffraction efficiency. Moreover, the refractive index modulation and the optical thickness of the transmission and reflection gratings were obtained, evaluated and compared to procure more information about the influence of the ACPA on them. PMID:28773322

  17. Rheology as a Tool to Predict the Release of Alpha-Lipoic Acid from Emulsions Used for the Prevention of Skin Aging

    PubMed Central

    Isaac, Vera Lucia Borges; Chiari-Andréo, Bruna Galdorfini; Marto, Joana Marques; Moraes, Jemima Daniela Dias; Leone, Beatriz Alves; Corrêa, Marcos Antonio; Ribeiro, Helena Margarida

    2015-01-01

    The availability of an active substance through the skin depends basically on two consecutive steps: the release of this substance from the vehicle and its subsequent permeation through the skin. Hence, studies on the specific properties of vehicles, such as their rheological behavior, are of great interest in the field of dermatological products. Recent studies have shown the influence of the rheological features of a vehicle on the release of drugs and active compounds from the formulation. In this context, the aim of this study was to evaluate the influence of the rheological features of two different emulsion formulations on the release of alpha-lipoic acid. Alpha-lipoic acid (ALA) was chosen for this study because of its antioxidant characteristics, which could be useful for the prevention of skin diseases and aging. The rheological and mechanical behavior and the in vitro release profile were assayed. The results showed that rheological features, such as viscosity, thixotropy, and compliance, strongly influenced the release of ALA from the emulsion and that the presence of a hydrophilic polymer in one of the emulsions was an important factor affecting the rheology and, therefore, the release of ALA. PMID:26788510

  18. Rating AAs.

    ERIC Educational Resources Information Center

    Carter, Susan J.

    2001-01-01

    Why alternative investments? In a word: performance. Many higher education endowment and foundation managers are making increasing commitments to alternative investments, or AAs, in order to obtain higher returns and broader diversification for their investment portfolios than public securities instruments can usually provide. Learn how to handle…

  19. Role of cellular antioxidants (glutathione and ascorbic acid) in the growth and development of wild carrot suspension cultures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Earnshaw, B.A.

    1986-01-01

    Determinations of endogenous glutathione (GSH), glutathione disulfide (GSSG), ascorbic acid (AA) and dehydroascorbic acid (DHA) in proliferating and developing wild carrot cultures showed that lower levels of GSH and AA were associated with developing cultures. The GSSG and DHA levels did not account for the changes in the levels of antioxidants between proliferating and developing cultures. Studies were designed to test an observed auxin (2,4-Dichlorophenoxyacetic acid, 2,4-D)-antioxidant association. Two fractions (embryo and less developed) were obtained by screening developed cultures which were previously grown in the presence of /sup 14/C-2, 4-D. The embryo fraction had a lower concentration of /supmore » 14/C than the less developed fraction, supporting the association, since the two fractions showed this relationship with respect to GSH and AA concentrations. Determinations of GSH and AA levels of cells grown in various concentrations of 2,4-D showed the association, decreases in the 2,4-D concentration correlated with decreases in the GSH and AA concentrations. The existence of a respiratory pathway involving GSSG reductase, DHA reductase, and AA oxidase was investigated to test whether inhibition of AA oxidase by 2,4-D could explain the auxin-antioxidant association; however, AA oxidase activity was not detected.« less

  20. IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids.

    PubMed

    Chung, Si-Yin; Reed, Shawndrika

    2015-01-01

    The objective of this study was to determine if D-amino acids (D-aas) bind and inhibit immunoglobulin E (IgE) binding to peanut allergens. D-aas such as D-Asp (aspartic acid), D-Glu (glutamic acid), combined D-[Asp/Glu] and others were each prepared in a cocktail of 9 other D-aas, along with L-amino acids (L-aas) and controls. Each sample was mixed with a pooled plasma from peanut-allergic donors, and tested by ELISA (enzyme-linked immunosorbent assay) and Western blots for IgE binding to peanut allergens. Results showed that D-[Asp/Glu] (4 mg/ml) inhibited IgE binding (75%) while D-Glu, D-Asp and other D-aas had no inhibitory effect. A higher inhibition was seen with D-[Asp/Glu] than with L-[Asp/Glu]. We concluded that IgE was specific for D-[Asp/Glu], not D-Asp or D-Glu, and that D-[Asp/Glu] was more reactive than was L-[Asp/Glu] in IgE inhibition. The finding indicates that D-[Asp/Glu] may have the potential for removing IgE or reducing IgE binding to peanut allergens in vitro. Published by Elsevier Ltd.

  1. Simulating the Fate and Transport of an Acid Mine Drainage Release Using the WASP model

    NASA Astrophysics Data System (ADS)

    Knightes, C. D.; Kate, S.; Avant, B. K.; Cyterski, M.; Washington, J.; Prieto, L.

    2016-12-01

    On August 5, 2015, approximately 3 million gallons of acid mine drainage were released from the Gold King Mine into Cement Creek in the San Juan River watershed (CO, NM, UT). The release further mobilized additional metals, which resulted in a large mass of solids and dissolved metals entering Cement Creek. These metals were released into the Animas River. As the release acidity was neutralized, the metals precipitated and formed the visually noticeable "yellow boy," which flowed down the San Juan River. We applied the Water Quality Analysis Simulation Program (WASP) using empirically based parameterization to simulate and describe the movement of the plume and total and dissolved concentrations of all metals, including Arsenic, Copper, Lead, and Zinc. We estimated that the plume took between approximately 1 to 3 days to pass any given location. The peak concentration of the plume took about 2 hours to reach Silverton, CO (16 rkm), 1.5 days to reach Durango, CO (94 rkm), 2.9 days to reach Farmington, NM, (190 rkm) and 5.8 days to reach Mexican Hat, UT (422 km). Total metal concentration decreased rapidly going downstream, dropping 80% upon entering the Animas at Silverton, CO, and 99.5% entering the San Juan at Farmington. Metal concentrations decreased by dilution, settling, and dispersion. Modeling suggests that deposition occurred primarily in the upper Animas River near Silverton and near Durango, which was supported with empirical evidence. This work demonstrates the utility of a combined empirical and mechanistic modeling analysis. We additionally investigate long-term residual effects and potential exposure concentrations during storm and snowmelt high flow periods after the visible plume had traversed the system.

  2. Metabolizable energy values and amino acid availability of vetch (Vicia sativa) and ervil (Vicia ervilia) seeds soaked in water and acetic acid.

    PubMed

    Farran, M T; Barbour, G W; Uwayjan, M G; Ashkarian, V M

    2001-07-01

    In two experiments we evaluated the effect of water and acetic acid soaking on ME, apparent amino acid (AA) availability, and true AA availability of vetch (V) and ervil (E) seeds. In Experiment 1, the feedstuffs were untreated (U) V or coarsely ground V soaked in water (1:10, wt/vol) at 40 C for 72 h with a water change every 12 h (40WV), vetch soaked in 1% acetic acid for 24 h at 40 C (40AAV) or at room temperature (RTAAV), or dehulled soybean meal (SBM). In Experiment 2, E seeds were subjected to the same soaking methods, and the ingredients were UE, 40WE, 40AAE, RTAAE, and SBM. Each feedstuff was precision-fed to five individually caged mature ISA Brown roosters. A group of five roosters was used to correct for metabolic and endogenous energy and amino acid losses. The AME, AMEn, TME, and TMEn of UV and UE (in parentheses) were 2,558 (2,663), 2,840 (3,098), 3,026 (3,154), and 2,934 (3,176) kcal/kg DM, respectively, and were, in general, higher than those of SBM. The TMEn of V increased as a result of soaking in water or acetic acid, whereas that of E decreased in 40WE and RTAAE by 492 and 920 kcal/kg DM, respectively (P < 0.05). The apparent availability of most essential amino acids in UV and UE was lower (P < 0.05) than that of SBM. Acetic acid soaking of V, irrespective of temperature, and E at 40 C resulted in apparent AA availability similar to that of SBM except for Met. The true AA availability of V treated or not, and that of E soaked at 40 C, were similar to that of SBM. Results indicated that UV and UE are energy rich ingredients but detrimental to amino acid availability. Soaking the seeds in acetic acid at room temperature and at 40 C improved the nutritional value of V and E, respectively.

  3. Determinants of urea nitrogen production in sepsis. Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids.

    PubMed

    Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Placko, R

    1989-03-01

    The major determinants of urea production were investigated in 26 patients with multiple trauma (300 studies). The body clearances (CLRs) of ten amino acids (AAs) were estimated as a ratio of muscle-released AAs plus total parenteral nutrition-infused AAs to their extracellular pool. While clinically septic trauma (ST) patients without multiple-organ failure syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/- 13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/- 7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per day), in all groups urea N production was found to be a function of muscle protein degradation (catabolism), total parenteral nutrition-administered AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P less than .0001). Since tyrosine is cleared almost exclusively by the liver, the L/T ratio may be regarded as an index of hepatic function. The significant differences between urea N production in ST and NST patients lay in an increased positive dependence on muscle catabolism and increased negative correlation with L/T in the ST group. At any L/T ratio, urea N production was increased in ST patients over NST patients, but in ST patients with MOFS, it fell to or below levels of NST patients. These data show that the ST process is associated with enhancement of ureagenesis, due to increased hepatic CLR of both exogenous and endogenous AAs. In sepsis with MOFS, a marked inhibition of urea synthesis occurs, partially explained by a decreased hepatic CLR of non-branched-chain AAs.

  4. The Effect of Ascorbic Acid and Garlic Administration on Lead-Induced Neural Damage in Rat Offspring's Hippocampus.

    PubMed

    Sadeghi, Akram; Ebrahimzadeh Bideskan, Alireza; Alipour, Fatemeh; Fazel, Alireza; Haghir, Hossein

    2013-02-01

    The aim of this study was to investigate ascorbic acid and garlic protective effects on lead-induced neurotoxicity during rat hippocampus development. 90 pregnant wistar rats were divided randomly into nine groups: 1- Animals received leaded water (L). 2- Rats received leaded water and ascorbic acid (L+AA). 3- Animals received leaded water and garlic juice (L+G). 4-Animals received leaded water, ascorbic acid and garlic juice (L+G+AA). 5- Rats treated with ascorbic acid (AA). 6- Rats treated with garlic juice (G). 7- Rats treated with ascorbic acid and garlic juice (AA+G). 8- Rats treated with tap water plus 0.4 ml/l normal hydrogen chloride (HCl) and 0.5 mg/l Glucose (Sham). 9- Normal group (N). Leaded water (1500 ppm), garlic juice (1 ml/100g/day, gavage) and ascorbic acid (500 mg/kg/day, IP) were used. Finally, blood lead levels (BLL) were measured in both rats and their offspring. The rat offspring brain sections were stained using Toluidine Blue and photographed. Dark neurons (DNs) were counted to compare all groups. BLL significantly increased in L group compared to control and sham groups and decreased in L+G and L+AA groups in comparison to the L group (P<0.05). the number of DNs in the CA1, CA3, and DG of rat offspring hippocampus significantly increased in L group in comparison to control and sham groups (P<0.05) and decreased in L+G and L+AA groups compared to L group (P<0.05). Garlic juice and ascorbic acid administration during pregnancy and lactation may protect lead-induced neural damage in rat offspring hippocampus.

  5. Oxalic acid pretreatment of rice straw particles and loblolly pine chips : release of hemicellulosic carbohydrates

    Treesearch

    Xianjun Li; Zhiyong Cai; Eric Horn; Jerrold E. Winandy

    2011-01-01

    This study was conducted to evaluate the effect of oxalic acid (OA) pretreatment on carbohydrates released from rice straw particles and wood chips. The results showed that OA treatment accelerated carbohydrates extraction from rice straw particles and wood chips. OA pretreatment dramatically increased the amount of carbohydrates extracted, up to 24 times for wood...

  6. ASCORBID ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

    EPA Science Inventory

    ABSTRACT
    Evidence suggests that the antioxidant ascorbic acid (AA), plays an essential role in defending against oxidant attack in the airways. Decreased levels of AA have been reported in asthmatics but not at the site directly proximal to asthma pathology, i.e. the bronchial...

  7. Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey.

    PubMed

    Weininger, J; King, J C

    1982-06-01

    Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.

  8. Controlled release of linalool using nanofibrous membranes of poly(lactic acid) obtained by electrospinning and solution blow spinning: A comparative study

    USDA-ARS?s Scientific Manuscript database

    The controlled-release of natural plant oils such as linalool is of interest in therapeutics, cosmetics, and antimicrobial and larvicidal products. The present study reports the release characteristics of linalool encapsulated at three concentrations (10, 15 and 20 wt.%) in poly(lactic acid) nanofib...

  9. Developmental toxicity of Japanese medaka embryos by silver nanoparticles and released ions in the presence of humic acid.

    PubMed

    Kim, Jun Y; Kim, Ki-Tae; Lee, Byeong G; Lim, Byung J; Kim, Sang D

    2013-06-01

    The final destination point of nanoparticles is the environment, where they remain a long period; therefore, a deep understanding of the relationship between nanoparticles and the environmental factors is required. Japanese medaka embryos were exposed to two differently prepared AgNPs: freshly prepared AgNPs and aged AgNPs. With these two AgNP preparations, we studied the impacts of humic acid in terms of embryonic toxicity, as well as the behavior of AgNPs. Aged AgNPs exhibited a lower lethal concentration (LC50) value (1.44mg/L) compared to fresh AgNPs (3.53mg/L) through 96h acute toxicity tests, due to the release of silver ions, as confirmed by kinetic analysis. The presence of humic acids considerably reduced the toxicity of aged AgNPs due to complexation with silver ions. Agglomeration, induced by interactions with humic acid, might reduce the bioavailability of AgNPs to Japanese medaka embryos. This study demonstrates that aged AgNPs releasing more silver ions are more toxic than fresh AgNPs, and humic acids play a role in reducing the toxicity of aged AgNPs. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. 7 CFR 51.596 - U.S. Grade AA.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false U.S. Grade AA. 51.596 Section 51.596 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Consumer Standards for Celery Stalks Grades § 51.596 U.S. Grade AA. U.S. Grade AA shall consist of stalks...

  11. 7 CFR 51.596 - U.S. Grade AA.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false U.S. Grade AA. 51.596 Section 51.596 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Consumer Standards for Celery Stalks Grades § 51.596 U.S. Grade AA. U.S. Grade AA shall consist of stalks...

  12. Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults.

    PubMed

    Seah, Jowy Yi Hoong; Gay, Gibson Ming Wei; Su, Jin; Tai, E-Shyong; Yuan, Jian-Min; Koh, Woon-Puay; Ong, Choon Nam; van Dam, Rob M

    2017-01-31

    High arachidonic acid (AA; 20:4 n - 6) status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n - 6 polyunsaturated fatty acids (PUFAs) are based on the premise that endogenous conversion from linoleic acid (LA; 18:2 n - 6) is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25-80 years old) with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44-74 years old) from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy) and food sources of PUFA (fish, red meat, poultry, soy and cooking oils) in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3 n - 6), alpha-linolenic acid (ALA; 18:3 n - 3), eicosapentaenoic acid (EPA; 20:5 n - 3), and docosahexaenoic acid (DHA; 22:6 n - 3)) concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05) in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population.

  13. Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults

    PubMed Central

    Seah, Jowy Yi Hoong; Gay, Gibson Ming Wei; Su, Jin; Tai, E-Shyong; Yuan, Jian-Min; Koh, Woon-Puay; Ong, Choon Nam; van Dam, Rob M.

    2017-01-01

    High arachidonic acid (AA; 20:4n-6) status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n-6 polyunsaturated fatty acids (PUFAs) are based on the premise that endogenous conversion from linoleic acid (LA; 18:2n-6) is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25–80 years old) with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44–74 years old) from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy) and food sources of PUFA (fish, red meat, poultry, soy and cooking oils) in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3n-6), alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), and docosahexaenoic acid (DHA; 22:6n-3)) concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05) in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population. PMID:28146136

  14. An electrochemical sensor for simultaneous determination of ascorbic acid, dopamine, uric acid and tryptophan based on MWNTs bridged mesocellular graphene foam nanocomposite.

    PubMed

    Li, Huixiang; Wang, Yi; Ye, Daixin; Luo, Juan; Su, Biquan; Zhang, Song; Kong, Jilie

    2014-09-01

    A multi-walled carbon nanotubes (MWNTs) bridged mesocellular graphene foam (MGF) nanocomposite (MWNTs/MGF) modified glassy carbon electrode was fabricated and successfully used for simultaneous determination of ascorbic acid (AA), dopamine (DA), uric acid (UA) and tryptophan (TRP). Comparing with pure MGF, MWNTs or MWNTs/GS (graphene sheets), MWNTs/MGF displayed higher catalytic activity and selectivity toward the oxidation of AA, DA, UA and TRP. Under the optimal conditions, MWCNs/MGF/GCE can simultaneously detect AA, DA, UA and TRP with high selectivity and sensitivity. The detection limits were 18.28 µmol L(-1), 0.06 µmol L(-1), 0.93 µmol L(-1) and 0.87 µmol L(-1), respectively. Moreover, the modified electrode exhibited excellent stability and reproducibility. Copyright © 2014. Published by Elsevier B.V.

  15. Prostaglandin F2 alpha and its analogs induce release of endogenous prostaglandins in iris and ciliary muscles isolated from cat and other mammalian species.

    PubMed

    Yousufzai, S Y; Ye, Z; Abdel-Latif, A A

    1996-09-01

    Prostaglandin F2 alpha (PGF 2 alpha) and its analog latanoprost are effective in lowering intraocular pressure (IOP) in both animal and human subjects. There is mounting experimental evidence now which indicates that the IOP-lowering effect of these PGs occurs through an increased uveoscleral outflow of aqueous humor. The ciliary muscle constitutes the main resistance in this pathway. Work from several laboratories, including our own, has shown that in this smooth muscle PGF 2 alpha has little effect on cAMP accumulation or on Ca2+ mobilization. In the present study, we hypothesized that some of the effects of PGF2 alpha and its analogs may be mediated through the release of endogenous PGs. The purpose of this work was to determine whether or not PGF2 alpha and its analogs can enhance the release of endogenous PGs in iris and ciliary muscles isolated from different species. This report documents for the first time that exogenous PGF2 alpha and its analogs, PhXA85 and latanoprost, stimulate the formation of PGE2, PGD2 and PGF2 alpha in iris and ciliary muscles isolated from cat, bovine, rabbit, dog, rhesus monkey and human. PG-induced PG release was demonstrated by means of both radioimmunoassay and radiochromatography. Kinetic studies on cat iris revealed that PGF2 alpha-induced PGE2 release is time (t 1/2 = 1.7 min) and dose-dependent (EC50 = 45 nM). The increase in PGE2 release was blocked by indomethacin (Indo) and by dexamethasone in a dose-dependent manner with IC50 s of 9.2 nM and 2.6 microM, respectively. Furthermore, dexamethasone inhibited arachidonic acid (AA) release, suggesting the involvement of phospholipase A2 in PGF2 alpha-induced PG release. The data presented demonstrate that PGF2 alpha and its analogs interact with the PG receptor to stimulate phospholipase A2 and release AA for PG synthesis. Relaxation of ciliary muscle by PGF2 alpha and its analogs, via release of endogenous PGE2, a potent activator of the adenylate cyclase system, could in

  16. Sensitive electrochemical sensors for simultaneous determination of ascorbic acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide nanocomposites.

    PubMed

    Jiang, Jingjing; Du, Xuezhong

    2014-10-07

    Sensitive electrochemical sensors were fabricated with reduced graphene oxide-supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd-RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 μM with detection limits of 0.02, 0.002, and 0.005 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 μM with detection limits of 0.28, 0.024, and 0.02 μM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing.

  17. Maternal nutritional determinants of colostrum fatty acids in the EDEN mother-child cohort.

    PubMed

    Armand, Martine; Bernard, Jonathan Y; Forhan, Anne; Heude, Barbara; Charles, Marie-Aline

    2017-10-21

    Programming of infant development and later health may depend on early-milk polyunsaturated fatty acids (PUFA) contents, that are very variable between women for reasons not well elucidated. Indeed, a high n-6/n-3 PUFA in milk was associated with higher adiposity, arterial pressure and lower psychomotor scores in childhood. We aimed to explore the respective contribution of several maternal and perinatal factors to the variability of linoleic (LA), α-linolenic (ALA), arachidonic (AA), and docosahexaenoic (DHA) acid levels in early milk. Fatty acids of 934 colostrum samples from the EDEN mother-child cohort were analyzed by gas chromatography. The dietary intakes during the last trimester of pregnancy were estimated using a quantitative food frequency questionnaire. Relationship between milk PUFA and dietary fatty acids, and other maternal or pregnancy variables were analyzed by multiple linear regression. The means (±SD) of colostrum LA, ALA, AA and DHA levels were, respectively, 9.85 ± 1.85, 0.65 ± 0.22, 0.86 ± 0.16, and 0.64 ± 0.19% of total fatty acids. Obese mothers colostrum contained the highest level of LA and AA and the lowest level of ALA and DHA. Colostrum LA, AA and DHA levels were higher in primiparous women. Mother's age was positively associated with colostrum AA and DHA. Dietary n-6 PUFA were associated with higher LA and lower DHA levels in colostrum, while dietary n-3 PUFA were related to higher LA and lower AA levels. Contrary to what was observed for DHA, AA level in colostrum was not related to its dietary intake. High dietary AA/DHA and total n-6/n-3 ratios were critical for the content of DHA in colostrum lipids. Our study brings new insights in the understanding of the main maternal factors involved in PUFA levels variability in early milk. These data are important to consider for dietary counseling for women prior to and during pregnancy. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

  18. Metabolism of uniformly labeled 13C-eicosapentaenoic acid and 13C-arachidonic acid in young and old men.

    PubMed

    Léveillé, Pauline; Chouinard-Watkins, Raphaël; Windust, Anthony; Lawrence, Peter; Cunnane, Stephen C; Brenna, J Thomas; Plourde, Mélanie

    2017-08-01

    Background: Plasma eicosapentaenoic acid (EPA) and arachidonic acid (AA) concentrations increase with age. Objective: The aim of this study was to evaluate EPA and AA metabolism in young and old men by using uniformly labeled carbon-13 ( 13 C) fatty acids. Design: Six young (∼25 y old) and 6 old (∼75 y old) healthy men were recruited. Each participant consumed a single oral dose of 35 mg 13 C-EPA and its metabolism was followed in the course of 14 d in the plasma and 28 d in the breath. After the washout period of ≥28 d, the same participants consumed a single oral dose of 50 mg 13 C-AA and its metabolism was followed for 28 d in plasma and breath. Results: There was a time × age interaction for 13 C-EPA ( P time × age = 0.008), and the shape of the postprandial curves was different between young and old men. The 13 C-EPA plasma half-life was ∼2 d for both young and old men ( P = 0.485). The percentage dose recovered of 13 C-EPA per hour as 13 CO 2 and the cumulative β-oxidation of 13 C-EPA did not differ between young and old men. At 7 d, however, old men had a >2.2-fold higher plasma 13 C-DHA concentration synthesized from 13 C-EPA compared with young men ( P age = 0.03). 13 C-AA metabolism was not different between young and old men. The 13 C-AA plasma half-life was ∼4.4 d in both young and old participants ( P = 0.589). Conclusions: The metabolism of 13 C-AA was not modified by age, whereas 13 C-EPA metabolism was slightly but significantly different in old compared with young men. The higher plasma 13 C-DHA seen in old men may be a result of slower plasma DHA clearance with age. This trial was registered at clinicaltrials.gov as NCT02957188. © 2017 American Society for Nutrition.

  19. 7 CFR 51.596 - U.S. Grade AA.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false U.S. Grade AA. 51.596 Section 51.596 Agriculture..., CERTIFICATION, AND STANDARDS) United States Consumer Standards for Celery Stalks Grades § 51.596 U.S. Grade AA. U.S. Grade AA shall consist of stalks of celery of similar varietal characteristics, which are well...

  20. 7 CFR 51.596 - U.S. Grade AA.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false U.S. Grade AA. 51.596 Section 51.596 Agriculture..., CERTIFICATION, AND STANDARDS) United States Consumer Standards for Celery Stalks Grades § 51.596 U.S. Grade AA. U.S. Grade AA shall consist of stalks of celery of similar varietal characteristics, which are well...

  1. High-efficiency extracellular release of free fatty acids from Aspergillus oryzae using non-ionic surfactants.

    PubMed

    Tamano, Koichi; Miura, Ai; Koike, Hideaki; Kamisaka, Yasushi; Umemura, Myco; Machida, Masayuki

    2017-04-20

    Free fatty acids (FFAs) are useful for generating biofuel compounds and functional lipids. Microbes are increasingly exploited to produce FFAs via metabolic engineering. However, in many microorganisms, FFAs accumulate in the cytosol, and disrupting cells to extract them is energy intensive. Thus, a simple cost-effective extraction technique must be developed to remove this drawback. We found that FFAs were released from cells of the filamentous fungus Aspergillus oryzae with high efficiency when they were cultured or incubated with non-ionic surfactants such as Triton X-100. The surfactants did not reduce hyphal growth, even at 5% (w/v). When the faaA disruptant was cultured with 1% Triton X-100, more than 80% of the FFAs synthesized de novo were released. When the disruptant cells grown without surfactants were incubated for 1h in 1% Triton X-100 solution, more than 50% of the FFAs synthesized de novo were also released. Other non-ionic surfactants in the same ether series, such as Brij 58, IGEPAL CA-630, and Tergitol NP-40, elicited a similar FFA release. The dry cell weight of total hyphae decreased when grown with 1% Triton X-100. The decrement was 4.9-fold greater than the weight of the released FFAs, implying release of other intracellular compounds. Analysis of the culture supernatant showed that intracellular lactate dehydrogenase was also released, suggesting that FFAs are not released by a specific transporter. Therefore, ether-type non-ionic surfactants probably cause non-specific release of FFAs and other intracellular compounds by increasing cell membrane permeability. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Absence of a Causal Relationship between Auxin-Induced Growth and Changes in the Content of Ascorbic and Dehydroascorbic Acids in Excised Plant Tissues 12

    PubMed Central

    Lin, C. Y.; Key, Joe L.

    1967-01-01

    The data reported indicate that the oxidation-reduction balance of the ascorbic acid system is not causally related to the auxin-regulation of cell elongation. There was no shift in the ascorbic acid (AA) to dehydroascorbic acid (DHA) ratio with growth-promoting concentration of auxin in several plant tissues. The AA to DHA ratio was experimentally increased without altering the growth rate. Inhibition of growth by supra-optimal auxin was associated with a decrease in the AA to DHA ratio. Since the AA to DHA ratio was lowered by EDTA treatment without altering growth, it seems unlikely that the decrease in the AA to DHA ratio related to the inhibition of growth by high levels of auxin. PMID:16656564

  3. Determination and stereochemistry of proteinogenic and non-proteinogenic amino acids in Saudi Arabian date fruits.

    PubMed

    Ali, Hatem Salama Mohamed; Alhaj, Omar Amin; Al-Khalifa, Abdulrahman Saleh; Brückner, Hans

    2014-09-01

    Whereas an abundance of literature is available on the occurrence of common proteinogenic amino acids (AAs) in edible fruits of the date palm (Phoenix dactylifera L.), recent reports on non-proteinogenic (non-coded) AAs and amino components are scarce. With emphasis on these components we have analyzed total hydrolysates of twelve cultivars of date fruits using automated ion-exchange chromatography, HPLC employing a fluorescent aminoquinolyl label, and GC-MS of total hydrolysates using the chiral stationary phases Chirasil(®)-L-Val and Lipodex(®) E. Besides common proteinogenic AAs, relatively large amounts of the following non-proteinogenic amino acids were detected: (2S,5R)-5-hydroxypipecolic acid (1.4-4.0 g/kg dry matter, DM), 1-aminocyclopropane-1-carboxylic acid (1.3-2.6 g/kg DM), γ-amino-n-butyric acid (0.5-1.2 g/kg DM), (2S,4R)-4-hydroxyproline (130-230 mg/kg DM), L-pipecolic acid (40-140 mg/kg DM), and 2-aminoethanol (40-160 mg/kg DM) as well as low or trace amounts (<70 mg/kg DM) of L-ornithine, 5-hydroxylysine, β-alanine, and in some samples (<20 mg/kg DM) of (S)-β-aminoisobutyric acid and (<10 mg/kg DM) L-allo-isoleucine. In one date fruit, traces of α-aminoadipic acid could be determined. Enantiomeric analysis of 6 M DCl/D2O hydrolysates of AAs using chiral capillary gas chromatography-mass spectrometry revealed the presence of very low amounts of D-Ala, D-Asp, D-Glu, D-Ser and D-Phe (1.2-0.4%, relative to the corresponding L-enantiomers), besides traces (0.2-1%) of other D-AAs. The possible relevance of non-proteinogenic amino acids in date fruits is briefly addressed.

  4. A Novel Concept of Amino Acid Supplementation to Improve the Growth of Young Malnourished Male Rats.

    PubMed

    Furuta, Chie; Murakami, Hitoshi

    2018-01-01

    This study was aimed at understanding the relationship between plasma amino acids and protein malnutrition and at determining whether amino acid supplementation associated with malnutrition and growth improves linear growth in growing rats. Body length and plasma amino acids were measured in young male rats that were fed the following diet for 3 weeks, mimicking a low and imbalanced protein diets based on maize, a major staple consumed in developing countries: a 70% calorically restricted cornmeal-based diet (C), C + micronutrients (CM), CM + casein (CMC), CM + soy protein (CMS) or CMS + 0.3% lysine. A correlation analysis of linear growth and plasma amino acids indicated that lysine, tryptophan, branched-chain amino acids, methionine, and phenylalanine significantly correlated with body length. Supplementation with these 5 amino acids (AA1) significantly improved the body length in rats compared to CMC treatment whereas, nitrogen-balanced amino acid supplemented controls (AA2) did not (CM +1.2 ± 0.2, CMC +2.7 ± 0.3, CMS +2.1 ± 0.3, AA1 +2.8 ± 0.2, and AA2 +2.5 ± 0.3 cm). With securing proper amino acid balance, supplementing growth-related amino acids is more effective in improving linear growth in malnourished growing male rats. Analysis of the correlation between plasma amino acids and growth represents a powerful tool to determine candidate amino acids for supplementation to prevent malnutrition. This technology is adaptable to children in developing countries. © 2018 S. Karger AG, Basel.

  5. Amino acid specific stable nitrogen isotope values in avian tissues: Insights from captive American kestrels and wild herring gulls

    USGS Publications Warehouse

    Hebert, Craig E.; Popp, B.N.; Fernie, K.J.; Ka'apu-Lyons, C.; Rattner, Barnett A.; Wallsgrove, N.

    2016-01-01

    Through laboratory and field studies, the utility of amino acid compound-specific nitrogen isotope analysis (AA-CSIA) in avian studies is investigated. Captive American kestrels (Falco sparverius) were fed an isotopically characterized diet and patterns in δ15N values of amino acids (AAs) were compared to those in their tissues (muscle and red blood cells) and food. Based upon nitrogen isotope discrimination between diet and kestrel tissues, AAs could mostly be categorized as source AAs (retaining baseline δ15N values) and trophic AAs (showing 15N enrichment). Trophic discrimination factors based upon the source (phenylalanine, Phe) and trophic (glutamic acid, Glu) AAs were 4.1 (muscle) and 5.4 (red blood cells), lower than those reported for metazoan invertebrates. In a field study involving omnivorous herring gulls (Larus argentatus smithsonianus), egg AA isotopic patterns largely retained those observed in the laying female’s tissues (muscle, red blood cells, and liver). Realistic estimates of gull trophic position were obtained using bird Glu and Phe δ15N values combined with β values (difference in Glu and Phe δ15N in primary producers) for aquatic and terrestrial food webs. Egg fatty acids were used to weight β values for proportions of aquatic and terrestrial food in gull diets. This novel approach can be applied to generalist species that feed across ecosystem boundaries.

  6. Differential effects of eicosapentaenoic acid and docosahexaenoic acid on human skin fibroblasts.

    PubMed

    Brown, E R; Subbaiah, P V

    1994-12-01

    To better understand the mode of action of omega 3 fatty acids in cell membranes, human foreskin fibroblasts were grown in serum-free medium supplemented with 50 microM oleic acid linoleic acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), and the effects on membrane composition, fluorescence polarization and enzyme activities were followed. The cells were enriched with EPA and DHA up to 7 and 13% of total lipids, respectively, of which > 95% was associated with phospholipids. In addition, the concentration of 22:5n-3 increased with both EPA and DHA to 7.5, and 2.1% of the total fatty acids, respectively. When compared to controls (oleic acid), cells treated with DHA showed a decrease in cholesterol, phospholipids, arachidonic acid (AA) and free cholesterol/phospholipid ratio (P < 0.05). In the presence of EPA, only decreases in AA and cholesterol were significant (P < 0.05). Membrane fluidity, assessed by fluorescence anisotropy, was increased 16% in cells enriched with DHA (P < 0.05), but showed no change with EPA or linoleic acid. There was an increase in membrane-associated 5'-nucleotidase (+27%) and adenylate cyclase (+19%) activities (P < 0.05), in DHA-enriched, but not in EPA-enriched cells, when compared with oleate controls. The studies show that incorporation of DHA, but not EPA, into cell membranes of fibroblasts alters membrane biophysical characteristics and function. We suggest that these two major n-3 fatty acids of fish oils have differential effects on cell membranes, and this may be related to the known differences in their physiological effects.

  7. Oxidation of formic acid by oxyanions of chlorine and its implications to the Viking Labeled Release experiment

    NASA Astrophysics Data System (ADS)

    Martinez, P.; Navarro-gonzalez, R.

    2013-05-01

    The Viking Landers that arrived on Mars in 1976 carried out three biological experiments designed to investigate if there was microbial life. These were the Gas-Exchange, Pyrolitic Release and Labeled Release experiments. The three experiments yielded positive responses but the Labeled Release experiment had a kinetic response indicative of microbial activity. The experiment consisted of adding a broth of nutrients (formic acid, glycolic acid, glycine, D- and L-alanine and D- and L-lactic acid uniformly marked with 14C) to martian soil samples. The results were surprising; the nutrients were consumed releasing radioactive gases in a manner that is compatible by terrestrial microorganisms. The existence of Martian life was contradicted by soil chemical analysis that indicated the absence of organic compounds above the detection limits of parts per billion (ppb). Instead the positive response of the Labeled Release Experiment was attributed to the existence of peroxides and/or superoxides in the Martian soils that destroyed the nutrients upon contact. Recently, the Phoenix mission that landed in the Martian Arctic in 2008 revealed the presence of a highly oxidized form of the element chlorine in the soil: perchlorate. Perchlorate is thought to have formed in the Martian atmosphere by the oxidation of chloride from volcanic sources with ozone. Therefore perchlorate is formed by the stepwise oxidation of hypochlorite, chlorite and chlorate. These oxyanions of chlorine are powerful oxidizers that may exist in the Martian soil and may have reacted with the nutrients of the Labeled Release Experiment. This paper aims to better understand these results by designing experiments to determine the kinetics of decomposition of formic acid to carbon dioxide with different oxidized forms of chlorine by headspace technique in gas chromatography coupled to mass spectrometry (GC / MS). Previous studies done in the laboratory showed that only hypochlorite quantitatively reacted with

  8. [An experimental study on a slow-release complex with rifampicin-polylactic-co-glycolic acid-calcium 
phosphate cement].

    PubMed

    Wu, Jianhuang; Ding, Zhou; Lei, Qing; Li, Miao; Liang, Yan; Lu, Tao

    2016-09-28

    To prepare the slow-release complex with rifampicin (RFP)-polylactic-co-glycolic acid (PLGA)-calcium phosphate cement (CPC) (RFP-PLGA-CPC complex), and to study its physical and chemical properties and drug release properties in vitro.
 The emulsification-solvent evaporation method was adopted to prepare rifampicin polylactic acid-glycolic acid (RFP-PLGA) slow-release microspheres, which were divided into 3 groups: a calcium phosphate bone cement group (CPC group), a CPC embedded with RFP group (RFP-CPC group), and a PLGA slow-release microspheres carrying RFP and the self-curing CPC group (RFP- PLGA-CPC complex group). The solidification time and porosity of materials were determined. The drug release experiments in vitro were carried out to observe the compressive strength, the change of section morphology before and after drug release. 
 The CPC group showed the shortest solidification time, while the RFP-PLGA-CPC complex group had the longest one. There was statistical difference in the porosity between the CPC group and the RFP-CPC group (P<0.05); Compared to the RFP-PLGA-CPC complex group, the porosity in the CPC group and the RFP-CPC group were significantly changed (both P<0.01). There was significant difference in the compressive strength between the RFP- PLGA-CPC complex group and the CPC group (P<0.01), while there was significant difference in the compressive strength between the RFP-CPC group and the CPC group (3 days: P<0.05; 30 and 60 days: P<0.01). The change of the compressive strength in the CPC was not significant in the whole process of degradation. The sizes of PLGA microspheres were uniform, with the particle size between 100-150 μm. The microspheres were spheres or spheroids, and their surface was smooth without the attached impurities. There was no significant change in the section gap in the CPC group after soaking for 3 to 60 days. The microstructure change in the RFP-CPC group was small, and the cross section was formed by small

  9. Modulating the gut flora alters amino acid metabolism in neonatal pigs

    USDA-ARS?s Scientific Manuscript database

    Intestinal microbes consume and produce amino acids (AA). This may impact intestinal threonine (THR) metabolism necessary for adequate gut function. We hypothesized that modulating the gut flora results in an alteration of intestinal THR utilization and hence whole body AA metabolism. Neonatal pigs ...

  10. Raman spectroscopy and capillary zone electrophoresis for the analysis of degradation processes in commercial effervescent tablets containing acetylsalicylic acid and ascorbic acid.

    PubMed

    Neuberger, Sabine; Jooß, Kevin; Flottmann, Dirk; Scriba, Gerhard; Neusüß, Christian

    2017-02-05

    In order to ensure the stability of pharmaceutical products appropriate manufacturing and storage conditions are required. In general, the degradation of active pharmaceutical ingredients (APIs) and subsequent formation of degradation products affect the pharmaceutical quality. Thus, a fast and effective detection and characterization of these substances is mandatory. Here, the applicability of Raman spectroscopy and CZE for the characterization of the degradation of effervescent tablets containing acetylsalicylic acid (ASA) and ascorbic acid (AA) was evaluated. Therefore, a degradation study was performed analyzing tablets from two different manufacturers at varying conditions (relative humidity (RH) 33%, 52% and 75% at 30°C). Raman spectroscopy combined with principal component analysis could be successfully applied for the fast and easy discrimination of non-degraded and degraded effervescent tablets after a storage period of approximately 24h (RH 52%). Nevertheless, a clear identification or quantification of APIs and degradation products within the analyzed tablets was not possible, i.a. due to missing reference materials. CZE-UV enabled the quantification of the APIs (ASA, AA) and related degradation products (salicylic acid (SA); semi-quantitative also mono- and diacetylated AA) within the complex tablet mixtures. The higher the RH, the faster the degradation of ASA and AA as well as the formation of the degradation products. Mono- and diacetylated AA are major primary degradation products of AA for the applied effervescent tablets. A significant degradation of the APIs was detected earlier by CZE (6-12h, RH 52%) than by Raman spectroscopy. Summarized, Raman spectroscopy is well-suited as quick test to detect degradation of these tablets and CZE can be utilized for further detailed characterization and quantification of specific APIs and related degradation products. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Degradation kinetics of the antioxidant additive ascorbic acid in packed table olives during storage at different temperatures.

    PubMed

    Montaño, A; Casado, F J; Rejano, L; Sanchez, A H; de Castro, A

    2006-03-22

    The kinetics of ascorbic acid (AA) loss during storage of packed table olives with two different levels of added AA was investigated. Three selected storage temperatures were assayed: 10 degrees C, ambient (20-24 degrees C), and 40 degrees C. The study was carried out in both pasteurized and unpasteurized product. The effect of pasteurization treatment alone on added AA was not significant. In the pasteurized product, in general AA degraded following a first-order kinetics. The activation energy calculated by using the Arrhenius model averaged 9 kcal/mol. For each storage temperature, the increase in initial AA concentration significantly decreased the AA degradation rate. In the unpasteurized product, AA was not detected after 20 days in samples stored at room temperature and AA degradation followed zero-order kinetics at 10 degrees C, whereas at 40 degrees C a second-order reaction showed the best fit. In both pasteurized and unpasteurized product, the low level of initial dehydroascorbic acid disappeared during storage. Furfural appeared to be formed during storage, mainly at 40 degrees C, following zero-order kinetics.

  12. The use of poly(methacrylic acid) nanogel to control the release of amoxycillin with lower cytotoxicity.

    PubMed

    Liu, Tao; Liu, Hongxi; Wu, Zhimin; Chen, Tao; Zhou, Lin; Liang, Yuanyuan; Ke, Bo; Huang, Hongxing; Jiang, Zhenyou; Xie, Mingqiang; Wu, Ting

    2014-10-01

    In order to control the release of amoxycillin (AM) with lower cytotoxicity and higher activity, ethylene glycol dimethacrylate was used as the cross-linker, and a series of poly(methacrylic acid) (PMAA) nanogels were prepared to load the AM. Then, the morphology, size, in vitro release property, long-term antibacterial performance, cytotoxicity, stability and activity of this novel AM/PMAA nanogel were investigated. The results showed that the AM/PMAA nanogel sustainably released AM with long-term antibacterial activity. Moreover, the AM/PMAA nanogel could improve the stability of AM. More importantly, this AM/PMAA nanogel showed slighter cytotoxicity than AM alone, suggesting that the AM/PMAA nanogel was a more useful dosage form than AM for infectious diseases. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  13. The ratio of serum n-3 to n-6 polyunsaturated fatty acids is associated with diabetes mellitus in patients with prior myocardial infarction: a multicenter cross-sectional study.

    PubMed

    Takahashi, Masao; Ando, Jiro; Shimada, Kazunori; Nishizaki, Yuji; Tani, Shigemasa; Ogawa, Takayuki; Yamamoto, Masato; Nagao, Ken; Hirayama, Atsushi; Yoshimura, Michihiro; Daida, Hiroyuki; Nagai, Ryozo; Komuro, Issei

    2017-01-26

    In prior myocardial infarction (PMI) patients, diabetes mellitus (DM), dyslipidemia, and hypertension increase the risk of secondary cardiovascular events. Although a decreased ratio of serum eicosapentaenoic acid (EPA) to arachidonic acid (AA; EPA/AA) has been shown to significantly correlate with the onset of acute coronary syndrome, the associations between polyunsaturated fatty acid (PUFA) levels and coronary risk factors in PMI patients have not been evaluated thoroughly. This study aimed to assess the associations between PUFAs levels and the risk factors in PMI patients. We enrolled 1733 patients with known PUFA levels who were treated in five divisions of cardiology in a metropolitan area of Japan, including 303 patients with PMI. EPA/AA and docosahexaenoic acid (DHA) to AA level ratio (DHA/AA) in patients with and without PMI were analyzed according to presence of coronary risk factors. Diabetes patients with PMI had significantly lower EPA/AA and DHA/AA than diabetes patients without PMI (EPA/AA: P <0.01; DHA/AA: P =0.003), with no such differences in dyslipidemia and hypertension patients. In DM patients with high high-sensitivity C-reactive protein (hs-CRP) levels (>0.1 mg/dL), EPA/AA was low in individuals who also had PMI, whereas DHA/AA was not (EPA/AA, with PMI: 0.43 ± 0.24; without PMI: 0.53 ± 0.30, P < 0.05). Moreover, patients on statins had significantly lower DHA/AA ratios, whereas the EPA/AA ratio did not depend on statin use. Multiple regression analysis revealed that statin use in DM patients was associated with low DHA/AA but not EPA/AA. PMI patients with DM have low EPA/AA and DHA/AA. EPA/AA and DHA/AA are differently related to hs-CRP level in DM patients with PMI. Statin use can potentially affect DHA/AA but not EPA/AA, and therefore EPA/AA ratio is a better marker of assessment for cardiovascular events.

  14. Risk of secondary lymphedema in breast cancer survivors is related to serum phospholipid fatty acid desaturation.

    PubMed

    Ryu, Eunjung; Yim, Seung Yun; Do, Hyun Ju; Lim, Jae-Young; Yang, Eun Joo; Shin, Min-Jeong; Lee, Seung-Min

    2016-09-01

    Secondary lymphedema is a common irreversible side effect of breast cancer surgery. We investigated if risk of secondary lymphedema in breast cancer survivors was related to changes in serum phospholipid fatty acid composition. Study subjects were voluntarily recruited into the following three groups: breast cancer survivors who had sentinel lymph node biopsy without lymphedema (SLNB), those who had auxillary lymph node dissection without lymphedema (ALND), and those who had ALND with lymphedema (ALND + LE). Body mass index (BMI), serum lipid profiles, bioimpedance data with single-frequency bioimpedance analysis (SFBIA), and serum phospholipid compositions were analyzed and compared among the groups. BMI, serum total cholesterol (total-C), and low-density lipoprotein cholesterol (LDL-C) and SFBIA ratios increased only in the ALND + LE. High polyunsaturated fatty acids (PUFAs) and high C20:4 to C18:2 n-6 PUFAs (arachidonic acid [AA]/linoleic acid [LA]) was detected in the ALND and ALND + LE groups compared to SLNB. The ALND + LE group showed increased activity indices for delta 6 desaturase (D6D) and D5D and increased ratio of AA to eicosapentaenoic acid (AA/EPA) compared to the ALND and SLNB groups. Correlation and regression analysis indicated that D6D, D5D, and AA/EPA were associated with SFBIA ratios. We demonstrated that breast cancer survivors with lymphedema had elevated total PUFAs, fatty acid desaturase activity indices, and AA/EPA in serum phospholipids. Our findings suggested that desaturation extent of fatty acid composition might be related to the risk of secondary lymphedema in breast cancer survivors.

  15. Association between neurotrophin 4 and long-chain polyunsaturated fatty acid levels in mid-trimester amniotic fluid.

    PubMed

    Benn, Kiesha; Passos, Mariana; Jayaram, Aswathi; Harris, Mary; Bongiovanni, Ann Marie; Skupski, Daniel; Witkin, Steven S

    2014-11-01

    The omega-3 long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) and the omega-6 LCPUFA arachidonic acid (AA) are essential nervous system components that increase in concentration throughout gestation. The neurotrophins, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) are small basic peptides crucial for fetal brain development. The DHA supplementation during pregnancy has been suggested to enhance neural development. We evaluated whether amniotic fluid DHA and AA concentrations correlated with intra-amniotic neurotrophin levels. Amniotic fluid, obtained at 15 to 19 weeks gestation from 62 women, was tested for BDNF, NGF, NT3, and NT4 by enzyme-linked immunosorbent assay. Concentrations of DHA and AA, and saturated and monounsaturated fatty acids, were determined by gas chromatography. Associations were analyzed by the Spearman rank correlation test. Median levels of AA and DHA were 2.3% and 1.3% of the total intra-amniotic fatty acids, respectively. Median neurotrophin levels (pg/mL) were 36.7 for NT3, 26.8 for BDNF, 5.2 for NT4, and 0.8 for NGF. Intra-amniotic NT4 and BDNF levels were correlated (P = .0016), while NT3 and NGF levels were unrelated to each other or to BDNF or NT4. Only NT4 was positively correlated with amniotic fluid DHA (P < .0001) and AA (P = .0003) concentrations. There were no associations between DHA, AA, or any neurotrophin and maternal age, gestational age at time of amniocentesis, amniocentesis indication, parity, or gestational age at delivery. Elevations in intra-amniotic NT4 with increasing levels of DHA and AA suggest that these LCPUFAs may specifically influence the extent of NT4-mediated fetal brain neurogenesis. © The Author(s) 2014.

  16. Enhancing the anti-gastric cancer activity of curcumin with biocompatible and pH sensitive PMMA-AA/ZnO nanoparticles.

    PubMed

    Dhivya, Raman; Ranjani, Jothi; Rajendhran, Jeyaprakash; Mayandi, Jeyanthinath; Annaraj, Jamespandi

    2018-01-01

    Curcumin loaded ZnO nanoparticles were successfully synthesised and encapsulated with co-polymer PMMA-AA (Cur/PMMA-AA/ZnO NPs). The ZnO nanoparticles have been converted as good cargo materials to carry the well-known hydrophobic drug curcumin by surface functionalization. Physical characteristics of these novel nanomaterials have been studied with transmission electron microscopy (TEM) and powder X-ray diffraction (XRD) in conjunction with spectral techniques. A narrow particle size distribution with an average value of 42nm was found via TEM. Most importantly, the pH-responsive release of curcumin from the nano-vehicle ensures safer, more controlled delivery of the drug at physiological pH. The drug entrapment efficiency and loading was evaluated and the in vitro efficacy as anticancer drug delivery vehicle was analyzed. The potential toxicity of Cur/PMMA-AA/ZnO NPs was studied by using AGS gastric cancer cell lines via MTT assay. These results revealed that the proposed nanomaterials induce a remarkable cell death in in-vitro models. The multifunctional properties of Cur/PMMA-AA/ZnO NPs may open up new avenues in cancer therapy through overcoming the limitations of conventional cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Time-dependent changes in the plasma amino acid concentration in diabetes mellitus.

    PubMed

    Mochida, Taiga; Tanaka, Takayuki; Shiraki, Yasuko; Tajiri, Hiroko; Matsumoto, Shirou; Shimbo, Kazutaka; Ando, Toshihiko; Nakamura, Kimitoshi; Okamoto, Masahiro; Endo, Fumio

    2011-08-01

    We investigated longitudinal change in the amino acid (AA) profile in type 1 diabetes mellitus (DM) using AKITA mice, which develop DM as a result of insulin deficiency. The plasma concentrations of valine, leucine, isoleucine, as well as the total branched chain amino acids, alanine, citrulline and proline, were significantly higher in the diabetic mice. We show that the degree and timing of the changes were different among the plasma amino acid concentrations (pAAs) during the development of type 1 DM. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Bombyx mori ABC transporter C2 structures responsible for the receptor function of Bacillus thuringiensis Cry1Aa toxin.

    PubMed

    Tanaka, Shiho; Endo, Haruka; Adegawa, Satomi; Iizuka, Ami; Imamura, Kazuhiro; Kikuta, Shingo; Sato, Ryoichi

    2017-12-01

    Because Bombyx mori ABC transporter C2 (BmABCC2) has 1000-fold higher potential than B. mori cadherin-like protein as a receptor for Bacillus thuringiensis Cry1Aa toxin (Tanaka et al., 2013), the gate-opening ability of the latent pore under six extracellular loops (ECLs) of BmABCC2 was expected to be the reason for its higher potential (Heckel, 2012). In this study, cell swelling assays in Sf9 cells showed that BmABCC2 mutants lacking substrate-excreting activity retained receptor activity, indicating that the gate-opening activity of BmABCC2 is not responsible for Cry1Aa toxicity. The analysis of 29 BmABCC2 mutants demonstrated that 770 DYWL 773 of ECL 4 comprise a putative binding site to Cry1Aa. This suggests that specific toxicity of Cry1Aa toxin to a restricted range of lepidopteran insects is dependent on conservation and variation in the amino acid residues around 770 DYWL 773 of ECL 4 in the ABCC2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Chlamydia trachomatis Scavenges Host Fatty Acids for Phospholipid Synthesis via an Acyl-Acyl Carrier Protein Synthetase*

    PubMed Central

    Yao, Jiangwei; Dodson, V. Joshua; Frank, Matthew W.; Rock, Charles O.

    2015-01-01

    The obligate intracellular parasite Chlamydia trachomatis has a reduced genome but relies on de novo fatty acid and phospholipid biosynthesis to produce its membrane phospholipids. Lipidomic analyses showed that 8% of the phospholipid molecular species synthesized by C. trachomatis contained oleic acid, an abundant host fatty acid that cannot be made by the bacterium. Mass tracing experiments showed that isotopically labeled palmitic, myristic, and lauric acids added to the medium were incorporated into C. trachomatis-derived phospholipid molecular species. HeLa cells did not elongate lauric acid, but infected HeLa cell cultures elongated laurate to myristate and palmitate. The elongated fatty acids were incorporated exclusively into C. trachomatis-produced phospholipid molecular species. C. trachomatis has adjacent genes encoding the separate domains of the bifunctional acyl-acyl carrier protein (ACP) synthetase/2-acylglycerolphosphoethanolamine acyltransferase gene (aas) of Escherichia coli. The CT775 gene encodes an acyltransferase (LpaT) that selectively transfers fatty acids from acyl-ACP to the 1-position of 2-acyl-glycerophospholipids. The CT776 gene encodes an acyl-ACP synthetase (AasC) with a substrate preference for palmitic compared with oleic acid in vitro. Exogenous fatty acids were elongated and incorporated into phospholipids by Escherichia coli-expressing AasC, illustrating its function as an acyl-ACP synthetase in vivo. These data point to an AasC-dependent pathway in C. trachomatis that selectively scavenges host saturated fatty acids to be used for the de novo synthesis of its membrane constituents. PMID:26195634

  20. Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid.

    PubMed

    Jhawat, Vikas; Gupta, Sumeet; Saini, Vipin

    2016-11-01

    In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56-5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.

  1. States' Flexibility Waiver Plans for Alternate Assessments Based on Alternate Achievement Standards (AA-AAS). Synthesis Report 96

    ERIC Educational Resources Information Center

    Lazarus, Sheryl S.; Edwards, Lynn M.; Thurlow, Martha L.; Hodgson, Jennifer R.

    2014-01-01

    All states have alternate assessments based on alternate achievement standards (AA-AAS) for students with the most significant cognitive disabilities. For accountability purposes, the Elementary and Secondary Education Act (ESEA) allows up to 1% of students to be counted as proficient with this assessment option. In 2011 the U.S. Department of…

  2. Comparison of PrestoBlue® and plating method to evaluate antimicrobial activity of ascorbic acid, boric acid and curcumin in an in vitro gastrointestinal model.

    PubMed

    Hernandez-Patlan, D; Solis-Cruz, B; Méndez-Albores, A; Latorre, J D; Hernandez-Velasco, X; Tellez, G; López-Arellano, R

    2018-02-01

    To compare the conventional plating method vs a fluorometric method using PrestoBlue ® as a dye by determining the antimicrobial activity of two organic acids and curcumin (CUR) against Salmonella Enteritidis in an avian in vitro digestion model that simulates the crop, proventriculus and intestine. A concentration of 10 8  CFU per ml of S. Enteritidis was exposed to groups with different rates of ascorbic acid (AA), boric acid (BA) and CUR. Significant differences were observed when the means of the treatments were compared with the controls in the compartments that simulate the crop and intestine (P < 0·05). Ascorbic acid alone and high rates of AA in the mixtures were the most efficient treatments in the crop compartment. However, in the intestinal compartment BA alone and at different rates in the mixture BA-CUR (1 : 1) were the best treatments to decrease the concentration of S. Enteritidis. The results of this study suggest that there could be an antagonistic bactericidal effect between AA and CUR and AA and BA as well as a synergistic bactericidal effect between BA and CUR. These findings may contribute to the development of a formulation with microencapsulated compounds to liberate them in different compartments to combat S. Enteritidis infections in broiler chickens. © 2017 The Society for Applied Microbiology.

  3. Ascorbic acid, but not dehydroascorbic acid increases intracellular vitamin C content to decrease Hypoxia Inducible Factor -1 alpha activity and reduce malignant potential in human melanoma.

    PubMed

    Fischer, Adam P; Miles, Sarah L

    2017-02-01

    Accumulation of hypoxia inducible factor-1 alpha (HIF-1α) in malignant tissue is known to contribute to oncogenic progression and is inversely associated with patient survival. Ascorbic acid (AA) depletion in malignant tissue may contribute to aberrant normoxic activity of HIF-1α. While AA supplementation has been shown to attenuate HIF-1α function in malignant melanoma, the use of dehydroascorbic acid (DHA) as a therapeutic means to increase intracellular AA and modulate HIF-1α function is yet to be evaluated. Here we compared the ability of AA and DHA to increase intracellular vitamin C content and decrease the malignant potential of human melanoma by reducing the activity of HIF-1α. HIF-1α protein accumulation was evaluated by western blot and transcriptional activity was evaluated by reporter gene assay using a HIF-1 HRE-luciferase plasmid. Protein expressions and subcellular localizations of vitamin C transporters were evaluated by western blot and confocal imaging. Intracellular vitamin C content following AA, ascorbate 2-phosphate (A2P), or DHA supplementation was determined using a vitamin C assay. Malignant potential was accessed using a 3D spheroid Matrigel invasion assay. Data was analyzed by One or Two-way ANOVA with Tukey's multiple comparisons test as appropriate with p<0.05 considered significant. Melanoma cells expressed both sodium dependent vitamin C (SVCT) and glucose (GLUT) transporters for AA and DHA transport respectively, however advanced melanomas responded favorably to AA, but not DHA. Physiological glucose conditions significantly impaired intracellular vitamin C accumulation following DHA treatment. Consequently, A2P and AA, but not DHA treated cells demonstrated lower HIF-1α protein expression and activity, and reduced malignant potential. The ability of AA to regulate HIF-1α was dependent on SVCT2 function and SVCT2 was not significantly inhibited at pH representative of the tumor microenvironment. The use of ascorbic acid as an

  4. Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

    PubMed

    Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

    2006-12-01

    We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

  5. Losartan increases NO release in afferent arterioles during regression of L-NAME-induced renal damage.

    PubMed

    Helle, Frank; Iversen, Bjarne M; Chatziantoniou, Christos

    2010-05-01

    Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of N(G)-nitro-L-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 ± 4 vs. 146 ± 5 mmHg, P < 0.01), reduced protein/creatinine ratio more (proteinuria decrease: Δ1,836 ± 214 vs. Δ1,024 ± 180 mg/mmol, P < 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 ± 0.05 vs. 2.09 ± 0.08, P < 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10(-7) M ACh (118 ± 4 vs. 90 ± 7%, t = 560 s, P < 0.001) and 10(-9) M ET (123 ± 4 vs. 101 ± 5%, t = 560 s, P < 0.001). There was also a blunted contractile response to 10(-7) M ET in AAs from losartan-treated animals compared with untreated animals (Δ4.01 ± 2.9 vs. Δ14.6 ± 1.7 μm, P < 0.01), which disappeared after acute NOS inhibition (Δ10.7 ± 3.7 vs. Δ12.5 ± 2.9 μm, not significant). Contractile dose responses to ET (10(-9), 10(-8), 10(-7) M) were enhanced by NOS inhibition and blunted by exogenous NO (10(-2) mM S-nitroso-N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial

  6. Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism.

    PubMed

    Pakula, Malgorzata M; Maier, Thorsten J; Vorup-Jensen, Thomas

    2017-06-01

    Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.

  7. A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid.

    PubMed

    Sevgi, Ferhan; Kaynarsoy, Buket; Ozyazici, Mine; Pekcetin, Cetin; Ozyurt, Dogan

    2008-01-01

    The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

  8. Increased dietary long-chain polyunsaturated fatty acids alter serum fatty acid concentrations and lower risk of urine stone formation in cats.

    PubMed

    Hall, Jean A; Brockman, Jeff A; Davidson, Stephen J; MacLeay, Jen M; Jewell, Dennis E

    2017-01-01

    The lifespan of cats with non-obstructive kidney stones is shortened compared with healthy cats indicating a need to reduce stone formation and minimize chronic kidney disease. The purpose of this study was to investigate the effects of increasing dietary polyunsaturated fatty acids (PUFA) on urine characteristics. Domestic-short-hair cats (n = 12; mean age 5.6 years) were randomized into two groups and fed one of two dry-cat foods in a cross-over study design. For one week before study initiation, all cats consumed control food that contained 0.07% arachidonic acid (AA), but no eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Group 1 continued eating control food for 56 days. Group 2 was fed test food for 56 days, which was control food plus fish oil and high-AA oil. Test food contained 0.17% AA, 0.09% EPA and 0.18% DHA. After 56 days, cats were fed the opposite food for another 56 days. At baseline and after each feeding period, serum was analyzed for fatty acid concentrations, and urine for specific gravity, calcium concentration, relative-super-saturation for struvite crystals, and a calcium-oxalate-titrimetric test was performed. After consuming test food, cats had increased (all P<0.001) serum concentrations of EPA (173%), DHA (61%), and AA (35%); decreased urine specific gravity (P = 0.02); decreased urine calcium concentration (P = 0.06); decreased relative-super-saturation for struvite crystals (P = 0.03); and increased resistance to oxalate crystal formation (P = 0.06) compared with cats consuming control food. Oxalate crystal formation was correlated with serum calcium concentration (r = 0.41; P<0.01). These data show benefits for reducing urine stone formation in cats by increasing dietary PUFA.

  9. Increased dietary long-chain polyunsaturated fatty acids alter serum fatty acid concentrations and lower risk of urine stone formation in cats

    PubMed Central

    Brockman, Jeff A.; Davidson, Stephen J.; MacLeay, Jen M.; Jewell, Dennis E.

    2017-01-01

    The lifespan of cats with non-obstructive kidney stones is shortened compared with healthy cats indicating a need to reduce stone formation and minimize chronic kidney disease. The purpose of this study was to investigate the effects of increasing dietary polyunsaturated fatty acids (PUFA) on urine characteristics. Domestic-short-hair cats (n = 12; mean age 5.6 years) were randomized into two groups and fed one of two dry-cat foods in a cross-over study design. For one week before study initiation, all cats consumed control food that contained 0.07% arachidonic acid (AA), but no eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Group 1 continued eating control food for 56 days. Group 2 was fed test food for 56 days, which was control food plus fish oil and high-AA oil. Test food contained 0.17% AA, 0.09% EPA and 0.18% DHA. After 56 days, cats were fed the opposite food for another 56 days. At baseline and after each feeding period, serum was analyzed for fatty acid concentrations, and urine for specific gravity, calcium concentration, relative-super-saturation for struvite crystals, and a calcium-oxalate-titrimetric test was performed. After consuming test food, cats had increased (all P<0.001) serum concentrations of EPA (173%), DHA (61%), and AA (35%); decreased urine specific gravity (P = 0.02); decreased urine calcium concentration (P = 0.06); decreased relative-super-saturation for struvite crystals (P = 0.03); and increased resistance to oxalate crystal formation (P = 0.06) compared with cats consuming control food. Oxalate crystal formation was correlated with serum calcium concentration (r = 0.41; P<0.01). These data show benefits for reducing urine stone formation in cats by increasing dietary PUFA. PMID:29073223

  10. Growth of various cell types in the presence of lactic and glycolic acids: the adverse effect of glycolic acid released from PLAGA copolymer on keratinocyte proliferation.

    PubMed

    Garric, Xavier; Molès, Jean-Pierre; Garreau, Henri; Braud, Christian; Guilhou, Jean-Jacques; Vert, Michel

    2002-01-01

    Poly(alpha-hydroxy-acid)s derived from lactic acid (LA) and glycolic acid (GA) are bioresorbable polymers that are currently used in human surgery and in pharmacology to make temporary therapeutic devices. Nowadays, increasing attention is paid to these polymers in the field of tissue engineering. However, the literature shows that a large number of factors can affect many of their properties and the responses of biological systems. As part of our investigation of the biocompatibility of degradable aliphatic polyesters, the effects of LA and GA on the proliferation of various cells under in vitro cell culture conditions were studied. The release of LA and GA from films made of a copolymer synthesized by the zinc lactate method and composed of 37.5% L-lactyl, 37.5% D-lactyl, and 25% glycolyl repeating units was first investigated over a period of 30 days under abiotic conditions in a cell culture medium in order to identify a range of acid concentrations consistent with releases to be expected in real cell cultures. Four cell lines, namely 3T3-J2, C3H10(1/2), A431, and HaCat, and three primary cell cultures, namely rat endothelial cells, rat smooth muscle cells, and human dermal fibroblasts, were then allowed to grow in the presence of LA and GA at various concentrations taken within the selected 10-1000 mg/cm3 range. Little or no effect was observed on the proliferation of all cells except human keratinocytes, whose growth was dramatically inhibited by GA at concentrations as low as 10 mg/cm3. The inhibiting effect of GA was confirmed by considering the growth of keratinocytes on films made of the same copolymer, in comparison with poly(DL-lactic acid) and polystyrene taken as references. This work shows that GA-releasing degradable matrices are not adapted to the culture of keratinocytes with the aim of making skin grafts.

  11. Diet quality influences isotopic discrimination among amino acids in an aquatic vertebrate

    PubMed Central

    Chikaraishi, Yoshito; Steffan, Shawn A; Takano, Yoshinori; Ohkouchi, Naohiko

    2015-01-01

    Stable nitrogen isotopic composition of amino acids (δ15NAA) has recently been employed as a powerful tool in ecological food web studies, particularly for estimating the trophic position (TP) of animal species in food webs. However, the validity of these estimates depends on the consistency of the trophic discrimination factor (TDF; - Δδ15NAA at each shift of trophic level) among a suite of amino acids within the tissues of consumer species. In this study, we determined the TDF values of amino acids in tadpoles (the Japanese toad, Bufo japonicus) reared exclusively on one of three diets that differed in nutritional quality. The diets were commercial fish-food pellets (plant and animal biomass), bloodworms (animal biomass), and boiled white rice (plant carbohydrate), representing a balanced, protein-rich, and protein-poor diet, respectively. The TDF values of two “source amino acids” (Src-AAs), methionine and phenylalanine, were close to zero (0.3–0.5‰) among the three diets, typifying the values reported in the literature (∼0.5‰ and ∼0.4‰, respectively). However, TDF values of “trophic amino acids” (Tr-AAs) including alanine, valine, leucine, isoleucine, and glutamic acid varied by diet: for example, the glutamic acid TDF was similar to the standard value (∼8.0‰) when tadpoles were fed either the commercial pellets (8.0‰) or bloodworms (7.9‰), but when they were fed boiled rice, the TDF was significantly reduced (0.6‰). These results suggest that a profound lack of dietary protein may alter the TDF values of glutamic acid (and other Tr-AAs and glycine) within consumer species, but not the two Src-AAs (i.e., methionine and phenylalanine). Knowledge of how a nutritionally poor diet can influence the TDF of Tr- and Src-AAs will allow amino acid isotopic analyses to better estimate TP among free-roaming animals. PMID:26045955

  12. SYNTHESIS AND IN VITRO CHARACTERIZATION OF HYDROXYPROPYL METHYLCELLULOSE-GRAFT-POLY (ACRYLIC ACID/2-ACRYLAMIDO-2-METHYL-1-PROPANESULFONIC ACID) POLYMERIC NETWORK FOR CONTROLLED RELEASE OF CAPTOPRIL.

    PubMed

    Furqan Muhammad, Iqbal; Mahmood, Ahmad; Aysha, Rashid

    2016-01-01

    A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension.

  13. Microsolvation of the acetanilide cation (AA(+)) in a nonpolar solvent: IR spectra of AA(+)-L(n) clusters (L = He, Ar, N2; n ≤ 10).

    PubMed

    Schmies, Matthias; Patzer, Alexander; Schütz, Markus; Miyazaki, Mitsuhiko; Fujii, Masaaki; Dopfer, Otto

    2014-05-07

    Infrared photodissociation (IRPD) spectra of mass-selected cluster ions of acetanilide (N-phenylacetamide), AA(+)-Ln, with the ligands L = He (n = 1-2), Ar (n = 1-7), and N2 (n = 1-10) are recorded in the hydride stretch (amide A, νNH, νCH) and fingerprint (amide I-III) ranges of AA(+) in its (2)A'' ground electronic state. Cold AA(+)-Ln clusters are generated in an electron impact ion source, which predominantly produces the most stable isomer of a given cluster ion. Systematic vibrational frequency shifts of the N-H stretch fundamentals (νNH) provide detailed information about the sequential microsolvation process of AA(+) in a nonpolar (L = He and Ar) and quadrupolar (L = N2) solvent. In the most stable AA(+)-Ln clusters, the first ligand forms a hydrogen bond (H-bond) with the N-H proton of trans-AA(+) (t-AA(+)), whereas further ligands bind weakly to the aromatic ring (π-stacking). There is no experimental evidence for complexes with the less stable cis-AA(+) isomer. Quantum chemical calculations at the M06-2X/aug-cc-pVTZ level confirm the cluster growth sequence derived from the IR spectra. The calculated binding energies of De(H) = 720 and 1227 cm(-1) for H-bonded and De(π) = 585 and 715 cm(-1) for π-bonded Ar and N2 ligands in t-AA(+)-L are consistent with the observed photofragmentation branching ratios of AA(+)-Ln. Comparison between charged and neutral AA((+))-L dimers indicates that ionization switches the preferred ion-ligand binding motif from π-stacking to H-bonding. Electron removal from the HOMO of AA(+) delocalized over both the aromatic ring and the amide group significantly strengthens the C[double bond, length as m-dash]O bond and weakens the N-H bond of the amide group.

  14. Observing HNO3 release dependent upon metal complexes in malonic acid/nitrate droplets.

    PubMed

    Shao, Xu; Wu, Feng-Min; Yang, Hui; Pang, Shu-Feng; Zhang, Yun-Hong

    2018-05-09

    Although the dicarboxylic acid has been reported to react with nitrate for aged internally mixed aerosols in atmosphere, the quantitative nitrate depletion dependent upon composition in particles is still not well constrained. The chemical composition evolutions for malonic acid/sodium nitrate (MA/SN), malonic acid/magnesium nitrate (MA/MN) and malonic acid/calcium nitrate (MA/CN) particles with the organic to inorganic molar ratio (OIR) of 1:1 are investigated by vacuum Fourier transform infrared spectroscopy (FTIR). Upon dehydration, the intensity of the asymmetric stretching mode of COO - group (ν as -COO - ) increases, accompanying the decrease in OH feather band and COOH band and NO 3 - band. These band changes suggest malonate salts formation and HNO 3 release. The quantitative NO 3 - depletion data shows that the reactivity of MA-MN is most and that of MA-SN is least. Analysis of the stretching mode of COO - indicates the different bond type between metal cation and carboxylate anion. In addition, water content in particles decreases at the constant RH, implying water loss with the chemical reaction. When the RH changes very quickly, water uptake delay during the humidification process reveals that water mass transport is limited below 37% RH. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Injectable biocompatible and biodegradable pH-responsive hollow particle gels containing poly(acrylic acid): the effect of copolymer composition on gel properties.

    PubMed

    Halacheva, Silvia S; Adlam, Daman J; Hendow, Eseelle K; Freemont, Tony J; Hoyland, Judith; Saunders, Brian R

    2014-05-12

    The potential of various pH-responsive alkyl (meth)acrylate ester- and (meth)acrylic acid-based copolymers, including poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) and poly(n-butyl acrylate-co-methacrylic acid) (PBA-MAA), to form pH-sensitive biocompatible and biodegradable hollow particle gel scaffolds for use in non-load-bearing soft tissue regeneration have been explored. The optimal copolymer design criteria for preparation of these materials have been established. Physical gels which are both pH- and redox-sensitive were formed only from PMMA-AA copolymers. MMA is the optimal hydrophobic monomer, whereas the use of various COOH-containing monomers, e.g., MAA and AA, will always induce a pH-triggered physical gelation. The PMMA-AA gels were prepared at physiological pH range from concentrated dispersions of swollen, hollow, polymer-based particles cross-linked with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP). A linear relationship between particle swelling ratios, gel elasticity, and ductility was observed. The PMMA-AA gels with lower AA contents feature lower swelling ratios, mechanical strengths, and ductilities. Increasing the swelling ratio (e.g., through increasing AA content) decreased the intraparticle elasticity; however, intershell contact and gel elasticity were found to increase. The mechanical properties and performance of the gels were tuneable upon varying the copolymers' compositions and the structure of the cross-linker. Compared to PMMA-AA/CYS, the PMMA-AA/DTP gels were more elastic and ductile. The biodegradability and cytotoxicity of the new hollow particle gels were tested for the first time and related to their composition, mechanical properties, and morphology. The new PMMA-AA/CYS and PMMA-AA/DTP gels have shown good biocompatibility, biodegradability, strength, and interconnected porosity and therefore have good potential as a tissue repair agent.

  16. Rapid microwave-assisted acid extraction of southern pine waste wood to remove metals from chromated copper arsenate (CCA) treatment

    Treesearch

    Chung-Yun Hse; Todd F. Shupe; Bin Yu

    2013-01-01

    Recovery of metals from chromated copper arsenate (CCA)-treated southern pine wood particles was investigated by extraction in a microwave reactor with binary combinations of acetic acid (AA), oxalic acid (OxA), and phosphoric acid (PhA). Use of OxA was not successful, as insoluble copper oxalate complexes impeded copper removal. The combination of OxA and AA also had...

  17. Synthesis and Biomedical Applications of Poly((meth)acrylic acid) Brushes.

    PubMed

    Qu, Zhenyuan; Xu, Hong; Gu, Hongchen

    2015-07-15

    Poly((meth)acrylic acid) (P(M)AA) brushes possess a number of distinctive properties that are particularly attractive for biomedical applications. This minireview summarizes recent advances in the synthesis and biomedical applications of P(M)AA brushes and brushes containing P(M)AA segments. First, we review different surface-initiated polymerization (SIP) methods, with a focus on recent progress in the surface-initiated controlled/living radical polymerization (SI-CLRP) techniques used to generate P(M)AA brushes with a tailored structure. Next, we discuss biomolecule immobilization methods for P(M)AA brushes, including physical adsorption, covalent binding, and affinity interactions. Finally, typical biomedical applications of P(M)AA brushes are reviewed, and their performance is discussed based on their unique properties. We conclude that P(M)AA brushes are promising biomaterials, and more potential biomedical applications are expected to emerge with the further development of synthetic techniques and increased understanding of their interactions with biological systems.

  18. Enhanced Nitrogen Availability in Karst Ecosystems by Oxalic Acid Release in the Rhizosphere

    PubMed Central

    Pan, Fujing; Liang, Yueming; Zhang, Wei; Zhao, Jie; Wang, Kelin

    2016-01-01

    In karst ecosystems, a high level of CaCO3 enhances the stabilization of soil organic matter (SOM) and causes nitrogen (N) and/or phosphorus (P) limitation in plants. Oxalic acid has been suggested to be involved in the nutrient-acquisition strategy of plants because its addition can temporarily relieve nutrient limitation. Therefore, understanding how oxalic acid drives N availability may help support successful vegetation restoration in the karst ecosystems of southwest China. We tested a model suggested by Clarholm et al. (2015) where oxalate reacts with Ca bridges in SOM, thus exposing previously protected areas to enzymatic attacks in a way that releases N for local uptake. We studied the effects of oxalic acid, microbial biomass carbon (MBC), and β-1,4-N-acetylglucosaminidase (NAG) on potential N mineralization rates in rhizosphere soils of four plant species (two shrubs and two trees) in karst areas. The results showed that rhizosphere soils of shrubs grown on formerly deforested land had significantly lower oxalic acid concentrations and NAG activity than that of trees in a 200-year-old forest. The levels of MBC in rhizosphere soils of shrubs were significantly lower than those of trees in the growing season, but the measure of shrubs and trees were similar in the non-growing season; the potential N mineralization rates showed a reverse pattern. Positive relationships were found among oxalic acid, MBC, NAG activity, and potential N mineralization rates for both shrubs and trees. This indicated that oxalic acid, microbes, and NAG may enhance N availability for acquisition by plants. Path analysis showed that oxalic acid enhanced potential N mineralization rates indirectly through inducing microbes and NAG activities. We found that the exudation of oxalic acid clearly provides an important mechanism that allows plants to enhance nutrient acquisition in karst ecosystems. PMID:27252713

  19. Low plasma eicosapentaenoic acid concentration as a possible risk factor for intracerebral hemorrhage.

    PubMed

    Ikeya, Yoshimori; Fukuyama, Naoto; Mori, Hidezo

    2015-03-01

    N-3 fatty acids, including eicosapentaenoic acid (EPA), prevent ischemic stroke. The preventive effect has been attributed to an antithrombic effect induced by elevated EPA and reduced arachidonic acid (AA) levels. However, the relationship between intracranial hemorrhage and N-3 fatty acids has not yet been elucidated. In this cross-sectional study, we compared common clinical and lifestyle parameters between 70 patients with intracranial hemorrhages and 66 control subjects. The parameters included blood chemistry data, smoking, alcohol intake, fish consumption, and the incidences of underlying diseases. The comparisons were performed using the Mann-Whitney U test followed by multiple logistic regression analysis. Nonparametric tests revealed that the 70 patients with intracerebral hemorrhages exhibited significantly higher diastolic blood pressures and alcohol intakes and lower body mass indices, high-density lipoprotein (HDL) cholesterol levels, EPA concentrations, EPA/AA ratios, and vegetable consumption compared with the 66 control subjects. A multiple logistic regression analysis revealed that higher diastolic blood pressure and alcohol intake and lower body mass index, HDL cholesterol, EPA/AA ratio, and vegetable consumption were relative risk factors for intracerebral hemorrhage. High HDL cholesterol was a common risk factor in both of the sex-segregated subgroups and the <65-year-old subgroup. However, neither EPA nor the EPA/AA ratio was a risk factor in these subgroups. Eicosapentaenoic acid was relative risk factor only in the ≥65-year-old subgroup. Rather than higher EPA levels, lower EPA concentrations and EPA/AA ratios were found to be risk factors for intracerebral hemorrhage in addition to previously known risk factors such as blood pressure, alcohol consumption, and lifestyle. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend.

    PubMed

    Kenawy, El-Refaie; Bowlin, Gary L; Mansfield, Kevin; Layman, John; Simpson, David G; Sanders, Elliot H; Wnek, Gary E

    2002-05-17

    Electrospun fiber mats are explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. The mats were made either from poly(lactic acid) (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two. The fibers were electrospun from chloroform solutions containing a small amount of methanol to solubilize the drug. The release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV-VIS spectroscopy. Release profiles from the electrospun mats were compared to a commercially available drug delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast films of the various formulations.

  1. Release of enzymes from lysosomes by irradiation and the relation of lipid peroxide formation to enzyme release

    PubMed Central

    Wills, E. D.; Wilkinson, A. E.

    1966-01-01

    1. Acid phosphatase, cathepsin and β-glucuronidase are released from rat-liver lysosomes by irradiation in vitro. Enzyme release is detectable after a dose of 1krad and increases with dose up to 100krads. 2. Maximum radiation effects were observed when the lysosomes were kept for 20hr. at 4° or 20° after irradiation. 3. An atmosphere of nitrogen considerably decreases enzyme release from lysosomes. 4. Enzyme release is enhanced by ascorbic acid and decreased by vitamin E. 5. Irradiation causes formation of lipid peroxides in lysosomes, and enzyme release increases with lipid peroxide formation. 6. It is suggested that lipid peroxide formation leads to rupture of the lysosome membrane and allows release of the contained hydrolytic enzymes. PMID:5964962

  2. Control of Meloidogyne incognita Using Mixtures of Organic Acids

    PubMed Central

    Seo, Yunhee; Kim, Young Ho

    2014-01-01

    This study sought to control the root-knot nematode (RKN) Meloidogyne incognita using benign organo-chemicals. Second-stage juveniles (J2) of RKN were exposed to dilutions (1.0%, 0.5%, 0.2%, and 0.1%) of acetic acid (AA), lactic acid (LA), and their mixtures (MX). The nematode bodies were disrupted severely and moderately by vacuolations in 0.5% of MX and single organic acids, respectively, suggesting toxicity of MX may be higher than AA and LA. The mortality of J2 was 100% at all concentrations of AA and MX and only at 1.0% and 0.5% of LA, which lowered slightly at 0.2% and greatly at 0.1% of LA. This suggests the nematicidal activity of MX may be mostly derived from AA together with supplementary LA toxicity. MX was applied to chili pepper plants inoculated with about 1,000 J2, for which root-knot gall formations and plant growths were examined 4 weeks after inoculation. The root gall formation was completely inhibited by 0.5% MX and standard and double concentrations of fosthiazate; and inhibited 92.9% and 57.1% by 0.2% and 0.1% MX, respectively. Shoot height, shoot weight, and root weight were not significantly (P ≤ 0.05) different among all treatments and the untreated and non-inoculated controls. All of these results suggest that the mixture of the organic acids may have a potential to be developed as an eco-friendly nematode control agent that needs to be supported by the more nematode control experiments in fields. PMID:25506312

  3. Long-chain polyunsaturated fatty acid sources and evaluation of their nutritional and functional properties

    PubMed Central

    Abedi, Elahe; Sahari, Mohammad Ali

    2014-01-01

    Recent studies have clearly shown the importance of polyunsaturated fatty acids (as essential fatty acids) and their nutritional value for human health. In this review, various sources, nutritional properties, and metabolism routes of long-chain polyunsaturated fatty acids (LC-PUFA) are introduced. Since the conversion efficiency of linoleic acid (LA) to arachidonic acid (AA) and also α-linolenic acid (ALA) to docosahexaenoic acid (DHA) and eicosatetraenoic acid (EPA) is low in humans, looking for the numerous sources of AA, EPA and EPA fatty acids. The sources include aquatic (fish, crustaceans, and mollusks), animal sources (meat, egg, and milk), plant sources including 20 plants, most of which were weeds having a good amount of LC-PUFA, fruits, herbs, and seeds; cyanobacteria; and microorganisms (bacteria, fungi, microalgae, and diatoms). PMID:25473503

  4. Synthesis and evaluation of chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) as a drug carrier for controlled release of tramadol hydrochloride

    PubMed Central

    Subramanian, Kaliappa gounder; Vijayakumar, Vediappan

    2011-01-01

    Chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) has been synthesized for different feed ratios of 2-hydroxyethyl methacrylate and itaconic acid and characterized by FT-IR, thermogravimetry and swelling in simulated biological fluids (SBF) and evaluated as a drug carrier with model drug, tramadol hydrochloride (TRM). Grafting decreased the thermal stability of chitosan. FT-IR spectra of tablet did not reveal any molecular level (i.e. at <10 nm scale) drug–polymer interaction. But differential scanning calorimetric studies indicated a probable drug–polymer interaction at a scale >100 nm level. The observed Korsmeyer–Peppas’s power law exponents (0.19–1.21) for the in vitro release profiles of TRM in SBF and other drugs such as 5-fluorouracil (FU), paracetamol (PCM) and vanlafaxine hydrochloride (VNF) with the copolymer carriers revealed an anomalous drug release mechanism. The decreased release rates for the grafted chitosan and the enhanced release rate for the grafts with increasing itaconic acid content in the feed were more likely attributed to the enhanced drug–matrix interaction and polymer–SBF interactions, respectively. The different release profiles of FU, PCM, TRM and VNF with the copolymer matrix are attributed to the different chemical structures of drugs. The above features suggest the graft copolymer’s candidature for use as a promising oral drug delivery system. PMID:23960799

  5. Dual-responsive surfaces modified with phenylboronic acid-containing polymer brush to reversibly capture and release cancer cells.

    PubMed

    Liu, Hongliang; Li, Yingying; Sun, Kang; Fan, Junbing; Zhang, Pengchao; Meng, Jingxin; Wang, Shutao; Jiang, Lei

    2013-05-22

    Artificial stimuli-responsive surfaces that can mimic the dynamic function of living systems have attracted much attention. However, there exist few artificial systems capable of responding to dual- or multistimulation as the natural system does. Herein, we synthesize a pH and glucose dual-responsive surface by grafting poly(acrylamidophenylboronic acid) (polyAAPBA) brush from aligned silicon nanowire (SiNW) array. The as-prepared surface can reversibly capture and release targeted cancer cells by precisely controlling pH and glucose concentration, exhibiting dual-responsive AND logic. In the presence of 70 mM glucose, the surface is pH responsive, which can vary from a cell-adhesive state to a cell-repulsive state by changing the pH from 6.8 to 7.8. While keeping the pH at 7.8, the surface becomes glucose responsive--capturing cells in the absence of glucose and releasing cells by adding 70 mM glucose. Through simultaneously changing the pH and glucose concentration from pH 6.8/0 mM glucose to pH 7.8/70 mM glucose, the surface is dual responsive with the capability to switch between cell capture and release for at least 5 cycles. The cell capture and release process on this dual-responsive surface is noninvasive with cell viability higher than 95%. Moreover, topographical interaction between the aligned SiNW array and cell protrusions greatly amplifies the responsiveness and accelerates the response rate of the dual-responsive surface between cell capture and release. The responsive mechanism of the dual-responsive surface is systematically studied using a quartz crystal microbalance, which shows that the competitive binding between polyAAPBA/sialic acid and polyAAPBA/glucose contributes to the dual response. Such dual-responsive surface can significantly impact biomedical and biological applications including cell-based diagnostics, in vivo drug delivery, etc.

  6. Pure hemozoin is inflammatory in vivo and activates the NALP3 inflammasome via release of uric acid

    PubMed Central

    Griffith, Jason W.; Sun, Tiffany; McIntosh, Michael T.; Bucala, Richard

    2013-01-01

    The role of pro-inflammatory cytokine production in the pathogenesis of malaria is well established, but the identification of the parasite products that initiate inflammation is not complete. Hemozoin is a crystalline metabolite of hemoglobin digestion that is released during malaria infection. In the present study, we characterized the immunostimulatory activity of pure synthetic hemozoin (sHz) in vitro and in vivo. Stimulation of naïve murine macrophages with sHz results in the MyD88-independent activation of NF-κB and ERK, and the release of the chemokine MCP-1; these responses are augmented by IFN-γ. In macrophages pre-stimulated with IFN-γ, sHz also results in a MyD88-dependent release of TNF-α. Endothelial cells, which encounter hemozoin after schizont rupture, respond to sHz by releasing IL-6 and the chemokines MCP-1 and IL-8. In vivo, the introduction of sHz into the peritoneal cavity produces an inflammatory response characterized by neutrophil recruitment and the production of MCP-1, KC, IL-6, IL-1α and IL-1β. MCP-1 and KC are produced independently of MyD88, TLR 2/4 and 9, and components of the inflammasome, however neutrophil recruitment, the localized production of IL-1β, and the increase in circulating IL-6 require MyD88 signaling, the IL-1R pathway and the inflammasome components ICE, ASC and NALP3. Of note, inflammasome activation by sHz is reduced by allopurinol, which is an inhibitor of uric acid synthesis. This data suggests that uric acid is released during malaria infection and may serve to augment the initial host response to hemozoin via activation of the NALP3 inflammasome. PMID:19783673

  7. Ligand-independent activation of EphA2 by arachidonic acid induces metastasis-like behaviour in prostate cancer cells

    PubMed Central

    Tawadros, T; Brown, M D; Hart, C A; Clarke, N W

    2012-01-01

    Background: High intake of omega-6 polyunsaturated fatty acids (PUFA) has been associated with clinical progression in prostate cancer (CaP). This study investigates the signalling mechanism by which the omega-6 PUFA arachidonic acid (AA) induces prostatic cellular migration to bone marrow stroma. Methods: Western blot analysis of the PC-3, PC3-GFP, DU 145 and LNCaP cells or their lipid raft (LR) components post AA stimulation was conducted in association with assays for adhesion and invasion through the bone marrow endothelial monolayers. Results: Arachidonic acid increased transendothelial migration of PC3-GFP cells (adhesion 37%±0.08, P=0.0124; transmigration 270%±0.145, P=0.0008). Akt, Src and focal adhesion kinase (FAK) pathways were induced by AA and integrally involved in transendothelial migration. LR were critical in AA uptake and induced Akt activity. Ephrin receptor A2 (EphA2), localised in LR, is expressed in DU 145 and PC-3 cells. Arachidonic acid induced a rapid increase of EphA2 Akt-dependent/ligand-independent activation, while knockdown of the EphrinA1 ligand decreased AA induced transendothelial migration, with an associated decrease in Src and FAK activity. Arachidonic acid activated Akt in EphA2− LNCaP cells but failed to induce BMEC transendothelial invasion. Conclusion: Arachidonic acid induced stimulation of EphA2 in vitro is associated fundamentally with CaP epithelial migration across the endothelial barrier. PMID:23037715

  8. Uronic Acid Products Release from Enzymically Active Cell Wall from Tomato Fruit and Its Dependency on Enzyme Quantity and Distribution 1

    PubMed Central

    Huber, Donald J.; Lee, James H.

    1988-01-01

    Isolated cell wall from tomato (Lycopersicon esculentum Mill. cv Rutgers) fruit released polymeric (degree of polymerization [DP] > 8), oligomeric, and monomeric uronic acids in a reaction mediated by bound polygalacturonase (PG) (EC 3.2.1.15). Wall autolytic capacity increased with ripening, reflecting increased levels of bound PG; however, characteristic oligomeric and monomeric products were recovered from all wall isolates exhibiting net pectin release. The capacity of wall from fruit at early ripening (breaker, turning) to generate oligomeric and monomeric uronic acids was attributed to the nonuniform ripening pattern of the tomato fruit and, consequently, a locally dense distribution of enzyme in wall originating from those fruit portions at more temporally advanced stages of ripening. Artificial autolytically active wall, prepared by permitting solubilized PG to bind to enzymically inactive wall from maturegreen fruit, released products which were similar in size characteristics to those recovered from active wall isolates. Extraction of wall-bound PG using high concentrations of NaCl (1.2 molar) did not attenuate subsequent autolytic activity but greatly suppressed the production of oligomeric and monomeric products. An examination of water-soluble uronic acids recovered from ripe pericarp tissue disclosed the presence of polymeric and monomeric uronic acids but only trace quantities of oligomers. The significance in autolytic reactions of enzyme quantity and distribution and their possible relevance to in vivo pectin degradation will be discussed. PMID:16666191

  9. Safety and tolerance of ester-C compared with regular ascorbic acid.

    PubMed

    Gruenwald, Joerg; Graubaum, Hans-Joachim; Busch, Regina; Bentley, Christine

    2006-01-01

    The goal of this randomized, double-blind crossover clinical trial in 50 healthy volunteers sensitive to acidic foods was to evaluate whether Ester-C calcium ascorbate causes fewer epigastric adverse effects than are produced by regular ascorbic acid (AA). Volunteers were randomly separated into 2 groups of 25. The study comprised an observation period of 9 days (phase 1 medication for 3 consecutive days, washout phase for 3 consecutive days, phase 2 medication for 3 consecutive days). Participants took 1000 mg vitamin C as Ester-C during phase 1 of the study followed by 1000 mg of vitamin C as AA during phase 2, or vice versa. During the course of the study, 3 examinations for the evaluation of epigastric adverse effects were performed (on days 0, 3, and 9). Participants used a diary to record epigastric adverse effects on a daily basis. In total, 28 (56%) of 50 participants reported 88 epigastric adverse effects of mild to moderate intensity. Of these 88 adverse effects, 33 (37.5%) occurred after intake of Ester-C and 55 (62.5%) were noted after intake of AA. The tolerability of Ester-C was rated "very good" by 72% of participants, whereas AA was rated "very good" by only 54%. This difference is statistically significant (P<.05). Investigators concluded that Ester-C compared with AA caused significantly fewer epigastric adverse effects in participants sensitive to acidic foods and that Ester-C is much better tolerated.

  10. Ascorbic acid, cognitive function, and Alzheimer’s disease: a current review and future direction

    PubMed Central

    Bowman, Gene L.

    2013-01-01

    This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer’s disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging. PMID:22419527

  11. Fatty acid composition of plasma and erythrocytes in term infants fed human milk and formulae with and without docosahexaenoic and arachidonic acids from egg yolk lecithin.

    PubMed

    Bondía-Martínez, E; López-Sabater, M C; Castellote-Bargalló, A I; Rodríguez-Palmero, M; González-Corbella, M J; Rivero-Urgell, M; Campoy-Folgoso, C; Bayés-García, R

    1998-12-01

    Human milk contains small but nutritionally significant amounts of long-chain polyunsaturated fatty acids (LCP), such as arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-3) acids, which are not present in most infant formulae. In the present study, the fatty acid composition of plasma and erythrocytes was determined at birth and again at 7 days, 1 and 3 months in 49 healthy full-term infants (37-42 week's gestation). One group of infants was fed exclusively with human milk (n=16) and the others were randomly assigned to a standard term formula (F) (n=15) or the same formula with egg yolk lecithin providing DHA (0.15%) and AA (0.30%) (LCP-F) (n=18). Plasma and erythrocyte LCP values of the three dietary groups did not differ at 7 days of age, but the contents of DHA and AA in plasma and erythrocytes at 1 and 3 months were significantly lower (P<0.05) in infants fed non supplemented formula than in infants fed breast milk and supplemented formula. There were no differences in plasma or erythrocyte AA or DHA concentrations between the group fed breast milk and the group fed supplemented formula during the period studied.

  12. Corrosion Behavior of Aluminum Alloys in Acidic Media

    NASA Astrophysics Data System (ADS)

    Ramli, Rosliza; Seoh, S. Y.; Nik, W. B. Wan; Senin, H. B.

    2007-05-01

    The corrosion inhibition of Al and its alloys are the subject of tremendous technological importance due to the increased industrial applications of these materials. This study will report the results of weight loss, polarization and electrochemical impedance spectroscopic (EIS) measurements on the corrosion inhibition of AA6061 and AA6063 aluminum alloys in acidic media using sodium benzoate as an inhibitor. The results showed that addition of sodium benzoate retards the rate of dissolution and hence inhibits the corrosion of the aluminum alloy in acidic media. The inhibition efficiency increases with the increase of immersion time in acetic acid however it displays a different behavior in sulfuric acid. Langmuir adsorption isotherm fits well with the experimental data. EIS studies showed that there was a significant increase in overall resistance after addition of sodium benzoate, when compared to the case without inhibitor. Langmuir adsorption isotherm fits well with the experimental data.

  13. Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study

    PubMed Central

    Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

    2017-01-01

    Background Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Methods Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Results Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Conclusions Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under

  14. Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study.

    PubMed

    Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

    2017-01-01

    Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under desflurane anesthesia, both glutamate

  15. Amino and fatty acid dynamics of octopus (Octopus vulgaris) early life stages under ocean warming.

    PubMed

    Lopes, Vanessa M; Faleiro, Filipa; Baptista, Miguel; Pimentel, Marta S; Paula, José R; Couto, Ana; Bandarra, Narcisa; Anacleto, Patrícia; Marques, António; Rosa, Rui

    2016-01-01

    The oceans are becoming warmer, and the higher temperatures are expected to have a major impact on marine life at different levels of biological organization, especially at the most vulnerable early life stages. Thus, we hypothesize that the future warmer scenarios (here +3 °C) will affect the biochemical composition (amino acid - AA, and fatty acid-FA) of octopod (Octopus vulgaris) embryos and recently-hatched pelagic paralarvae. The main essential amino acids found in octopus embryos were arginine, leucine and lysine; while aspartic and glutamic acids, and taurine were the main non-essential amino acids. Palmitic, eicosapentaenoic and docosahexaenoic acids were the main FAs found in octopus tissues. Relevant ontogenetic changes were observed, namely a steep decrease in the content of many AAs, and a selective retention of FAs, thus evidencing the protein-based metabolism of these cephalopods. Temperature per si did not elicit significant changes in the overall FA composition, but was responsible for a significant decrease in the content of several AAs, indicating increased embryonic consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. ET AAS evaluation of the stability and pH-sensitivity of, pH-sensitive stealth liposomes containing cisplatin in mouse plasma.

    PubMed

    Vieira, F P; Mesquita, T L; Lara, P C P; Ramaldes, G A; Beinner, M A; Silva, J B B; Oliveira, M C; Silveira, J N

    2013-10-01

    In this work, stability and the pH-sensitivity of pH-sensitive stealth liposomes containing cisplatin exposed to plasma medium and their subsequent responses to pH modifications were evaluated. A method to determine platin in mouse plasma by electrothermal atomic absorption spectroscopy (ET AAS) was developed and validated. At first, a comparative study of sample preparation treatments with basic, acidic, and acidic added with Triton X-100 as a modifier was done. The best treatment was obtained with HCl 3% (v/v). The ET AAS method with acid treatment presented linearity at a range of 10-160 ng Pt/mL. The limits of detection (LOD) was 3.1 ng/mL Pt for acid treatment, while the limit quantification (LOQ) was 10 ng/mL Pt. The acid treatment presented good repeatability (VC<15.0%) and recovery close to 100%. This treatment was chosen for subsequent studies due to its best value of repeatability, recovery, LOD and lowest cost. pH-sensitive stealth liposomes, containing cisplatin, demonstrated low stability and poor response to pH variation after plasma incubation. These findings suggest that further studies are needed to improve liposome formulation i.e., to reduce its size. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Arachidonate-Regulated Ca2+ Influx in Human Airway Smooth Muscle

    PubMed Central

    Thompson, Michael A.; Prakash, Y. S.

    2014-01-01

    Plasma membrane Ca2+ influx, especially store-operated Ca2+ entry triggered by sarcoplasmic reticulum (SR) Ca2+ release, is a key component of intracellular calcium concentration ([Ca2+]i) regulation in airway smooth muscle (ASM). Agonist-induced Ca2+ oscillations in ASM that involve both influx and SR mechanisms have been previously demonstrated. In nonexcitable cells, [Ca2+]i oscillations involve Ca2+ influx via arachidonic acid (AA) –stimulated channels, which show similarities to store-operated Ca2+ entry, although their molecular identity remains undetermined. Little is known about AA-regulated Ca2+ channels or their regulation in ASM. In enzymatically dissociated human ASM cells loaded with the Ca2+ indicator, fura-2, AA (1–10 μM) triggered [Ca2+]i oscillations that were inhibited by removal of extracellular Ca2+. Other fatty acids, such as the diacylglycerol analog, 1-oleoyl-2-acetyl-SN-glycerol, oleic acid, and palmitic acid (10 μM each), failed to elicit similar [Ca2+]i responses. Preincubation with LaCl3 (1 μM or 1 mM) inhibited AA-induced oscillations. Inhibition of receptor-operated channels (SKF96,365 [10 μM]), lipoxygenase (zileuton [10 μM]), or cyclooxygenase (indomethacin [10 μM]) did not affect oscillation parameters. Inhibition of SR Ca2+ release (ryanodine [10 μM] or inositol 1,4,5-trisphosphate receptor inhibitor, xestospongin C [1 μM]) decreased [Ca2+]i oscillation frequency and amplitude. Small interfering RNA against caveolin-1, stromal interaction molecule 1, or Orai3 (20 nM each) reduced the frequency and amplitude of AA-induced [Ca2+]i oscillations. In ASM cells derived from individuals with asthma, AA increased oscillation amplitude, but not frequency. These results are highly suggestive of a novel AA-mediated Ca2+–regulatory mechanism in human ASM, reminiscent of agonist-induced oscillations. Given the role of AA in ASM intracellular signaling, especially with inflammation, AA-regulated Ca2+ channels could potentially

  18. Amino Acid Intakes Are Inversely Associated with Arterial Stiffness and Central Blood Pressure in Women.

    PubMed

    Jennings, Amy; MacGregor, Alex; Welch, Ailsa; Chowienczyk, Phil; Spector, Tim; Cassidy, Aedín

    2015-09-01

    Although data suggest that intakes of total protein and specific amino acids (AAs) reduce blood pressure, data on other cardiovascular disease risk factors are limited. We examined associations between intakes of AAs with known mechanistic links to cardiovascular health and direct measures of arterial stiffness, central blood pressure, and atherosclerosis. In a cross-sectional study of 1898 female twins aged 18-75 y from the TwinsUK registry, intakes of 7 cardioprotective AAs (arginine, cysteine, glutamic acid, glycine, histidine, leucine, and tyrosine) were calculated from food-frequency questionnaires. Direct measures of arterial stiffness and atherosclerosis included central systolic blood pressure (cSBP), mean arterial pressure (MAP), augmentation index (AI), pulse wave velocity (PWV), and intima-media thickness (IMT). ANCOVA was used to assess the associations between endpoints of arterial stiffness and intake (per quintile), adjusting for potential confounders. In multivariable analyses, higher intakes of total protein and 7 potentially cardioprotective AAs were associated with lower cSBP, MAP, and PWV. Higher intakes of glutamic acid, leucine, and tyrosine were most strongly associated with PWV, with respective differences of -0.4 ± 0.2 m/s (P-trend = 0.02), -0.4 ± 0.2 m/s (P-trend = 0.03), and -0.4 ± 0.2 m/s (P-trend = 0.03), comparing extreme quintiles. There was a significant interaction between AA intakes and protein source, and higher intakes of AAs from vegetable sources were associated with lower central blood pressure and AI. Higher intakes of glutamic acid, leucine, and tyrosine from animal sources were associated with lower PWV. These data provide evidence to suggest that intakes of several AAs are associated with cardiovascular benefits beyond blood pressure reduction in healthy women. The magnitude of the observed associations was similar to those previously reported for other lifestyle factors. Increasing intakes of these AAs could be an

  19. Erythrocyte polyunsaturated fatty acid composition is associated with depression and FADS genotype in Caucasians.

    PubMed

    Cribb, Lachlan; Murphy, Jenifer; Froud, Amy; Oliver, Georgina; Bousman, Chad A; Ng, Chee H; Sarris, Jerome

    2017-05-29

    Polyunsaturated fatty acids (PUFAs) play an important role in the pathophysiology of major depressive disorder (MDD), related, in part, to their role in inflammatory systems. The enzymes δ-5 and δ-6 desaturase are the rate-limiting steps in the metabolism of PUFAs and are encoded in the genes fatty acid desaturase (FADS) 1 and 2, respectively. Single nucleotide polymorphisms (SNPs) and haplotypes within the FADS gene cluster have been shown to influence PUFA composition. The objective of this study was to determine whether key omega-3 (n-3) and omega-6 (n-6) fatty acids may be associated with depression, and to explore the role of FADS genotype in PUFA variation. Four erythrocyte long chain (LC) fatty acids (linoleic acid [LA], α-linolenic acid [ALA], arachidonic acid [AA] and Eicosapentaenoic acid [EPA]), as well as six SNPs (rs174537, rs174547, rs174570, rs174575, rs498793 and rs3834458) within the FADS gene cluster were measured in a sample of 207 participants (154 with MDD versus 53 non-depressed controls). The precursor LC-PUFAs LA and ALA appeared to be negatively associated with depression (P < 0.001 and P < 0.01, respectively), while AA:LA (surrogate measure of desaturase activity) was positively associated with depression (P < 0.01). No significant differences were noted in erythrocyte EPA, AA or AA:EPA between groups. Minor alleles of each SNP (excluding rs498793) were associated with variation in desaturase activity and LA. Both rs174537 and rs174547 were associated with ALA. No genotype was associated with EPA or AA. Minor alleles of rs174537 and rs174547 were significantly associated with lower odds of MDD (although significance was lost after correction for multiple comparisons). Precursor LC-PUFAs, LA and ALA, appear to be associated with MDD and potentially modulated by genetic variation in the FADS gene cluster. These results provide support for the consideration of PUFA composition, diet and FADS genetic variation in the

  20. Efficient inhibition of heavy metal release from mine tailings against acid rain exposure by triethylenetetramine intercalated montmorillonite (TETA-Mt).

    PubMed

    Gong, Beini; Wu, Pingxiao; Huang, Zhujian; Li, Yuanyuan; Yang, Shanshan; Dang, Zhi; Ruan, Bo; Kang, Chunxi

    2016-11-15

    The potential application of triethylenetetramine intercalated montmorillonite (TETA-Mt) in mine tailings treatment and AMD (acid mine drainage) remediation was investigated with batch experiments. The structural and morphological characteristics of TETA-Mt were analyzed with XRD, FTIR, DTG-TG and SEM. The inhibition efficiencies of TETA-Mt against heavy metal release from mine tailings when exposed to acid rain leaching was examined and compared with that of triethylenetetramine (TETA) and Mt. Results showed that the overall inhibition by TETA-Mt surpassed that by TETA or Mt for various heavy metal ions over an acid rain pH range of 3-5.6 and a temperature range of 25-40°C. When mine tailings were exposed to acid rain of pH 4.8 (the average rain pH of the mining site where the mine tailings were from), TETA-Mt achieved an inhibition efficiency of over 90% for Cu(2+), Zn(2+), Cd(2+) and Mn(2+) release, and 70% for Pb(2+) at 25°C. It was shown that TETA-Mt has a strong buffering capacity. Moreover, TETA-Mt was able to adsorb heavy metal ions and the adsorption process was fast, suggesting that coordination was mainly responsible. These results showed the potential of TETA-Mt in AMD mitigation, especially in acid rain affected mining area. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Contribution of Fermentation Yeast to Final Amino Acid Profile in DDGS

    USDA-ARS?s Scientific Manuscript database

    One major factor affecting DDGS quality and market values is amino acid (AA) composition. DDGS proteins come from corn and yeast. Yet, the effect of fermentation yeast on DDGS protein quantity and quality (AA profile) has not been well documented. Based on literature review, there are at least 4 met...

  2. Synthesis of organic/inorganic hybrid gel with acid activated clay after γ-ray radiation.

    PubMed

    Kim, Donghyun; Lee, Hoik; Sohn, Daewon

    2014-08-01

    A hybrid gel was prepared from acid activated clay (AA clay) and acrylic acid by gamma ray irradiation. Irradiated inorganic particles which have peroxide groups act as initiator because it generates oxide radicals by increasing temperature. Inorganic nanoparticles which are rigid part in hybrid gel also contribute to increase the mechanical property as a crosslinker. We prepared two hybrid gels to compare the effect of acid activated treatment of clay; one is synthesized with raw clay particles and another is synthesized with AA clay particles. The composition and structure of AA clay particles and raw clay particles were confirmed by X-ray diffraction (XRD), X-ray fluorescence instrument and surface area analyzer. And chemical and physical property of hybrid gel with different ratios of acrylic acid and clay particle was tested by Raman spectroscope and universal testing machine (UTM). The synthesized hydrogel with 76% gel contents can elongated approximately 1000% of its original size.

  3. The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters

    PubMed Central

    Hu, Rujiu; Li, Jing; Soomro, Rab Nawaz; Wang, Fei; Feng, Yan; Yang, Xiaojun

    2017-01-01

    This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs) in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg) were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05) across all treatments. The amino acid (AA) profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05) by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05). The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients. PMID:29166671

  4. The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters.

    PubMed

    Hu, Rujiu; Li, Jing; Soomro, Rab Nawaz; Wang, Fei; Feng, Yan; Yang, Xiaojun; Yao, Junhu

    2017-01-01

    This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs) in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg) were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05) across all treatments. The amino acid (AA) profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05) by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05). The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients.

  5. Selection of the Strain Lactobacillus acidophilus ATCC 43121 and Its Application to Brewers' Spent Grain Conversion into Lactic Acid

    PubMed Central

    Liguori, Rossana; Soccol, Carlos Ricardo; Vandenberghe, Luciana Porto de Souza; Woiciechowski, Adenise Lorenci; Ionata, Elena; Marcolongo, Loredana; Faraco, Vincenza

    2015-01-01

    Six Lactobacillus strains were analyzed to select a bacterium for conversion of brewers' spent grain (BSG) into lactic acid. Among the investigated strains, L. acidophilus ATCC 43121 showed the highest yield of lactic acid production (16.1 g/L after 48 hours) when grown in a synthetic medium. It was then analyzed for its ability to grow on the hydrolysates obtained from BSG after acid-alkaline (AAT) or aqueous ammonia soaking (AAS) pretreatment. The lactic acid production by L. acidophilus ATCC 43121 through fermentation of the hydrolysate from AAS treated BSG was 96% higher than that from the AAT treated one, although similar yields of lactic acid per consumed glucose were achieved due to a higher (46%) glucose consumption by L. acidophilus ATCC 43121 in the AAS BSG hydrolysate. It is worth noting that adding yeast extract to the BSG hydrolysates increased both the yield of lactic acid per substrate consumed and the volumetric productivity. The best results were obtained by fermentation of AAS BSG hydrolysate supplemented by yeast extract, in which the strain produced 22.16 g/L of lactic acid (yield of 0.61 g/g), 27% higher than the value (17.49 g/L) obtained in the absence of a nitrogen source. PMID:26640784

  6. Morphology-dependent Electrochemical Enhancements of Porous Carbon as Sensitive Determination Platform for Ascorbic Acid, Dopamine and Uric Acid

    NASA Astrophysics Data System (ADS)

    Cheng, Qin; Ji, Liudi; Wu, Kangbing; Zhang, Weikang

    2016-02-01

    Using starch as the carbon precursor and different-sized ZnO naoparticles as the hard template, a series of porous carbon materials for electrochemical sensing were prepared. Experiments of scanning electron microscopy, transmission electron microscopy and Nitrogen adsorption-desorption isotherms reveal that the particle size of ZnO has big impacts on the porous morphology and surface area of the resulting carbon materials. Through ultrasonic dispersion of porous carbon and subsequent solvent evaporation, different sensing interfaces were constructed on the surface of glassy carbon electrode (GCE). The electrochemical behaviors of ascorbic acid (AA), dopamine (DA) and uric acid (UA) were studied. On the surface of porous carbon materials, the accumulation efficiency and electron transfer ability of AA, DA and UA are improved, and consequently their oxidation signals enhance greatly. Moreover, the interface enhancement effects of porous carbon are also controlled by the particle size of hard template. The constructed porous carbon interface displays strong signal amplification ability and holds great promise in constructing a sensitive platform for the simultaneous determination of AA, DA and UA.

  7. Gas release-based prescreening combined with reversed-phase HPLC quantitation for efficient selection of high-γ-aminobutyric acid (GABA)-producing lactic acid bacteria.

    PubMed

    Wu, Qinglong; Shah, Nagendra P

    2015-02-01

    High γ-aminobutyric acid (GABA)-producing lactobacilli are promising for the manufacture of GABA-rich foods and to synthesize GRAS (generally recognized as safe)-grade GABA. However, common chromatography-based screening is time-consuming and inefficient. In the present study, Korean kimchi was used as a model of lactic acid-based fermented foods, and a gas release-based prescreening of potential GABA producers was developed. The ability to produce GABA by potential GABA producers in de Man, Rogosa, and Sharpe medium supplemented with or without monosodium glutamate was further determined by HPLC. Based on the results, 9 isolates were regarded as high GABA producers, and were further genetically identified as Lactobacillus brevis based on the sequences of 16S rRNA gene. Gas release-based prescreening combined with reversed-phase HPLC confirmation was an efficient and cost-effective method to identify high-GABA-producing LAB, which could be good candidates for probiotics. The GABA that is naturally produced by these high-GABA-producing LAB could be used as a food additive. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Characteristics of AA amyloidosis patients in San Francisco.

    PubMed

    Lejmi, Hiba; Jen, Kuang-Yu; Olson, Jean L; James, Sam H; Sam, Ramin

    2016-04-01

    AA amyloidosis due to subcutaneous injection of drugs of abuse has been described in the USA, but all the existing literature is from more than 20 years ago. There is more recent literature from Europe. We have observed a high incidence of AA amyloidosis in the county hospital in San Francisco. Here, we describe 24 patients who had kidney biopsy-proven AA amyloidosis from our hospital from 1998 to 2013. All the patients were thought to have AA amyloidosis from skin popping of illicit drugs after having exhausted the intravenous route. These patients with biopsy-proven AA amyloidosis were analysed further. All patients were found to have hepatitis C infection, hypertension was not common, most had advanced kidney failure, and acidosis was common as was tubulointerstitial involvement on the kidney biopsy. Other organ involvement included hepatomegaly and splenomegaly in a number of patients; direct myocardial involvement was not seen, but pulmonary hypertension, history of deep vein thrombosis and pulmonary embolism were common. The prognosis of these patients was poor. The mortality rate approached 50% 1 year after biopsy, and most of the patient needed dialysis shortly after diagnosis. Cessation of drug use seemed beneficial but rarely achievable. AA amyloidosis from skin popping is common in San Francisco. Most patients with renal involvement end up on dialysis, and mortality rates are exceedingly high. © 2015 Asian Pacific Society of Nephrology.

  9. Prediction protein structural classes with pseudo-amino acid composition: approximate entropy and hydrophobicity pattern.

    PubMed

    Zhang, Tong-Liang; Ding, Yong-Sheng; Chou, Kuo-Chen

    2008-01-07

    Compared with the conventional amino acid (AA) composition, the pseudo-amino acid (PseAA) composition as originally introduced for protein subcellular location prediction can incorporate much more information of a protein sequence, so as to remarkably enhance the power of using a discrete model to predict various attributes of a protein. In this study, based on the concept of PseAA composition, the approximate entropy and hydrophobicity pattern of a protein sequence are used to characterize the PseAA components. Also, the immune genetic algorithm (IGA) is applied to search the optimal weight factors in generating the PseAA composition. Thus, for a given protein sequence sample, a 27-D (dimensional) PseAA composition is generated as its descriptor. The fuzzy K nearest neighbors (FKNN) classifier is adopted as the prediction engine. The results thus obtained in predicting protein structural classification are quite encouraging, indicating that the current approach may also be used to improve the prediction quality of other protein attributes, or at least can play a complimentary role to the existing methods in the relevant areas. Our algorithm is written in Matlab that is available by contacting the corresponding author.

  10. Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke

    PubMed Central

    Rink, Cameron

    2011-01-01

    Abstract The significance of the hypoxia component of stroke injury is highlighted by hypermetabolic brain tissue enriched with arachidonic acid (AA), a 22:6n-3 polyunsaturated fatty acid. In an ischemic stroke environment in which cerebral blood flow is arrested, oxygen-starved brain tissue initiates the rapid cleavage of AA from the membrane phospholipid bilayer. Once free, AA undergoes both enzyme-independent and enzyme-mediated oxidative metabolism, resulting in the formation of number of biologically active metabolites which themselves contribute to pathological stroke outcomes. This review is intended to examine two divergent roles of molecular dioxygen in brain tissue as (1) a substrate for life-sustaining homeostatic metabolism of glucose and (2) a substrate for pathogenic metabolism of AA under conditions of stroke. Recent developments in research concerning supplemental oxygen therapy as an intervention to correct the hypoxic component of stroke injury are discussed. Antioxid. Redox Signal. 14, 1889–1903. PMID:20673202

  11. Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

    PubMed

    Modi, Hiren R; Ma, Kaizong; Chang, Lisa; Chen, Mei; Rapoport, Stanley I

    2017-08-01

    Valproic acid (VPA), used for treating bipolar disorder (BD), is teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic constitutional isomer of VPA amide, reported effective in BD, also inhibits recombinant Acsl-4 in vitro. VCD like VPA will reduce brain AA turnover in unanaesthetized rats. A therapeutically relevant (50mg/kg i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA turnover and related parameters were determined using our kinetic model, following intravenous [1- 14 C]AA in unanaesthetized rats for 10min, and measuring labeled and unlabeled lipids in plasma and high-energy microwaved brain. VCD, compared with vehicle, increased λ, the ratio of brain AA-CoA to unesterified plasma AA specific activities; and decreased turnover of AA in individual and total brain phospholipids. VCD's ability like VPA to reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in BD, suggest that VCD be further considered as a non-teratogenic VPA substitute for treating BD. Published by Elsevier B.V.

  12. The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model.

    PubMed

    Ren, Xiaobin; Zhang, Mingzhu; Chen, Lingxiang; Zhang, Wanli; Huang, Yu; Luo, Huazhen; Li, Ling; He, Hongbing

    2017-10-01

    The traditional Chinese medicine Yunnan Baiyao (YNB) has been reported to possess anti‑inflammatory properties, however its mechanism of action remains unclear. It was previously reported that YNB ameliorated depression of arachidonic acid (AA) levels in a rat model of collagen-induced arthritis. In the current study, the capacity of YNB to ameliorate inflammation was compared in carrageenan‑induced and AA‑induced acute inflammation of the rat paw with celecoxib and mizolastine, respectively (n=24 per group). The capacity of YNB to affect the phospholipase A2 (PLA2)/AA pathway (using reverse transcription‑quantitative polymerase chain reaction) and release of inflammatory lipid mediators (by ELISA) were investigated. Celecoxib ameliorated carrageenan‑induced paw edema, and mizolastine ameliorated AA‑induced rat paw edema. YNB alleviated paw edema and inhibited inflammatory cell infiltration in the two models. YNB inhibited production of 5‑LOX AA metabolite leukotriene B4 (LTB4), and suppressed expression of 5‑LOX, cytosolic PLA2 (cPLA2), 5‑LOX‑activating protein, and LTB4 receptor mRNA in the AA‑induced inflammation model (P<0.05). YNB Inhibited the production of the COX‑2 AA metabolite prostaglandin E2 (PGE2) and suppressed expression of COX‑2, cPLA2, PGE2 mRNA in the carrageenan‑induced inflammation mode (P<0.05). Taken together, the data suggest that modulation of COX and LOX pathways in AA metabolism represent a novel anti-inflammatory mechanism of YNB.

  13. Cooking methods employing natural anti-oxidant food additives effectively reduced concentration of nephrotoxic and carcinogenic aristolochic acids in contaminated food grains.

    PubMed

    Li, Weiwei; Chan, Chi-Kong; Wong, Yee-Lam; Chan, K K Jason; Chan, Ho Wai; Chan, Wan

    2018-10-30

    Emerging evidence suggests that aristolochic acids (AA) produced naturally by a common weed Aristolochia clematitis in the cultivation fields is contaminating the food products in Balkan Peninsula and acting as the etiological agent in the development of Balkan endemic nephropathy. In this study, we investigated the combined use of natural anti-oxidative "food additives" and different cooking methods to find a solution for the widespread contamination of AA in food products. The results indicated that the addition of healthy dietary supplements (such as cysteine, glutathione, ascorbic acid, citric acid and magnesium) during cooking, is a highly efficient method in lowering the concentration of AA in the final food products. Because previous observation indicated one of the toxicological mechanisms by which AA exert its toxicity is to induce oxidative stress in internal organs, it is anticipated that these added anti-oxidants will also help to attenuate the nephrotoxicity of AA. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. THE COMBINATION OF α-LIPOIC ACID INTAKE WITH ECCENTRIC EXERCISE MODULATES ERYTHROPOIETIN RELEASE

    PubMed Central

    Morawin, B.; Turowski, D.; Naczk, M.; Siatkowski, I.

    2014-01-01

    The generation of reactive nitrogen/oxygen species (RN/OS) represents an important mechanism in erythropoietin (EPO) expression and skeletal muscle adaptation to physical and metabolic stress. RN/OS generation can be modulated by intense exercise and nutrition supplements such as α-lipoic acid, which demonstrates both anti- and pro-oxidative action. The study was designed to show the changes in the haematological response through the combination of α-lipoic acid intake with running eccentric exercise. Sixteen healthy young males participated in the randomised and placebo-controlled study. The exercise trial involved a 90-min run followed by a 15-min eccentric phase at 65% VO2max (-10% gradient). It significantly increased serum concentrations of nitric oxide (NO), hydrogen peroxide (H2O2) and pro-oxidative products such as 8-isoprostanes (8-iso), lipid peroxides (LPO) and protein carbonyls (PC). α-Lipoic acid intake (Thiogamma: 1200 mg daily for 10 days prior to exercise) resulted in a 2-fold elevation of serum H2O2 concentration before exercise, but it prevented the generation of NO, 8-iso, LPO and PC at 20 min, 24 h, and 48 h after exercise. α-Lipoic acid also elevated serum EPO level, which highly correlated with NO/H2O2 ratio (r = 0.718, P < 0.01). Serum total creatine kinase (CK) activity, as a marker of muscle damage, reached a peak at 24 h after exercise (placebo 732 ± 207 IU · L-1, α-lipoic acid 481 ± 103 IU · L-1), and correlated with EPO (r = 0.478, P < 0.01) in the α-lipoic acid group. In conclusion, the intake of high α-lipoic acid modulates RN/OS generation, enhances EPO release and reduces muscle damage after running eccentric exercise. PMID:25177095

  15. THE COMBINATION OF α-LIPOIC ACID INTAKE WITH ECCENTRIC EXERCISE MODULATES ERYTHROPOIETIN RELEASE.

    PubMed

    Morawin, B; Turowski, D; Naczk, M; Siatkowski, I; Zembron-Lacny, A

    2014-08-01

    The generation of reactive nitrogen/oxygen species (RN/OS) represents an important mechanism in erythropoietin (EPO) expression and skeletal muscle adaptation to physical and metabolic stress. RN/OS generation can be modulated by intense exercise and nutrition supplements such as α-lipoic acid, which demonstrates both anti- and pro-oxidative action. The study was designed to show the changes in the haematological response through the combination of α-lipoic acid intake with running eccentric exercise. Sixteen healthy young males participated in the randomised and placebo-controlled study. The exercise trial involved a 90-min run followed by a 15-min eccentric phase at 65% VO2max (-10% gradient). It significantly increased serum concentrations of nitric oxide (NO), hydrogen peroxide (H2O2) and pro-oxidative products such as 8-isoprostanes (8-iso), lipid peroxides (LPO) and protein carbonyls (PC). α-Lipoic acid intake (Thiogamma: 1200 mg daily for 10 days prior to exercise) resulted in a 2-fold elevation of serum H2O2 concentration before exercise, but it prevented the generation of NO, 8-iso, LPO and PC at 20 min, 24 h, and 48 h after exercise. α-Lipoic acid also elevated serum EPO level, which highly correlated with NO/H2O2 ratio (r = 0.718, P < 0.01). Serum total creatine kinase (CK) activity, as a marker of muscle damage, reached a peak at 24 h after exercise (placebo 732 ± 207 IU · L(-1), α-lipoic acid 481 ± 103 IU · L(-1)), and correlated with EPO (r = 0.478, P < 0.01) in the α-lipoic acid group. In conclusion, the intake of high α-lipoic acid modulates RN/OS generation, enhances EPO release and reduces muscle damage after running eccentric exercise.

  16. MDCT evaluation of acute aortic syndrome (AAS)

    PubMed Central

    Rossi, Giovanni; Lassandro, Francesco; Rea, Gaetano; Marino, Maurizio; Muto, Maurizio; Molino, Antonio; Scaglione, Mariano

    2016-01-01

    Non-traumatic acute thoracic aortic syndromes (AAS) describe a spectrum of life-threatening aortic pathologies with significant implications on diagnosis, therapy and management. There is a common pathway for the various manifestations of AAS that eventually leads to a breakdown of the aortic intima and media. Improvements in biology and health policy and diffusion of technology into the community resulted in an associated decrease in mortality and morbidity related to aortic therapeutic interventions. Hybrid procedures, branched and fenestrated endografts, and percutaneous aortic valves have emerged as potent and viable alternatives to traditional surgeries. In this context, current state-of-the art multidetector CT (MDCT) is actually the gold standard in the emergency setting because of its intrinsic diagnostic value. Management of acute aortic disease has changed with the increasing realization that endovascular therapies may offer distinct advantages in these situations. This article provides a summary of AAS, focusing especially on the MDCT technique, typical and atypical findings and common pitfalls of AAS, as well as recent concepts regarding the subtypes of AAS, consisting of aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer and unstable aortic aneurysm or contained aortic rupture. MDCT findings will be related to pathophysiology, timing and management options to achieve a definite and timely diagnostic and therapeutic definition. In the present article, we review the aetiology, pathophysiology, clinical presentation, outcomes and therapeutic approaches to acute aortic syndromes. PMID:27033344

  17. Dose- and Glucose-Dependent Effects of Amino Acids on Insulin Secretion from Isolated Mouse Islets and Clonal INS-1E Beta-Cells

    PubMed Central

    Liu, Zhenping; Jeppesen, Per B.; Gregersen, Søren; Chen, Xiaoping; Hermansen, Kjeld

    2008-01-01

    BACKGROUND: The influence of glucose and fatty acids on beta-cell function is well established whereas little is known about the role of amino acids (AAs). METHODS: Islets isolated from NMRI mice were incubated overnight. After preincubation, isolated islets as well as clonal INS-1E beta-cells were incubated for 60 min in a modified Krebs Ringer buffer containing glucose and AAs. RESULTS: At 16.7 mmol/l (mM) glucose, L-arginine, L-lysine, L-alanine, L-proline, L-leucine, and L-glutamine potentiated glucose-stimulated insulin secretion dose-dependently, while DL-homocysteine inhibited insulin secretion. Maximal insulin stimulation was obtained at 20 mM L-proline, L-lysine, L-alanine, L-arginine (islets: 2.5 to 6.7 fold increase; INS-1E cells: 1.6 to 2.2 fold increase). L-glutamine and L-leucine only increased glucose-stimulated (16.7 mM) insulin secretion (INS-1E cells: 1.5 and 1.3 fold, respectively) at an AA concentration of 20 mM. Homocysteine inhibited insulin secretion both at 5.6 mM and 16.7 mM glucose. At glucose levels ranging from 1.1 to 25 mM, the equimolar concentration of 10 mM, L-proline, L-lysine, L-arginine increased insulin secretion from mouse islets and INS-1E cells at all glucose levels applied, with a maximal effect obtained at 25 mM glucose. At a concentration of 10 mM, L-arginine and L-lysine had the highest insulinotropic potency among the AAs investigated. CONCLUSION: L-arginine, L-lysine, L-alanine, L-proline, L-leucine and L-glutamine acutely stimulate insulin secretion from mouse islets and INS-1E cells in a dose- and glucose-dependent manner, whereas DL-homocysteine inhibits insulin release. PMID:19290384

  18. The multiplicity of spinal AA-5-HT anti-nociceptive action in a rat model of neuropathic pain.

    PubMed

    Malek, Natalia; Kostrzewa, Magdalena; Makuch, Wioletta; Pajak, Agnieszka; Kucharczyk, Mateusz; Piscitelli, Fabiana; Przewlocka, Barbara; Di Marzo, Vincenzo; Starowicz, Katarzyna

    2016-09-01

    There is considerable evidence to support the role of anandamide (AEA), an endogenous ligand of cannabinoid receptors, in neuropathic pain modulation. AEA also produces effects mediated by other biological targets, of which the transient receptor potential vanilloid type 1 (TRPV1) has been the most investigated. Both, inhibition of AEA breakdown by fatty acid amide hydrolase (FAAH) and blockage of TRPV1 have been shown to produce anti-nociceptive effects. Recent research suggests the usefulness of dual-action compounds, which may afford greater anti-allodynic efficacy. Therefore, in the present study, we examined the effect of N-arachidonoyl-serotonin (AA-5-HT), a blocker of FAAH and TRPV1, in a rat model of neuropathic pain after intrathecal administration. We found that treatment with AA-5-HT increased the pain threshold to mechanical and thermal stimuli, with highest effect at the dose of 500nM, which was most strongly attenuated by AM-630, CB2 antagonist, administration. The single action blockers PF-3845 (1000nM, for FAAH) and I-RTX (1nM, for TRPV1) showed lower efficacy than AA-5-HT. Moreover AA-5-HT (500nM) elevated AEA and palmitoylethanolamide (PEA) levels. Among the possible targets of these mediators, only the mRNA levels of CB2, GPR18 and GPR55, which are believed to be novel cannabinoid receptors, were upregulated in the spinal cord and/or DRG of CCI rats. It was previously reported that AA-5-HT acts in CB1 and TRPV1-dependent manner after systemic administration, but here for the first time we show that AA-5-HT action at the spinal level involves CB2, with potential contributions from GRP18 and/or GPR55 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers.

    PubMed

    Morelli, G; Chen, H; Rossiter, G; Rege, B; Lu, Y

    2011-04-01

    Novel rabeprazole extended-release (ER) formulations were developed to provide prolonged gastric acid suppression and potentially improved clinical outcomes in GERD patients. To evaluate the pharmacodynamics and pharmacokinetics of six rabeprazole-ER formulations vs. esomeprazole 40 mg and rabeprazole delayed-release (DR) 20 mg. Helicobacter pylori-negative healthy subjects were randomised to receive one of eight treatments once daily for 5 days. Twenty-four-hour intragastric pH was monitored on days -1, 1 and 5. Rabeprazole plasma concentrations were measured on day 5. A total of 248 subjects (N=31/group) were enrolled in the study. On day 5, rabeprazole-ER groups provided mean durations of 18.5-20.2 h (77.0-84.1% of 24-h) with intragastric pH >4.0 vs. esomeprazole 40 mg (15.9 h/66.1% of 24-h) and rabeprazole-DR 20 mg (15.2 h/63.2% of 24-h). A similar increase was observed on day 1. While percentage of daytime (8 am-10 pm) with intragastric pH >4.0 on day 5 was overall similar across the groups, percentage of night-time (10 pm-8 am) with intragastric pH >4.0 was higher with the rabeprazole-ER groups (57.0-72.4%) vs. esomeprazole 40 mg (32.8%) and rabeprazole-DR 20 mg (34.0%). Rabeprazole-ER once daily for 5 days demonstrated a significantly longer duration of gastric acid suppression in 24 h vs. esomeprazole 40 mg and rabeprazole-DR 20 mg. The increase in acid suppression was predominantly due to prolonged acid suppression during the night-time; this was supported by the extended-release pharmacokinetic characteristics. © 2011 Blackwell Publishing Ltd.

  20. Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline

    PubMed Central

    Harrison, Fiona E.; Bowman, Gene L.; Polidori, Maria Cristina

    2014-01-01

    This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. PMID:24763117