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Sample records for deuterated arachidonic acids

  1. Is arachidonic acid an endoschistosomicide?

    Directory of Open Access Journals (Sweden)

    Violette Said Hanna

    2018-05-01

    Full Text Available Schistosoma mansoni and Schistosoma haematobium are intravascular, parasitic flatworms that infect >250 million people in 70 developing countries, yet not all people of the same community and household are afflicted. Regarding laboratory rodents, mice but not rats are susceptible to infection with S. mansoni and hamsters but not mice are entirely permissive to infection with S. haematobium. A recent Brazilian publication has demonstrated that resistance of the water-rat, Nectomys squamipes to S. mansoni infection might be ascribed to stores of arachidonic acid (ARA-rich lipids in liver. Several reports have previously shown that ARA is a safe and effective schistosomicide in vitro, and in vivo in mice, hamsters and in children. Schistosoma haematobium appeared more sensitive than S. mansoni to ARA in in vitro and in vivo experiments. Accordingly, it was proposed that ARA increased levels might be predominantly responsible for natural attrition of S. mansoni and S. haematobium in resistant experimental rodents. Therefore, the levels of ARA in serum, lung, and liver of rats (resistant and mice (susceptible at 1, 2, 3, 4 and 6 weeks after infection with S. mansoni cercariae and between mice (semi-permissive and hamster (susceptible at 1, 2, 3, 4, and 12 weeks after infection with S. haematobium cercariae were compared and contrasted. Neutral triglycerides and ARA levels were assessed in serum using commercially available assays and in liver and lung sections by transmission electron microscopy, Oil Red O staining, and specific anti-ARA antibody-based immunohistochemistry assays. Significant (P < .05, consistent, and reproducible correlation was recorded between ARA content in serum, lung, and liver and rodent resistance to schistosome infection, thereby implicating ARA as an endoschistosomicide. Keywords: Schistosoma mansoni, Schistosoma haematobium, Rat schistosomiasis, Arachidonic acid, Oil Red O staining, Immunohistochemistry

  2. Methods for preparation of deuterated amino acids

    International Nuclear Information System (INIS)

    Pshenichnikova, A.B.; Karnaukhova, E.N.; Zvonkova, E.N.

    1995-01-01

    The current state and prospects for the use of amino acids labeled with stable isotopes are considered. Methods for the preparation of deuterated amino acids, including synthetic, chemicoenzymatic, and biosynthetic ones, and deuterium exchange reactions are summarized. Problems in the preparation of optically pure amino acids are discussed. 120 refs., 15 figs

  3. Dietary arachidonic acid in perinatal nutrition

    DEFF Research Database (Denmark)

    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 lev...

  4. Arachidonic acid is a chemoattractant for Dictyostelium discoideum

    Indian Academy of Sciences (India)

    Arachidonic acid is a chemoattractant for Dictyostelium discoideum cells ... Arachidonic acid; chemotaxis; fatty acids; iplA ... Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca2+ concentration by causing the release of Ca2+ from intracellular stores and activating influx of ...

  5. Preparation of deuterated succinic acids

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Masashi; Tsuzuki, Hirohisa; Goto, Hideyuki; Ogasahara, Shoji; Mataka, Shuntaro (Kyushu Univ., Fukuoka (Japan)); Isobe, Shin-ichiro; Yonemitsu, Tadashi (Kyushu Sangyo Univ., Fukuoka (Japan). Dept. of Industrial Chemistry)

    1991-04-01

    Succinic (2,3-{sup 2}H{sub 2})- and (2,2,3,3-{sup 2}H{sub 4})-acids were prepared from maleic anhydride and dimethyl fumarate, and acetylene dicarboxylic acid and its dimethyl ester by treatment with Cu-Al and Ni-Al alloys in 10% NaOD-D{sub 2}0 in 95% to 100% isotopic purity. The succinic {sup 2}H{sub 4} acid having high isotopic purity was also obtained on the hydrolysis of 1,2-ethanedinitrile with alkaline deuterium oxide. Based on the {sup 1}H({sup 2}H) spectra analysis of N-(o-biphenyl)(2,3-{sup 2}H{sub 2})succinimide, it was elucidated that the Raney alloy reduction with alkaline deuterium oxide proceeds stepwise. (author).

  6. Bacterial metabolism of human polymorphonuclear leukocyte-derived arachidonic acid.

    Science.gov (United States)

    Sorrell, T C; Muller, M; Sztelma, K

    1992-05-01

    Evidence for transcellular bacterial metabolism of phagocyte-derived arachidonic acid was sought by exposing human blood polymorphonuclear leukocytes, prelabelled with [3H]arachidonic acid, to opsonized, stationary-phase Pseudomonas aeruginosa (bacteria-to-phagocyte ratio of 50:1) for 90 min at 37 degrees C. Control leukocytes were stimulated with the calcium ionophore A23187 (5 microM) for 5 min. Radiochromatograms of arachidonic acid metabolites, extracted from A23187-stimulated cultures and then separated by reverse-phase high-performance liquid chromatography, revealed leukotriene B4, its omega-oxidation products, and 5-hydroxy-eicosatetraenoic acid. In contrast, two major metabolite peaks, distinct from known polymorphonuclear leukocyte arachidonic acid products by high-performance liquid chromatography or by thin-layer chromatography, were identified in cultures of P. aeruginosa with [3H]arachidonic acid-labelled polymorphonuclear leukocytes. Respective chromatographic characteristics of these novel products were identical to those of two major metabolite peaks produced by incubation of stationary-phase P. aeruginosa with [3H]arachidonic acid. Production of the metabolites was dependent upon pseudomonal viability. UV spectral data were consistent with a conjugated diene structure. Metabolism of arachidonic acid by P. aeruginosa was not influenced by the presence of catalase, superoxide dismutase, nordihydroguaiaretic acid, ethanol, dimethyl sulfoxide, or ferrous ions but was inhibited by carbon monoxide, ketoconazole, and 1,2-epoxy-3,3,3-trichloropropane. Our data suggest that pseudomonal metabolism of polymorphonuclear leukocyte-derived arachidonic acid occurs during phagocytosis, probably by enzymatic epoxidation and hydroxylation via an oxygenase. By this means, potential proinflammatory effects of arachidonic acid or its metabolites may be modulated by P. aeruginosa at sites of infection in vivo.

  7. Docosahexaenoic acid affects arachidonic acid uptake in megakaryocytes

    International Nuclear Information System (INIS)

    Schick, P.K.; Webster, P.

    1987-01-01

    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 [ 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 [ 14 C]-20:4 into total MK phospholipids, 16% and 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 [ 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 [ 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

  8. Arachidonic acid assimilation by thrombocytes from white carneau pigeons

    International Nuclear Information System (INIS)

    Saxon, D.J.; Blankenship, T.

    1986-01-01

    The metabolism of arachidonic acid was investigated using thrombocyte-enriched-plasma from RBWC and WC-II white carneau pigeons, which differ genetically in their susceptibility to atherosclerosis. Thrombocytes were incubated at 42 C with [ 14 C] arachidonate in Puck's solution. After a 1 hour labeling period the WC-II cells had taken up 69% and RBWC 77% of the [ 14 C]arachidonate from the medium. When 8,11,14-eicosatrienoic acid or 5,8,11,14,17-eicosapentaenoic acid were added to incubation media the [ 14 C] uptake was reduced in each type cell, with WC-II exhibiting the greatest effect. Release of [ 14 C]molecules from cells labeled with [ 14 ]Carachidonate was studied using calcium ionophore and indomethacin. Indomethacin inhibited [ 14 C] molecule release similarly in both RBWC and WC-II cells. Calcium ionophore was twice as effective in stimulating [ 14 C]molecule release from WC-II than RBWC cells. Therefore, the WE-II cells (from pigeons greater in susceptibility to atherosclerosis) are more sensitive to calcium ionophore than the REWC cells

  9. Measurement of the incorporation of orally administered arachidonic acid into tissue lipids

    International Nuclear Information System (INIS)

    Kulmacz, R.J.; Sivarajan, M.; Lands, W.E.

    1986-01-01

    The applicability of a stable isotope method to monitor the mixing of dietary arachidonic acid with endogenous arachidonic acid in tissue lipids was evaluated. Rats were fed octadeuterated arachidonic acid during a 20-day period, and the entry of the dietary acid into lipid esters of various tissues was examined by gas chromatography-mass spectrometric (GC-MS) analysis of their fatty acids. The rats were maintained on a fat-free diet from weaning until 63 days old to enhance the ratio of the dietary acid to endogenous arachidonate. Three separate forms of eicosatetraenoic acid in the tissue lipids could be distinguished by GC-MS: octadeuterated arachidonic acid (recent dietary origin), unlabeled arachidonic acid (maternal origin) and unlabeled 4,7,10,13-eicosatetraenoic acid (originating from palmitoleic acid). The total eicosatetraenoic acid in the tissue lipids contained about 90% arachidonate from recent dietary origin in lung, kidney, heart and fat, 70% in muscle and liver and 27% in brain. The n-7 isomer of eicosatetraenoic acid was estimated to make up 6% or less of the total eicosatetraenoic acid in lung, kidney, brain, muscle and heart tissue lipids, but it comprised around 15% of the total eicosatetraenoic acid in liver. The unlabeled arachidonic acid of maternal origin thus comprised only about 10% of the eicosatetraenoic acid in all tissues examined except muscle and brain, where it was 24% and 70% of the eicosatetraenoic acid, respectively

  10. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-12-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  11. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-01-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  12. Novel metabolic pathways for linoleic and arachidonic acid metabolism.

    Science.gov (United States)

    Moghaddam, M; Motoba, K; Borhan, B; Pinot, F; Hammock, B D

    1996-08-13

    Mouse liver microsomes oxidized linoleic acid to form 9,10- or 12,13-epoxyoctadecenoate. These monoepoxides were subsequently hydrolyzed to their corresponding diols in the absence of the microsomal epoxide hydrolase inhibitor, 1,2-epoxy-3,3,3-trichloropropane. Furthermore, both 9,10- and 12,13-epoxyoctadecenoates were oxidized to diepoxyoctadecanoate at apparently identical rates by mouse liver microsomal P-450 epoxidation. Both epoxyoctadecanoates and diepoxyoctadecanoates were converted to tetrahydrofuran-diols by microsomes. Tetrahydroxides of linoleate were produced as minor metabolites. Arachidonic acid was metabolized to epoxyeicosatrienoates, dihydroxyeicosatrienoates, and monohydroxyeicosatetraenoates by the microsomes. Microsomes prepared from clofibrate (but not phenobarbital) -treated mice exhibited much higher production rates for epoxyeicosatrienoates and vic-dihydroxyeicosatrienoates. This indicated an induction of P-450 epoxygenase(s) and microsomal epoxide hydrolase in mice by clofibrate and not by phenobarbital. Incubation of synthetic epoxyeicosatrienoates with microsomes led to the production of diepoxyeicosadienoates. Among chemically generated diepoxyeicosadienoate isomers, three of them possessing adjacent diepoxides were hydrolyzed to their diol epoxides which cyclized to the corresponding tetrahydrofuran-diols by microsomes as well as soluble epoxide hydrolase at a much higher rate. Larger cyclic products from non-adjacent diepoxides were not observed. The results of our in vitro experiments suggest that linoleic and arachidonic acid can be metabolized to their tetrahydrofuran-diols by two consecutive microsomal cytochrome P-450 epoxidations followed by microsomal or soluble epoxide hydrolase catalyzed hydrolysis of the epoxides. Incubation experiments with the S-9 fractions indicate that the soluble epoxide hydrolase is more important in this conversion. This manuscript is the first report of techniques for the separation and

  13. DEUTERIUM FRACTIONATION DURING AMINO ACID FORMATION BY PHOTOLYSIS OF INTERSTELLAR ICE ANALOGS CONTAINING DEUTERATED METHANOL

    Energy Technology Data Exchange (ETDEWEB)

    Oba, Yasuhiro; Watanabe, Naoki; Kouchi, Akira [Institute of Low Temperature Science, Hokkaido University, N19W8, Kita-ku, Sapporo, Hokkaido 060-0819 (Japan); Takano, Yoshinori, E-mail: oba@lowtem.hokudai.ac.jp [Department of Biogeochemistry, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), 2-15 Natsushima, Yokosuka, Kanagawa 237-0061 (Japan)

    2016-08-10

    Deuterium (D) atoms in interstellar deuterated methanol might be distributed into complex organic molecules through molecular evolution by photochemical reactions in interstellar grains. In this study, we use a state-of-the-art high-resolution mass spectrometer coupled with a high-performance liquid chromatography system to quantitatively analyze amino acids and their deuterated isotopologues formed by the photolysis of interstellar ice analogs containing singly deuterated methanol CH{sub 2}DOH at 10 K. Five amino acids (glycine, α -alanine, β -alanine, sarcosine, and serine) and their deuterated isotopologues whose D atoms are bound to carbon atoms are detected in organic residues formed by photolysis followed by warming up to room temperature. The abundances of singly deuterated amino acids are in the range of 0.3–1.1 relative to each nondeuterated counterpart, and the relative abundances of doubly and triply deuterated species decrease with an increasing number of D atoms in a molecule. The abundances of amino acids increase by a factor of more than five upon the hydrolysis of the organic residues, leading to decreases in the relative abundances of deuterated species for α -alanine and β -alanine. On the other hand, the relative abundances of the deuterated isotopologues of the other three amino acids did not decrease upon hydrolysis, indicating different formation mechanisms of these two groups upon hydrolysis. The present study facilitates both qualitative and quantitative evaluations of D fractionation during molecular evolution in the interstellar medium.

  14. DEUTERIUM FRACTIONATION DURING AMINO ACID FORMATION BY PHOTOLYSIS OF INTERSTELLAR ICE ANALOGS CONTAINING DEUTERATED METHANOL

    International Nuclear Information System (INIS)

    Oba, Yasuhiro; Watanabe, Naoki; Kouchi, Akira; Takano, Yoshinori

    2016-01-01

    Deuterium (D) atoms in interstellar deuterated methanol might be distributed into complex organic molecules through molecular evolution by photochemical reactions in interstellar grains. In this study, we use a state-of-the-art high-resolution mass spectrometer coupled with a high-performance liquid chromatography system to quantitatively analyze amino acids and their deuterated isotopologues formed by the photolysis of interstellar ice analogs containing singly deuterated methanol CH 2 DOH at 10 K. Five amino acids (glycine, α -alanine, β -alanine, sarcosine, and serine) and their deuterated isotopologues whose D atoms are bound to carbon atoms are detected in organic residues formed by photolysis followed by warming up to room temperature. The abundances of singly deuterated amino acids are in the range of 0.3–1.1 relative to each nondeuterated counterpart, and the relative abundances of doubly and triply deuterated species decrease with an increasing number of D atoms in a molecule. The abundances of amino acids increase by a factor of more than five upon the hydrolysis of the organic residues, leading to decreases in the relative abundances of deuterated species for α -alanine and β -alanine. On the other hand, the relative abundances of the deuterated isotopologues of the other three amino acids did not decrease upon hydrolysis, indicating different formation mechanisms of these two groups upon hydrolysis. The present study facilitates both qualitative and quantitative evaluations of D fractionation during molecular evolution in the interstellar medium.

  15. DMPD: Regulation of arachidonic acid release and cytosolic phospholipase A2activation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10080535 Regulation of arachidonic acid release and cytosolic phospholipase A2activ...on of arachidonic acid release and cytosolic phospholipase A2activation. PubmedID 10080535 Title Regulation ...of arachidonic acid release and cytosolic phospholipase A2activation. Authors Gij

  16. Human milk arachidonic acid and docosahexaenoic acid contents increase following supplementation during pregnancy and lactation

    NARCIS (Netherlands)

    van Goor, Saskia A.; Dijick-Brouwer, D. A. Janneke; Hadders-Algra, Mijna; Doornbos, Bennard; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Muskiet, Frits A. J.; Djick-Brouwer, D.A.J.

    Introduction: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. Maternal diet influences milk DHA, whereas milk AA seems rather constant. We investigated milk AA, DHA and DHA/AA after supplementation of AA plus DHA, or DHA alone during pregnancy and lactation.

  17. Intrauterine, postpartum and adult relationships between arachidonic acid (AA) and docosahexaenoic acid (DHA)

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    Erythrocyte (RBC) fatty acid compositions from populations with stable dietary habits but large variations in RBC-arachidonic (AA) and RBC-docosahexaenoic acid (DHA) provided us with insight into relationships between DHA and AA. It also enabled us to estimate the maternal RBC-DHA (mRBC-DHA) status

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

    Science.gov (United States)

    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.

  19. A human dietary arachidonic acid supplementation study conducted in a metabolic research unit: rationale and design.

    Science.gov (United States)

    Nelson, G J; Kelley, D S; Emken, E A; Phinney, S D; Kyle, D; Ferretti, A

    1997-04-01

    While there are many reports of studies that fed arachidonic acid (AA) to animals, there are very few reports of AA feeding to humans under controlled conditions. This 130-d study was conceived as a controlled, symmetrical crossover design with healthy, adult male volunteers. They lived in the metabolic research unit (MRU) of the Western Human Nutrition Research (WHNRC) for the entire study. All food was prepared by the WHNRC kitchen. The basal (low-AA) diet consisted of natural foods (30 en% fat, 15 en% protein, and 55 en% carbohydrate), containing 210 mg/d of AA, and met the recommended daily allowance for all nutrients. The high-AA (intervention) diet was similar except that 1.5 g/d of AA in the form of a triglyceride containing 50% AA replaced an equal amount of high-oleic safflower oil in the basal diet. The subjects (ages 20 to 39) were within -10 to +20% of ideal body weight, nonsmoking, and not allowed alcohol in the MRU. Their exercise level was constant, and their body weights were maintained within 2% of entry level. Subjects were initially fed the low-AA diet for 15 d. On day 16, half of the subjects (group A) wee placed on the high-AA diet, and the other group (B) remained on the low-AA diets. On day 65, the two groups switched diets. On day 115, group B returned to the low-AA diet. This design, assuming no carryover effect, allowed us to merge the data from the two groups, with the data comparison days being 65 (low-AA) and 115 (high-AA) for group B and 130 (low-AA) and 65 (high-AA) for group A. The main indices studied were the fatty acid composition of the plasma, red blood cells, platelets, and adipose tissue; in vitro platelet aggregation, bleeding times, clotting factors; immune response as measured by delayed hypersensitivity skin tests, cellular proliferation of peripheral blood mononuclear cells in response to various mitogens and antigens, natural killer cell activity, and response to measles/mumps/rubella and influenza vaccines; the

  20. Arachidonic acid metabolism in silica-stimulated bovine alveolar macrophages

    International Nuclear Information System (INIS)

    Englen, M.D.

    1989-01-01

    The in vitro production of arachidonic acid (AA) metabolites in adherent bovine alveolar macrophages (BAM) incubated with silica was investigated. BAM were pre-labelled with 3 H-AA, and lipid metabolites released into the culture medium were analyzed by high performance liquid chromatography (HPLC). Lactate dehydrogenase (LDH) release was simultaneously assayed to provide an indication of cell injury. Increasing doses of silica selectively stimulated the 5-lipoxygenase pathway of AA metabolism, while cyclooxygenase metabolite output was suppressed. LDH release increased in a linear, dose-dependent fashion over the range of silica doses used. Moreover, within 15 min following addition of a high silica dose, a shift to the production of 5-lipoxygenase metabolites occurred, accompanied by a reduction in cyclooxygenase products. This rapid alteration in AA metabolism preceded cell injury. To examine the relationship between cytotoxicity and AA metabolite release by BAM exposed to silicas with different cytotoxic and fibrogenic activities, BAM were exposed to different doses of DQ-12, Minusil-5, and Sigma silicas, and carbonyl iron beads. The median effective dose (ED 50 ) of each particulate to stimulate the release of AA metabolites and LDH was calculated. The ED 50 values for DQ-12, Minusil-5, and Sigma silica showed that the relative cytotoxicities of the different silicas for BAM corresponded to the relative potencies of the silicas to elicit 5-lipoxygenase metabolites from BAM. These results indicate that the cytotoxic, and presumed fibrogenic potential, of a silica is correlated with the potency to stimulate the release of leukotrienes from AM

  1. Ultraviolet radiation stimulates the release of arachidonic acid from mammalian cells in culture

    International Nuclear Information System (INIS)

    De Leo, V.A.; Hanson, D.; Weinstein, I.B.; Harber, L.C.

    1985-01-01

    C3H 10T1/2 cells in culture were prelabelled with [ 3 H]arachidonic acid and exposed to UVB radiation. Almost immediately after irradiation cells released labelled arachidonate metabolites into media in a dose dependent manner. This release was inhibited by removing calcium ions from the system and by the addition of dexamethasone and parabromophenacyl bromide to the system. This suggests that the UVB stimulated release of arachidonic acid from membrane phospholipids is, in part, mediated by a phospholipase A 2 enzyme system. Thin layer chromatographic examination of media extracts revealed a dose dependent UVB stimulation of prostaglandin production by cultured cells. (author)

  2. Role of Lipoxygenase Metabolites of Arachidonic Acid in Enhanced Pulmonary Artery Contractions of Female Rabbits

    OpenAIRE

    Pfister, Sandra L.

    2011-01-01

    Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4 fold greater than that in men. Studies suggest sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared to ma...

  3. Arachidonic acid metabolites and endothelial dysfunction of portal hypertension.

    Science.gov (United States)

    Sacerdoti, David; Pesce, Paola; Di Pascoli, Marco; Brocco, Silvia; Cecchetto, Lara; Bolognesi, Massimo

    2015-07-01

    Increased resistance to portal flow and increased portal inflow due to mesenteric vasodilatation represent the main factors causing portal hypertension in cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the synthesis, release, and effect of endothelial mediators of vascular tone, inflammation, thrombosis, and angiogenesis, plays a major role in the increase of resistance in portal circulation, in the decrease in the mesenteric one, in the development of collateral circulation. Reduced response to vasodilators in liver sinusoids and increased response in the mesenteric arterioles, and, viceversa, increased response to vasoconstrictors in the portal-sinusoidal circulation and decreased response in the mesenteric arterioles are also relevant to the pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450 monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial cells (LSECs) via increased COX-1 activity/expression, increased leukotriens, increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial circulation, but vasoconstrictors of the portal-sinusoidal circulation), represent a major component in the increased portal resistance, in the decreased portal response to vasodilators and in the hyper-response to vasoconstrictors. Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived hyperpolarizing factor system) play a major role in mesenteric vasodilatation, hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs, mediators of liver regeneration after hepatectomy and of angiogenesis, may play a role in the development of regenerative nodules and collateral circulation, through stimulation of vascular endothelial

  4. In vitro release of arachidonic acid and in vivo responses to respirable fractions of cotton dust

    International Nuclear Information System (INIS)

    Thomson, T.A.; Edwards, J.H.; Al-Zubaidy, T.S.; Brown, R.C.; Poole, A.; Nicholls, P.J.

    1986-01-01

    It was considered that the fall in lung function seen after exposure to cotton dust may be attributable in part to the activity of arachidonic acid metabolites, such as leucotrienes as well as to the more established release of histamine by cotton dust. However, we found that cotton and barley dusts elicited poor release of arachidonic acid from an established macrophage like cell line compared with that observed with other organic dusts. In the experimental animal, pulmonary cellular responses to both cotton and barley dust were similar to those evoked by moldy hay and pigeon dropping dusts, although after multiple doses a more severe response was seen to cotton and barley. Since both moldy hay and pigeon droppings elicit a greater arachidonic acid release than cotton or barley, a role for arachidonic acid in inducing the cellular response is less likely than other factors. There are limitations to our conclusions using this system, i.e., the arachidonic acid may be released in a nonmetabolized form, although it is noted that the two dusts with the greatest arachidonic acid release produce their clinical responses in humans largely by hypersensitivity mechanisms

  5. Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils

    International Nuclear Information System (INIS)

    Tao, W.

    1988-01-01

    Arachidonic acid release in rabbit neutrophils can be enhanced by the addition of chemotactic fMet-Leu-Phe, platelet-activating factor, PAF, or the calcium ionophore A23187. Over 80% of the release [ 3 H]arachidonic acid comes from phosphatidylcholine and phosphatidylinositol. The release is dose-dependent and increases with increasing concentration of the stimulus. The A23187-induced release increases with increasing time of the stimulation. [ 3 H]arachidonic acid release, but not the rise in the concentration of intracellular calcium, is inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The [ 3 H]arachidonic acid released by A23187 is potentiated while that release by fMET-Leu-Phe or PAF is inhibited in phorbol 12-myristate 13-acetate, PMA, treated rabbit neutrophils. The protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, H-7, has no effect on the potentiation by PMA of the A23187-induced release, it prevents the inhibition by PMA of the release produced by PAF or fMet-Leu-Phe. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. The diacylglycerol kinase inhibitor R59022 increases the level of diacylglycerol in neutrophils stimulated with fMet-Leu-Phe. Furthermore, R59022 potentiates [ 3 H] arachidonic acid release produced by fMet-Leu-Phe. This potentiation is not inhibited by H-7, in fact, it is increased in H-7-treated neutrophils

  6. Arachidonic acid triggers an oxidative burst in leukocytes

    Directory of Open Access Journals (Sweden)

    Pompeia C.

    2003-01-01

    Full Text Available The change in cellular reducing potential, most likely reflecting an oxidative burst, was investigated in arachidonic acid- (AA stimulated leukocytes. The cells studied included the human leukemia cell lines HL-60 (undifferentiated and differentiated into macrophage-like and polymorphonuclear-like cells, Jurkat and Raji, and thymocytes and macrophages from rat primary cultures. The oxidative burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative burst until an optimum AA concentration was reached and the burst decreased thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to 400 µM (up to 16-fold, whereas in rat cells it varied from 10 to 20 µM. Initial rates of superoxide generation were high, decreasing steadily and ceasing about 2 h post-treatment. The continuous presence of AA was not needed to stimulate superoxide generation. It seems that the NADPH oxidase system participates in AA-stimulated superoxide production in these cells since the oxidative burst was stimulated by NADPH and inhibited by N-ethylmaleimide, diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the oxidative burst may be due to its detergent action. There apparently was no contribution of other superoxide-generating systems such as xanthine-xanthine oxidase, cytochromes P-450 and mitochondrial electron transport chain, as assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem to interfere with the AA-stimulated oxidative burst since there was no systematic effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but lipid peroxides may play a role, as indicated by the inhibition of nitroblue tetrazolium reduction promoted by tocopherol.

  7. Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment

    International Nuclear Information System (INIS)

    Billi de Catabbi, Silvia C.; Faletti, Alicia; Fuentes, Federico; San Martin de Viale, Leonor C.; Cochon, Adriana C.

    2005-01-01

    Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A 2 (cPLA 2 ) activity were investigated in an experimental model of porphyria cutanea tarda induced by HCB. Female Wistar rats were treated with a single daily dose of HCB (100 mg kg -1 body weight) for 5 days and were sacrificed 3, 10, 17, and 52 days after the last dose. HCB treatment induced the accumulation of hepatic porhyrins from day 17 and increased the activities of liver ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine N-demethylase (APND) from day 3 after the last dose. Liver microsomes from control and HCB-treated rats generated, in the presence of NADPH, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 11,12-Di HETE, and ω-OH/ω-1-OH AA. HCB treatment caused an increase in total NADPH CYP-dependent AA metabolism, with a higher response at 3 days after the last HCB dose than at the other time points studied. In addition, HCB treatment markedly enhanced PGE production and release in liver slices. This HCB effect was time dependent and reached its highest level after 10 days. At this time cPLA 2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA 2 activity on the 17th and 52nd day. Our results demonstrated for the first time that HCB induces both the cyclooxygenase and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were previous to the onset of a marked porphyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Observations also suggested that a possible role of cPLA 2 in

  8. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition

    NARCIS (Netherlands)

    Smit, EN; Koopmann, M; Boersma, ER; Muskiet, FAJ

    We investigated whether supplementation with arachidonic acid (20:4 omega 6; AA), ora combination of AA and docosahexaenoic acid (22:6 omega 3; DHA) would affect human milk polyunsaturated fatty acid (PUFA) composition. Ten women were daily supplemented with 300 mg AA, eight with 300 mg AA, 110 mg

  9. Prenatal long-chain polyunsaturated fatty acid status : the importance of a balanced intake of docosahexaenoic acid and arachidonic acid

    NARCIS (Netherlands)

    Hadders-Algra, Mijna

    2008-01-01

    This review addresses the effect of prenatal long-chain polyunsaturated fatty acid (LCPUFA) status on neuro-developmental outcome. It focuses on the major LPCUFA doxosahexaenoic acid (DNA; 22:6 omega 3) and arachidonic acid (AA; 20:4 omega 6). Due to enzymatic competition high DHA intake results in

  10. Arachidonic acid reduces the stress response of gilthead seabream Sparus aurata L.

    NARCIS (Netherlands)

    Anholt, R.D. van; Spanings, F.A.T.; Koven, WM; Nixon, O.; Wendelaar Bonga, S.E.

    2004-01-01

    In this study the influence of the dietary level of the fatty acid arachidonic acid (ArA, 20:4n-6) was determined on the acute stress response and osmoregulation of adult gilthead seabream Sparus aurata L. Seabream were fed a diet containing either 0.9% or 2.4% of total fatty acids as ArA for 18

  11. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

  12. Metabolism and incorporation of orally administrated arachidonic acid in rats

    International Nuclear Information System (INIS)

    Magni, F.; Kikawa, Y.; Jedlinski, A.; Lands, W.E.M.

    1986-01-01

    50 mg 3 H 2 H-20: 4n-6 was administered by oral intubation to rats maintained on a normal diet. The distribution of radioactive arachidonate esterified in the various tissues was similar to that for EFA-deficient rats from their previous study. The amount incorporated in the tissues was 14% in normal rats and 16% in EFA-deficient rats. At 24 hrs, the relative radioactivity in PC was higher (and lower in PE) than after 20 days in the previous study. Urine had 3-4% of initial radioactivity in the first 12 hours and only 1% more by 24 hours. Urine components were analyzed as methyl ester-methoxime-t-butyldimethylsilyl ethers. Most of the arachidonate metabolites in urine reported in the literature have expected ECL values between 26 to 32, whereas they found 68% of radioactivity with ECL values below 26. This represents a substantial divergence from arachidonate metabolite patterns described for injected prostaglandins and indicates the need of examining the metabolites formed from endogenously formed eicosanoids

  13. The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism

    NARCIS (Netherlands)

    Demetz, Egon; Schroll, Andrea; Auer, Kristina; Heim, Christiane; Patsch, Josef R.; Eller, Philipp; Theurl, Markus; Theurl, Igor; Theurl, Milan; Seifert, Markus; Lener, Daniela; Stanzl, Ursula; Haschka, David; Asshoff, Malte; Dichtl, Stefanie; Nairz, Manfred; Huber, Eva; Stadlinger, Martin; Moschen, Alexander R.; Li, Xiaorong; Pallweber, Petra; Scharnagl, Hubert; Stojakovic, Tatjana; Maerz, Winfried; Kleber, Marcus E.; Garlaschelli, Katia; Uboldi, Patrizia; Catapano, Alberico L.; Stellaard, Frans; Rudling, Mats; Kuba, Keiji; Imai, Yumiko; Arita, Makoto; Schuetz, John D.; Pramstaller, Peter P.; Tietge, Uwe J. F.; Trauner, Michael; Norata, Giuseppe D.; Claudel, Thierry; Hicks, Andrew A.; Weiss, Guenter; Tancevski, Ivan

    2014-01-01

    Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By

  14. Use of deuterated tyrosine and phenylalanine in the study of catecholamine and aromatic acid metabolism

    International Nuclear Information System (INIS)

    Curtius, H.C.; Redweik, U.; Steinmann, B.; Leimbacher, W.; Wegmann, H.

    1975-01-01

    Deuterated tyrosine and phenylalanine have been used for the study of their respective metabolism in patients with phenylketonuria (PKU) and in healthy persons. Urinary excretion of dopamine and its metabolites was studied by GC-MS after oral administration of deuterated L-tyrosine in 2 patients with PKU and in normal controls at low and high plasma phenylalanine levels. From these studies it seemed that the in vivo tyrosine 3-hydroxylase activity and thus the formation of L-dopa depend on the phenylalanine concentration in plasma and also in tissues. After loading 3 mentally retarded patients with 3,5-[ 2 H 2 ]-4-hydroxyphenylalanine, we found, among others, excretion of deuterated m-hydroxyphenyl-hydracrylic acid, p-hydroxymandelic acid, p-hydroxybenzoic acid, p-hydroxyhippuric acid, benzoic acid and hippuric acid. An intramolecular rearrangement is postulated. Deuterated phenylalanine was used to investigate phenylalanine and dopa metabolism in PKU. In addition, one untreated person with PKU of normal intelligence and normal excretion of catecholamines at high plasma phenylalanine concentration was investigated in order to see whether there exists an alternative metabolic pathway from phenylalanine to dopa formation

  15. The influence of arachidonic acid metabolites on cell division in the intestinal epithelium and in colonic tumors.

    Science.gov (United States)

    Petry, F M; Tutton, P J; Barkla, D H

    1984-09-01

    Various metabolites of arachidonic acid are now known to influence cell division. In this paper the effects on cell proliferation of arachidonic acid, some inhibitors of arachidonic acid metabolism and some analogs of arachidonic acid metabolites is described. The epithelial cell proliferation rate in the jejunum, in the descending colon and in dimethylhydrazine-induced tumors of rat colon was measured using a stathmokinetic technique. Administration of arachidonic acid resulted in retardation of cell proliferation in each of the tissues examined. A cyclooxygenase inhibitor (Flurbiprofen) prevented this effect of arachidonic acid in the jejunal crypts and in colonic tumors, but not in colonic crypts. In contrast, inhibitors of both cyclooxygenase and lipoxygenase (Benoxaprofen and BW755c) prevented the effect of arachidonic acid in the colonic crypts and reduced its effect on colonic tumours but did not alter its effect on the jejunum. An inhibitor of thromoboxane A2 synthetase (U51,605) was also able to prevent the inhibitory effect of arachidonic acid on colonic tumors. Treatment with 16,16-dimethyl PGE2 inhibited cell proliferation in jejunal crypts and in colonic tumors, as did a thromboxane A2 mimicking agent, U46619. Nafazatrom, an agent that stimulates prostacyclin synthesis and inhibits lypoxygenase, promoted cell proliferation in the jejunal crypts and colonic crypts, but inhibited cell proliferation in colonic tumours.

  16. Preparation of α-deuterated L-amino acids using E.coli cells containing tryptophanase

    International Nuclear Information System (INIS)

    Faleev, N.G.; Ruvinov, S.B.; Saporovskaya, M.B.; Belikov, V.M.; Zakomyrdina, L.N.; Sakharova, I.S.; Torchinskij, Yu.M.

    1989-01-01

    Method for preparation of a series of α-deuterated L-amino acids of high optical purity with quantitative chemica yield, suing stereospecific isotopic exchange in D 2 O under the effect of E.coli cells with high tryptophanase activity was developed

  17. The effect of cigarette smoke on the metabolism of arachidonic acid in isolated hamster lungs

    International Nuclear Information System (INIS)

    Maennistoe, J.; Toivonen, H.; Hartiala, J.; Bakhle, Y.S.; Uotila, P.

    1981-01-01

    The effects of cigarette smoke on the metabolism of exogenous arachidonic acid (AA) were investigated in isolated hamster lungs. Arachidonate was injected into the pulmonary circulation and the metabolites were analysed from the nonrecirculating perfusion effluent by thin layer chromatography. After the pulmonary injection of 66 nmol of 14C-AA about 20% of the injected radioactivity appeared in the perfusion effluent mostly as metabolites in six minutes. When isolated lungs were ventilated with cigarette smoke during the perfusion, the amounts of PGF2 alpha, PGE2 and two unidentified metabolite groups increased in the lung effluent. In two other experimental series hamsters were exposed to cigarette smoke before the lung perfusion either once for 30 min or during one hour daily for ten consecutive days. Neither pre-exposures caused any changes in the amounts of arachidonate metabolites in the lung effluent

  18. Production of arachidonic and linoleic acid metabolites by guinea pig tracheal epithelial cells

    International Nuclear Information System (INIS)

    Oosthuizen, M.J.; Engels, F.; Van Esch, B.; Henricks, P.A.; Nijkamp, F.P.

    1990-01-01

    Pulmonary epithelial cells may be responsible for regulating airway smooth muscle function, in part by release of fatty acid-derived mediators. Incubation of isolated guinea pig tracheal epithelial cells with radiolabeled arachidonic acid (AA) leads to the production of 5- and 15-hydroxyeicosatetraenoic acid (5- and 15-HETE) and smaller amounts of leukotriene (LT) B4 and C4 and 12-hydroxyheptadecatrienoic acid (HHT). Epithelial cells also are able to release linoleic acid (LA) metabolites. Incubation with radiolabeled linoleic acid leads to the formation of 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE). The biological significance of these mediators produced by epithelial cells is discussed

  19. Arachidonic acid metabolism in fibroblasts derived from canine myocardium

    International Nuclear Information System (INIS)

    Weber, D.R.; Prescott, S.M.

    1986-01-01

    Canine fibroblasts from normal or healing infarcted myocardium were grown in culture. The cells were morphologically indistinguishable, but the doubling time of cells from healing myocardium was 39.6 +/- 3.5 hr whereas that of normals was 24 +/- 3.7 (n=5, p 3 H]arachidonate (AA) into phospholipids. Calcium ionophore A23187 (10 μM) caused release and metabolism of [ 3 H] AA. A23187 or AA (10μM) induced production of 6-keto PGF1α, PGE2, and a hydroxy metabolite of AA. RIA of 6-keto PGF1α showed that subconfluent cells from healing myocardium produced 1202 +/- 354 pg/mg protein whereas that of normals was 551 +/- 222 (n=7, p 3 H]AA released but did not metabolize [ 3 H]AA. In coincubations, fibroblasts incorporated myocyte-derived AA. Subsequent stimulation of the fibroblasts with A23187 induced the synthesis of 6-keto PGF1α, PGE2 and a hydroxy metabolite. The fibroblast content of healing myocardium was 35-1000 times that of normal tissue (n=7). Thus even a moderate change in AA metabolism, amplified by the AA released from deteriorating myocytes, may be a significant physiologic or pathologic event

  20. Reactions of tritium atoms with amino acids, deuterated amino acids and mixtures of amino acids. Additivity property and isotope effect

    International Nuclear Information System (INIS)

    Badun, G.A.; Filatov, Eh.S.

    1988-01-01

    Interaction of tritium atoms with glycine (1) and leucine (2) amino acids, deuterated amino acids, their mixtures and glycylleucine (3) peptide in the 77-300 K temperature range is studied in isothermal and gradient regimes. Tagged amino acids were separated from targets after conducting the reaction. At T 150 K are associated with intermolecular transmission of free valence in the mixture of amino acids. Regularities of the reaction found for the mixture of amino acids are conserved for (3) as well, i.e. the peptide bond does not essentially affect the reaction of isotopic exchange conditioned by atomic tritium

  1. The effect of endogenous essential and nonessential fatty acids on the uptake and subsequent agonist-induced release of arachidonate

    International Nuclear Information System (INIS)

    Furth, E.E.; Hurtubise, V.; Schott, M.A.; Laposata, M.

    1989-01-01

    We have demonstrated that the uptake and agonist-induced release of a pulse of arachidonate are influenced by the size and composition of preexisting endogenous fatty acid pools. EFD-1 cells, an essential fatty acid-deficient mouse fibrosarcoma cell line, were incubated with radiolabeled (14C or 3H) arachidonate, linoleate, eicosapentaenoate (EPA), palmitate, or oleate in concentrations of 0-33 microM for 24 h. After 24 h, the cells were pulsed with 0.67 microM radiolabeled (3H or 14C, opposite first label) arachidonate for 15 min and then stimulated with 10 microM bradykinin for 4 min. Because EFD-1 cells contain no endogenous essential fatty acids, we were able to create essential fatty acid-repleted cells for which the specific activity of the newly constructed endogenous essential fatty acid pool was known. Loading the endogenous pool with the essential fatty acids arachidonate, eicosapentaenoate, or linoleate (15-20 nmol of fatty acid incorporated/10(6) cells) decreased the uptake of a pulse of arachidonate from 200 to 100 pmol/10(6) cells but had no effect on palmitate uptake. The percent of arachidonate incorporated during the pulse which was released upon agonist stimulation increased 2-fold (4-8%) as the endogenous pool of essential fatty acids was increased from 0 to 15-20 nmol/10(6) cells. This 8% release was at least 3-fold greater than the percent release from the various endogenous essential fatty acid pools. In contrast, loading the endogenous pool with the nonessential fatty acids oleate or palmitate to more than 2-3 times their preexisting cellular level had no effect on the uptake of an arachidonate pulse. Like the essential fatty acids, increasing endogenous oleate increased (by 2-fold) the percent release of arachidonate incorporated during the pulse, whereas endogenous palmitate had no effect on subsequent agonist-induced release from this arachidonate pool

  2. Incorporation and distribution of dihomo-gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid in cultured human keratinocytes

    International Nuclear Information System (INIS)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.

    1986-01-01

    Human keratinocytes in culture were labelled with 14 C-dihomo-gamma-linolenic acid, 14 C-arachidonic acid or 14 C-eicosapentaenoic acid. All three eicosanoid precursor fatty acids were effectively incorporated into the cells. In phospholipids most of the radioactivity was recovered, in neutral lipids a substantial amount, and as free unesterified fatty acids only a minor amount. Most of the radioactivity was found in phosphatidylethanolamine which was also the major phospholipid as measured by phosphorous assay. The incorporation of dihomo-gamma-linolenic acid and arachidonic acid into lipid subfractions was essentially similar. Eicosapentaenoic acid was, however, much less effectively incorporated into phosphatidylinositol + phosphatidylserine and, correspondingly, more effectively into triacylglycerols as compared to the two other precursor fatty acids. Once incorporated, the distribution of all three precursor fatty acids was relatively stable, and only minor amounts of fatty acids were released into the culture medium during short term culture (two days). Our study demonstrates that eicosanoid precursor fatty acids are avidly taken up by human keratinocytes and esterified into membrane lipids. The clinical implication of this finding is that dietary manipulations might be employed to cause changes in the fatty acid composition of keratinocytes

  3. Differential stimulation of luminol-enhanced chemiluminescence (CL) and arachidonic acid metabolism in rat peritoneal neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, R.J.; Adams, L.M.; Cullinan, C.A.; Berkenkopf, J.W.; Weichman, B.M.

    1986-03-05

    Phorbol 12-myristate, 13-acetate (PMA) induced the production of radical oxygen species (ROS) from rat peritoneal neutrophils as assessed by CL. ROS generation occurred in a time- (maximum at 13.5 min) and dose- (concentration range of 1.7-498 nM) related fashion. However, 166 nM PMA did not induce either cyclooxygenase (CO) or lipoxygenase (LPO) product formation by 20 min post-stimulation. Conversely, A23187, at concentrations between 0.1 and 10 ..mu..M, stimulated both pathways of arachidonic acid metabolism, but had little or no effect upon ROS production. When suboptimal concentrations of PMA (5.5 nM) and A23187 (0.1-1 ..mu..M) were coincubated with the neutrophils, a synergistic ROS response was elicited. However, arachidonic acid metabolism in the presence of PMA was unchanged relative to A12187 alone. Nordihydroguaiaretic acid (NDGA) inhibited both PMA-induced CL (IC/sub 50/ = 0.9 ..mu..M) and A23187-induced arachidonic acid metabolism (IC/sub 50/ = 1.7 ..mu..M and 6.0 ..mu..M for LPO and CO, respectively). The mixed LPO-CO inhibitor, BW755C, behaved in a qualitatively similar manner to NDGA, whereas the CO inhibitors, indomethacin, piroxicam and naproxen had no inhibitory effect on ROS generation at concentrations as high as 100 ..mu..M. These results suggest that NDGA and BW755C may inhibit CL and arachidonic acid metabolism by distinct mechanisms in rat neutrophils.

  4. A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

    Science.gov (United States)

    Shak, S; Perez, H D; Goldstein, I M

    1983-12-25

    We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

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

    Science.gov (United States)

    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.

  6. A new model to study the role of arachidonic acid in colon cancer pathophysiology

    OpenAIRE

    Fan, Yang-Yi; Callaway, Evelyn; Monk, Jennifer M.; Goldsby, Jennifer S.; Yang, Peiying; Vincent, Logan; Chapkin, Robert S.

    2016-01-01

    A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA) derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression and metastasis. We have recently developed a novel Fads1 knockout mouse model, which allows for the investigation of AA...

  7. Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Gert T. Verhoeven

    2001-01-01

    Full Text Available Background: In smoking COPD patients the bronchoalveolar lavage (BAL fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA metabolites, which contribute to inflammation and an increased bronchomotor tone.

  8. Lowering dietary n-6 polyunsaturated fatty acids: interaction with brain arachidonic and docosahexaenoic acids.

    Science.gov (United States)

    Alashmali, Shoug M; Hopperton, Kathryn E; Bazinet, Richard P

    2016-02-01

    Arachidonic (ARA) and docosahexaenoic (DHA) acids are the most abundant polyunsaturated fatty acids (PUFA) in the brain, where they have many biological effects, including on inflammation, cell-signaling, appetite regulation, and blood flow. The Western diet contains a high ratio of n-6: n-3 PUFA. Although interest in lowering this ratio has largely focused on increasing intake of n-3 PUFA, few studies have examined lowering dietary n-6 PUFA. This review will evaluate the effect of lowering dietary n-6 PUFA on levels and metabolism of ARA and DHA in animal models and in humans, with a primary focus on the brain. In animal models, lowering dietary ARA or linoleic acid generally lowers levels of brain ARA and raises DHA. Lowering dietary n-6 PUFA can also modulate the levels of ARA and DHA metabolizing enzymes, as well as their associated bioactive mediators. Human studies examining changes in plasma fatty acid composition following n-6 PUFA lowering demonstrate no changes in levels of ARA and DHA, though there is evidence of alterations in their respective bioactive mediators. Lowering dietary n-6 PUFA, in animal models, can alter the levels and metabolism of ARA and DHA in the brain, but it remains to be determined whether these changes are clinically meaningful.

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

    DEFF Research Database (Denmark)

    Silva-Martínez, Guillermo A.; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda

    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....... 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...

  10. Lipoxygenase-mediated pro-radical effect of melatonin via stimulation of arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Radogna, F.; Sestili, P.; Martinelli, C.; Paolillo, M.; Paternoster, L.; Albertini, M.C.; Accorsi, A.; Gualandi, G.; Ghibelli, L.

    2009-01-01

    We have shown that melatonin immediately and transiently stimulates intracellular free radical production on a set of leukocytes, possibly as a consequence of calmodulin binding. We show here that melatonin-induced ROS are produced by lipoxygenase (LOX), since they are prevented by a set of LOX inhibitors, and are accompanied by increase of the 5-LOX product 5-HETE. LOX activation is accompanied by strong liberation of AA; inhibition of Ca 2+ -independent, but not Ca 2+ -dependent, phospholipase A2 (PLA2), prevents both melatonin-induced arachidonic acid and ROS production, whereas LOX inhibition only prevents ROS, indicating that PLA2 is upstream with respect to LOX, as occurs in many signaling pathways. Chlorpromazine, an inhibitor of melatonin-calmodulin interaction, inhibits both ROS and arachidonic acid production, thus possibly placing calmodulin at the origin of a melatonin-induced pro-radical pathway. Interestingly, it is known that Ca 2+ -independent PLA2 binds to calmodulin: our results are compatible with PLA2 being liberated by melatonin from a steady-state calmodulin sequestration, thus initiating an arachidonate signal transduction. These results delineate a novel molecular pathway through which melatonin may participate to the inflammatory response.

  11. Arachidonic acid production by the oleaginous fungus Mortierella alpina 1S-4: A review

    Directory of Open Access Journals (Sweden)

    Hiroshi Kikukawa

    2018-05-01

    Full Text Available The filamentous fungus Mortierella alpina 1S-4 is capable of accumulating a large amount of triacylglycerol containing C20 polyunsaturated fatty acids (PUFAs. Indeed, triacylglycerol production by M. alpina 1S-4 can reach 20 g/L of culture broth, and the critical cellular signaling and structural PUFA arachidonic acid (ARA comprises 30%–70% of the total fatty acid. The demonstrated health benefits of functional PUFAs have in turn encouraged the search for rich sources of these compounds, including fungal strains showing enhanced production of specific PUFAs. Screening for mutants and targeted gene manipulation of M. alpina 1S-4 have elucidated the functions of various enzymes involved in PUFA biosynthesis and established lines with improved PUFA productivity. In some cases, these strains have been used for indistrial-scale production of PUFAs, including ARA. In this review, we described practical ARA production through mutant breeding, functional analyses of genes encoding enzymes involved in PUFA biosynthesis, and recent advances in the production of specific PUFAs through molecular breeding of M. alpina 1S-4. Keywords: Arachidonic acid, Mortierella alpina, Molecular breeding, Fatty acid desaturase

  12. Role of lipoxygenase metabolites of arachidonic acid in enhanced pulmonary artery contractions of female rabbits.

    Science.gov (United States)

    Pfister, Sandra L

    2011-04-01

    Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4-fold greater than that in men. Studies suggest that sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase (LO) metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared with males. Because treatment with a nonspecific LO inhibitor reduced contractions in females but not males, the present study identified which LO isoform contributes to sex-specific pulmonary artery vasoconstriction. The 15- and 5- but not 12-LO protein expressions were greater in females. Basal and A23187-stimulated release of 15-, 5-, and 12-hydroxyeicosatetraenoic acids (HETEs) from females and males were measured by liquid chromatography/mass spectrometry. Only 15-HETE synthesis was greater in females compared with males under both basal and stimulated conditions. Vascular contractions to 15-HETE were enhanced in females compared with males (maximal contraction: 44±6%versus 25±3%). The specific 15-LO inhibitor PD146176 (12 μmol/L) decreased arachidonic acid-induced contractions in females (maximal contraction: 93±4% versus 57±10%). If male pulmonary arteries were incubated with estrogen (1 μmol/L, 18 hours), protein expression of 15-LO and 15-HETE production increased. Mechanisms to explain the increased incidence of pulmonary hypertension in women are not known. Results suggest that the 15-LO pathway is different between females and males and is regulated by estrogen. Understanding this novel sex-specific mechanism may provide insight into the increased incidence of pulmonary hypertension in females.

  13. Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

    NARCIS (Netherlands)

    van Goor, Saskia A; Dijck-Brouwer, D A Janneke; Fokkema, M Rebecca; van der Iest, Theo Hans; Muskiet, Frits A J

    We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from

  14. Nitric oxide production from macrophages is regulated by arachidonic acid metabolites.

    Science.gov (United States)

    Imai, Y; Kolb, H; Burkart, V

    1993-11-30

    In activated macrophages the inducible form of the enzyme nitric oxide (NO) synthase generates high amounts of the toxic mediator NO. After 20 h of treatment with LPS rat peritoneal macrophages release 12-16 nmol NO2-/10(5) cells which is detectable in the culture supernatant by the Griess reaction as a measure of NO formation. The addition of aminoguanidine (1 mM), a preferential inhibitor of the inducible NO-synthase, completely abolished NO2-accumulation. Incubation with indomethacin or acetyl-salicylic acid, preferential inhibitors of the cyclooxygenase pathway of the arachidonic acid metabolism, did not influence NO2- levels. Nordihydro-guaiaretic acid (50 microM), a preferential inhibitor of the lipoxygenase pathway, caused strong reduction of NO2- accumulation to 1.9 +/- 0.3 nmol/200 microliter. Simultaneous inhibition of cyclo- and lipoxygenase by BW755c resulted in an intermediate effect (7.3 +/- 1.1 nmol/200 microliter NO2-). These results show that the induction of NO production in activated macrophages is regulated by products of the lipoxygenase-pathway of the arachidonic acid metabolism.

  15. The influence of supplemental docosahexaenoic and arachidonic acids during pregnancy and lactation on neurodevelopment at eighteen months

    NARCIS (Netherlands)

    van Goor, Saskia A.; Dijck-Brouwer, D. A. Janneke; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Hadders-Algra, Mijna

    2011-01-01

    Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. The effects of DHA (220 mg/day, n=41), DHA+AA (220 mg/day, n=39) or placebo (n=34) during pregnancy and lactation on neurodevelopment at 18 months, and the relations between umbilical cord DHA, AA and Mead acid

  16. Effect of amiloride on arachidonic acid and histamine release from rat mast cells

    DEFF Research Database (Denmark)

    Linnebjerg, H.; Hansen, Harald S.; Jensen, B.

    1989-01-01

    The effect of a putative Na/H exchange inhibition on histamine and [C]arachidonic acid ([C]AA) release has been examined in rat peritoneal mast cells, using either addition of amiloride or removal of extracellular Na. The cells were stimulated by non-immunological agents, i.e. calcium ionophore A......23187, nerve growth factor (NGF), thapsigargin and compound 48/80. On the basis of the results obtained, a possible role for Na/H exchange in rat mast cell secretion is discussed....

  17. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental outcomes.

    Science.gov (United States)

    Colombo, John; Jill Shaddy, D; Kerling, Elizabeth H; Gustafson, Kathleen M; Carlson, Susan E

    2017-06-01

    The DHA Intake and Measurement of Neural Development (DIAMOND) trial represents one of only a few studies of the long-term dose-response effects of LCPUFA-supplemented formula feeding during infancy. The trial contrasted the effects of four formulations: 0.00% docosahexaenoic acid (DHA)/0.00% arachidonic acid (ARA), 0.32% DHA/0.64% ARA, 0.64% DHA/0.64% ARA, and 0.96% DHA/0.64% ARA against a control condition (0.00% DHA/0.00% ARA). The results of this trial have been published elsewhere, and show improved cognitive outcomes for infants fed supplemented formulas, but a common finding among many of the outcomes show a reduction of benefit for the highest DHA dose (i.e., 0.96%DHA/0.64% ARA, that is, a DHA: ARA ratio 1.5:1.0). The current paper gathers and summarizes the evidence for the reduction of benefit at this dose, and in an attempt to account for this reduced benefit, presents for the first time data from infants' red blood cell (RBC) assays taken at 4 and 12 months of age. Those assays indicate that blood DHA levels generally rose with increased DHA supplementation, although those levels tended to plateau as the DHA-supplemented level exceeded 0.64%. Perhaps more importantly, ARA levels showed a strong inverted-U function in response to increased DHA supplementation; indeed, infants assigned to the formula with the highest dose of DHA (and highest DHA/ARA ratio) showed a reduction in blood ARA relative to more intermediate DHA doses. This finding raises the possibility that reduced ARA may be responsible for the reduction in benefit on cognitive outcomes seen at this dose. The findings implicate the DHA/ARA balance as an important variable in the contribution of LCPUFAs to cognitive and behavioral development in infancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Tang, Yuting; Zhou, Lubing; Gunnet, Joseph W.; Wines, Pamela G.; Cryan, Ellen V.; Demarest, Keith T.

    2006-01-01

    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 2 (PLA 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 therapeutic 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 2+ -mobilization and enhanced bradykinin-promoted Ca 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 PPARγ agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs

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

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yuting [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Zhou, Lubing [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Gunnet, Joseph W [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Wines, Pamela G [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Cryan, Ellen V [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Demarest, Keith T [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States)

    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 therapeutic 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.

  20. Effect of ethanol amine plasmalogens on Fe-induced peroxidation of arachidonic acid in dipalmitoylphosphatidylcholine vesicles.

    Science.gov (United States)

    Omodeo Salè, M F; Rizzo, A M; Masserini, M

    2000-12-01

    We have investigated the influence of ethanolamine plasmalogens on iron-induced oxidation of arachidonic acid in dipalmitoylphosphatidylcholine (DPPC) vesicles. Lipoperoxidation was induced by the addition of 50 microM FeSO4 and studied above (50 degrees C) and below (15 degrees C) the gel-to liquid transition temperature of the vesicles, at two different pH values (7.4 or 6.4). The extent of peroxidation was measured as thiobarbituric reactive product formed and the influence exerted by ethanolamine plasmalogens (PEPL) in this process was compared to that of dipalmitoylphosphatidylethanolamine (DPPE) and diacylphosphatidylethanolamines (DAPE). The extent of peroxidation of arachidonic acid embedded in DPPC vesicles was similar at the two temperatures and greater at 50 degrees C under acidic conditions. However, the peroxidative process was significantly decreased at 50 degrees C in the presence of PEPL, but not of DPPE or DAPE and the inhibitory effect was enhanced at pH 6.4. The possibility that a different phase distribution of the phospholipids, namely a transition from a lamellar to a hexagonal phase, may play a role in the scavenger effect of ethanolamine plasmalogens is discussed.

  1. Arachidonic acid in health and disease with focus on hypertension and diabetes mellitus: A review

    Directory of Open Access Journals (Sweden)

    Undurti N. Das

    2018-05-01

    Full Text Available Arachidonic acid (AA 20:4n-6 is an essential component of cell membranes and modulates cell membrane fluidity. AA is metabolized by cyclo-oxygenase (COX, lipoxygenase (LOX and cytochrome P450 enzymes to form several metabolites that have important biological actions. Of all the actions, role of AA in the regulation of blood pressure and its ability to prevent both type 1 and type 2 diabetes mellitus seems to be interesting. Studies showed that AA and its metabolites especially, lipoxin A4 (LXA4 and epoxyeicosatrienoic acids (EETs, potent anti-inflammatory metabolites, have a crucial role in the pathobiology of hypertension and diabetes mellitus. AA, LXA4 and EETs regulate smooth muscle function and proliferation, voltage gated ion channels, cell membrane fluidity, membrane receptors, G-coupled receptors, PPARs, free radical generation, nitric oxide formation, inflammation, and immune responses that, in turn, participate in the regulation blood pressure and pathogenesis of diabetes mellitus. In this review, role of AA and its metabolites LXA4 and EETs in the pathobiology of hypertension, pre-eclampsia and diabetes mellitus are discussed. Based on several lines of evidences, it is proposed that a combination of aspirin and AA could be of benefit in the prevention and management of hypertension, pre-eclampsia and diabetes mellitus. Keywords: Arachidonic acid, Lipoxin A4, Hypertension, Pre-eclampsia, Diabetes mellitus, Inflammation, Cytokines, Free radicals, Nitric oxide

  2. Food Polyphenol Apigenin Inhibits the Cytochrome P450 Monoxygenase Branch of the Arachidonic Acid Cascade.

    Science.gov (United States)

    Steuck, Maryvonne; Hellhake, Stefan; Schebb, Nils Helge

    2016-11-30

    The product of cytochrome P450 monooxygenase (P450) ω-hydroxylation of arachidonic acid (AA), 20- hydroxyeicosatetraenoic acid (HETE), is a potent vasoconstrictor. Utilizing microsomes as well as individual CYP4 isoforms we demonstrate here that flavonoids can block 20-HETE formation. Apigenin inhibits CYP4F2 with an IC 50 value of 4.6 μM and 20-HETE formation in human liver and kidney microsomes at 2.4-9.8 μM. Interestingly, the structurally similar naringenin shows no relevant effect on the formation of 20-HETE. Based on these in vitro data, it is impossible to evaluate if a relevant blockade of 20-HETE formation can result in humans from intake of polyphenols with the diet. However, the potency of apigenin is comparable to those of P450 inhibitors such as ketoconazole. Moreover, an IC 50 value in the micromolar range is also described for the inhibition of CYP-mediated drug metabolism leading to food-drug interactions. The modulation of the arachidonic acid cascade by food polyphenols therefore warrants further investigation.

  3. Hydrogen/deuterium exchange of cross-linkable alpha-amino acid derivatives in deuterated triflic acid

    OpenAIRE

    Wang, Lei; Murai, Yuta; Yoshida, Takuma; Okamoto, Masashi; Masuda, Katsuyoshi; Sakihama, Yasuko; Hashidoko, Yasuyuki; Hatanaka, Yasumaru; Hashimoto, Makoto

    2014-01-01

    In this paper we report here a hydrogen/deuterium exchange (H/D exchange) of cross-linkable alpha-amino acid derivatives with deuterated trifluoromethanesulfonic acid (TfOD). H/D exchange with TfOD was easily applied to o-catechol containing phenylalanine (DOPA) within an hour. A partial H/D exchange was observed for trifluoromethyldiazirinyl (TFMD) phenylalanine derivatives. N-Acetyl-protected natural aromatic alpha-amino acids (Tyr and Trp) were more effective in H/D exchange than unprotect...

  4. Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway.

    Science.gov (United States)

    De, Soumita; Maroo, Niteeka; Saha, Piu; Hazra, Samik; Chatterjee, Mitali

    2013-01-01

    The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action. Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA) and generation of reactive oxygen species (ROS) was measured by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate. PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001). In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01. The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration.

  5. mRNA levels of enzymes and receptors implicated in arachidonic acid metabolism in gliomas.

    Science.gov (United States)

    De Armas, Rafael; Durand, Karine; Guillaudeau, Angélique; Weinbreck, Nicolas; Robert, Sandrine; Moreau, Jean-Jacques; Caire, François; Acosta, Gisela; Pebet, Matias; Chaunavel, Alain; Marin, Benoît; Labrousse, François; Denizot, Yves

    2010-07-01

    Gliomas are tumors of the central nervous system derived from glial cells. They show cellular heterogeneity and lack specific diagnostic markers. Although a possible role for the eicosanoid cascade has been suggested in glioma tumorigenesis, the relationship between enzymes and receptors implicated in arachidonic acid metabolism, with histological tumor type has not yet been determined. Quantitative real-time reverse transcription-polymerase chain reaction was performed to measure and compare transcript levels of enzymes and receptors implicated in both lipoxygenase and cyclooxygenase pathways between oligodendrogliomas, astrocytomas, glioblastomas and mixed oligoastrocytomas. Arachidonic acid metabolism-related enzymes and receptor transcripts (i) were underexpressed in classical oligodendrogliomas compared to astrocytomas and/or glioblastomas, (ii) differed between astrocytomas and glioblastomas and (iii) had an intermediate expression in mixed oligoastrocytomas. mRNA levels of enzymes and receptors implicated both in lipoxygenase and cyclooxygenase pathways differed significantly in gliomas according to the histological type. Copyright 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  6. Equine tracheal epithelial membrane strips - An alternate method for examining epithelial cell arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Gray, P.R.; Derksen, F.J.; Robinson, N.E.; Peter-Golden, M.L.

    1990-01-01

    Arachidonic acid metabolism by tracheal epithelium can be studied using enzymatically dispersed cell suspensions or cell cultures. Both techniques require considerable tissue disruption and manipulation and may not accurately represent in vivo activity. The authors have developed an alternate method for obtaining strips of equine tracheal epithelium without enzymatic digestion. In the horse, a prominent elastic lamina supports the tracheal epithelium. By physical splitting this lamina, they obtained strips (≤12 x 1.5 cm) of pseudostratified columnar epithelium attached to a layer of elastic tissue 30-100 μm thick. Epithelial strips (1.2 x 0.5 cm) were attached to plexiglass rods and incubated with [ 3 H]arachidonic acid in M199 medium (0.5 μCi/ml) for 24 hours at 37C. The strips incorporated 36±4% (mean ± SEM) of the total radioactivity and released 8.0±1.2% of incorporated radioactivity when stimulated by 5.0 μM calcium ionophore A23187. The extracted supernatant was processed using HPLC, resulting in peaks of radioactivity that co-eluted with authentic PGE 2 , PGF 2 α, and 12-HETE standards. The greatest activity corresponded to the PGE 2 and PGF 2 α standards, which is a similar pattern to that reported for cultured human tracheal epithelium

  7. Lung, aorta, and platelet metabolism of 14C-arachidonic acid in vitamin E deficient rats

    International Nuclear Information System (INIS)

    Valentovic, M.A.; Gairola, C.; Lubawy, W.C.

    1982-01-01

    14 C-arachidonic acid metabolism was determined in aortas, platelets, and perfused lungs from rats pair fed a basal diet supplemented with 0 or 100 ppm vitamin E for 11 weeks. Spontaneous erythrocyte hemolysis tests showed 92% and 8% hemolysis for the 0 and 100 ppm vitamin E groups, respectively. Elevated lung homogenate levels of malonaldehyde in the 0 ppm group confirmed its deficient vitamin E status. Aortas from the vitamin E deficient group synthesized 54% less prostacyclin than aortas from the supplemented group (p less than 0.05). Although thromboxane generation by platelets from the vitamin E deficient group exhibited a 37% increase, this difference was not statistically significant compared to the supplemented animals. Greater amounts of PGE2, PGF2 alpha, TXB2, and 6-keto-PGF1 alpha were obtained in albumin buffer perfusates from lungs of vitamin E deficient rats than in those from supplemented rats. Significant differences (p less than 0.05) were noticed, however, only for PGE2 and PGF2 alpha. These studies indicate that vitamin E quantitatively alters arachidonic acid metabolism in aortic and lung tissue but its effect on thromboxane synthesis by platelets is less marked

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

    International Nuclear Information System (INIS)

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

    1984-01-01

    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, 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

  9. Pulmonary arachidonic acid metabolism following acute exposures to ozone and nitrogen dioxide

    International Nuclear Information System (INIS)

    Schlesinger, R.B.; Driscoll, K.E.; Gunnison, A.F.; Zelikoff, J.T.

    1990-01-01

    Ozone (O 3 ) and nitrogen dioxide (NO 2 ) are common air pollutants, and exposure to these gases has been shown to affect pulmonary physiology, biochemistry, and structure. This study examined their ability to modulate arachidonic acid metabolites (eicosanoids) in the lungs. Rabbits were exposed for 2 h to O 3 at 0.1, 0.3, or 1 ppm; NO 2 at 1, 3, or 10 ppm; or to a mixture of 0.3 ppm O 3 and 3 ppm NO 2 . Groups of animals sacrificed either immediately or 24 h after each exposure underwent broncho-pulmonary lavage. Selected eicosanoids were assessed in lavage fluid by radioimmunoassay. Increases in prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) were found immediately after exposure to 1 ppm O 3 . Exposure to 10 ppm NO 2 resulted in a depression of 6-keto-PGF1 alpha, while thromboxane B2 (TxB2) was elevated after exposure to 1 ppm NO 2 and depressed following 3 and 10 ppm. The O 3 /NO 2 mixture resulted in synergistic increases in PGE2 and PGF2 alpha, with the response appearing to be driven by O 3 . This study has demonstrated that acute exposure to either O 3 or NO 2 can alter pulmonary arachidonic acid metabolism and that the responses to these oxidants differ, both quantitatively and qualitatively

  10. Effect of selenium and vitamin E deficiencies on the fate of arachidonic acid in rat isolated lungs

    International Nuclear Information System (INIS)

    Uotila, P.; Puustinen, T.

    1985-01-01

    The fate of exogenous 14 C-arachidonic acid ( 14 C-AA) was investigated in the isolated lungs of rats fed selenium and vitamin E deficient diet or diets supplemented with selenium and/or vitamin E. When 80 nmol of 14 C-AA was infused into the pulmonary circulation most of the infused 14 C-AA was found in different phospholipid and neutral lipid fractions of the perfused lungs. Only less than ten percent of the infused radioactivity was recovered in the perfusion effluent. The amount of arachidonate metabolites in the perfusion effluent was negligible, and most of the radioactivity in the perfusion effluent consisted of unmetabolized arachidonate. Selenium deficiency had no significant effect on the distribution of 14 C-AA in different lung lipid fractions. However, in the lungs of vitamin E deficient rats the amount of radioactivity was slightly increased in the neutral lipid fraction, which was due to the increased amount of 14 C-AA in the diacylglycerols. The amount of radioactivity was increased especially in the 1,3-diacylglycerols. The amount of radioactivity was increased especially in the 1,3-diacylglycerols. The amount of 14 C-AA in the triacylglycerols and in different phospholipids was not significantly changed. The present study might indicate that selenium deficiency has no significant effect on the fate of exogenous arachidonic acid in isolated rat lungs, and that vitamin E deficiency would slightly increase the amount of arachidonic acid in the diacylglycerols

  11. Carbon monoxide is not responsible for the cigarette smokeinduced changes in the pulmonary metabolism of arachidonic acid and prostaglandin E2

    International Nuclear Information System (INIS)

    Maennistoe, J.; Puustinen, T.; Uotila, P.

    1985-01-01

    Cigarette smoke is known to interfere with the pulmonary metabolism of arachidomic acid and prostaglandin E 2 (PGE 2 ). We investigated the possible role of carbon monoxide in these cigarette smoke-infuced alterations. 4 C-Arachidonic acid (50 nmol) was indused into the pulmonary circulation of isolated perfused hamster lungs and the radioactive metabolites in the perfusion effluent, as well as the distribution of incorporated radioactive arachidonic acid within the lung lipids, were analysed. Carbon monoxide, added into the ventilatory air, had no effect on the oxidative metabolism of arachidonic acid or on the distribution of radioactive arachidonic acid within the lung. In addition, carbon monoxide had no effect on the metabolism of PGE 2 following infusion of 100 nmol of 14 C-PGE 2 into the rat pulmonary circulation. The present study suggests that carbon monoxide is not responsible for the cigarette smoke-induced changes in the pulmonary metabolism of arachidonic acid and PGE 2 . (author)

  12. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

    Science.gov (United States)

    Norambuena, Fernando; Morais, Sofia; Emery, James A; Turchini, Giovanni M

    2015-01-01

    Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

  13. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

    Directory of Open Access Journals (Sweden)

    Fernando Norambuena

    Full Text Available Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3, with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher

  14. Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: A targeted metabolomic approach.

    Science.gov (United States)

    Yao, Xuan; Sa, Rina; Ye, Cheng; Zhang, Duo; Zhang, Shengjie; Xia, Hongfeng; Wang, Yu-cheng; Jiang, Jingjing; Yin, Huiyong; Ying, Hao

    2015-01-01

    Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determined by a mass spectrometry-based method. Over ten arachidonic acid metabolites belonging to three catalytic pathways: cyclooxygenases, lipoxygenases, and cytochrome P450, were quantified simultaneously and displayed characteristic profiles under different thyroid hormone status. The level of 20-hydroxyeicosatetraenoic acid, a cytochrome P450 metabolite, was positively correlated with thyroid hormone level and possibly contributed to the elevated blood pressured in hyperthyroidism. The increased prostanoid (PG) I2 and decreased PGE2 levels in hypothyroid patients might serve to alleviate atherosclerosis associated with dyslipidemia. The elevated level of thromboxane (TX) A2, as indicated by TXB2, in hyperthyroid patients and mice treated with thyroid hormone might bring about pulmonary hypertension frequently found in hyperthyroid patients. In conclusion, our prospective study revealed that arachidonic acid metabolites were differentially affected by thyroid hormone status. Certain metabolites may be involved in cardiovascular disorders associated with thyroid diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    DEFF Research Database (Denmark)

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A

    2002-01-01

    The lipid mediators generated by phospholipases A(2) (PLA(2)), free arachidonic acid (AA), eicosanoids, and platelet-activating factor, modulate neuronal activity; when overproduced, some of them become potent neurotoxins. We have shown, using primary cortical neuron cultures, that glutamate...... and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate......) and in minor changes in other phospholipids. A similar profile, although of greater magnitude, was observed 20 hr posttreatment. Glutamate (80 microM) induced much less mobilization of (3)H-AA than did sPLA(2) and resulted in a threefold greater degradation of (3)H-AA PE than of (3)H-AA PC by 20 hr...

  16. Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, J.; Spriggs, D.; Imamura, K.; Stone, R.; Luebbers, R.; Kufe, D.

    1989-01-01

    The treatment of human HL-60 promyelocytic leukemia cells with 12-0 tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcripts. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNS mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase, A/sub 2/ blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B/sub 4/. In contrast, the cyclooxygenase metabolite prostaglandin E/sub 2/ inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B/sub 4/ and prostaglandin E/sub 2/.

  17. Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267

    International Nuclear Information System (INIS)

    Amin, D.

    1986-01-01

    The mechanism of the release of arachidonic acid from phospholipids after the stimulation of guinea pig platelets with collagen, thrombin and platelet activating factor (PAF) was studied. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. Platelets were labeled with ( 14 C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. In the present investigation it is shown that collagen, thrombin and PAF increased phospholipase C activity. It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. The guinea pig platelet is an ideal model to study phospholipase C-diacylglycerol lipase pathway for the release of arachidonic acid from platelet phospholipids because it does not have any phospholipase A 2 activity. It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. Indomethacin completely inhibited collagen-induced platelet aggregation, was less effective against thrombin, and had no effect on PAF-induced platelet aggregation. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents

  18. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

    Science.gov (United States)

    Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

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

    Science.gov (United States)

    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

  20. Specific acid catalyzed deuteration of the acetyl groups of 2,4-diacetyldeuterohemin-OMe

    International Nuclear Information System (INIS)

    Oster, O.; Neireiter, G.W.; Gurd, F.R.N.

    1975-01-01

    The methyl group of the acetyl groups in 2,4-diacetyldeuterohemin-OMe has been selectively deuterated. After removal of the iron, D 6 -2,4-diacetyl-deuteroporphyrin-OMe can be reduced to the corresponding hematoporphyrin and subsequent dehydration gives deuterated vinylic groups for protoporphyrin IX-OMe. (orig.) [de

  1. Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling.

    Science.gov (United States)

    Grabner, Gernot F; Zimmermann, Robert; Schicho, Rudolf; Taschler, Ulrike

    2017-07-01

    Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoyl glycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body. Importantly, recent observations demonstrate that 2-AG represents a quantitatively important source for arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. Accordingly, MGL-mediated 2-AG degradation affects lipid signaling by cannabinoid receptor-dependent and independent mechanisms. Recent genetic and pharmacological studies gave important insights into MGL's role in (patho-)physiological processes, and the enzyme is now considered as a promising drug target for a number of disorders including cancer, neurodegenerative and inflammatory diseases. This review summarizes the basics of MG (2-AG) metabolism and provides an overview on the therapeutic potential of MGL. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Pregnancy duration and the ratio of long-chain n-3 fatty acids to arachidonic acid in erythrocytes from Faroese women

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, Harald S.; Jensen, B.

    1989-01-01

    of long-chain n-3 FA to arachidonic acid (the (3/6) ratio) was used as the most relevant single measure of exposure. In 18 women with certain gestational age and with spontaneous onset of delivery, gestational age was significantly associated with the (3/6) ratio quantified in PC (correlation coefficient......Dietary long-chain n-3 fatty acids (FA) may prolong gestation by inhibiting formation of prostaglandins from arachidonic acid. FA were quantified in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and total lipids (TL) of red cells sampled during pregnancy from 29 Faroese women. The ratio...

  3. The TIP30 protein complex, arachidonic acid and coenzyme A are required for vesicle membrane fusion.

    Directory of Open Access Journals (Sweden)

    Chengliang Zhang

    Full Text Available Efficient membrane fusion has been successfully mimicked in vitro using artificial membranes and a number of cellular proteins that are currently known to participate in membrane fusion. However, these proteins are not sufficient to promote efficient fusion between biological membranes, indicating that critical fusogenic factors remain unidentified. We have recently identified a TIP30 protein complex containing TIP30, acyl-CoA synthetase long-chain family member 4 (ACSL4 and Endophilin B1 (Endo B1 that promotes the fusion of endocytic vesicles with Rab5a vesicles, which transport endosomal acidification enzymes vacuolar (H⁺-ATPases (V-ATPases to the early endosomes in vivo. Here, we demonstrate that the TIP30 protein complex facilitates the fusion of endocytic vesicles with Rab5a vesicles in vitro. Fusion of the two vesicles also depends on arachidonic acid, coenzyme A and the synthesis of arachidonyl-CoA by ACSL4. Moreover, the TIP30 complex is able to transfer arachidonyl groups onto phosphatidic acid (PA, producing a new lipid species that is capable of inducing close contact between membranes. Together, our data suggest that the TIP30 complex facilitates biological membrane fusion through modification of PA on membranes.

  4. A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology.

    Science.gov (United States)

    Fan, Yang-Yi; Callaway, Evelyn; M Monk, Jennifer; S Goldsby, Jennifer; Yang, Peiying; Vincent, Logan; S Chapkin, Robert

    2016-09-01

    A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA)-derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression, and metastasis. We have recently developed a novel Fads1 knockout mouse model that allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1-null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1%, 0.4%, 0.6%, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P sibling littermate control mice. These data indicate that (i) basal/minimal dietary AA supplementation (0.6%) expands the utility of the Fads1-null mouse model for long-term cancer prevention studies and (ii) that AA content in the colonic epithelium modulates colon cancer risk. Cancer Prev Res; 9(9); 750-7. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Effect of oxygen deprivation on metabolism of arachidonic acid by cultures of rat heart cells

    International Nuclear Information System (INIS)

    Freyss-Beguin, M.; Millanvoye-van Brussel, E.; Duval, D.

    1989-01-01

    To investigate the mechanisms responsible for the impairment of phospholipid metabolism observed in ischemic cells, we have studied the effect of conditions simulating ischemia on the metabolism of arachidonic acid (AA) by muscle (M-) and nonmuscle (F-) cells isolated from newborn rat hearts and cultured separately. In muscle cells, oxygen deprivation induces a significant stimulation of the release of [ 14 C]AA from prelabeled cells associated with a preferential redistribution of [ 14 C]AA into cell triglycerides but not formation of radioactive prostaglandins. Moreover, the fatty acid content of phospholipids, as measured by capillary gas chromatography, appears markedly reduced in ischemic myocardial cells. This fact may be related to phospholipase stimulation during ischemia as suggested by the antagonistic effect of mepacrine or p-bromophenacyl bromide. In contrast, oxygen deprivation failed to induce any significant alteration of AA metabolism in fibroblast-like heart cells. Our results indicate that these cultures of newborn rat heart cells, which exhibit many of the features observed in intact organ during ischemia, may represent a useful experimental model to investigate the pharmacological control of the membrane phospholipid turnover

  6. Effects of sexually dimorphic growth hormone secretory patterns on arachidonic acid metabolizing enzymes in rodent heart

    International Nuclear Information System (INIS)

    Zhang, Furong; Yu, Xuming; He, Chunyan; Ouyang, Xiufang; Wu, Jinhua; Li, Jie; Zhang, Junjie; Duan, Xuejiao; Wan, Yu; Yue, Jiang

    2015-01-01

    The arachidonic acid (AA) metabolizing enzymes are the potential therapeutic targets of cardiovascular diseases (CVDs). As sex differences have been shown in the risk and outcome of CVDs, we investigated the regulation of heart AA metabolizing enzymes (COXs, LOXs, and CYPs) by sex-dependent growth hormone (GH) secretory patterns. The pulsatile (masculine) GH secretion at a physiological concentration decreased CYP1A1 and CYP2J3 mRNA levels more efficiently in the H9c2 cells compared with the constant (feminine) GH secretion; however, CYP1B1 mRNA levels were higher following the pulsatile GH secretion. Sex differences in CYP1A1, CYP1B1, and CYP2J11 mRNA levels were observed in both the wild-type and GHR deficient mice. No sex differences in the mRNA levels of COXs, LOXs, or CYP2E1 were observed in the wild-type mice. The constant GH infusion induced heart CYP1A1 and CYP2J11, and decreased CYP1B1 in the male C57/B6 mice constantly infused with GH (0.4 μg/h, 7 days). The activity of rat Cyp2j3 promoter was inhibited by the STAT5B protein, but was activated by C/EBPα (CEBPA). Compared with the constant GH administration, the levels of the nuclear phosphorylated STAT5B protein and its binding to the rat Cyp2j3 promoter were higher following the pulsatile GH administration. The constant GH infusion decreased the binding of the nuclear phosphorylated STAT5B protein to the mouse Cyp2j11 promoter. The data suggest the sexually dimorphic transcription of heart AA metabolizing enzymes, which might alter the risk and outcome of CVDs. GHR-STAT5B signal transduction pathway may be involved in the sex difference in heart CYP2J levels. - Highlights: • The transcription of heart Cyp1a1, Cyp1b1 and Cyp2j genes is sexually dimorphic. • There are no sex differences in the mRNA levels of heart COXs, LOXs, or CYP2E1. • GHR-STAT5B pathway is involved in sexually dimorphic transcription of heart Cpy2j genes. • Heart CYPs-mediated metabolism pathway of arachidonic acid may be sex

  7. Effects of sexually dimorphic growth hormone secretory patterns on arachidonic acid metabolizing enzymes in rodent heart

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Furong; Yu, Xuming [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); He, Chunyan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Ouyang, Xiufang; Wu, Jinhua; Li, Jie; Zhang, Junjie; Duan, Xuejiao [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Wan, Yu [Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yue, Jiang, E-mail: yuejiang@whu.edu.cn [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-12-15

    The arachidonic acid (AA) metabolizing enzymes are the potential therapeutic targets of cardiovascular diseases (CVDs). As sex differences have been shown in the risk and outcome of CVDs, we investigated the regulation of heart AA metabolizing enzymes (COXs, LOXs, and CYPs) by sex-dependent growth hormone (GH) secretory patterns. The pulsatile (masculine) GH secretion at a physiological concentration decreased CYP1A1 and CYP2J3 mRNA levels more efficiently in the H9c2 cells compared with the constant (feminine) GH secretion; however, CYP1B1 mRNA levels were higher following the pulsatile GH secretion. Sex differences in CYP1A1, CYP1B1, and CYP2J11 mRNA levels were observed in both the wild-type and GHR deficient mice. No sex differences in the mRNA levels of COXs, LOXs, or CYP2E1 were observed in the wild-type mice. The constant GH infusion induced heart CYP1A1 and CYP2J11, and decreased CYP1B1 in the male C57/B6 mice constantly infused with GH (0.4 μg/h, 7 days). The activity of rat Cyp2j3 promoter was inhibited by the STAT5B protein, but was activated by C/EBPα (CEBPA). Compared with the constant GH administration, the levels of the nuclear phosphorylated STAT5B protein and its binding to the rat Cyp2j3 promoter were higher following the pulsatile GH administration. The constant GH infusion decreased the binding of the nuclear phosphorylated STAT5B protein to the mouse Cyp2j11 promoter. The data suggest the sexually dimorphic transcription of heart AA metabolizing enzymes, which might alter the risk and outcome of CVDs. GHR-STAT5B signal transduction pathway may be involved in the sex difference in heart CYP2J levels. - Highlights: • The transcription of heart Cyp1a1, Cyp1b1 and Cyp2j genes is sexually dimorphic. • There are no sex differences in the mRNA levels of heart COXs, LOXs, or CYP2E1. • GHR-STAT5B pathway is involved in sexually dimorphic transcription of heart Cpy2j genes. • Heart CYPs-mediated metabolism pathway of arachidonic acid may be sex

  8. 2-hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug.

    Directory of Open Access Journals (Sweden)

    Daniel H Lopez

    Full Text Available BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs are a family of COX1 and COX2 inhibitors used to reduce the synthesis of pro-inflammatory mediators. In addition, inflammation often leads to a harmful generation of nitric oxide. Efforts are being done in discovering safer NSAIDs molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators and nitric oxide to reduce the side effects associated with long term therapies. METHODOLOGY/PRINCIPAL FINDINGS: The analogue of arachidonic acid (AA, 2-hydroxy-arachidonic acid (2OAA, was designed to inhibit the activities of COX1 and COX2 and it was predicted to have similar binding energies as AA for the catalytic sites of COX1 and COX2. The interaction of AA and 2OAA with COX1 and COX2 was investigated calculating the free energy of binding and the Fukui function. Toxicity was determined in mouse microglial BV-2 cells. COX1 and COX2 (PGH2 production activities were measured in vitro. COX1 and COX2 expression in human macrophage-like U937 cells were carried out by Western blot, immunocytochemistry and RT-PCR analysis. NO production (Griess method and iNOS (Western blot were determined in mouse microglial BV-2 cells. The comparative efficacy of 2OAA, ibuprofen and cortisone in lowering TNF-α serum levels was determined in C57BL6/J mice challenged with LPS. We show that the presence of the -OH group reduces the likelihood of 2OAA being subjected to H* abstraction in COX, without altering significantly the free energy of binding. The 2OAA inhibited COX1 and COX2 activities and the expression of COX2 in human U937 derived macrophages challenged with LPS. In addition, 2OAA inhibited iNOS expression and the production of NO in BV-2 microglial cells. Finally, oral administration of 2OAA decreased the plasma TNF-α levels in vivo. CONCLUSION/SIGNIFICANCE: These findings demonstrate the potential of 2OAA as a NSAID.

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

    Science.gov (United States)

    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 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 AA represents a useful predictor of cardiac events in adult patients with congenital heart disease.

  10. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

    Science.gov (United States)

    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.

  11. Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions.

    Science.gov (United States)

    Manolios, N; Bakiera, B; Geczy, C L; Schrieber, L

    1991-02-01

    In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.

  12. Ultrastructural autoradiographic localization of exogenous arachidonic acid in cultured endothelial and smooth muscle cells

    International Nuclear Information System (INIS)

    Tasca, S.I.; Galis, Z.

    1988-01-01

    The uptake and intracellular localization of exogenous arachidonic acid (AA) were investigated in cultured endothelial (EC) and smooth muscle cells (SMC) isolated from bovine aorta. The [ 14 C]AA uptake was assessed biochemically and by light and electron microscopic autoradiography. The highest values of silver grain surface density were associated with the mitochondria, lysosomes, and the Golgi apparatus of the EC. The grain linear density was greater on the nuclear envelope than on plasmalemma. On SMC, the grain density was highest on lipid droplets whereas the linear densities of the nuclear envelope and plasmalemma were similar. The share of each subcellular compartment in the AA distribution was estimated as the percentage of the individual silver grain count out of the total cell-associated radioactivity. The results showed that cytoplasm (including endoplasmic reticulum, ribosomes, and small vesicles) made the main contribution followed by the nucleus and at lower values by other organelles. These subcompartments may represent the intracellular sites from which AA could be mobilized for prostanoid synthesis by EC and SMC. (author)

  13. Combination Therapy of PPAR Ligands and Inhibitors of Arachidonic Acid in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jordi Tauler

    2008-01-01

    Full Text Available Lung cancer is the leading cause of cancer death in the United States and five-year survival remains low. Numerous studies have shown that chronic inflammation may lead to progression of carcinogenesis. As a result of inflammatory stimulation, arachidonic acid (AA metabolism produces proliferation mediators through complex and dynamic interactions of the products of the LOX/COX enzymes. One important mediator in the activation of the AA pathways is the nuclear protein PPAR. Targeting LOX/COX enzymes and inducing activation of PPAR have resulted in significant reduction of cell growth in lung cancer cell lines. However, specific COX-inhibitors have been correlated with an increased cardiovascular risk. Clinical applications are still being explored with a novel generation of dual LOX/COX inhibitors. PPAR activation through synthetic ligands (TZDs has revealed a great mechanistic complexity since effects are produced through PPAR-dependent and -independent mechanisms. Furthermore, PPAR could also be involved in regulation of COX-2. Overexpression of PPAR has reported to play a role in control of invasion and differentiation. Exploring the function of PPAR, in this new context, may provide a better mechanistic model of its role in cancer and give an opportunity to design a more efficient therapeutic approach in combination with LOX/COX inhibitors.

  14. Influence of whole-body gamma irradiation upon arachidonic acid metabolism in rat platelets

    International Nuclear Information System (INIS)

    Lognonne, J.L.; Ducousso, R.; Rocquet, G.; Kergonou, J.F.

    1985-01-01

    The effects of whole-body gamma irradiation (8.4 Gy) were studied on arachidonic acid (AA) metabolism in rat's blood platelets, from day D + 1 to day D + 10 after irradiation. AA conversion into thromboxane B 2 (TxB 2 ) increased at D + 1 and then gradually decreased to very low values from D + 7 to D + 10. This decrease in the conversion of exogenous AA into TxB 2 was due to a lower AA incorporation into platelets and not to a decrease of cyclooxygenase and thromboxane-synthetase activities. AA incorporation into membrane phospholipids of blood platelets was much more decreased than AA incorporation into whole platelets; moreover, the lipid composition of the platelet membranes was markedly modified after irradiation, which must have resulted in structural and functional changes in these membranes; from these effects of whole-body gamma irradiation on platelets, the latter's membranes appeared as a major site of in vivo radiation damage in these cells

  15. Early docosahexaenoic and arachidonic acid supplementation in extremely-low-birth-weight infants.

    Science.gov (United States)

    Robinson, Daniel T; Caplan, Michael; Carlson, Susan E; Yoder, Rachel; Murthy, Karna; Frost, Brandy

    2016-10-01

    Extremely-low-birth-weight (ELBW) infants accrue large deficits in docosahexaenoic acid (DHA) and arachidonic acid (ARA) and require improved supplementation strategies. We hypothesized that once daily DHA+ARA drops applied to buccal mucosa will increase blood levels. Thirty ELBW infants were randomized to receive DHA 20 mg/kg/d + ARA 40 or 60 mg/kg/d + ARA 120 mg/kg/d or placebo within 72 h of age for 8 wk duration. Red blood cell phospholipid levels of DHA (primary) and ARA (secondary) were measured at 2 and 8 wk of age. Twenty-eight survivors with a median birth weight of 806 g completed dosing and sampling. Red blood cell levels were similar between the three groups at 2 wk (DHA: 4.62 wt% (interquartile range (IQR) 4.1-5.5) for all, P = 0.29 between groups; ARA: 21.1 wt% (IQR 18.78-22.6) for all, P = 0.41 between groups) and 8 wk (DHA: 6.0 wt% (IQR 5.1-7.1) for all, P = 0.57 between groups; ARA: 20.1 wt% (IQR 18.3-23.1) for all, P = 0.63 between groups). DHA in all infants showed a median increase of 31% from 2 to 8 wk (P 0.6). Daily buccal DHA and ARA supplements did not affect fatty acid levels in ELBW infants.

  16. Application of a ω-3 Desaturase with an Arachidonic Acid Preference to Eicosapentaenoic Acid Production in Mortierella alpina

    Directory of Open Access Journals (Sweden)

    Chengfeng Ge

    2018-01-01

    Full Text Available In the industrial oleaginous fungus Mortierella alpina, the arachidonic acid (AA; C20:4; ω-6 fraction can reach 50% of the total fatty acids (TFAs in vivo. However, the eicosapentaenoic acid (EPA; C20:5; ω-3 fraction is less than 3% when this fungus is cultivated at a low temperature (12°C. Omega-3 fatty acid desaturase is a key enzyme in ω-3 long-chain polyunsaturated fatty acids biosynthesis pathways. To enhance EPA production, we transformed the ω-3 fatty acid desaturase (PaD17, which exhibits strong Δ-17 desaturase activity, into M. alpina, thus increasing the AA to EPA conversion rate to 49.8%. This PaD17-harboring M. alpina reconstruction strain produced 617 mg L−1 of EPA at room temperature in broth medium, this yield was increased to 1.73 g L−1 after culture medium optimization (i.e., about threefold higher than that under original culture conditions, with concomitant respective increases in dry cell weight and TFA content to 16.55 and 6.46 g L−1. These findings suggest a new platform for the future industrial production of EPA.

  17. Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

    Directory of Open Access Journals (Sweden)

    Ramzi J Khairallah

    Full Text Available Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP. We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA docosahexaenoic acid (DHA; 22:6n3 and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6 in mitochondrial membranes is associated with a greater Ca(2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6. Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca(2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

  18. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

    DEFF Research Database (Denmark)

    Kolko, M; DeCoster, M A; de Turco, E B

    1996-01-01

    glutamate and sPLA2 from bee venom. sPLA2, at concentrations eliciting low neurotoxicity (acid into triacylglycerols. Free [3H]arachidonic acid accumulated at higher enzyme concentrations......, from Taipan snake venom. The NMDA receptor antagonist MK-801 blocked glutamate effects and partially inhibited sPLA2 OS2 but not sPLA2 from bee venom-induced arachidonic acid release. Thus, the synergy with glutamate and very low concentrations of exogenously added sPLA2 suggests a potential role......Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding...

  19. Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in 12-week-old term infants

    NARCIS (Netherlands)

    van Goor, Saskia A.; Dijck-Brouwer, D. A. Janneke; Doornbos, Bennard; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Muskiet, Frits A. J.; Hadders-Algra, Mijna

    2010-01-01

    DHA and arachidonic acid (AA) are important for neurodevelopment. A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants. Mildly abnormal general movement,,; at 3 months have been

  20. Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

    International Nuclear Information System (INIS)

    Lubawy, W.C.; Valentovic, M.A.; Atkinson, J.E.; Gairola, G.C.

    1983-01-01

    Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14 C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14 C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

  1. Ultraviolet B irradiation induces changes in the distribution and release of arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture

    International Nuclear Information System (INIS)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.

    1987-01-01

    There is increasing evidence that derivatives of 20-carbon polyunsaturated fatty acids, the eicosanoids, play an important role in the inflammatory responses of the human skin. To better understand the metabolic fate of fatty acids in the skin, the effect of ultraviolet B (UVB) irradiation (280-320 nm) on the distribution and release of 14 C-labeled arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture was investigated. Ultraviolet B irradiation induced the release of all three 14 C-labeled fatty acids from the phospholipids, especially from phosphatidylethanolamine, and this was accompanied by increased labeling of the nonphosphorus lipids. This finding suggests that UVB induces a significant liberation of eicosanoid precursor fatty acids from cellular phospholipids, but the liberated fatty acids are largely reincorporated into the nonphosphorus lipids. In conclusion, the present study suggests that not only arachidonic acid but also dihomo-gamma-linolenic acid, and eicosapentaenoic acid might be involved in the UVB irradiation-induced inflammatory reactions of human skin

  2. A new model to study the role of arachidonic acid in colon cancer pathophysiology

    Science.gov (United States)

    Fan, Yang-Yi; Callaway, Evelyn; Monk, Jennifer M.; Goldsby, Jennifer S.; Yang, Peiying; Vincent, Logan; Chapkin, Robert S.

    2016-01-01

    A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA) derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression and metastasis. We have recently developed a novel Fads1 knockout mouse model, which allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1 null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1, 0.4, 0.6, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P diet were injected with a colon-specific carcinogen (azoxymethane) in order to assess cancer susceptibility. Null mice exhibited significantly (P < 0.05) reduced levels/multiplicity of aberrant crypt foci (ACF) as compared to wild type sibling littermate control mice. These data indicate that (i) basal/minimal dietary AA supplementation (0.6%) expands the utility of the Fads1 Null mouse model for long-term cancer prevention studies, and (ii) that AA content in the colonic epithelium modulates colon cancer risk. PMID:27339171

  3. Arachidonic acid metabolism by bovine placental tissue during the last month of pregnancy

    International Nuclear Information System (INIS)

    Hoedemaker, M.; Weston, P.G.; Wagner, W.C.

    1991-01-01

    Conversion of tritiated arachidonic acid (AA) into metabolites of the cyclo- and lipoxygenase pathways by bovine fetal placental tissue (200 mg) and fetal plus maternal placental tissue (400 mg) of Days 255, 265, 275 of gestation and at parturition (n = 5) during a 30 min incubation was measured using reverse-phase high pressure liquid chromatography. Fetal placental tissue produced 13,14-dihydro-15-keto-prostaglandin E2 (PGEM) as the major metabolite, the synthesis of which increased from Day 265 to Day 275 and parturition by 150% and 475%, respectively. In tissues collected at parturition, PGE2 synthesis was also detected. On Day 275 and at parturition fetal placental tissue synthesized the metabolite 12-hydroxyheptadecatrienoic acid (HHT), and throughout the experimental period the lipoxygenase product 15-HETE was detected with synthesis rates increasing over time of gestation. In addition, an unidentified metabolite was regularly found in the radiochromatograms which eluted at 1 h and 1 min (U101), between HHT and 15-HETE. The synthesis of this metabolite decreased as pregnancy progressed. Furthermore, various other polar and nonpolar metabolites pooled under the heading UNID were eluted, the production of which increased over time of gestation. The presence of maternal placental tissue did not influence the synthesis of PGEM, 15-HETE and U101, but the production of HHT was decreased when maternal tissue was present. Also, as pregnancy progressed, maternal placental tissue seemed to contribute to the pool of unidentified metabolites. In conclusion, fetal placental tissue seems to be the major source of the AA metabolites when compared with maternal placental tissue, and AA metabolism by bovine placental tissue is markedly increased throughout the last month of pregnancy, suggesting a role for AA metabolites in mechanisms controlling parturition

  4. Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Thaiz F. Borin

    2017-12-01

    Full Text Available Metastatic breast cancer (BC (also referred to as stage IV spreads beyond the breast to the bones, lungs, liver, or brain and is a major contributor to the deaths of cancer patients. Interestingly, metastasis is a result of stroma-coordinated hallmarks such as invasion and migration of the tumor cells from the primary niche, regrowth of the invading tumor cells in the distant organs, proliferation, vascularization, and immune suppression. Targeted therapies, when used as monotherapies or combination therapies, have shown limited success in decreasing the established metastatic growth and improving survival. Thus, novel therapeutic targets are warranted to improve the metastasis outcomes. We have been actively investigating the cytochrome P450 4 (CYP4 family of enzymes that can biosynthesize 20-hydroxyeicosatetraenoic acid (20-HETE, an important signaling eicosanoid involved in the regulation of vascular tone and angiogenesis. We have shown that 20-HETE can activate several intracellular protein kinases, pro-inflammatory mediators, and chemokines in cancer. This review article is focused on understanding the role of the arachidonic acid metabolic pathway in BC metastasis with an emphasis on 20-HETE as a novel therapeutic target to decrease BC metastasis. We have discussed all the significant investigational mechanisms and put forward studies showing how 20-HETE can promote angiogenesis and metastasis, and how its inhibition could affect the metastatic niches. Potential adjuvant therapies targeting the tumor microenvironment showing anti-tumor properties against BC and its lung metastasis are discussed at the end. This review will highlight the importance of exploring tumor-inherent and stromal-inherent metabolic pathways in the development of novel therapeutics for treating BC metastasis.

  5. Arachidonic acid-mediated inhibition of a potassium current in the giant neurons of Aplysia

    International Nuclear Information System (INIS)

    Carlson, R.O.

    1990-01-01

    Biochemical and electrophysiological approaches were used to investigate the role of arachidonic acid (AA) in the modulation of an inwardly rectifying potassium current (I R ) in the giant neurons of the marine snail, Aplysia californica. Using [ 3 H]AA as tracer, the intracellular free AA pool in Aplysia ganglia was found to be in a state of constant and rapid turnover through deacylation and reacylation of phospholipid, primarily phosphatidyl-inositol. This constant turnover was accompanied by a constant release of free AA and eicosanoids into the extracellular medium. The effects of three pharmacological agents were characterized with regard to AA metabolism in Aplysia ganglia. 4-O-tetra-decanoylphorbol 13-acetate (TPA), an activator of protein kinase C, stimulated liberation of AA from phospholipid, and 4-bromophenacylbromide (BPB), an inhibitor of phospholipate A 2 , inhibited this liberation. Indomethacin at 250 μM was found to inhibit uptake of AA, likely through inhibition of acyl-CoA synthetase. These agents were also found to modulate I R in ways which were consistent with their biological effects: TPA inhibited I R , and both BPB and indomethacin stimulated I R . Modulation of I R by these substances was found not to involve cAMP metabolism. Acute application of exogenous AA did not affect I R ; however, I R in giant neurons was found to be inhibited after dialysis with AA or other unsaturated fatty acids. Also, after perfusion with BSA overnight, a treatment which strips the giant neurons of AA in lipid storage, I R was found to have increased over 2-fold. This perfusion-induced increase was inhibited by the presence of AA or by pretreatment of the giant neurons with BPB. These results suggest AA, provided through constant turnover from phospholipid, mediates constitutive inhibition of I R

  6. Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial.

    Science.gov (United States)

    Alshweki, Ayham; Muñuzuri, Alejandro Pérez; Baña, Ana M; de Castro, Ma José; Andrade, Fernando; Aldamiz-Echevarría, Luís; de Pipaón, Miguel Sáenz; Fraga, José M; Couce, María L

    2015-09-30

    Nutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment, but it is not known if the omega-6/omega-3 ratio affects this process. This study was designed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk. This was a randomized trial, in which newborns psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age. A control group, for comparison of Brunet Lézine score, was made up of 25 newborns from the SEN1500 project, who were fed exclusively with breast milk. At 12 months, arachidonic acid values were significantly higher in group A than in group B (6.95 ± 1.55% vs. 4.55 ± 0.78%), as were polyunsaturated fatty acids (41.02 ± 2.09% vs. 38.08 ± 2.32%) achieved a higher average. Group A achieved a higher average Brunet Lézine score at 24 months than group B (99.9 ± 9 vs. 90.8 ± 11, p =0.028). The Brunet Lézine results from group A were compared with the control group results, with very similar scores registered between the two groups (99.9 ± 9 vs. 100.5 ± 7). There were no significant differences in growth or evoked potentials between the two formula groups. Very preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1. Therefore, formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants. ClinicalTrials.gov Identifier NCT02503020.

  7. Relative turnover of [3H]arachidonic acid and [14C]eicosapentaenoic acid in stimulated human platelets

    International Nuclear Information System (INIS)

    Weaver, B.J.; Holub, B.J.

    1986-01-01

    The relative release of arachidonic acid (AA) versus eicosapentaenoic acid (EPA) from platelet phospholipids may be important in accounting for the potential of dietary fish oil containing EPA to alter platelet reactivity. Human platelets enriched in EPA and prelabelled with [ 3 H]AA and [ 14 C]EPA were used to examine the relative losses of these fatty acids from platelet phospholipids upon stimulation. Washed dual-labelled platelets were incubated with and without thrombin in the presence of BW755C and in the presence and absence of trifluoperazine. The platelet lipids were extracted and the individual phospholipids as well as diacylglycerol (DG), phosphatidic acid (PA), etc. were separated by thin-layer chromatography and the radioactivity in each fraction determined. The [ 3 H]AA/[ 14 C]EPA dpm ratio for the loss in radioactivity from PC upon thrombin stimulation was similar to that for the PC in resting platelets. This suggests no marked selectivity in the degradation of AA versus EPA species of PC during platelet activation. The [ 3 H]/[ 14 C] ratios for the increased radioactivity in DG and PA upon thrombin stimulation were slightly higher than the ratio in PI from resting platelets suggesting only a minor preference for 1-acyl 2-arachidonoyl PI over 1-acyl 2-eicosapentaenoyl PI in the pathway from PI to DG to PA

  8. Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites

    Science.gov (United States)

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

    2010-01-01

    Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

  9. Arachidonic acid-induced Ca2+ entry and migration in a neuroendocrine cancer cell line.

    Science.gov (United States)

    Goswamee, Priyodarshan; Pounardjian, Tamar; Giovannucci, David R

    2018-01-01

    Store-operated Ca 2+ entry (SOCE) has been implicated in the migration of some cancer cell lines. The canonical SOCE is defined as the Ca 2+ entry that occurs in response to near-maximal depletion of Ca 2+ within the endoplasmic reticulum. Alternatively, arachidonic acid (AA) has been shown to induce Ca 2+ entry in a store-independent manner through Orai1/Orai3 hetero-multimeric channels. However, the role of this AA-induced Ca 2+ entry pathway in cancer cell migration has not been adequately assessed. The present study investigated the involvement of AA-induced Ca 2+ entry in migration in BON cells, a model gastro-enteropancreatic neuroendocrine tumor (GEPNET) cell line using pharmacological and gene knockdown methods in combination with live cell fluorescence imaging and standard migration assays. We showed that both the store-dependent and AA-induced Ca 2+ entry modes could be selectively activated and that exogenous administration of AA resulted in Ca 2+ entry that was pharmacologically distinct from SOCE. Also, whereas homomeric Orai1-containing channels appeared to largely underlie SOCE, the AA-induced Ca 2+ entry channel required the expression of Orai3 as well as Orai1. Moreover, we showed that AA treatment enhanced the migration of BON cells and that this migration could be abrogated by selective inhibition of the AA-induced Ca 2+ entry. Taken together, these data revealed that an alternative Orai3-dependent Ca 2+ entry pathway is an important signal for GEPNET cell migration.

  10. Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia.

    Directory of Open Access Journals (Sweden)

    Gaoliang Yan

    Full Text Available Arachidonic acid (AA and its metabolites, prostaglandins (PG are known to be involved in regulation of vascular homeostasis including vascular tone and vessel wall tension, but their potential role in Hypoxic pulmonary vasoconstriction (HPV remains unclear. In this study, we examined the effects of AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries (IPAs.We carried out the investigation on IPAs by vessel tension measurement. Isotetrandrine (20 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 µM and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic response of rat IPAs. PGE2 alone caused a significant vasoconstriction in isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L-161982 (1 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. However, AH6809 (3 µM, an antagonist of EP1, EP2, EP3 and DP1 receptors, exerted no effect on KPSS or hypoxia induced vessel contraction. Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced vessel contraction and abolish phase I, phase II b and phase II c of HPV.Our results demonstrated a vasoconstrictive effect of PGE2 on rat IPAs and this effect is via activation of EP4. Furthermore, our results suggest that intracellular cAMP plays dual roles in regulation of vascular tone, depending on the spatial distribution of cAMP and its coupling with EP receptor and Ca(2+ channels.

  11. Thiyl radical-induced cis-trans-isomerization of arachidonic acid inhibits prostaglandin metabolism

    International Nuclear Information System (INIS)

    Kratzsch, S.; Droessler, K.; Sprinz, H.; Brede, O.

    2002-01-01

    Complete text of publication follows. Thiyl radicals radiolytically generated from thiophenol in methanolic solution are known to isomerise double bonds of poly-unsaturated fatty acids (PUFA). γ-irradiating of such a system containing all-cis 5,8,11,14 eicosatetraenoic acid (arachidonic acid, AA) with low doses (0.1-0.8 kGy) results in a mixture of 8 to 32% mono-trans-isomers. Here we report about the influence of mono-trans-AA on the primary steps of AA-metabolism and prostaglandin synthesis, catalysed by cyclooxygenase (COX). In the cell-free model system the reaction of COX-1 with AA was analysed by controlling the oxygen level during the enzymatic reaction. As an example, a mixture of a low quantity of mono-trans-isomerized AA (10%) and 90% all-cis-isomer exhibits a marked reduced oxygen consumption by 45%. As further proofs - the yield of reactive oxygen species (ROS) generated by the COX-coupled peroxidase reaction was detected, - and the COX-1 activity in presence of different amounts of trans-AA was characterized using a photometric assay based on the oxidation of TMPD. All these methods indicated semiquantitatively a reduced activity of COX-1, depending on the trans-isomer yield. Therefore, an inhibition of COX-1 activity by only one trans-double-bond in AA could be concluded. Furthermore, in vitro cell-line experiments were performed analysing the influence of mono-trans-isomerized AA on the activity of the cell-own COX-2. Hence, VD 3 -differentiated and LPS-stimulated monocyte-like cells were incubated with mono-trans-AA and ROS-production was detected by the chemiluminescence measurements mentioned above. Compared to the reaction with all-cis-AA we found a considerable lowered formation of ROS. Likewise, we obtained a reduced PGE 2 -expression between 15 and 40% for cells treated with 8 to 29% trans-AA. The model as well as in vivo experiments demonstrate an inhibition effect of mono-trans-AA and give rise for postulating an enzyme blocking mechanism

  12. Participation of Arachidonic Acid Metabolism in the Aortic Aneurysm Formation in Patients with Marfan Syndrome

    Directory of Open Access Journals (Sweden)

    María E. Soto

    2018-02-01

    Full Text Available Marfan syndrome (MFS is a pleiotropic genetic disease involving the cardiovascular system where a fibrillin-1 mutation is present. This mutation is associated with accelerated activation of transforming growth factor β (TGFβ1 which contributes to the formation of aneurysms in the root of the aorta. There is an imbalance in the synthesis of thromboxane A2 (TXA2 and prostacyclin, that is a consequence of a differential protein expression of the isoforms of cyclooxygenases (COXs, suggesting an alteration of arachidonic acid (AA metabolism. The aim of this study was to analyze the participation of AA metabolism associated with inflammatory factors in the dilation and dissection of the aortic aneurysm in patients with MFS. A decrease in AA (p = 0.02, an increase in oleic acid (OA, TGFβ1, tumor necrosis factor alpha (TNFα, prostaglandin E2 (PGE2 (p < 0.05, and COXs activity (p = 0.002 was found. The expressions of phospholipase A2 (PLA2, cytochrome P450 (CYP450 4A, 5-lipoxygenase (5-LOX, COX2 and TXA2R (p < 0.05 showed a significant increase in the aortic aneurysm of patients with MFS compared to control subjects. COX1, 6-keto-prostaglandin 1 alpha (6-keto-PG1α and 8-isoprostane did not show significant changes. Histological examination of the aortas showed an increase of cystic necrosis, elastic fibers and collagen in MFS. The results suggest that there are inflammatory factors coupled to genetic factors that predispose to aortic endothelial dysfunction in the aortic tissue of patients with MFS. There is a decrease in the percentage of AA, associated with an increase of PLA2, COX2/TXA2R, CYP450 4A, and 5-LOX which leads to a greater synthesis of PGE2 than of 6-keto-PGF1α, thus contributing to the formation of the aortic aneurysm. The evident loss of the homeostasis in these mechanisms confirms that there is a participation of the AA pathway in the aneurysm progression in MFS.

  13. Tamoxifen and the Rafoxifene analog LY117018: their effects on arachidonic acid release from cells in culture and on prostaglandin I2 production by rat liver cells

    International Nuclear Information System (INIS)

    Levine, Lawrence

    2004-01-01

    Tamoxifen is being used successfully to treat breast cancer. However, tamoxifen also increases the risk of developing endometrial cancer in postmenopausal women. Raloxifene also decreases breast cancer in women at high risk and may have a lower risk at developing cancer of the uterus. Tamoxifen has been shown to stimulate arachidonic acid release from rat liver cells. I have postulated that arachidonic acid release from cells may be associated with cancer chemoprevention. Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [ 3 H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I 2 produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. Tamoxifen is about 5 times more effective than LY117018 at releasing arachidonic acid from all the cells tested. In rat liver cells only tamoxifen stimulates basal prostaglandin I 2 production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I 2 production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. Tamoxifen and the raloxifene analog, LY117018, may prevent estrogen-independent as well as estrogen-dependent breast cancer by stimulating phospholipase activity and initiating arachidonic acid release. The release of arachidonic acid and/or molecular reactions that accompany that release may initiate pathways that prevent tumor growth. Oxygenation of the intracellularly released arachidonic acid and its metabolic products may mediate some of the pharmacological actions of tamoxifen and raloxifene

  14. Docosahexaenoic acid (DHA) supplementation in pregnancy differentially modulates arachidonic acid and DHA status across FADS genotypes in pregnancy.

    Science.gov (United States)

    Scholtz, S A; Kerling, E H; Shaddy, D J; Li, S; Thodosoff, J M; Colombo, J; Carlson, S E

    2015-03-01

    Some FADS alleles are associated with lower DHA and ARA status assessed by the relative amount of arachidonic acid (ARA) and docosahexaenoic acid (DHA) in plasma and red blood cell (RBC) phospholipids (PL). We determined two FADS single nucleotide polymorphisms (SNPs) in a cohort of pregnant women and examined the relationship of FADS1rs174533 and FADS2rs174575 to DHA and ARA status before and after supplementation with 600mg per day of DHA. The 205 pregnant women studied were randomly assigned to placebo (mixed soy and corn oil) (n=96) or 600mg algal DHA (n=109) in 3 capsules per day for the last two trimesters of pregnancy. Women homozygous for the minor allele of FADS1rs174533 (but not FADS2rs174575) had lower DHA and ARA status at baseline. At delivery, minor allele homozygotes of FADS1rs174533 in the placebo group had lower RBC-DHA compared to major-allele carriers (P=0.031), while in the DHA-supplemented group, all genotypes had higher DHA status compared to baseline (P=0.001) and status did not differ by genotype (P=0.941). Surprisingly, DHA but not the placebo decreased ARA status of minor allele homozygotes of both FADS SNPs but not major allele homozygotes at delivery. Any physiological effects of changing the DHA to ARA ratio by increasing DHA intake appears to be greater in minor allele homozygotes of some FADS SNPs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Effect of dietary arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on survival, growth and pigmentation in larvae of common sole ( Solea solea L.)

    DEFF Research Database (Denmark)

    Lund, Ivar; Steenfeldt, Svend Jørgen; Hansen, B.W.

    2007-01-01

    Evidence confirms that polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid, DHA are involved in growth as well in pigmentation of marine fish larvae. In the present study we examined the performance of common sole larvae reared...... on Artemia enriched with 10 formulated emulsions, differing in inclusions of ARA, EPA, and DHA. The specific growth rate of the sole larvae until late metamorphosis, 21 days after hatching (dah) was 20 to 27% d(-1). Even though the relative tissue essential fatty acid (EFA) concentrations significantly...... reflected dietary composition, neither standard growth nor larval survival were significantly related to the absolute concentrations of ARA, EPA and DHA or their ratios. This suggests low requirements for essential polyunsaturated fatty acids (PUFAs) in common sole. Malpigmentation was significantly related...

  16. Regulation of the arachidonic acid mobilization in macrophages by combustion-derived particles

    Directory of Open Access Journals (Sweden)

    Weiss Carsten

    2011-08-01

    Full Text Available Abstract Background Acute exposure to elevated levels of environmental particulate matter (PM is associated with increasing morbidity and mortality rates. These adverse health effects, e.g. culminating in respiratory and cardiovascular diseases, have been demonstrated by a multitude of epidemiological studies. However, the underlying mechanisms relevant for toxicity are not completely understood. Especially the role of particle-induced reactive oxygen species (ROS, oxidative stress and inflammatory responses is of particular interest. In this in vitro study we examined the influence of particle-generated ROS on signalling pathways leading to activation of the arachidonic acid (AA cascade. Incinerator fly ash particles (MAF02 were used as a model for real-life combustion-derived particulate matter. As macrophages, besides epithelial cells, are the major targets of particle actions in the lung murine RAW264.7 macrophages and primary human macrophages were investigated. Results The interaction of fly ash particles with macrophages induced both the generation of ROS and as part of the cellular inflammatory responses a dose- and time-dependent increase of free AA, prostaglandin E2/thromboxane B2 (PGE2/TXB2, and 8-isoprostane, a non-enzymatically formed oxidation product of AA. Additionally, increased phosphorylation of the mitogen-activated protein kinases (MAPK JNK1/2, p38 and ERK1/2 was observed, the latter of which was shown to be involved in MAF02-generated AA mobilization and phosphorylation of the cytosolic phospolipase A2. Using specific inhibitors for the different phospolipase A2 isoforms the MAF02-induced AA liberation was shown to be dependent on the cytosolic phospholipase A2, but not on the secretory and calcium-independent phospholipase A2. The initiation of the AA pathway due to MAF02 particle exposure was demonstrated to depend on the formation of ROS since the presence of the antioxidant N-acetyl-cysteine (NAC prevented the MAF02

  17. Deuteration of lidocaine

    International Nuclear Information System (INIS)

    Haedener, A.

    1988-01-01

    Stepwise deuteration of the acidic methylene group of lidocaine on a large scale using a moderate excess of 2 H 2 O in triethylamine/pyridine at 200 0 is described. The efficient and economical preparation of bideuterated lidocaine facilitates the use of this compound as an excellent internal standard in lidocaine determination or as a tracer in lidocaine pharmacokinetics. (author)

  18. Deuteration of lidocaine

    Energy Technology Data Exchange (ETDEWEB)

    Haedener, A.

    1988-01-01

    Stepwise deuteration of the acidic methylene group of lidocaine on a large scale using a moderate excess of /sup 2/H/sub 2/O in triethylaminepyridine at 200/sup 0/ is described. The efficient and economical preparation of bideuterated lidocaine facilitates the use of this compound as an excellent internal standard in lidocaine determination or as a tracer in lidocaine pharmacokinetics.

  19. Dietary fatty acids and the stress response of fish. Arachidonic acid in seabream and tilapia

    NARCIS (Netherlands)

    Anholt, R.D. van

    2004-01-01

    A key factor in the production of fish in commercial aquaculture is the optimization of the artificial diets, not only to achieve optimal growth, but also to maximize fish health. Evidence is accumulating that dietary lipids, particularly the fatty acid composition, can have a direct effect on the

  20. Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation

    International Nuclear Information System (INIS)

    Storniolo, C.E.; Moreno, J.J.

    2016-01-01

    The mediterranean diet (MD) reduced the risk of colorectal cancer (CRC), and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO) is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA) cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development. [es

  1. Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    C. E. Storniolo

    2016-12-01

    Full Text Available The mediterranean diet (MD reduced the risk of colorectal cancer (CRC, and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development.

  2. Arachidonic acid and other unsaturated fatty acids and some of their metabolites function as endogenous antimicrobial molecules: A review

    Directory of Open Access Journals (Sweden)

    Undurti N. Das

    2018-05-01

    Full Text Available Our body is endowed with several endogenous anti-microbial compounds such as interferon, cytokines, free radicals, etc. However, little attention has been paid to the possibility that lipids could function as antimicrobial compounds. In this short review, the antimicrobial actions of various polyunsaturated fatty acids (PUFAs, mainly free acids and their putative mechanisms of action are described. In general, PUFAs kill microbes by their direct action on microbial cell membranes, enhancing generation of free radicals, augmenting the formation of lipid peroxides that are cytotoxic, and by increasing the formation of their bioactive metabolites, such as prostaglandins, lipoxins, resolvins, protectins and maresins that enhance the phagocytic action of leukocytes and macrophages. Higher intakes of α-linolenic and cis-linoleic acids (ALA and LA respectively and fish (a rich source of eicosapentaenoic acid and docosahexaenoic acid might reduce the risk pneumonia. Previously, it was suggested that polyunsaturated fatty acids (PUFAs: linoleic, α-linolenic, γ-linolenic (GLA, dihomo-GLA (DGLA, arachidonic (AA, eicosapentaenoic (EPA, and docosahexaenoic acids (DHA function as endogenous anti-bacterial, anti-fungal, anti-viral, anti-parasitic, and immunomodulating agents. A variety of bacteria are sensitive to the growth inhibitory actions of LA and ALA in vitro. Hydrolyzed linseed oil can kill methicillin-resistant Staphylococcus aureus. Both LA and AA have the ability to inactivate herpes, influenza, Sendai, and Sindbis virus within minutes of contact. AA, EPA, and DHA induce death of Plasmodium falciparum both in vitro and in vivo. Prostaglandin E1 (PGE1 and prostaglandin A (PGA, derived from DGLA, AA, and EPA inhibit viral replication and show anti-viral activity. Oral mucosa, epidermal cells, lymphocytes and macrophages contain and release significant amounts of PUFAs on stimulation. PUFAs stimulate NADPH-dependent superoxide production by

  3. Biotransformation of arachidonic acid (AA) and eicosapentaenoic acid (EPA) into lipoxins and lipoxenes by porcine leukocytes

    International Nuclear Information System (INIS)

    Wong, P.Y.K.; Spur, B.; Hirai, A.; Yoshida, S.; Tamura, Y.; Lam, B.K.

    1986-01-01

    Lipoxins and lipoxenes have been reported to be formed after incubation of 15-hydroperoxyeicosatetraenoic acid and 15-hydroperoxyeicosapentaenoic acid with human leukocytes and porcine leukocytes, respectively. The authors examined the ability of porcine leukocytes to metabolize [ 14 C]-AA and [ 14 C]-EPA (100 μM) to lipoxins and lipoxenes. Incubation products were separated by RP-HPLC and identified by U.V. spectrum and GC/MS. Porcine leukocytes metabolized both AA and EPA to form lipoxins and lipoxenes in addition to mono- and di-hydroxyl fatty acids. Quantitative analysis from U.V. absorbance after RP-HPLC revealed that about 0.05% of AA was converted to lipoxins A and B and 0.1% of EPA was converted to lipoxenes A and B. In addition, treatment of leukotriene A 4 and leukotriene A 5 with 15-lipoxygenase also gave rise to several isomers of lipoxin and lipoxene. Thus, lipoxins and lipoxenes would have been derived from AA and EPA after dioxygenation by 5-lipoxygenase and 15-lipoxygenase, respectively. When tested for biological activity, lipoxene A (2 μM), like lipoxin A, induced superoxide anion generation in canine neutrophils but had no effect on lysosomal enzyme release on neutrophil aggregation

  4. LIF excitation spectra for S 0 → S 1 transition of deuterated anthranilic acid COOD, ND 2 in supersonic-jet expansion

    Science.gov (United States)

    Kolek, Przemysław; Leśniewski, Sebastian; Andrzejak, Marcin; Góra, Maciej; Cias, Pawel; Weģrzynowicz, Adam; Najbar, Jan

    2010-12-01

    Laser induced fluorescence (LIF) excitation spectrum for the S 0 → S 1 transition of anthranilic acid molecules deuterated in the substituent groups (COOD, ND 2) was investigated. Analysis of the LIF spectrum allowed for the assignment of the six most prominent fundamental in-plane modes of frequencies up to ca. 850 cm. The experimental results show good correlation with the frequency changes upon deuteration computed with CIS (CI-Singles) and TD-DFT for the S 1 state. Deuteration induced red-shifts of the identified fundamental bands are used for examination of the alternative assignments proposed in earlier studies. Potential energy distributions (PED) and overlaps of the in-plane normal modes with frequencies below 850 cm indicate that the correspondence of the respective vibrations of the deuterated and non-deuterated molecule is very good. A blue-shift of the 00 transition due to the isotopic substitution, is equal to 47 cm. This relatively large value is caused primarily by a significant decrease of the N-H stretching frequency associated with the increase of strength of the intramolecular hydrogen bond upon the electronic excitation. The deuteration shift of the 00 band was interpreted in terms of the differences of the zero point energy (ZPE) between the S 0 and S 1 electronic states, computed with DFT and TD-DFT methods, respectively.

  5. Hypersensitivity to norepinephrine in vasa deferentia from diabetic rats. Possible participation of metabolic products of arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Peredo, H; Agostini, M D; Gimeno, M F; Borda, E S

    1984-08-01

    Contractile responses to norepinephrine of the vas deferens isolated from normal and diabetic rats as well as tissue radio-conversion of exogenous arachidonic acid, were studied. Vasa deferentia from rats with acute streptozotocin-induced diabetes showed hypersensitivity to exogenous norepinephrine (NE). This increased contractile response was associated with the interaction of the agonist with alpha adrenoceptors. Inhibitors of cyclooxygenase increased and inhibitors of lipoxygenase(s) abolished the enhanced response to NE of diabetic vas deferens. Vasa deferentia from both normal and diabetic rats, converted (1-/sup 14/C)-arachidonic acid (AA) into PGF, PGE, PGD and thromboxane (TX) B2, but the % of AA metabolites formed was significantly higher in the diabetic than in the normal condition. Moreover, the predominant prostanoid generated by tissue preparations from diabetic animals was PGD2. Taken together the present experimental findings indicate that preparations from rats with acute streptozotocin-induced diabetes have an augmented reactivity towards NE, which appeared associated with changes in metabolites of AA generated via cyclooxygenase and lipoxygenase catalized pathways.

  6. Identification of rabbit cytochromes P450 2C1 and 2C2 as arachidonic acid epoxygenases.

    Science.gov (United States)

    Laethem, R M; Koop, D R

    1992-12-01

    Microsomes prepared from COS-1 cells transiently expressing rabbit cytochromes P450 2C1 and 2C2 catalyzed the metabolism of arachidonic acid to predominantly 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) when microsomal epoxide hydrolase activity was inhibited by 0.2 mM 1,2-epoxy-3,3,3-trichloropropane. P450 2C2 catalyzed the formation of 11,12-EET and 14,15-EET at a ratio of 3.0 and also produced 19-hydroxyeicosatetraenoic acid (19-HETE). The 11,12-EET, 14,15-EET, and 19-HETE represented 48.3, 15.9, and 12.8%, respectively, of the total metabolites formed. P450 2C1 produced a similar but distinct ratio of 11,12-EET to 14,15-EET (2.0) and did not produce any detectable 19-HETE. The 11,12-EET and 14,15-EET represented 63.0 and 31.1%, respectively, of the total metabolites formed. The 8,9- and 5,6-EETs were not detected with either enzyme. The ratio of the 11,12-EET to 14,15-EET was 1.5 with P450 2CAA, a P450 arachidonic acid epoxygenase (P450 2CAA) that had an amino-terminal sequence identical to that of P450 2C2 [J. Biol. Chem. 267:5552-5559 (1992)]. P450 2C1, 2C2, and 2CAA metabolized lauric acid. The ratio of omega-1- to omega-hydroxylated laurate was 3.6, 3.4, and 2.4 for P450 2CAA, P450 2C2, and P450 2C1, respectively. Purified P450 2CAA had a slightly greater apparent molecular weight than expressed P450 2C2 on sodium dodecyl sulfate-polyacrylamide gels. The results clearly establish that rabbit P450 2C1 and 2C2 are arachidonic acid epoxygenases, and they suggest that P450 2CAA and 2C2 are very similar but may not be identical isoforms.

  7. Group I mGlu receptors potentiate synaptosomal [3H]glutamate release independently of exogenously applied arachidonic acid

    International Nuclear Information System (INIS)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J.

    1999-01-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [ 3 H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 μM) increased 4AP-evoked [ 3 H]glutamate release (143.32±2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC 50 =1.60±0.25 μM; E max =147.61±10.96% control) 4AP-evoked [ 3 H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu 1 receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 μM) and was BSA-insensitive. The selective mGlu 5 receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300μM) was without effect. DHPG (100 μM) also potentiated both 30 mM and 50 mM K + -evoked [ 3 H]glutamate release (121.60±12.77% and 121.50±4.45% control, respectively). DHPG (100 μM) failed to influence both 4AP-stimulated 45 Ca 2+ influx and 50 mM K + -induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A 1 receptor, group II/III mGlu receptors or GABA B receptor activity is unlikely since 4AP-evoked [ 3 H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-α-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu 1 receptor-like' receptor potentiates [ 3 H]glutamate release from cerebrocortical synaptosomes in the absence of exogenously applied arachidonic acid. This PKC dependent effect is unlikely to be via modulation of synaptosomal membrane

  8. Evidence of quantum correlations in the H/D-transfer dynamics in the hydrogen bonds in partially deuterated benzoic acid crystals

    Science.gov (United States)

    Takeda, Sadamu; Tsuzumitani, Akihiko; Chatzidimitriou-Dreismann, C. A.

    1992-10-01

    A precise investigation of spin—lattice relaxation rates for protons and deuterons of partially deuterated benzoic acid crystals showed a remarkable quenching of the transfer rate of an HD pair in hydrogen-bonded dimeric units of carboxyl groups with increasing concentration of D in the surrounding hydrogen bonds. A similar effect was also observed for partially deuterated crystals of acetylenedicarboxylic acid. This finding supports recent theoretical predictions of thermally activated protonic quantum correlation in condensed matter and proposes a new mechanism for the proton transfer in hydrogen bonds in condensed matter.

  9. Heterologous expression of a deuterated membrane-integrated receptor and partial deuteration in methylotrophic yeasts

    International Nuclear Information System (INIS)

    Massou, S.; Puech, V.; Talmont, F.; Demange, P.; Lindley, N.D.; Tropis, M.; Milon, A.

    1999-01-01

    Methylotrophic yeast has previously been shown to be an excellent system for the cost-effective production of perdeuterated biomass and for the heterologous expression of membrane receptors. A protocol for the expression of 85% deuterated, functional human μ-opiate receptor was established. For partially deuterated biomass, deuteration level and distribution were determined for fatty acids, amino acids and carbohydrates. It was shown that prior to biosynthesis of lipids and amino acids (and of carbohydrates, to a lower extent), exchange occurs between water and methanol hydrogen atoms, so that 80%-90% randomly deuterated biomass and over-expressed proteins may be obtained using only deuterated water

  10. Hydrogen exchange during cell-free incorporation of deuterated amino acids and an approach to its inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Tonelli, Marco; Singarapu, Kiran K. [University of Wisconsin-Madison, National Magnetic Resonance Facility at Madison (NMRFAM), Department of Biochemistry (United States); Makino, Shin-ichi; Sahu, Sarata C.; Matsubara, Yuko [University of Wisconsin-Madison, Center for Eukaryotic Structural Genomics (CESG), Department of Biochemistry (United States); Endo, Yaeta [Ehime University, Cell-Free Science and Technology Research Center (Japan); Kainosho, Masatsune [Tokyo Metropolitan University, Center for Priority Areas (Japan); Markley, John L., E-mail: markley@nmrfam.wisc.edu [University of Wisconsin-Madison, National Magnetic Resonance Facility at Madison (NMRFAM), Department of Biochemistry (United States)

    2011-12-15

    Perdeuteration, selective deuteration, and stereo array isotope labeling (SAIL) are valuable strategies for NMR studies of larger proteins and membrane proteins. To minimize scrambling of the label, it is best to use cell-free methods to prepare selectively labeled proteins. However, when proteins are prepared from deuterated amino acids by cell-free translation in H{sub 2}O, exchange reactions can lead to contamination of {sup 2}H sites by {sup 1}H from the solvent. Examination of a sample of SAIL-chlorella ubiquitin prepared by Escherichia coli cell-free synthesis revealed that exchange had occurred at several residues (mainly at Gly, Ala, Asp, Asn, Glu, and Gln). We present results from a study aimed at identifying the exchanging sites and level of exchange and at testing a strategy for minimizing {sup 1}H contamination during wheat germ cell-free translation of proteins produced from deuterated amino acids by adding known inhibitors of transaminases (1 mM aminooxyacetic acid) and glutamate synthetase (0.1 mM l-methionine sulfoximine). By using a wheat germ cell-free expression system, we produced [U-{sup 2}H, {sup 15}N]-chlorella ubiquitin without and with added inhibitors, and [U-{sup 15}N]-chlorella ubiquitin as a reference to determine the extent of deuterium incorporation. We also prepared a sample of [U-{sup 13}C, {sup 15}N]-chlorella ubiquitin, for use in assigning the sites of exchange. The added inhibitors did not reduce the protein yield and were successful in blocking hydrogen exchange at C{sup {alpha}} sites, with the exception of Gly, and at C{sup {beta}} sites of Ala. We discovered, in addition, that partial exchange occurred with or without the inhibitors at certain side-chain methyl and methylene groups: Asn-H{sup {beta}}, Asp-H{sup {beta}}, Gln-H{sup {gamma}}, Glu-H{sup {gamma}}, and Lys-H{sup {epsilon}}. The side-chain labeling pattern, in particular the mixed chiral labeling resulting from partial exchange at certain sites, should be of

  11. Decreased arachidonic acid content and metabolism in tissues of NZB/W F1 females fed a diet containing 0.45% dehydroisoandrosterone (DHA)

    International Nuclear Information System (INIS)

    Matsunaga, A.; Cottam, G.L.

    1987-01-01

    A diet containing 0.45% DHA fed to NZB/W mice, a model of systemic lupus erythematosus, delays the time of onset, improves survival and decreases the formation of antibodies to ds-DNA. Essential fatty acid-deficient diets or inclusion of eicosapentaenoic acid have similar beneficial effects and led them to investigate arachidonic acid metabolism in response to feeding DHA. The arachidonic acid content of plasma cholesteryl ester decreased from 37.4 +/- 2.2 to 28.2 +/- 1.3 mg%. In total liver phospholipid the value decreased from 18.1 +/- 0.52 to 13.7 +/- 1.3 mg%, in total kidney phospholipid the value decreased from 24.10 +/- 0.87 to 20.7 +/- 0.32 mg% and in resident peritoneal macrophages the value decreased from 15.4 +/- 4.6 to 3.6 +/- 1.4 mg%. The metabolism of exogenous [1- 14 C]arachidonic acid by resident peritoneal macrophages in response to Zymosan stimulation for 2 hr was examined by extraction of metabolites and separation by HPLC. Cells isolated from DHA-fed animals produced less PGE2 than controls, yet similar amounts of 6-keto PGF1α were produced. Arachidonic acid metabolites have significant effects on the immune system and may be a mechanism involved in the benefits obtained by inclusion of DHA in the diet

  12. Lipoxin A4 and lipoxin B4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: Dissociation between lipid remodeling and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Nigam, S.; Fiore, S.; Luscinskas, F.W.; Serhan, C.N. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-06-01

    The profiles of actions of lipoxin A4 (LXA4) and lipoxin B4 (LXB4), two lipoxygenase-derived eicosanoids, were examined with human neutrophils. At nanomolar concentrations, LXA4 and LXB4 each stimulated the release of (1-14C)arachidonic acid from esterified sources in neutrophils. Lipoxin-induced release of (1-14C)arachidonic acid was both dose- and time-dependent and was comparable to that induced by the chemotactic peptide f-met-leu-phe. Time-course studies revealed that lipoxin A4 and lipoxin B4 each induced a biphasic release of (1-14C)arachidonic acid, which was evident within seconds (5-15 sec) in its initial phase and minutes (greater than 30 sec) in the second phase. In contrast, the all-trans isomers of LXA4 and LXB4 did not provoke (1-14C)AA release. Lipoxin-induced release of arachidonic acid was inhibited by prior treatment of the cells with pertussis toxin but not by its beta-oligomers, suggesting the involvement of guaninine nucleotide-binding regulatory proteins in this event. Dual radiolabeling of neutrophil phospholipid classes with (1-14C)arachidonic acid and (3H)palmitic acid showed that phosphatidylcholine was a major source of lipoxin-induced release of (1-14C)arachidonic acid. They also demonstrated that lipoxins rapidly stimulate both formation of phosphatidic acid as well as phospholipid remodeling. Although both LXA4 and LXB4 (10(-8)-10(-6) M) stimulated the release of (1-14C)arachidonic acid, neither compound evoked its oxygenation by either the 5- or 15-lipoxygenase pathways (including the formation of LTB4, 20-COOH-LTB4, 5-HETE, or 15-HETE). LXA4 and LXB4 (10(-7) M) each stimulated the elevation of cytosolic Ca2+ as monitored with Fura 2-loaded cells, albeit to a lesser extent than equimolar concentrations of FMLP. Neither lipoxin altered the binding of (3H)LTB4 to its receptor on neutrophils.

  13. Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: Implications for its efficacy in bipolar disorder

    Science.gov (United States)

    Ramadan, Epolia; Basselin, Mireille; Rao, Jagadeesh S.; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.

    2011-01-01

    An upregulated brain arachidonic acid (AA) cascade and a hyperglutamatergic state characterize bipolar disorder (BD). Lamotrigine (LTG), a mood stabilizer approved for treating BD, is reported to interfere with glutamatergic neurotransmission involving N-methyl-D-aspartate receptors (NMDARs). NMDARs allow extracellular calcium into the cell, thereby stimulating calcium-dependent cytosolic phospholipase A2 (cPLA2) to release arachidonic acid (AA) from membrane phospholipid. We hypothesized that LTG, like other approved mood stabilizers, would reduce NMDAR-mediated AA signaling in rat brain. An acute subconvulsant dose of NMDA (25 mg/kg) or saline was administered intraperitoneally to unanesthetized rats that had been treated p.o. daily for 42 days with vehicle or a therapeutically relevant dose of LTG (10 mg/kg/.d). Regional brain AA incorporation coefficients k* and rates Jin, AA signals, were measured using quantitative autoradiography after intravenous [1-14C]AA infusion, as were other AA cascade markers. In chronic vehicle-treated rats, acute NMDA compared to saline increased k* and Jin in widespread regions of the brain, as well as prostaglandin (PG)E2 and thromboxane B2 concentrations. Chronic LTG treatment compared to vehicle reduced brain cyclooxygenase (COX) activity, PGE2 concentration, and DNA binding activity of the COX-2 transcription factor, NF-κB. Pretreatment with chronic LTG blocked the acute NMDA effects on AA cascade markers. In summary, chronic LTG like other mood stabilizers blocks NMDA-mediated signaling involving the AA metabolic cascade. Since markers of the AA cascade and of NMDAR signaling are up-regulated in the postmortem BD brain, mood stabilizers generally may be effective in BD by dampening NMDAR signalling and the AA cascade. PMID:21733229

  14. Aryl hydrocarbon receptor–ligand axis mediates pulmonary fibroblast migration and differentiation through increased arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Su, Hsiang-Han; Lin, Hsin-Ting; Suen, Jau-Ling; Sheu, Chau Chyun; Yokoyama, Kazunari K.; Huang, Shau-Ku; Cheng, Chih Mei

    2016-01-01

    Pulmonary fibroblast migration and differentiation are critical events in fibrogenesis; meanwhile, fibrosis characterizes the pathology of many respiratory diseases. The role of aryl hydrocarbon receptor (AhR), a unique cellular chemical sensor, has been suggested in tissue fibrosis, but the mechanisms through which the AhR-ligand axis influences the fibrotic process remain undefined. In this study, the potential impact of the AhR-ligand axis on pulmonary fibroblast migration and differentiation was analyzed using human primary lung fibroblasts HFL-1 and CCL-202 cells. Boyden chamber-based cell migration assay showed that activated AhR in HFL-1cells significantly enhanced cell migration in response to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), and a known AhR antagonist, CH223191, inhibited its migratory activity. Furthermore, the calcium mobilization and subsequent upregulated expression of arachidonic acid metabolizing enzymes, including cyclooxygenase2 (COX-2) and 5-lipoxygenase (5-LOX), were observed in TCDD-treated HFL-1 cells, concomitant with elevated levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) secretion. Also, significantly increased expression of α-smooth muscle actin α-SMA), a fibroblast differentiation marker, was also noted in TCDD-treated HFL-1 cells (p < 0.05), resulting in a dynamic change in cytoskeleton protein levels and an increase in the nuclear translocation of the myocardin-related transcription factor. Moreover, the enhanced levels of α-SMA expression and fibroblast migration induced by TCDD, PGE2 and LTB4 were abrogated by selective inhibitors for COX-2 and 5-LOX. Knockdown of AhR by siRNA Completely diminished intracellular calcium uptake and reduced α-SMA protein verified by promoter-reporter assays and chromatin immunoprecipitation. Taken together, our results suggested the importance of the AhR-ligand axis in fibroblast migration and differentiation through its capacity in enhancing arachidonic acid metabolism.

  15. Effects of arachidonic acid and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine on prolactin secretion from anterior pituitary cells

    International Nuclear Information System (INIS)

    Camoratto, A.M.

    1988-01-01

    The role of two lipids, arachidonic acid and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, as modulators or prolactin secretion has been examined. Stimulators of phospholipase A 2 activity, melittin and mastoparan, were found to increase prolactin release. Melittin also caused release of previously incorporated 3 H-arachidonic acid and this effect was associated with loss of radiolabel from the phospholipid fraction. Exogenous arachidonic acid also stimulated prolactin secretion. Conversely, inhibitors of phospholipase A 2 activity, dibromoacetophenone and U10029A, decreased basal and stimulated prolactin release. Prolactin release could also be lowered by ETYA, BW755C and NDGA, inhibitors of arachidonic acid metabolism. In the second series of experiments the effects of the biologically active phospholipid 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor, PAF) on prolactin release were examined. PAF is an ether-linked phospholipid known to stimulate granule release in a variety of cell types including both inflammatory and noninflammatory cells. PAF increased release of prolactin from dispersed rat anterior pituitary cells; stimulation was not due to cell lysis. PAF-induced prolactin release could be blocked by the dopaminergic agonists apomorphine and bromocriptine as well as by two PAF receptor antagonists, SRI 63-072 and L-652-731

  16. Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells

    Czech Academy of Sciences Publication Activity Database

    Kleban, J.; Mikeš, J.; Szilárdiová, B.; Koval, J.; Sačková, V.; Solár, P.; Horváth, Viktor; Hofmanová, Jiřina; Kozubík, Alois; Fedoročko, P.

    2007-01-01

    Roč. 83, č. 5 (2007), s. 1174-1185 ISSN 0031-8655 R&D Projects: GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hypericin * photodynamic therapy * arachidonic acid inhibitors Subject RIV: BO - Biophysics Impact factor: 2.172, year: 2007

  17. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

    2000-01-01

    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm,

  18. The relation between the omega-3 index and arachidonic acid is bell shaped : Synergistic at low EPA plus DHA status and antagonistic at high EPA plus DHA status

    NARCIS (Netherlands)

    Luxwolda, Martine F.; Kuipers, Remko S.; Smit, Ella N.; Velzing-Aarts, Francien V.; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2011-01-01

    Introduction: The relation between docosahexaenoic (DHA) and eicosapentaenoic (EPA) vs. arachidonic acid (AA) seems characterized by both synergism and antagonism. Materials and methods: Investigate the relation between EPA + DHA and AA in populations with a wide range of EPA + DHA status and across

  19. High contents of both docosahexaenoic and arachidonic acids in milk of women consuming fish from lake Kitangiri (Tanzania) : targets for infant formulae close to our ancient diet?

    NARCIS (Netherlands)

    Kuipers, RS; Fokkema, MR; Smit, EN; van der Meulen, J; Boersma, ER; Muskiet, FAJ

    Current recommendations for arachidonic (AA) and docosahexaenoic (DHA) acids in infant formulae are based on milk of Western mothers. Validity may be questioned in view of the profound dietary changes in the past 100 years, as opposed to our slowly adapting genome. Hominin evolution occurred in the

  20. Group I mGlu receptors potentiate synaptosomal [{sup 3}H]glutamate release independently of exogenously applied arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J. [Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD (United Kingdom)

    1999-04-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [{sup 3}H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 {mu}M) increased 4AP-evoked [{sup 3}H]glutamate release (143.32{+-}2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC{sub 50}=1.60{+-}0.25 {mu}M; E{sub max}=147.61{+-}10.96% control) 4AP-evoked [{sup 3}H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu{sub 1} receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 {mu}M) and was BSA-insensitive. The selective mGlu{sub 5} receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300{mu}M) was without effect. DHPG (100 {mu}M) also potentiated both 30 mM and 50 mM K{sup +}-evoked [{sup 3}H]glutamate release (121.60{+-}12.77% and 121.50{+-}4.45% control, respectively). DHPG (100 {mu}M) failed to influence both 4AP-stimulated {sup 45}Ca{sup 2+} influx and 50 mM K{sup +}-induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A{sub 1} receptor, group II/III mGlu receptors or GABA{sub B} receptor activity is unlikely since 4AP-evoked [{sup 3}H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-{alpha}-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu{sub 1} receptor-like' receptor potentiates [{sup 3}H]glutamate release from cerebrocortical synaptosomes in the absence of

  1. An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region.

    Science.gov (United States)

    Fu, Yuanqing; Liu, Xin; Zhou, Bing; Jiang, Alice C; Chai, Lingying

    2016-10-01

    We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status. Descriptive review conducted on English publications reporting breast-milk DHA and AA levels. We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included. Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals. Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, Pworldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations.

  2. Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

    Science.gov (United States)

    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.

  3. Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3 Leiden mice

    NARCIS (Netherlands)

    Wielinga, P.Y.; Harthoorn, L.F.; Verschuren, L.; Schoemaker, M.H.; Jouni, Z.E.; Tol, E.A.F. van; Kleemann, R.; Kooistra, T.

    2012-01-01

    Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic

  4. Platelet Arachidonic Acid Deficiency May Contribute to Abnormal Platelet Function During Parenteral Fish Oil Monotherapy in a Piglet Model.

    Science.gov (United States)

    Turner, Justine M; Field, Catherine J; Goruk, Sue; Wizzard, Pamela; Dicken, Bryan J; Bruce, Aisha; Wales, Paul W

    2016-05-01

    Fish oil monotherapy has been an advance for treating intestinal failure-associated liver disease (IFALD). However, such patients are at risk of bleeding complications from liver disease and because fish oil can inhibit thrombosis. We have previously reported abnormal platelet function in neonatal piglets given fish oil monotherapy during parenteral nutrition (PN). The purpose of this study was to determine if abnormal fatty acid composition of the platelets could explain the prior observed antiplatelet effect. Neonatal piglets were assigned to 2 treatments: PN with fish oil monotherapy (FO; n = 4) or PN with soy oil (SO; n = 5). On day 14, plasma was collected and platelets isolated by centrifuging. The fatty acid content in plasma and platelet plug were measured using gas liquid chromatography and compared with controls (CON; n = 5). The arachidonic acid (AA) content in the FO group was on average half that of the SO group, in both the platelets (FO, 3.5% vs SO, 7.6%; P = .021; CON, 4.5%-11%) and the plasma (FO, 3.8% vs SO, 9.2%; P = .002; CON, 6.1%-9.5%). No bleeding complications were observed for any piglets during PN treatment. Using platelet mapping, we have previously shown that neonatal piglets given fish oil monotherapy have abnormal platelet function in the AA pathway. This report demonstrates that such an abnormality can be explained by platelet AA deficiency. Platelet mapping and platelet fatty acid analysis should be undertaken in human infants treated with fish oil monotherapy during PN. © 2015 American Society for Parenteral and Enteral Nutrition.

  5. 12(R)-hydroxyicosatetraenoic acid: a cytochrome P450-dependent arachidonate metabolite that inhibits Na+, K+-ATPase in the cornea

    International Nuclear Information System (INIS)

    Schwartzman, M.L.; Balazy, M.; Masferrer, J.; Abraham, N.G.; McGiff, J.C.; Murphy, R.C.

    1987-01-01

    When corneal microsomes were incubated with arachidonic acid in the presence of an NADPH-generating system, four polar metabolites (compounds A-D) were formed. Synthesis of these metabolites could be inhibited by carbon monoxide, SKF 525A, and anti-cytochrome c reductase antibodies. One of the metabolites, compound C, was found to inhibit partially purified Na + , K + -ATPase from the corneal epithelium in a dose-dependent manner. After compound C was purified by TLC and HPLC, it was found to have a UV absorption spectrum with a maximum absorbance at 236 nm suggesting the presence of a conjugated diene. Mass spectrometric analysis using positive- and negative-ionization modes was carried out on derivatized compound C. Abundant fragment ions were consistent with compound C being a monooxygenated derivative of arachidonic acid with a hydroxyl substituent at carbon-12 of the icosanoid backbone; all deuterium atoms from [ 2 H 8 ]arachidonate were retained in the structure. Compound C was characterized as a 12-hydroxyicosatetraenoic acid. However, only 12(R) isomer was found to be an inhibitor of the Na + , K + -ATPase from the corneal epithelium, suggesting that the biologically active compound C was 12(R)-hydroxyy-5,8,10,14-icosatetraenoic acid. Such an inhibitor of Na + , K + -ATPase synthesized in the cornea may have an important role in regulating ocular transparency and aqueous human secretion

  6. 12(R)-hydroxyicosatetraenoic acid: a cytochrome P450-dependent arachidonate metabolite that inhibits Na/sup +/, K/sup +/-ATPase in the cornea

    Energy Technology Data Exchange (ETDEWEB)

    Schwartzman, M.L.; Balazy, M.; Masferrer, J.; Abraham, N.G.; McGiff, J.C.; Murphy, R.C.

    1987-11-01

    When corneal microsomes were incubated with arachidonic acid in the presence of an NADPH-generating system, four polar metabolites (compounds A-D) were formed. Synthesis of these metabolites could be inhibited by carbon monoxide, SKF 525A, and anti-cytochrome c reductase antibodies. One of the metabolites, compound C, was found to inhibit partially purified Na/sup +/, K/sup +/-ATPase from the corneal epithelium in a dose-dependent manner. After compound C was purified by TLC and HPLC, it was found to have a UV absorption spectrum with a maximum absorbance at 236 nm suggesting the presence of a conjugated diene. Mass spectrometric analysis using positive- and negative-ionization modes was carried out on derivatized compound C. Abundant fragment ions were consistent with compound C being a monooxygenated derivative of arachidonic acid with a hydroxyl substituent at carbon-12 of the icosanoid backbone; all deuterium atoms from (/sup 2/H/sub 8/)arachidonate were retained in the structure. Compound C was characterized as a 12-hydroxyicosatetraenoic acid. However, only 12(R) isomer was found to be an inhibitor of the Na/sup +/, K/sup +/-ATPase from the corneal epithelium, suggesting that the biologically active compound C was 12(R)-hydroxyy-5,8,10,14-icosatetraenoic acid. Such an inhibitor of Na/sup +/, K/sup +/-ATPase synthesized in the cornea may have an important role in regulating ocular transparency and aqueous human secretion.

  7. cPLA2a-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic ß-cells

    DEFF Research Database (Denmark)

    Juhl, Kirstine; Høy, Marianne; Olsen, Hervør L.

    2003-01-01

    Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2 ) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic -cells. cPLA2 dose dependently......–80 to 280–300. cPLA2 -stimulated exocytosis was antagonized by the specific cPLA2 inhibitor AACOCF3. Ca2+-evoked exocytosis was reduced by 40% in cells treated with AACOCF3 or an antisense oligonucleotide against cPLA2 . The action of cPLA2 was mimicked by a combination of arachidonic acid...... and lysophosphatidylcholine (470% stimulation) in which each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl- uptake through ClC-3 Cl- channels. Accordingly, the stimulatory action of cPLA2 was inhibited by the Cl- channel inhibitor DIDS...

  8. cPLA2alpha-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic beta-cells

    DEFF Research Database (Denmark)

    Juhl, Kirstine; Høy, Marianne; Olsen, Hervør L

    2003-01-01

    Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2alpha) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic beta-cells. cPLA2alpha...... from 70-80 to 280-300. cPLA2alpha-stimulated exocytosis was antagonized by the specific cPLA2 inhibitor AACOCF3. Ca2+-evoked exocytosis was reduced by 40% in cells treated with AACOCF3 or an antisense oligonucleotide against cPLA2alpha. The action of cPLA2alpha was mimicked by a combination...... of arachidonic acid and lysophosphatidylcholine (470% stimulation) in which each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl- uptake through ClC-3 Cl- channels. Accordingly, the stimulatory action of cPLA2alpha was inhibited...

  9. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Science.gov (United States)

    Ryan, Veronica H; Primiani, Christopher T; Rao, Jagadeesh S; Ahn, Kwangmi; Rapoport, Stanley I; Blanchard, Helene

    2014-01-01

    The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  10. Metabolism of arachidonic acid in 1 yr old New Zealand white (NZW) and watanabe heritable hyperlipidemic (WHHL) rabbit aortas

    International Nuclear Information System (INIS)

    Pfister, S.L.; Schmitz, J.M.; Willerson, J.T.; Campbell, W.B.

    1986-01-01

    This study was designed to characterize the metabolism of arachidonic acid (AA) in normal and atherosclerotic aortas. Segments of aortas were obtained from 1 yr old NZW rabbits, and WHHL rabbits, a genetic model of athero-sclerosis resembling familial hypercholesterolemia. Aortas were incubated at 37 0 C for 15 min with 14 C-AA (5 x 10 -5 M) during stimulation by A23187. The media was extracted using octadecylsilica columns and resolved into metabolites by reverse-phase HPLC. Prostaglandins (PGs) were identified by comigration of 14 C-metabolites with standards. The monoxygenated metabolites of AA (HETEs) were resolved by normal-phase HPLC, and their structures confirmed by GC-MS. In extracts from NZW and WHHL aortas, approximately 14% and 6% of the total radioactivity was converted to PGs and HETEs, respectively. The major PG produced by NZW and WHHL aortas was 6-keto PGF/sub 1α/ with lesser amounts of PGE 2 . Similarly, NZW and WHHL aortas produced primarily 12- and 15-HETE with lesser amounts of 11-, 9-, 8-, and 5-HETE. There were no qualitative differences between NZW and WHHL aortas in PG and HETE production. Therefore, despite extensive atherosclerosis in aortas of WHHL rabbits, the vessels maintain the ability to synthesize PGs and HETEs

  11. The role of arachidonic acid metabolites in signal transduction in an identified neural network mediating presynaptic inhibition in Aplysia

    International Nuclear Information System (INIS)

    Shapiro, E.; Piomelli, D.; Feinmark, S.; Vogel, S.; Chin, G.; Schwartz, J.H.

    1988-01-01

    Neuromodulation is a form of signal transduction that results in the biochemical control of neuronal excitability. Many neurotransmitters act through second messengers, and the examination of biochemical cascades initiated by neurotransmitter-receptor interaction has advanced the understanding of how information is acquired and stored in the nervous system. For example, 5-HT and other facilitory transmitters increase cAMP in sensory neurons of Aplysia, which enhances excitability and facilitates transmitter output. The authors have examined the role of arachidonic acid metabolites in a neuronal circuit mediating presynaptic inhibition. L32 cells are a cluster of putative histaminergic neurons that each make dual-action synaptic potentials onto two follower neurons, L10 and L14. The synaptic connections, biophysical properties, and roles in behavior of the L10 and L14 follower cells have been well studied. The types of ion channels causing each component of the L32-L10 and L32-L14 dual actions have been characterized and application of histamine mimics the effects of stimulating L32 in both L10 and L14

  12. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Directory of Open Access Journals (Sweden)

    Veronica H Ryan

    Full Text Available The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades.AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging.The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism.Expression patterns were split into Development (0 to 20 years and Aging (21 to 78 years intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2, cyclooxygenases (COX-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA and PTGS2 (COX-2 genes at 1q25, highly inter-correlated genes were at distant chromosomal loci.Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  13. Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury.

    Directory of Open Access Journals (Sweden)

    Tomohiro Banno

    Full Text Available Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics. Although lipids make up to half of the dry weight of the spinal cord, their relation with the development of neuropathic pain is poorly understood. We aimed to elucidate the regulation of spinal lipids in response to neuropathic peripheral nerve injury in mice by utilizing matrix-assisted laser desorption/ionization imaging mass spectrometry, which allows visualization of lipid distribution within the cord. We found that arachidonic acid (AA containing [PC(diacyl-16:0/20:4+K]+ was increased temporarily at superficial ipsilateral dorsal horn seven days after spared nerve injury (SNI. The spatiotemporal changes in lipid concentration resembled microglia activation as defined by ionized calcium binding adaptor molecule 1 (Iba1 immunohistochemistry. Suppression of microglial function through minocycline administration resulted in attenuation of hypersensitivity and reduces [PC(diacyl-16:0/20:4+K]+ elevation in the spinal dorsal horn. These data suggested that AA containing [PC(diacyl-16:0/20:4+K]+ is related to hypersensitivity evoked by SNI and implicate microglial cell activation in this lipid production.

  14. Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    A. A. Daak

    2011-01-01

    Full Text Available The cytotoxic compound hydroxyurea (HU is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n=19 and HU-untreated (n=17 sickle cell patients and controls (n=20. The HU-treated compared with the HU-untreated patients had lower arachidonic (AA acid level in ethanolamine, physphoglycerids (EPG (22.9±1.2   versus   24.0±1.1%,  P<0.05 serine SPG (22.13±2.2   versus   24.9±2.3%,  P<0.01 phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG. In contrast, the untreated group had significantly (P<0.05 lower DHA and total n-3 compared with the controls in EPG (2.7±0.4   versus   3.2±0.6% and 4.6±0.5   versus   5.2±0.7% and CPG (0.7±0.2   versus   1.0±0.2% and 1.2±0.2   versus   1.4±0.3. HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.

  15. Food sources of arachidonic acid (PFA 20:4), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006

    Science.gov (United States)

    Food sources of arachidonic acid (PFA 20:4), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006

  16. The effect of the antipsoriatic drug metabolite etretin (Ro 10-1670) on UVB irradiation induced changes in the metabolism of arachidonic acid in human keratinocytes in culture

    International Nuclear Information System (INIS)

    Punnonen, Kari; Jansen, C.T.; Puustinen, Tapio

    1986-01-01

    [ 14 C]Arachidonic acid was avidly incorporated into human keratinocytes in culture and following exposure to UVB irradiation of 9 mJ/cm 2 (erythemally effective, EE) substantial amounts of 14 C-radiolabel were released from the cells. The release of radiolabel was accompanied by a decrease in the labelling of phosphatidylethanolamine whereas the labelling of triacylglycerols and cholesteryl esters was increased. Keratinocytes produced significant amounts of prostaglandin E 2 (PGE 2 ) and following UVB irradiation of 9 mJ/cm 2 (EE) the formation of prostaglandin E 2 was increased. Etretin (Ro 10-1670), the active metabolite of the antipsoriatic drug etretinate (Ro 10-9359), affected significantly neither the total release of radiolabel induced by UVB nor the formation of prostaglandin E 2 . However, in the presence of etretin the UVB irradiation induced transfer of [ 14 C]arachidonic acid into triacylglycerols and cholesteryl esters was not increased as much as in the corresponding experiments without etretin. On the basis of the present study it appears that etretin dose not interfere with the release of arachidonic acid in amounts which could be related to the therapeutic effects of the combination of retinoids with UVB irradiation (Re-UVB) in the treatment of psoriasis. (author)

  17. Roles of phospholipase A2 isoforms in swelling- and melittin-induced arachidonic acid release and taurine efflux in NIH3T3 fibroblasts

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Poulsen, Kristian Arild; Lambert, Ian H.

    2006-01-01

    Osmotic swelling of NIH3T3 mouse fibroblasts activates a bromoenol lactone (BEL)-sensitive taurine efflux, pointing to the involvement of a Ca2+-independent phospholipase A2 (iPLA2) (Lambert IH. J Membr Biol 192: 19-32, 2003). We report that taurine efflux from NIH3T3 cells was not only increased...... by cell swelling but also decreased by cell shrinkage. Arachidonic acid release to the cell exterior was similarly decreased by shrinkage yet not detectably increased by swelling. NIH3T3 cells were found to express cytosolic calcium-dependent cPLA2-IVA, cPLA2-IVB, cPLA2-IVC, iPLA2-VIA, iPLA2-VIB......, and secretory sPLA2-V. Arachidonic acid release from swollen cells was partially inhibited by BEL and by the sPLA2-inhibitor manoalide. Cell swelling elicited BEL-sensitive arachidonic acid release from the nucleus, to which iPLA2-VIA localized. Exposure to the bee venom peptide melittin, to increase PLA2...

  18. Effect of Isotopic Substitution on Elementary Processes in Dye-Sensitized Solar Cells: Deuterated Amino-Phenyl Acid Dyes on TiO2

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    Sergei Manzhos

    2013-03-01

    Full Text Available We present the first computational study of the effects of isotopic substitution on the operation of dye-sensitized solar cells. Ab initio molecular dynamics is used to study the effect of deuteration on light absorption, dye adsorption dynamics, the averaged over vibrations driving force to injection (∆Gi and regeneration (∆Gr, as well as on promotion of electron back-donation in dyes NK1 (2E,4E-2-cyano-5-(4-dimethylaminophenylpenta-2,4-dienoic acid and NK7 (2E,4E-2-cyano-5-(4-diphenylaminophenylpenta-2,4-dienoic acid adsorbed in monodentate molecular and bidentate bridging dissociative configurations on the anatase (101 surface of TiO2. Deuteration causes a red shift of the absorption spectrum of the dye/TiO2 complex by about 5% (dozens of nm, which can noticeably affect the overlap with the solar spectrum in real cells. The dynamics effect on the driving force to injection and recombination (the difference between the averaged <∆Gi,r> and ∆Gi,requil at the equilibrium configuration is strong, yet there is surprisingly little isotopic effect: the average driving force to injection <∆Gi> and to regeneration <∆Gr> changes by only about 10 meV upon deuteration. The nuclear dynamics enhance recombination to the dye ground state due to the approach of the electron-donating group to TiO2, yet this effect is similar for deuterated and non-deuterated dyes. We conclude that the nuclear dynamics of the C-H(D bonds, mostly affected by deuteration, might not be important for the operation of photoelectrochemical cells based on organic dyes. As the expectation value of the ground state energy is higher than its optimum geometry value (by up to 0.1 eV in the present case, nuclear motions will affect dye regeneration by recently proposed redox shuttle-dye combinations operating at low driving forces.

  19. Arachidonic acid metabolomic study of BPH in rats and the interventional effects of Zishen pill, a traditional Chinese medicine.

    Science.gov (United States)

    Bian, Qiaoxia; Wang, Weihui; Wang, Nannan; Peng, Yan; Ma, Wen; Dai, Ronghua

    2016-09-05

    Zishen pill (ZSP) is a traditional Chinese medicine (TCM) used to treat benign prostatic hyperplasia (BPH). The study used a metabolomic approach based on UHPLC-MS/MS to profile arachidonic acid (AA) metabolic changes and to investigate the interventional mechanisms of ZSP in testosterone- induced BPH rats. In order to explore the potential therapeutic effect of ZSP, rat models were constructed and orally administrated with ZSP. Plasma and urine samples were collected after four weeks and then eleven potential biomarkers (15-HETE, 12-HETE, TXA2, 5-HETE, AA, PGI2, PGF2α, 8-HETE, PGD2, PGE2 and LTB4) were identified and quantified by UHPLC-MS/MS. The chromatographic separation was carried out with gradient elution using a mobile phase comprised of 0.05% formic acid aqueous solution (pH=3.3) (A) and acetonitrile: methanol (80:20, V/V) (B), and each AA metabolites was measured using electrospray ionization source with negative mode and multiple reaction monitoring. The eleven biomarkers in BPH group rat plasma and urine were significant higher than those in sham group rats. Using the potential biomarkers as a screening index, the results suggest that ZSP can potentially reverse the process of BPH by partially regulating AA metabolism through refrain the expression of cyclooxygenase (COX) and lipoxygenase (LOX). This study demonstrates that a metabolomic strategy is useful for identifying potential BPH biomarkers and investigating the underlying mechanisms of a TCM in BPH treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    OpenAIRE

    Roberts Matthew A; Berger Alvin; Hoff Bruce

    2006-01-01

    Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA) on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6), FISH (rich in 20:5n3, 22:5n3, and 22:6n3) and COMB, the combination of the two. Results Using a variance-stab...

  1. Associations between dietary n-6 and n-3 fatty acids and arachidonic acid compositions in plasma and erythrocytes in young and elderly Japanese volunteers

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    Kawabata Terue

    2011-08-01

    Full Text Available Abstract Background We reported that the compositions of arachidonic acid (ARA in erythrocytes and plasma phospholipids (PL in the elderly were lower than those in the young, though the ARA intake was nearly identical. Objective We further analyzed data in four study groups with different ages and sexes, and determined that the blood ARA levels were affected by the kinds of dietary fatty acids ingested. Methods One hundred and four healthy young and elderly volunteers were recruited. Dietary records together with photographic records from 28 consecutive days were reviewed and the fatty acid composition in plasma lipid fractions and erythrocyte PL was analyzed. Results No correlations for ARA between dietary fatty acids and blood lipid fractions were observed. A significant negative correlation between eicosapentaenoic acid (EPA + docosahexaenoic acid (DHA intake and ARA composition in erythrocyte PL was observed. ARA composition in erythrocyte PL was significantly lower in elderly subjects than in young subjects, because EPA and DHA intake in elderly subjects was higher than in young subjects. However, after removing the effect of dietary EPA+DHA intake, the ARA composition in erythrocyte PL in elderly subjects was significantly lower than that in young subjects. Conclusions Changes in physical conditions with aging influenced the low ARA composition of erythrocyte in elderly subjects in addition to the effects of dietary EPA and DHA.

  2. Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations.

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    Eduardo O De Souza

    Full Text Available The primary purpose of this investigation was to examine the effects of arachidonic acid (ARA supplementation on functional performance and body composition in trained males. In addition, we performed a secondary study looking at molecular responses of ARA supplementation following an acute exercise bout in rodents.Thirty strength-trained males (age: 20.4 ± 2.1 yrs were randomly divided into two groups: ARA or placebo (i.e. CTL. Then, both groups underwent an 8-week, 3-day per week, non-periodized training protocol. Quadriceps muscle thickness, whole-body composition scan (DEXA, muscle strength, and power were assessed at baseline and post-test. In the rodent model, male Wistar rats (~250 g, ~8 weeks old were pre-fed with either ARA or water (CTL for 8 days and were fed the final dose of ARA prior to being acutely strength trained via electrical stimulation on unilateral plantar flexions. A mixed muscle sample was removed from the exercised and non-exercised leg 3 hours post-exercise.Lean body mass (2.9%, p<0.0005, upper-body strength (8.7%, p<0.0001, and peak power (12.7%, p<0.0001 increased only in the ARA group. For the animal trial, GSK-β (Ser9 phosphorylation (p<0.001 independent of exercise and AMPK phosphorylation after exercise (p-AMPK less in ARA, p = 0.041 were different in ARA-fed versus CTL rats.Our findings suggest that ARA supplementation can positively augment strength-training induced adaptations in resistance-trained males. However, chronic studies at the molecular level are required to further elucidate how ARA combined with strength training affect muscle adaptation.

  3. Melatonin prevents maternal fructose intake-induced programmed hypertension in the offspring: roles of nitric oxide and arachidonic acid metabolites.

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    Tain, You-Lin; Leu, Steve; Wu, Kay L H; Lee, Wei-Chia; Chan, Julie Y H

    2014-08-01

    Fructose intake has increased globally and is linked to hypertension. Melatonin was reported to prevent hypertension development. In this study, we examined whether maternal high fructose (HF) intake causes programmed hypertension and whether melatonin therapy confers protection against the process, with a focus on the link to epigenetic changes in the kidney using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received regular chow or chow supplemented with HF (60% diet by weight) alone or with additional 0.01% melatonin in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to four groups: control, HF, control + melatonin (M), and HF + M. Maternal HF caused increases in blood pressure (BP) in the 12-wk-old offspring. Melatonin therapy blunted the HF-induced programmed hypertension and increased nitric oxide (NO) level in the kidney. The identified differential expressed gene (DEGs) that are related to regulation of BP included Ephx2, Col1a2, Gucy1a3, Npr3, Aqp2, Hba-a2, and Ptgs1. Of which, melatonin therapy inhibited expression and activity of soluble epoxide hydrolase (SEH, Ephx2 gene encoding protein). In addition, we found genes in arachidonic acid metabolism were potentially involved in the HF-induced programmed hypertension and were affected by melatonin therapy. Together, our data suggest that the beneficial effects of melatonin are attributed to its ability to increase NO level in the kidney, epigenetic regulation of genes related to BP control, and inhibition of SEH expression. The roles of DEGs by the NGS in long-term epigenetic changes in the adult offspring kidney require further clarification. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages.

    Science.gov (United States)

    Shoeb, Mohammad; Ramana, Kota V

    2012-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-κB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Anti-Inflammatory Effects of Benfotiamine are Mediated Through the Regulation of Arachidonic Acid Pathway in Macrophages

    Science.gov (United States)

    Shoeb, Mohammad; Ramana, Kota V

    2011-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating the arachidonic acid (AA) pathway generated inflammatory lipid mediators in RAW 264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes (LTB4), prostaglandin E2 (PGE2), thromboxanes 2 (TXB2) and prostacyclin (PGI2) in macrophages. Further, LPS-induced expressions of AA metabolizing enzymes such as COX-2, LOX-5, TXB synthase and PGI2 synthase were significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-kB, and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adducts formation. Most importantly, as compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented the LPS-induced macrophage death and monocytes adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. PMID:22067901

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

    Science.gov (United States)

    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.

  7. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    Directory of Open Access Journals (Sweden)

    Roberts Matthew A

    2006-04-01

    Full Text Available Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6, FISH (rich in 20:5n3, 22:5n3, and 22:6n3 and COMB, the combination of the two. Results Using a variance-stabilized F-statistic, 371 probe sets (out of 13 K probe sets in the Affymetrix Mu11K chip set were changed by dietary treatment (P Conclusion Distinct transcriptomic, signaling cascades, and predicted affects on murine liver metabolism have been elucidated for 20:4n6-rich dietary oils, 22:6n3-rich oils, and a surprisingly distinct set of genes were affected by the combination of the two. Our results emphasize that the balance of dietary n6 and n3 LC-PUFA provided for infants and in nutritional and neutraceutical applications could have profoundly different affects on metabolism and cell signaling, beyond that previously recognized.

  8. Arachidonic Acid-Induced Expression of the Organic Solute and Steroid Transporter-beta (Ost-beta) in a Cartilaginous Fish Cell Line

    Science.gov (United States)

    Hwang, Jae-Ho; Parton, Angela; Czechanski, Anne; Ballatori, Nazzareno; Barnes, David

    2008-01-01

    The organic solute and steroid transporter (OST/Ost) is a unique membrane transport protein heterodimer composed of subunits designated alpha and beta, that transports conjugated steroids and prostaglandin E2 across the plasma membrane. Ost was first identified in the liver of the cartilaginous fish Leucoraja erinacea, the little skate, and subsequently was found in many other species, including humans and rodents. The present study describes the isolation of a new cell line, LEE-1, derived from an early embryo of L. erinacea, and characterizes the expression of Ost in these cells. The mRNA size and amino acid sequence of Ost-beta in LEE-1 was identical to that previously reported for Ost-beta from skate liver, and the primary structure was identical to that of the spiny dogfish shark (Squalus acanthias) with the exception of a single amino acid. Ost-beta was found both on the plasma membrane and intracellularly in LEE-1 cells, consistent with its localization in other cell types. Interestingly, arachidonic acid, the precursor to eiconsanoids, strongly induced Ost-beta expression in LEE-1 cells and a lipid mixture containing arachidonic acid also induced Ost-alpha. Overall, the present study describes the isolation of a novel marine cell line, and shows that this cell line expresses relatively high levels of Ost when cultured in the presence of arachidonic acid. Although the function of this transport protein in embryo-derived cells is unknown, it may play a role in the disposition of eicosanoids or steroid-derived molecules. PMID:18407792

  9. Arachidonic Acid Metabolism Pathway Is Not Only Dominant in Metabolic Modulation but Associated With Phenotypic Variation After Acute Hypoxia Exposure

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    Chang Liu

    2018-03-01

    Full Text Available Background: The modulation of arachidonic acid (AA metabolism pathway is identified in metabolic alterations after hypoxia exposure, but its biological function is controversial. We aimed at integrating plasma metabolomic and transcriptomic approaches to systematically explore the roles of the AA metabolism pathway in response to acute hypoxia using an acute mountain sickness (AMS model.Methods: Blood samples were obtained from 53 enrolled subjects before and after exposure to high altitude. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and RNA sequencing were separately performed for metabolomic and transcriptomic profiling, respectively. Influential modules comprising essential metabolites and genes were identified by weighted gene co-expression network analysis (WGCNA after integrating metabolic information with phenotypic and transcriptomic datasets, respectively.Results: Enrolled subjects exhibited diverse response manners to hypoxia. Combined with obviously altered heart rate, oxygen saturation, hemoglobin, and Lake Louise Score (LLS, metabolomic profiling detected that 36 metabolites were highly related to clinical features in hypoxia responses, out of which 27 were upregulated and nine were downregulated, and could be mapped to AA metabolism pathway significantly. Integrated analysis of metabolomic and transcriptomic data revealed that these dominant molecules showed remarkable association with genes in gas transport incapacitation and disorders of hemoglobin metabolism pathways, such as ALAS2, HEMGN. After detailed description of AA metabolism pathway, we found that the molecules of 15-d-PGJ2, PGA2, PGE2, 12-O-3-OH-LTB4, LTD4, LTE4 were significantly up-regulated after hypoxia stimuli, and increased in those with poor response manner to hypoxia particularly. Further analysis in another cohort showed that genes in AA metabolism pathway such as PTGES, PTGS1, GGT1, TBAS1 et al. were excessively

  10. Maternal dietary n-6 polyunsaturated fatty acid deprivation does not exacerbate post-weaning reductions in arachidonic acid and its mediators in the mouse hippocampus.

    Science.gov (United States)

    Alashmali, Shoug M; Kitson, Alex P; Lin, Lin; Lacombe, R J Scott; Bazinet, Richard P

    2017-09-13

    The present study examines how lowering maternal dietary n-6 polyunsaturated fatty acids (PUFA) (starting from pregnancy) compared to offspring (starting from post-weaning) affect the levels of n-6 and n-3 fatty acids in phospholipids (PL) and lipid mediators in the hippocampus of mice. Pregnant mice were randomly assigned to consume either a deprived or an adequate n-6 PUFA diet during pregnancy and lactation (maternal exposure). On postnatal day (PND) 21, half of the male pups were weaned onto the same diet as their dams, and the other half were switched to the other diet for 9 weeks (offspring exposure). At PND 84, upon head-focused high-energy microwave irradiation, hippocampi were collected for PL fatty acid and lipid mediator analyses. Arachidonic acid (ARA) concentrations were significantly decreased in both total PL and PL fractions, while eicosapentaenoic acid (EPA) concentrations were increased only in PL fractions upon n-6 PUFA deprivation of offspring, regardless of maternal exposure. Several ARA-derived eicosanoids were reduced, while some of the EPA-derived eicosanoids were elevated by n-6 PUFA deprivation in offspring. There was no effect of diet on docosahexaenoic acid (DHA) or DHA-derived docosanoids concentrations under either maternal or offspring exposure. These results indicate that the maternal exposure to dietary n-6 PUFA may not be as important as the offspring exposure in regulating hippocampal ARA and some lipid mediators. Results from this study will be helpful in the design of experiments aimed at testing the significance of altering brain ARA levels over different stages of life.

  11. Differentiation of U937 cells induced by 5,8,11,14-eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism

    International Nuclear Information System (INIS)

    Ondrey, F.; Anderson, K.; Hoeltgen, D.; Harris, J.

    1988-01-01

    5,8,11,14-Eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism, rapidly and reversibly inhibited DNA synthesis in U937 cells. This inhibition was not due to cytotoxicity, as judged by studies with trypan blue, release of 51 Cr-labeled proteins, and its reversibility. When cells were cultured in the presence of ETYA for several days, morphologic, enzymatic, and functional changes consistent with differentiation occurred. The cells enlarged, the ratio of cytoplasm to nuclei increased, secretory granules and vacuoles developed, the apparent activity of nonspecific esterase rose, and ingestion of latex particles increased. A morphology consistent with that of an immature monocyte was evident by electron microscopy. When cells differentiated by ETYA were cultured in media free of the inhibitor, DNA synthesis reinitiated and the cell number increased; differentiation was phenotypic and not genotypic. To examine whether ETYA-induced differentiation was obligatorily related to its suppression of DNA synthesis, cells were incubated in 50 μM hydroxyurea and DNA synthesis was inhibited for 24 to 36 h without morphologic evidence of cellular differentiation. However, addition of ETYA to cells prevented from dividing by hydroxyurea and subsequent culture for 72 h induced morphologic evidence of differentiation. The effects of ETYA on cell division and cell differentiation are closely related but can be dissociated

  12. Applications of deuteration for neutron scattering, at the Australian National Deuteration Facility

    International Nuclear Information System (INIS)

    Holden, Peter

    2009-01-01

    ANSTO and Australia National Collaborative Research Infrastructure Strategy have funded a 4 year program to establish the National Deuteration Facility (NDF) which offers both in vivo deuteration of biomolecules and chemical deuteration of synthesised organic molecules to the structural biology and soft matter communities in Australia and internationally. The NDF has bio deuterated a range of native and novel polyhydroxy alkanoate (PHA) bio polyesters and is using deuterated polymers to probe interfacial phenomena in PHA/ ethyl cellulose blends and the chain behaviour of PHAs in solution using SANS. The NDF has also undertaken partial deuteration of proteins to investigate the disposition of protein subunits in complexes and protein interactions using SANS as well as per deuteration of proteins for neutron crystallographic studies.αB-crystalline is a molecular chaperone of the small heat shock protein family which prevents the formation of amyloid fibrils in various proteins including α-synuclein which is implicated in Parkinson disease. Deuteration is being used to facilitate investigation of the multimeric distribution of the A and B subunits in the 32 mer chaperone, and the mode of interaction with α-synuclein in prevention of fibril formation. Similarly, deuteration of selected subunits of magnesium chelatase (the enzyme responsible for insertion of Mg 2+ into protoporphyrin) and SANS will be used to support or exclude competing models of their organisation. Two laboratories for chemical synthesis and characterisation of completely, partially, or selectively deuterated compounds were established during 2008. Methodological trials have commenced and success demonstrated for deuterated fatty acids, alcohols, surfactants, glycols and amino acids. Such deuterated molecules will be useful in investigation of co-polymer structure, polymer behaviour in solution, micelle behaviour and bio membrane phenomena using SANS and neutron reflectometry. For example, NDF

  13. The effects of the oral administration of fish oil concentrate on the release and the metabolism of [14C]arachidonic acid and [14C]eicosapentaenoic acid by human platelets

    International Nuclear Information System (INIS)

    Hirai, A.; Terano, T.; Hamazaki, T.

    1982-01-01

    It has been suggested by several investigators that eicosapentaenoic acid (C20:5 omega 3, EPA) might have anti-thrombotic effects. In this experiment, the effect of the oral administration of EPA rich fish oil concentrate on platelet aggregation and the release and the metabolism of [ 1 - 14 C]arachidonic acid and [(U)- 14 C]eicosapentaenoic acid by human platelets was studied. Eight healthy male subjects ingested 18 capsules of fish oil concentrate (EPA 1.4 g) per day for 4 weeks. Plasma and platelet concentrations of EPA markedly increased, while those of arachidonic acid (C20:4 omega 6, AA) and docosahexaenoic acid (C22:6 omega 3, DHA) did not change. Platelet aggregation induced by collagen and ADP was reduced. Collagen induced [ 14 C]thromboxane B2 (TXB2) formation from [ 14 C]AA prelabeled platelets decreased. There was no detectable formation of [ 14 C]TXB3 from [ 14 C]EPA prelabeled platelets, and the conversion of exogenous [ 14 C]EPA to [ 14 C]TXB3 was lower than that of [ 14 C]AA to [ 14 C]TXB2. The release of [ 14 C]AA from [ 14 C]AA prelabeled platelets by collagen was significantly decreased. These observations raise the possibility that the release of arachidonic acid from platelet lipids might be affected by the alteration of EPA content in platelets

  14. Diffusion of intracerebrally injected [1-14C]arachidonic acid and [2-3H]glycerol in the mouse brain. Effects of ischemia and electroconvulsive shock

    International Nuclear Information System (INIS)

    Pediconi, M.F.; Rodriguez de Turco, E.B.; Bazan, N.G.

    1982-01-01

    [2- 3 H]Glycerol and [1- 14 C]arachidonic acid were injected into the region of the frontal horn of the left ventricle of mice and were distributed rapidly throughout the brain. After 10 sec, most of the radioactive fatty acid was found in the hemisphere near the injection site; after 10 min, it was recovered in similar proportions in the cerebellum and brain stem. [2- 3 H]Glycerol showed a heterogeneous distribution, with most of the label remaining in the left hemisphere even after 10 min. On a fresh weight basis, cerebrum, cerebellum, and brain stem were found to contain similar amounts of labeled glycerol. However, the amount of [1- 14 C]arachidonate in cerebrum was only 50% of that recovered from cerebellum or brain stem. Brain ischemia or a single electroconvulsive shock reduced the spread of the label, producing an accumulation of radioactivity in the injected hemisphere, except for an increase in [2- 3 H]glycerol in the brain stem during ischemia. Despite the significant decrease in available precursor in the cerebellum and brain stem after electroshock, the amount of label incorporated into lipids was not altered in these areas and only slightly diminished in the cerebrum

  15. Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Angela M. Devlin

    2017-09-01

    Full Text Available Little is known about arachidonic acid (ARA and docosahexaenoic acid (DHA requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers (n = 133 age 13.4 ± 0.9 months (mean ± standard deviation, randomized to receive a DHA (200 mg/day and ARA (200 mg/day supplement (supplement or a corn oil supplement (control until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III cognitive and language composites and Beery–Buktenica Developmental Test of Visual–Motor Integration (Beery VMI at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC, phosphatidylethanolamine (PE, and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21–9.00, B (95% CI, p = 0.045 in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10–17.94, p < 0.001 and girls (11.19 (4.69–17.68, p = 0.001. These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months.

  16. Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial

    Science.gov (United States)

    Devlin, Angela M.; Chau, Cecil M. Y.; Matheson, Julie; McCarthy, Deanna; Yurko-Mauro, Karin; Innis, Sheila M.; Grunau, Ruth E.

    2017-01-01

    Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers (n = 133) age 13.4 ± 0.9 months (mean ± standard deviation), randomized to receive a DHA (200 mg/day) and ARA (200 mg/day) supplement (supplement) or a corn oil supplement (control) until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) cognitive and language composites and Beery–Buktenica Developmental Test of Visual–Motor Integration (Beery VMI) at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC), phosphatidylethanolamine (PE), and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21–9.00), B (95% CI), p = 0.045) in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10–17.94), p < 0.001) and girls (11.19 (4.69–17.68), p = 0.001). These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months. PMID:28878181

  17. Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets.

    Science.gov (United States)

    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.

  18. The effect of non-steroidal anti-inflammatory drugs on the metabolism of /sup 14/C-arachidonic acid by human gingival tissue in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Elattar, T.M.; Lin, H.S.; Tira, D.E.

    1983-09-01

    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with /sup 14/C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam.

  19. The effect of non-steroidal anti-inflammatory drugs on the metabolism of 14C-arachidonic acid by human gingival tissue in vitro

    International Nuclear Information System (INIS)

    Elattar, T.M.; Lin, H.S.; Tira, D.E.

    1983-01-01

    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with 14 C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam

  20. Peroxisome proliferation activation receptor alpha modulation of Ca2+-regulated exocytosis via arachidonic acid in guinea-pig antral mucous cells.

    Science.gov (United States)

    Sawabe, Yukinori; Shimamoto, Chikao; Sakai, Akiko; Kuwabara, Hiroko; Saad, Adel H; Nakano, Takashi; Takitani, Kimitaka; Tamai, Hiroshi; Mori, Hiroshi; Marunaka, Yoshinori; Nakahari, Takashi

    2010-08-01

    Indomethacin (IDM, 10 microm), not aspirin (ASA; 10 microm), enhanced the Ca(2+)-regulated exocytosis stimulated by 1 microm acetylcholine (ACh) in guinea-pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15R-hydroperoxy-eicosatetraenoic acid (15R-HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R-HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 microm) enhanced Ca(2+)-regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF(3)), also enhanced Ca(2+)-regulated exocytosis, indicating that AA, not products from AA, enhances Ca(2+)-regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor alpha (PPARalpha), because AA is a natural ligand for PPARalpha. A PPARalpha agonist (WY14643; 1 microm) enhanced Ca(2+)-regulated exocytosis, and a PPARalpha blocker (MK886; 50 microm) abolished the enhancement of Ca(2+)-regulated exocytosis induced by AA, IDM, AACOCF(3) and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARalpha exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca(2+)-regulated exocytosis activated by 1 microm ACh or 2 microm thapsigargin alone by 25-30%. Thus, ACh stimulates AA accumulation via an [Ca(2+)](i) increase, which activates PPARalpha, leading to enhancement of Ca(2+)-regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARalpha enhances Ca(2+)-regulated exocytosis in guinea-pig antral mucous cells.

  1. Preparation of. alpha. -deuterated L-amino acids using E. coli cells containing tryptophanase. Poluchenie. alpha. -dejterirovannykh L-aminokislot s ispol'zovaniem kletok E. coli, soderzhashchikh triptofanazy

    Energy Technology Data Exchange (ETDEWEB)

    Faleev, N G; Ruvinov, S B; Saporovskaya, M B; Belikov, V M; Zakomyrdina, L N; Sakharova, I S; Torchinskij, Yu M [AN SSSR, Moscow (USSR). Inst. Ehlementoorganicheskikh Soedinenij AN SSSR, Moscow (USSR). Inst. Molekulyarnoj Biologii AN SSSR, Moscow (USSR)

    1989-10-01

    Method for preparation of a series of {alpha}-deuterated L-amino acids of high optical purity with quantitative chemica yield, suing stereospecific isotopic exchange in D{sub 2}O under the effect of E.coli cells with high tryptophanase activity was developed.

  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.

    Science.gov (United States)

    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 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. The influence of dietary concentrations of arachidonic acid and eicosapentaenoic acid at various stages of larval ontogeny on eye migration, pigmentation and prostaglandin content of common sole larvae ( Solea solea L.)

    DEFF Research Database (Denmark)

    Lund, Ivar; Steenfeldt, Svend Jørgen; Banta, G.

    2008-01-01

    Dietary manipulations of arachidonic acid, ARA and eicosapentaenoic acid, EPA may have an influence on pigmentation in common sole larvae (Solea solea L., Linnaeus 1758) which may be related to a "pigmentation window". This is a specific period in the larval ontogeny where nutritional factors...... metamorphosis. Initiation of metamorphosis (i.e. start of eye migration) was related to the size of larvae and not related to ARA or EPA content. Dietary EPA or DHA did not retard the advance of eye migration. More than 90 % of highly malpigmented juveniles, (i.e. "albinos") had a permanent aberrant eye...

  4. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer

    International Nuclear Information System (INIS)

    Li, Ying; Zhao, Haixia; Wang, Yuzhong; Zheng, Hao; Yu, Wei; Chai, Hongyan; Zhang, Jing; Falck, John R.; Guo, Austin M.; Yue, Jiang; Peng, Renxiu; Yang, Jing

    2013-01-01

    Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2′-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E 2 (PGE 2 ) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B 4 (LTB 4 ). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser 241 ), phospho-Akt (Thr 308 ), phospho-Bad (Ser 136 ), and Bcl-x L expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE 2 , LTB 4 and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr 308 ). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in

  5. Prostacyclin production in rabbit arteries in situ: inhibition by arachidonic acid-induced endothelial cell damage or by low-dose aspirin.

    Science.gov (United States)

    Ingerman-Wojenski, C; Silver, M J; Smith, J B; Nissenbaum, M; Sedar, A W

    1981-04-01

    The central artery of the rabbit ear was perfused in situ and effluent fractions from the artery were assayed for 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha) and thromboxane B2 (TxB2), the stable metabolites of prostacyclin (PGI2) and TxA2, using specific radioimmunoassays. These metabolites of arachidonic acid (AA) were not detected in the effluent during infusion of Tyrode's solution but both metabolites were detected when small amounts of AA were infused into the artery. Examination of the arteries by scanning electron microscopy revealed that high concentrations of AA which caused a short burst of 6-K-PGF1 alpha and TxB2 production damaged the endothelial cells while lower concentrations which stimulated continuous production did not cause damage. When a non-damaging concentration of AA was infused into an artery that had previously received a damaging concentration, PG production was greatly reduced. Pretreatment of the rabbits with 4 mg/kg acetyl-salicylic acid (ASA) inhibited 6-K-PGF1 alpha production by the rabbit ear artery in response to AA and 70% inhibition was still evident 18 hours after ASA.

  6. Arachidonic acid and DHA status in pregnant women is not associated with cognitive performance of their children at 4 or 6-7 years.

    Science.gov (United States)

    Crozier, Sarah R; Sibbons, Charlene M; Fisk, Helena L; Godfrey, Keith M; Calder, Philip C; Gale, Catharine R; Robinson, Sian M; Inskip, Hazel M; Baird, Janis; Harvey, Nicholas C; Cooper, Cyrus; Burdge, Graham C

    2018-06-01

    Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6-7 years in 724 mother-child pairs from the Southampton Women's Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, PDHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, PDHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6-7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.

  7. Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

    Science.gov (United States)

    Richard, Caroline; Lewis, Erin D; Field, Catherine J

    2016-05-01

    Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.

  8. Use of reversed-phase gel partition chromatography for the purification of chemically synthesized (5,6,8,9,11,12,14,15(n)) octadeuterium- and octatritium-labelled arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Wollard, P M; Lascelles, P T [Department of Chemical Pathology, Institute of Neurology, London, Great Britain; Hensby, C N [Hammersmith Hospital, London (UK). Postgraduate Medical School

    1978-12-11

    The development of a method is described for the preparation and purification of (5,6,8,9,11,12,14,15(n)-/sup 2/H)arachidonic acid (/sup 2/H/sub 8/-AA). The /sup 2/H/sub 8/-AA was chemically synthesised by the selective reduction of 5,8,11,14-eiconsatetraynoic acid (ETYA) with deuterium gas. Using reversed-phase partition chromatography on a Lipidex 5000 column support, it was shown that: (1) The reaction products could readily be separated from each other to yield /sup 2/H/sub 8/-AA of greater than 98% mass purity by gas chromatography. (2) Closely related C20 cis-ethylenic fatty acids differing only in the degree of unsaturation are efficiently separated. The resolution increases exponentially on saturation of double bonds. (3) Commercially available (5,6,8,9,11,12,14,15(n))octatritium-labelled arachidonic acid (/sup 3/H/sub 8/-AA) was readily purified. Both (/sup 3/H/sub 8/)- and (1-/sup 14/C)arachidonic acid (/sup 14/C-AA) co-chromatographed with /sup 2/H/sub 8/-AA. (4) The mass spectra of the methyl ester and trimethylsilyl ester of the purified /sup 2/H/sub 8/-AA showed molecular ions at m/e 326 and 384, respectively.

  9. De novo arachidonic acid synthesis in Perkinsus marinus, a protozoan parasite of the eastern oyster Crassostrea virginica.

    Science.gov (United States)

    Chu, Fu-Lin E; Lund, Eric; Soudant, Philippe; Harvey, Ellen

    2002-02-01

    The capability of synthesizing fatty acids de novo in the meront stage of the oyster protozoan parasite, Perkinsus marinus, was investigated employing stable-isotope-labeled precursors (1,2 13C-acetate and palmitic-d(31) acid). Fatty acid methyl esters derived from 1,2 13C-acetate and palmitic-d(31) acid were analyzed using gas chromatography/mass spectrometry and gas chromatography/flame ionization detection. Results revealed that in vitro cultured P. marinus meronts utilized 13C-acetate to synthesize a range of saturated and unsaturated fatty acids. The saturated fatty acids 14:0, 16:0, 18:0, 20:0, 22:0, 24:0 and the unsaturated fatty acids, 18:1(n-9), 18:2(n-6), 20:1(n-9), 20:2(n-6), 20:2(n-9), 20:3(n-6), 20:4(n-6) were found to contain 13C, after 7, 14, and 21 days incubation with the precursor. This indicates that meronts can synthesize fatty acid de novo using acetate as a substrate. Meronts efficiently elongated 16:0-d(31) to 18:0, 20:0, 22:0, 24:0, but desaturation activity was limited, after 7 and 14 days cultivation. Only a small quantity of 18:1-d(29) was detected. This suggests that meronts cannot directly convert exogenous palmitic acid or its products of elongation to unsaturated counterparts. The ability to synthesize 20:4(n-6) from acetate is particularly interesting. No parasitic protozoan has been reported to be capable of synthesizing long chain essential fatty acids, such as 20:4(n-6) de novo. Future study will be directed to determine whether the observed in vitro activities indeed reflect the in vivo activities, when meronts are associated with the host.

  10. An SFG study of interfacial amino acids at the hydrophilic SiO2 and hydrophobic deuterated polystyrene surfaces.

    Science.gov (United States)

    Holinga, George J; York, Roger L; Onorato, Robert M; Thompson, Christopher M; Webb, Nic E; Yoon, Alfred P; Somorjai, Gabor A

    2011-04-27

    Sum frequency generation (SFG) vibrational spectroscopy was employed to characterize the interfacial structure of eight individual amino acids--L-phenylalanine, L-leucine, glycine, L-lysine, L-arginine, L-cysteine, L-alanine, and L-proline--in aqueous solution adsorbed at model hydrophilic and hydrophobic surfaces. Specifically, SFG vibrational spectra were obtained for the amino acids at the solid-liquid interface between both hydrophobic d(8)-polystyrene (d(8)-PS) and SiO(2) model surfaces and phosphate buffered saline (PBS) at pH 7.4. At the hydrophobic d(8)-PS surface, seven of the amino acids solutions investigated showed clear and identifiable C-H vibrational modes, with the exception being l-alanine. In the SFG spectra obtained at the hydrophilic SiO(2) surface, no C-H vibrational modes were observed from any of the amino acids studied. However, it was confirmed by quartz crystal microbalance that amino acids do adsorb to the SiO(2) interface, and the amino acid solutions were found to have a detectable and widely varying influence on the magnitude of SFG signal from water at the SiO(2)/PBS interface. This study provides the first known SFG spectra of several individual amino acids in aqueous solution at the solid-liquid interface and under physiological conditions.

  11. Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.

    Science.gov (United States)

    Yuan, Zhi-Xin; Rapoport, Stanley I

    2015-10-01

    Transient postnatal exposure of rodents to the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine alters behavior and brain 5-HT neurotransmission during adulthood, and also reduces brain arachidonic (ARA) metabolic consumption and protein level of the ARA metabolizing enzyme, cytochrome P4504A (CYP4A). Brain 20-hydroxyeicosatetraenoic acid (20-HETE), converted by CYP4A from ARA, will be reduced in adult mice treated transiently and postnatally with fluoxetine. Male mice pups were injected i.p. daily with fluoxetine (10mg/kg) or saline during P4-P21. At P90 their brain was high-energy microwaved and analyzed for 20-HETE and six other ARA metabolites by enzyme immunoassay. Postnatal fluoxetine vs. saline significantly decreased brain concentrations of 20-HETE (-70.3%) and 15-epi-lipoxin A4 (-60%) in adult mice, but did not change other eicosanoid concentrations. Behavioral changes in adult mice treated postnatally with fluoxetine may be related to reduced brain ARA metabolism involving CYP4A and 20-HETE formation. Published by Elsevier Ltd.

  12. Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells

    Science.gov (United States)

    Chen, Y.; Hughes-Fulford, M.

    2000-01-01

    Arachidonic acid (AA) is the precursor for prostaglandin E2 (PGE2) synthesis and increases growth of prostate cancer cells. To further elucidate the mechanisms involved in AA-induced prostate cell growth, induction of c-fos expression by AA was investigated in a human prostate cancer cell line, PC-3. c-fos mRNA was induced shortly after addition of AA, along with a remarkable increase in PGE2 production. c-fos expression and PGE2 production induced by AA was blocked by a cyclo-oxygenase inhibitor, flurbiprofen, suggesting that PGE2 mediated c-fos induction. Protein kinase A (PKA) inhibitor H-89 abolished induction of c-fos expression by AA, and partially inhibited PGE2 production. Protein kinase C (PKC) inhibitor GF109203X had no significant effect on c-fos expression or PGE2 production. Expression of prostaglandin (EP) receptors, which mediate signal transduction from PGE2 to the cells, was examined by reverse transcription polymerase chain reaction in several human prostate cell lines. EP4 and EP2, which are coupled to the PKA signalling pathway, were expressed in all cells tested. Expression of EP1, which activates the PKC pathway, was not detected. The current study showed that induction of the immediate early gene c-fos by AA is mediated by PGE2, which activates the PKA pathway via the EP2/4 receptor in the PC-3 cells.

  13. Chronic dietary n-6 PUFA deprivation leads to conservation of arachidonic acid and more rapid loss of DHA in rat brain phospholipids.

    Science.gov (United States)

    Lin, Lauren E; Chen, Chuck T; Hildebrand, Kayla D; Liu, Zhen; Hopperton, Kathryn E; Bazinet, Richard P

    2015-02-01

    To determine how the level of dietary n-6 PUFA affects the rate of loss of arachidonic acid (ARA) and DHA in brain phospholipids, male rats were fed either a deprived or adequate n-6 PUFA diet for 15 weeks postweaning, and then subjected to an intracerebroventricular infusion of (3)H-ARA or (3)H-DHA. Brains were collected at fixed times over 128 days to determine half-lives and the rates of loss from brain phospholipids (J out). Compared with the adequate n-6 PUFA rats, the deprived n-6-PUFA rats had a 15% lower concentration of ARA and an 18% higher concentration of DHA in their brain total phospholipids. Loss half-lives of ARA in brain total phospholipids and fractions (except phosphatidylserine) were longer in the deprived n-6 PUFA rats, whereas the J out was decreased. In the deprived versus adequate n-6 PUFA rats, the J out of DHA was higher. In conclusion, chronic n-6 PUFA deprivation decreases the rate of loss of ARA and increases the rate of loss of DHA in brain phospholipids. Thus, a low n-6 PUFA diet can be used to target brain ARA and DHA metabolism. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  14. The role of the arachidonic acid cascade in the species-specific X-ray-induced inflammation of the rabbit eye

    International Nuclear Information System (INIS)

    Bito, L.Z.; Klein, E.M.

    1982-01-01

    To identify the mediator(s) of the apparently species-specific X-ray-induced inflammation of the rabbit eye, inhibitors of the synthesis and/or release of known or putative mediators of ocular inflammation were administered prior to irradiation. The X-ray-induced ocular inflammation, particularly the rise in intraocular pressure, was found to be inhibited by intravenous pretreatment of rabbits with flurbiprofen, indomethacin, or imidazole (1, 10, and 100 mg/kg i.v., respectively), or by combined intravitreal and topical administration of flurbiprofen. Systemic, intravitreal, and/or topical pretreatment with prednisolone or disodium cromoglycate or the retrobulbar injection of ethyl alcohol or capsaicin failed to block the inflammatory response, whereas vitamin E apparently exerted some protective effect. These findings show that the X-ray-induced inflammation of the rabbit eye is mediated, at least in part, by prostaglandins (PGs) and/or related autacoids. In addition, these results suggest that the unique sensitivity of the rabbit eye to X-ray-induced inflammation is due either to the presence in this species of a unique or uniquely effective triggering mechanism for the release of PG precursors or to the greater sensitivity of this species to the ocular inflammatory effects of PGs. Thus the rabbit eye may provide a unique model for studying some aspects of arachidonic acid release or ocular PG effects, but extreme caution must be exercised in generalizing such findings to other species

  15. Suppression of Remodeling Behaviors with Arachidonic Acid Modification for Enhanced in vivo Antiatherogenic Efficacies of Lovastatin-loaded Discoidal Recombinant High Density Lipoprotein.

    Science.gov (United States)

    He, Hongliang; Zhang, Mengyuan; Liu, Lisha; Zhang, Shuangshuang; Liu, Jianping; Zhang, Wenli

    2015-10-01

    A series of in vitro evaluation in our previous studies had proved that arachidonic acid (AA) modification could suppress the remodeling behaviors of lovastatin-loaded discoidal reconstituted high density lipoprotein (LT-d-rHDL) by restraining the reactivity with lecithin cholesterol acyltransferase (LCAT) for reducing undesired drug leakage. This study focuses on the investigation of AA-modified LT-d-rHDL (AA-LT-d-rHDL) in atherosclerotic New Zealand White (NZW) rabbit models to explore whether AA modification could enhance drug targeting delivery and improve antiatherogenic efficacies in vivo. After pharmacokinetics of AA-LT-d-rHDL modified with different AA amount were investigated in atherosclerotic NZW rabbits, atherosclerotic lesions targeting property was assessed by ex vivo imaging of aortic tree and drug distribution. Furthermore, their antiatherogenic efficacies were elaborately evaluated and compared by typical biochemical indices. With AA modification amount augmenting, circulation time of AA-LT-d-rHDL was prolonged, and drug accumulation in the target locus was increased, eventually the significant appreciation in antiatherogenic efficacies were further supported by lower level of bad cholesterol, decreased atherosclerotic lesions areas and mean intima-media thickness (MIT), markedly attenuated matrix metalloproteinase-9 (MMP-9) protein expression and macrophage infiltration. This proof-of-concept study demonstrated that AA-LT-d-rHDL could enhance drug accumulation in atherosclerotic lesion and impede atherosclerosis progression more effectively.

  16. On methods for the detection of reactive oxygen species generation by human spermatozoa: analysis of the cellular responses to catechol oestrogen, lipid aldehyde, menadione and arachidonic acid.

    Science.gov (United States)

    Aitken, R J; Smith, T B; Lord, T; Kuczera, L; Koppers, A J; Naumovski, N; Connaughton, H; Baker, M A; De Iuliis, G N

    2013-03-01

    Oxidative stress is known to have a major impact on human sperm function and, as a result, there is a need to develop sensitive methods for measuring reactive oxygen species (ROS) generation by these cells. A variety of techniques have been developed for this purpose including chemiluminescence (luminol and lucigenin), flow cytometry (MitoSOX Red, dihydroethidium, 4,5-diaminofluorescein diacetate and 2',7'-dichlorodihydrofluorescein diacetate) and spectrophotometry (nitroblue tetrazolium). The relative sensitivity of these assays and their comparative ability to detect ROS generated in different subcellular compartments of human spermatozoa, have not previously been investigated. To address this issue, we have compared the performance of these assays when ROS generation was triggered with a variety of reagents including 2-hydroxyestradiol, menadione, 4-hydroxynonenal and arachidonic acid. The results revealed that menadione predominantly induced release of ROS into the extracellular space where these metabolites could be readily detected by luminol-peroxidase and, to a lesser extent, 2',7'-dichlorodihydrofluorescein. However, such sensitivity to extracellular ROS meant that these assays were particularly vulnerable to interference by leucocytes. The remaining reagents predominantly elicited ROS generation by the sperm mitochondria and could be optimally detected by MitoSOX Red and DHE. Examination of spontaneous ROS generation by defective human spermatozoa revealed that MitoSOX Red was the most effective indicator of oxidative stress, thereby emphasizing the general importance of mitochondrial dysregulation in the aetiology of defective sperm function. © 2013 American Society of Andrology and European Academy of Andrology.

  17. Comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, O.H.; Ahnfelt-Roenne, I. Department of Pharmacology, Leo Pharmaceutical Products, Ballerup; Elmgreen, J.

    1988-01-01

    The effect of timegadine, a novel experimental antirheumatic drug, on human neutrophil (PMN) 5-lipoxygenase activity and leukotriene B/sub 4/ (LTB/sub 4/) chemotaxis was compared with that of two second-line antiinflammatory drugs, D-penicillamine and levamisole. 1-/sup 14/C-Arachidonic acid (AA) was incorporated into the purified cells until steady state conditions were obtained. After preincubation with serial dilutions of the three drugs, AA release and metabolism was stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thinlayer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxi of PMNs towards LTB/sub 4/ was measured in a modified Boyden chamber. Timegardine showed dose-dependent inhibition of both the 5-lipoxygenase pathway (IC50 3.4 x 10/sup -5/ M), and of chemotaxis (IC50 3 x 10/sup -4/ M). Inhibition of the release of AA from phospholipids, however, occurred only at therapeutically irrelevant doses (millimolar concentrations). Levamisole and D-penicillamine did not inhibit any of the cell functions investigated. Inhibition of both neutrophil motility and cellular synthesis of pro-inflammatory eicosanoids, may thus contribute to the clinical effects of timegadine in rheumatoid arthritis.

  18. Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Concepcion, M.; Gruissem, W. [Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

    1999-01-01

    Regulation of isoprenoid end-product synthesis required for normal growth and development in plants is not well understood. To investigate the extent to which specific genes for the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) are involved in end-product regulation, the authors manipulated expression of the HMG1 and HMG2 genes in tomato (Lycopersicon esculentum) fruit using arachidonic acid (AA). In developing young fruit AA blocked fruit growth, inhibited HMG1, and activated HMG2 expression. These results are consistent with other reports indicating that HMG1 expression is closely correlated with growth processes requiring phytosterol production. In mature-green fruit AA strongly induced the expression of HMG2, PSY1 (the gene for phytoene synthase), and lycopene accumulation before the normal onset of carotenoid synthesis and ripening. The induction of lycopene synthesis was not blocked by inhibition of HMGR activity using mevinolin, suggesting that cytoplasmic HMGR is not required for carotenoid synthesis. Their results are consistent with the function of an alternative plastid isoprenoid pathway (the Rohmer pathway) that appears to direct the production of carotenoids during tomato fruit ripening.

  19. Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults

    Directory of Open Access Journals (Sweden)

    Jowy Yi Hoong Seah

    2017-01-01

    Full Text Available 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.

  20. Safflower and olive oil dietary treatments rescue aberrant embryonic arachidonic acid and nitric oxide metabolism and prevent diabetic embryopathy in rats.

    Science.gov (United States)

    Higa, R; White, V; Martínez, N; Kurtz, M; Capobianco, E; Jawerbaum, A

    2010-04-01

    Aberrant arachidonic acid and nitric oxide (NO) metabolic pathways are involved in diabetic embryopathy. Previous works have found diminished concentrations of PGE(2) and PGI(2) in embryos from diabetic rats, and that PGI(2) is capable of increasing embryonic PGE(2) concentrations through the activation of the nuclear receptor PPARdelta. PPARdelta activators are lipid molecules such as oleic and linoleic acids, present in high concentrations in olive and safflower oils, respectively. The aim of this study was to analyze the capability of dietary supplementation with either 6% olive or 6% safflower oils to regulate PGE(2), PGI(2) and NO concentrations in embryos and deciduas from control and diabetic rats during early organogenesis. Diabetes was induced by a single injection of streptozotocin (55 mg/kg) 1 week before mating. Animals were fed with the oil-supplemented diets from Days 0.5 to 10.5 of gestation. PGI(2) and PGE(2) were measured by EIA and NO through the evaluation of its stable metabolites nitrates-nitrites in 10.5 day embryos and deciduas. We found that the olive and safflower oil-supplemented treatments highly reduced resorption and malformation rates in diabetic animals, and that they were able to prevent maternal diabetes-induced alterations in embryonic and decidual PGI(2) and PGE(2) concentrations. Moreover, these dietary treatments prevented NO overproduction in embryos and deciduas from diabetic rats. These data indicate that in maternal diabetes both the embryo and the decidua benefit from the olive and safflower oil supplementation probably through mechanisms that involve the rescue of aberrant prostaglandin and NO generation and that prevent developmental damage during early organogenesis.

  1. Arachidonic acid and lipoxin A4 attenuate alloxan-induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo.

    Science.gov (United States)

    Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

    2017-03-01

    We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action. In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied. Expression of PDX1, P65 NF-kB and IKB in RIN5F cells and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue and plasma glucose, insulin and tumor necrosis factor-α and antioxidants, lipid peroxides and nitric oxide were measured. Of all, arachidonic acid (AA) was found to be the most effective against alloxan-induced cytotoxicity to RIN5F cells and preventing type 1 DM. Both cyclo-oxygenase and lipoxygenase inhibitors did not block the beneficial actions of AA in vitro and in vivo. Alloxan inhibited LXA4 production by RIN5F cells and in alloxan-induced type 1 DM Wistar rats. AA-treatment restored LXA4 levels to normal both in vitro and in vivo. LXA4 protected RIN5F cells against alloxan-induced cytotoxicity and prevented type 1 DM and restored expression of Nrf2, Glut2, COX2, and iNOS genes and abnormal antioxidants to near normal. AA seems to bring about its beneficial actions against alloxan-induced cytotoxicity and type 1 DM by enhancing the production of LXA4. © 2016 BioFactors, 43(2):251-271, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

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

    Science.gov (United States)

    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.

  3. Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

    Directory of Open Access Journals (Sweden)

    Jennifer M. Monk

    2014-01-01

    Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

  4. Immunoregulation of antitumor response; differential secretion of arachidonic acid metabolites by macrophages during stimulation ''in vitro'' with BCG and ''Corynebacterium parvum''

    International Nuclear Information System (INIS)

    Tomecki, Jaroslaw; Sukiennik, Jadwiga; Kordowiak, Anna

    1993-01-01

    The level of arachidonic acid (AA) metabolites in the supernatants of cultures peritoneal exudate cells (PEC) were studied under various conditions using BCG and ''Corynebacterium parvum'' as stimulators. The metabolite levels were analyzed by thin layer chromatography (TLC). The degree of macrophage cytotoxic/cytostatic activity was dependent on the dose and character of stimulators used and the source of macrophages. The application of micro cytotoxicity assay for the evaluation of tumor cell lysis (lung sarcoma SaL-1) ''in vitro'' revealed that peritoneal macrophages from healthy and tumor bearing BALB/c mice may affect the degree of antitumor response. In the supernatants of cultured PEC from tumor bearing mice AA level increased (by 10-fold) in comparison with PEC from healthy mice. Stimulation with BCG induced over a double level of AA in PEC isolated from tumor bearing mice non-stimulated or stimulated with ''C.parvum''. A lower level of prostaglandins (PGs) was found in the supernatants of cultured PEC isolated from healthy mice (stimulated and non-stimulated), but the highest level of PGs was observed in the supernatants of cultured PEC isolated from tumor bearing mice stimulated with BCG. The unique metabolite of AA was found only in the supernatants form non-stimulated PEC from tumor bearing mice. PEC from tumor bearing mice produced metabolites of AA which were not detected in control group. These results suggest that macrophages also play a regulatory role by secretion of AA. This process can be modified by bacterial antigens. (author). 21 refs, 7 figs

  5. Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin

    International Nuclear Information System (INIS)

    Murayama, T.; Ui, M.

    1985-01-01

    Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased 45 Ca 2+ uptake into the cell monolayer, and (f) increased 86 Rb + uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca 2+ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca 2+ -mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca 2+ gating

  6. Autoradiographic observations of the induced vascular injuries by arachidonic acid in rabbit's brain and lung using 111In-oxine labeled platelets

    International Nuclear Information System (INIS)

    Fujimoto, Tsukasa; Fukushima, Yoshiharu; Suzuki, Hidenori; Kuroiwa, Kyoko; Tanoue, Kenjiro; Yamazaki, Hiroh.

    1985-01-01

    Autoradiography using 111 In-oxine labeled autologous platelets was performed to observe the behavior of platelets in induced vascular injury by activated platelets in rabbit's brain and lung. Cerebrovascular injuries were induced by injection of arachidonic acid (AA) (0.7 mg/kg) into right internal carotid artery. Fourteen animals were pretreated with antiplatelet drug, ticlopidine (200 mg/kg) and 10 were controls. Before the AA injection, 111 In-oxine (300 μCi) labeled platelets were injected intravenously. Evans blue was given as a marker of disturbances of blood brain barrier. Sixty min after the AA injection, brains were removed and autoradiographic and electron microscopic studies were done. In the nontreated animals and some of the treated animals whose platelet aggregability was not suppressed, blue staining were seen in the cerebral hemisphere of injection side and hot radioactivity in autoradiogram were revealed in corresponding area. In the treated animals whose platelet aggregability was remarkably suppressed, no or slight blue staining or radioactivity were recognized. Only in hot radioactive area, platelet thrombi and vascular injuries were seen. Vascular injuries of lung were produced by decompression after keeping animals under hyperbalic condition (6 atomosphere absolute for 40 min). Before this procedure, 111 In-oxine labeled platelets were injected. Lungs of both 4 control and 4 decompression sickness animals were removed and autoradiographic and lightmicroscopic observations were performed. In lungs of decompression sickness animals remarkable spotty high radioactivity and prominent platelet aggregates in the vessels were seen. These findings were not seen in control animals. Our results suggested important roles of platelets in induced vascular injuries. And this autoradiographic approach seemed to be quite useful for observation of platelet's behavior in injured vessels and evaluation of antiplatelet drugs. (author)

  7. 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.

    Science.gov (United States)

    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.

  8. Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and a-linolenate

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.

    1985-01-01

    sphingolipids. These rats showed increased evaporation which was comparable to that of essential fatty acid-deficient rats. We interpret these results as strong evidence for a very specific and essential function of linoleic acid in maintaining the integrity of the epidermal water permeability barrier......Essential fatty acid-deficient rats were supplemented with 300 mg per day of pure fatty acid esters: oleate (O), linoleate (L), arachidonate (A), and columbinate (C) for 10 days. During this period, the rats in groups L, A, and C all showed a decrease in their initially high trans-epidermal water...... loss, a classical essential fatty acid-deficiency symptom, to a level seen in non-deficient rats (group N). The trans-epidermal water loss in rats of group O was unaffected by the supplementation. Fatty acid composition of two epidermal sphingolipids, acylglucosylceramide and acylceramide, from...

  9. Catalytic Stereoinversion of L-Alanine to Deuterated D-Alanine.

    Science.gov (United States)

    Moozeh, Kimia; So, Soon Mog; Chin, Jik

    2015-08-03

    A combination of an achiral pyridoxal analogue and a chiral base has been developed for catalytic deuteration of L-alanine with inversion of stereochemistry to give deuterated D-alanine under mild conditions (neutral pD and 25 °C) without the use of any protecting groups. This system can also be used for catalytic deuteration of D-alanine with retention of stereochemistry to give deuterated D-alanine. Thus a racemic mixture of alanine can be catalytically deuterated to give an enantiomeric excess of deuterated D-alanine. While catalytic deracemization of alanine is forbidden by the second law of thermodynamics, this system can be used for catalytic deracemization of alanine with deuteration. Such green and biomimetic approach to catalytic stereocontrol provides insights into efficient amino acid transformations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Nitric oxide donors prevent while the nitric oxide synthase inhibitor L-NAME increases arachidonic acid plus CYP2E1-dependent toxicity

    International Nuclear Information System (INIS)

    Wu Defeng; Cederbaum, Arthur

    2006-01-01

    Polyunsaturated fatty acids such as arachidonic acid (AA) play an important role in alcohol-induced liver injury. AA promotes toxicity in rat hepatocytes with high levels of cytochrome P4502E1 and in HepG2 E47 cells which express CYP2E1. Nitric oxide (NO) participates in the regulation of various cell activities as well as in cytotoxic events. NO may act as a protectant against cytotoxic stress or may enhance cytotoxicity when produced at elevated concentrations. The goal of the current study was to evaluate the effect of endogenously or exogenously produced NO on AA toxicity in liver cells with high expression of CYP2E1 and assess possible mechanisms for its actions. Pyrazole-induced rat hepatocytes or HepG2 cells expressing CYP2E1 were treated with AA in the presence or absence of an inhibitor of nitric oxide synthase L-N G -Nitroarginine Methylester (L-NAME) or the NO donors S-nitroso-N-acetylpenicillamine (SNAP), and (Z)-1-[-(2-aminoethyl)-N-(2-aminoethyl)]diazen-1-ium-1,2-diolate (DETA-NONO). AA decreased cell viability from 100% to 48 ± 6% after treatment for 48 h. In the presence of L-NAME, viability was further lowered to 23 ± 5%, while, SNAP or DETA-NONO increased viability to 66 ± 8 or 71 ± 6%. The L-NAME potentiated toxicity was primarily necrotic in nature. L-NAME did not affect CYP2E1 activity or CYP2E1 content. SNAP significantly lowered CYP2E1 activity but not protein. AA treatment increased lipid peroxidation and lowered GSH levels. L-NAME potentiated while SNAP prevented these changes. Thus, L-NAME increased, while NO donors decreased AA-induced oxidative stress. Antioxidants prevented the L-NAME potentiation of AA toxicity. Damage to mitochondria by AA was shown by a decline in the mitochondrial membrane potential (MMP). L-NAME potentiated this decline in MMP in association with its increase in AA-induced oxidative stress and toxicity. NO donors decreased this decline in MMP in association with their decrease in AA-induced oxidative stress and

  11. Urinary excretion of deuterated metabolites in patients with tyrosinemia type I after oral loading with deuterated L-tyrosine

    International Nuclear Information System (INIS)

    Wadman, S.K.; Duran, M.; Ketting, D.; Bruinvis, L.; Sprang, F.J. van; Berger, R.; Smit, G.P.A.; Divry, P.; Farriaux, J.P.; Cartigny, B.

    1983-01-01

    The metabolic fate of orally given deuterated L-tyrosine, 50 mg/kg body weight, was investigated in seven patients with tyrosinemia type I in order to obtain evidence that the primary defect is at the level of fumarylacetoacetase. The absence of fumarylacetoacetase could be proved in liver biopsy specimens obtained from four patients. All patients excreted deuterated succinylacetoacetate and deuterated succinylacetone was detected in six out of seven. The total amount of these compounds was rather low; maximal 8.3% of the dose. The peak of the excretion occurred 3-6 h after loading, indicating an endogenous formation of the metabolites. All patients excreted deuterated 4-hydroxyphenyl acids, probably reflecting secondary 4-hydroxyphenylpyruvate dioxygenase deficiency connected with liver damage. 5. No evidence for other secondary routes of tyrosine metabolism was found. (Auth.)

  12. Synthesis of deuterated 1-phenylpropenols

    International Nuclear Information System (INIS)

    Denhez, J.P.; Girault, G.; Dizabo, P.

    1981-01-01

    The synthesis of deuterated 1-phenylpropenols is reported. The methods involve either Grignard reactions or selective reduction of α, β unsaturated ketones. These ketones are obtained by degradation of ammonium salts of the Mannich bases. (author)

  13. Synthesis of (9Z, 12E-, (9E, 12Z-[1-14C]-linoleic acid, (9Z, 12Z, 15E-, (9E, 12Z, 15Z-[1-14C]-linolenic acid and (5Z, 8Z, 11Z, 14E-[1-14C]-arachidonic acid

    Directory of Open Access Journals (Sweden)

    Enard, Thierry

    1996-04-01

    Full Text Available Trans polyunsaturated fatty acids are produced in vegetable oils during heat treatment (240-250 °C.ln order to study the metabolic pathway of 9c, 12t and 9t, 12c linoleic acid and 9c, 12c, 15t and 9t, 12c, 15c linolenic acid, these products were prepared labelled with carbon 14 in the carboxylic position. 5c, 8c, 11c, 14t-Arachidonic acid was also labelled on the carboxylic position with carbon 14 in order to study its physiological effects. To introduce the labelling (E-bromo precursors with a 17 carbons chain or a 19 carbon chain were needed. The different syntheses were done by elongation steps and creation of cis double bonds via highly stereospecific Wittig reactions. The radioactive carbon atom was introduced from [14C]-potassium cyanide. The final radioactive fatty acids had a specific activity greater than 50 mCi/mmol and a radioactive purity better than 99 % for linoleic and linolenic and better than 98.6 % for arachidonic acid.

  14. Deuteration kinetics of the graphene

    Energy Technology Data Exchange (ETDEWEB)

    Nefedov, Alexei; Woell, Christof [KIT, Leopoldshafen (Germany); Paris, Alessio; Calliari, Lucia [FBK-CMM, Trento (Italy); Verbitskiy, Nikolay [MSU, Moscow (Russian Federation); University of Vienna, Vienna (Austria); Wang, Ying; Irle, Stephan [Nagoya University, Nagoya (Japan); Fedorov, Alexander [IFW Dresden, Dresden (Germany); St. Petersburg University, St. Petersburg (Russian Federation); Haberer, Danny; Knupfer, Martin; Buechner, Bernd [IFW Dresden, Dresden (Germany); Oetzelt, Martin [BESSY II, Berlin (Germany); Petaccia, Luca [Elettra, Trieste (Italy); Usachov, Dmitry [St. Petersburg University, St. Petersburg (Russian Federation); Vyalikh, Denis [St. Petersburg University, St. Petersburg (Russian Federation); TU Dresden, Dresden (Germany); Sagdev, Hermann [MPI fuer Polymerforschung, Mainz (Germany); Yashina, Lada [MSU, Moscow (Russian Federation); Grueneis, Alexander [IFW Dresden, Dresden (Germany); University of Vienna, Vienna (Austria)

    2013-07-01

    The kinetics of the hydrogenation/deuteration reaction of graphene was studied by time-dependent x-ray photoemission spectroscopy (XPS). The graphene layer was then exposed to hydrogen or deuterium atomic gas beams, obtained by thermal cracking in a tungsten capillary at T=3000 K. After each step XPS of the C1s line was performed in order to measure H/C and D/C ratios. We have observed a strong kinetic isotope effect for the hydrogenation/deuteration reaction leading to substantially faster adsorption and higher maximum D/C ratios as compared to H/C (D/C 35% vs. H/C 25%).

  15. beta-oxidation modulates metabolic competition between eicosapentaenoic acid and arachidonic acid regulating prostaglandin E(2) synthesis in rat hepatocytes-Kupffer cells

    DEFF Research Database (Denmark)

    Du, Zhen-Yu; Ma, Tao; Winterthun, Synnøve

    2010-01-01

    and eicosapentaenoic acid (EPA) for PGE(2) synthesis in a rat hepatocyte-Kupffer cell (HPC/KC) co-culture system when the cellular oxidation capacity was enhanced by exogenous l-carnitine. We demonstrate that in the absence of l-carnitine, 1) beta-oxidation rates of EPA and AA were comparable in HPCs and in KCs; 2) AA...... and not EPA was preferentially incorporated into glycerolipids; and 3) addition of EPA significantly decreased AA-dependent PGE(2) synthesis in HPCs and cyclooxygenase-2 (COX-2) expression in co-cultured HPCs/KCs. However, enhancing the cellular oxidation capacity by the addition of l-carnitine 1...... inhibition of AA-dependent PGE(2) synthesis and COX-2 expression by EPA. Taken together, the results strongly suggest that l-carnitine affects competition between AA and EPA in PG synthesis in liver cells by enhancing oxidation of EPA in HPCs. This implies that the beneficial effects of n-3 PUFA, especially...

  16. Deuteration of metals through electric discharges

    International Nuclear Information System (INIS)

    Balderas G, L.M.

    1995-01-01

    In this work deuteration of titanium and a stainless steel through electrical discharges in a vacuum chamber was performed at different thermodynamic conditions. The samples were plates of 0.03 x 4.5 x 54 cm. The titanium sample was first cleaning with chloroform. The oxide layer was removed by cleaning the sample with a 1:1:1 mixture of water, nitric acid and sulphuric acid. Later was rinsed in water and dried with acetone. Finally, was treated with HCl to form an hydride layer on the surface. The stainless steel sample was only cleaned with soap and cleaning with acetone. The samples were cleaning at low pressure for several days with high temperature short cycles. The deuterium was loaded to the chamber at room temperature having absorption on the titanium samples at 10 3 at 10 1 mbar. Afterwards that the samples were heated up at 330 C and was observed the deuterium absorption in the same pressure range. Forced deuteration through electrical discharges between the sample and the chamber was tried obtaining absorption in the range of 10 3 at 10 2 mbar, however the deuterium absorption only was observed in specific cases. In order to detect neutron emission or released particles in this experiment were used alanine detectors and series of plastic CR-39 and borate films. No neutron were detected in the passive systems used in the experiments. (Author)

  17. Liver conversion of docosahexaenoic and arachidonic acids from their 18-carbon precursors in rats on a DHA-free but α-LNA-containing n-3 PUFA adequate diet.

    Science.gov (United States)

    Gao, Fei; Kim, Hyung-Wook; Igarashi, Miki; Kiesewetter, Dale; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I

    2011-01-01

    The long-chain polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6), are critical for health. These PUFAs can be synthesized in liver from their plant-derived precursors, α-linolenic acid (α-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6). Vegetarians and vegans may have suboptimal long-chain n-3 PUFA status, and the extent of the conversion of α-LNA to EPA and DHA by the liver is debatable. We quantified liver conversion of DHA and other n-3 PUFAs from α-LNA in rats fed a DHA-free but α-LNA (n-3 PUFA) adequate diet, and compared results to conversion of LA to AA. [U-(13)C]LA or [U-(13)C]α-LNA was infused intravenously for 2h at a constant rate into unanesthetized rats fed a DHA-free α-LNA adequate diet, and published equations were used to calculate kinetic parameters. The conversion coefficient k(⁎) of DHA from α-LNA was much higher than for AA from LA (97.2×10(-3) vs. 10.6×10(-3)min(-1)), suggesting that liver elongation-desaturation is more selective for n-3 PUFA biosynthesis on a per molecule basis. The net daily secretion rate of DHA, 20.3μmol/day, exceeded the reported brain DHA consumption rate by 50-fold, suggesting that the liver can maintain brain DHA metabolism with an adequate dietary supply solely of α-LNA. This infusion method could be used in vegetarians or vegans to determine minimal daily requirements of EPA and DHA in humans. Published by Elsevier B.V.

  18. Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index

    Czech Academy of Sciences Publication Activity Database

    Šerý, Omar; Hlinecká, L.; Povová, J.; Bonczek, Ondřej; Zeman, T.; Janout, V.; Ambrož, P.; Khan, N. A.; Balcar, V. J.

    2016-01-01

    Roč. 362, č. 1 (2016), s. 27-32 ISSN 0022-510X Institutional support: RVO:67985904 Keywords : Arachidonic acid * genetics * inflammation * leukotrienes * curcumin Subject RIV: FH - Neurology Impact factor: 2.295, year: 2016

  19. Arachidonic Acid, but Not Omega-3 Index, Relates to the Prevalence and Progression of Abdominal Aortic Aneurysm in a Population-Based Study of Danish Men

    DEFF Research Database (Denmark)

    Lindholt, Jes S; Kristensen, Katrine L; Burillo, Elena

    2018-01-01

    BACKGROUND: Animal models support dietary omega-3 fatty acids protection against abdominal aortic aneurysm (AAA), but clinical data are scarce. The sum of red blood cell proportions of the omega-3 eicosapentaenoic and docosahexaenoic acids, known as omega-3 index, is a valid surrogate for long-te...

  20. Study of the deuterated albumin by FT-IR spectroscopy

    International Nuclear Information System (INIS)

    Stoenescu, Daniela; Sahini, V.E.

    2000-01-01

    The albumin is a protein from the soluble or corpuscular protein class, which exists in cells, in dissolved state or in form of a hydrated gel. Proteins are essential constituents beside water, inorganic salts, lipids, carbon hydrates, vitamins, enzymes. The albumin is also a protein soluble in water and in diluted electrolyte solutions (acids, bases and salts). The investigation of the vibration isotopic effect has a great importance both for the diatomic molecules and for the polyatomic molecules. This paper is the first from a series of works which are intended to study the physico-chemical properties of the deuterated albumin and of the albumin solutions in heavy water by an isotopic exchange method. To put in evidence H-D exchange, the FT-IR spectroscopy is used when the deuterated albumin has different layer thickness. It is also of interest to elucidate the isotopic exchange between the hydrogen and oxygen atoms in bovine serum albumin macromolecules. (authors)

  1. Synthesis and characterization of deuterated polyethylene

    International Nuclear Information System (INIS)

    Jia Xianbin; Luo Xuan; Chang Guanjun; Du Kai; Zhang Lin; Xie Zhengwei; Li Xinjuan; Lu Zaijun

    2009-01-01

    Due to its remarkable isotope effects, excellent kinetic stability towards C-D bond break, high degree of deuteration, and being non-radioactive, deuterated polyethylene (d-PE) is widely used in many fields, such as in inertially confined fusion (ICF) as target material, in production of low loss plastic optical fibers, and in study of the compatibility of different polymers. For the necessary of ICF, the d-PE was synthesized by the anionic polymerization and palladium-catalyzed hydrogenation. Furthermore, by the method of FTIR, 1H NMR and GPC, the deuterated ratio and structure of d-PE have been characterized. The results show that the d-PE has the high deuterated ratio and molecular weight, narrow molecular-weight distribution, the polymer material fits the basic necessary of ICF. (authors)

  2. Synthesis, purification and physico-chemical characterization of the deuterized chloroform

    International Nuclear Information System (INIS)

    Mihaila, Vasile; Chiper, Diana

    1999-01-01

    This work refers to deuterized chloroform synthesis and purification methods. Three preparation methods of deuterized chloroform are presented. In the first method the direct chlorination of methane (CH 4 + 3Cl 2 ) in the presence of light and in an oxygen-free atmosphere results in CHCl 3 + 3HCl. The method's drawback is that the resulting product is impure, being obtained also secondary chlorinated compounds, such as CHCl, CH 2 Cl 2 and CCl 4 . The second method consists in chlorination of acetaldehyde or acetone, in basic catalysis and in halogen excess (α substitution with direct synthesis of trihalogen compound), followed by a haloform reaction (hydrolytic splitting) in the presence of chlorinated lime. This method makes use of decarbolyzing of trichlor acetate acid (as a sodium salt), what results in CL 3 CH + NaHCO 3 . This method is the most suitable for the deuterized chloroform synthesis, since the reaction takes place in absence of other hydrogen atoms (protons) and in deuterized water of 99.87% purity, according to the following reaction: Cl 3 C-COONa → (D 2 O) → Cl 2 CD + NaDCO 3 . Another advantage is that this method avoids the synthesis of secondary products, which could entail additional purifications (distillations, rectification, a.s.o.). The deuterized chloroform is separated from the deuterized sodium bicarbonate aqueous solution by washing with deuterized water, in a liquid to liquid separating funnel. After separation, deuterized chloroform is dried in nitrogen atmosphere. The characterization of the final product is carried out by nuclear magnetic resonance spectrometry. (authors)

  3. Synthesis, purification and physico-chemical characterization of the deuterized chloroform

    International Nuclear Information System (INIS)

    Mihaila, V.; Olteanu-Chiper, D.

    1999-01-01

    This work refers to deuterized chloroform synthesis and purification methods. Three methods for obtaining deuterized chloroform are presented. 1. The direct chlorination of methane, in presence of light and in oxygen-free atmosphere: CH 4 + 3 Cl 2 + ℎν→ CHCl 3 + 3 HCl. The method's drawback is that the product obtained is impure, as other chlorinated compounds such as CH 3 Cl, CH 2 Cl 2 , CCl 4 also result. 2. Chlorination of acetaldehyde or acetone, in basic catalysis and in halogen excess (α substitution with direct synthesis of trihalogen compound), followed by a haloform reaction (hydrolytic splitting) in presence of chlorinated lime: CH 3 CHO (Cl 2 /HO - )/(-HCl)Cl 3 C-CHO (CaCl 2 /HOH)/(-(HCOO) 2 Ca) CHCl 3 and CH 3 -CO-CH 3 (Cl 2 /HO)/(-HCl) Cl 3 C-CO-CH 3 (NaOH)/(-CH 3 COONa) CHCl 3 . 3. Decarboxylizing of trichloroacetate acid (as sodium salt): Cl 3 C-COONa (t deg C)/(H 2 O) Cl 3 CH + NaHCO 3 . This method is the most suitable for the deuterized chloroform synthesis since the reaction takes place in absence of other hydrogen atoms (protons) and in deuterized water 99,87% purity, according to the following reaction: Cl 3 C-COONa (t deg C)/(D 2 O) Cl 3 CD + NaDCO 3 . Another advantage is that this method avoids the synthesis of secondary products which could entail additional purifications (distillations, rectifications, a.s.o.). The deuterized chloroform is separated from the deuterized sodium bicarbonate aqueous solution by washing with deuterized water, in a liquid-to-liquid separating funnel. After separation, the deuterized chloroform is dried in nitrogen atmosphere. The characterization of the final product is carried out through Nuclear Magnetic Resonance Spectrometry. (authors)

  4. Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo.

    Science.gov (United States)

    Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

    2017-03-01

    The aim of this study was to observe whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5 F) cells against streptozotocin (STZ)-induced apoptosis in vitro and type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) in vivo and if so, what would be the mechanism of this action. RIN5 F cells were used for the in vitro study, whereas the in vivo study was performed in Wistar rats. STZ was used to induce apoptosis of RIN5 F cells in vitro and T1- and T2DM in vivo. The effect of PUFAs: γ-linolenic acid (GLA), arachidonic acid (AA) of ω-6 series, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of ω-3 series; cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors and antiinflammatory metabolite of AA and DHA, lipoxin A4 (LXA4), and resolvin D2 and protectin, respectively against STZ-induced cytotoxicity to RIN5 F cells in vitro and LXA4 against T1- and T2DM in vivo was studied. Changes in the antioxidant content, lipid peroxides, nitric oxide, and expression of PDX1, P65, nuclear factor-κb (NF-κb), and IKB genes in STZ-treated RIN5 F cells in vitro and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue of T1- and T2DM and LPCLN2 (lipocalin 2), NF-κb, IKB I in adipose tissue of T2DM after LXA4 treatment were studied. Plasma glucose, insulin, and tumor necrosis factor (TNF)-α levels also were measured in STZ-induced T1- and T2DM Wistar rats. Among all PUFAs tested, AA and EPA are the most effective against STZ-induced cytotoxicity to RIN5 F cells in vitro. Neither COX nor LOX inhibitors blocked the cytoprotective action of AA in vitro and T1- and T2DM by STZ. LXA4 production by RIN5 F cells in vitro and plasma LXA4 levels in STZ-induced T1- and T2DM animals were decreased by STZ that reverted to normal after AA treatment. AA prevented both T1- and T2DM induced by STZ. Antiinflammatory metabolite of AA and LXA4 prevented both T1- and T2DM induced by STZ. The expression of Pdx1, NF-κb, IKB genes in the

  5. Deuteration of benzen derivatives and condensed aromatics

    International Nuclear Information System (INIS)

    Ichikawa, Masaru.

    1970-01-01

    A process for the deuteration of aromatic compounds (benzene derivatives having one or more cyano, halogeno, nitro or other electron attractive groups, and condensed ring aromatics) is provided. The process comprises reducing said aromatic compound with an alkali metal (preferably K, Rb or Cs) in a solvent (dimethoxyethane, tetrahydrofuran, etc.) to provide an electron-acceptor-donor complex, which is followed by introducing gaseous deuterium into the solution. The deuteration takes place selectively at the position of highest electron density in accordance with nature of the substituent, regardless of steric hindrance. The process is applicable to a wide variety of aromatics to give deuterated compounds in high yields. In one example, 5x10 -3 mole of anthracene (An) was reacted with 2g of metallic potassium in 80cc of dimethoxyethane in a N 2 atmosphere. Into the resulting solution of An=2K + was introduced D 2 gas (30 cmHg) at 25 0 C. After decomposition with air and washing with alcohol, the precipitate was recrystallized from benzene. Yield of recovered AN: more than 90%. Yield of deuteration: 100%. Position of deuteration: 9 and 10 (revealed by NMR and mass spectroscopy). (Kaichi, S.)

  6. Synthesis and properties of deuterated polystyrene

    International Nuclear Information System (INIS)

    Liu Chang; Jin Rong; Xu Yewei; Zhang Lin; Yan Hongwei; Du Kai; Wei Chengfu

    2012-01-01

    Deuterated poly(vinylcyclohexane) (D-PVCH, C 8 H 8 D 6 ) was successfully prepared via deuterated catalytic technology of polystyrene (PS). The structure of D-PVCH was characterized by FT-IR and 1 HNMR spectroscopy, and the results show good agreement with the proposed structure and the deuterated ratio is 41.5%. DSC and TG analyses of the D-PVCH show that D-PVCH possesses good thermal stability (glass transition temperature of 125 ℃, 5% weight loss temperature of 403 ℃). Additionally, D-PVCH dissolves in common solvents such as petroleum ether, cyclohexane and toluene at room temperature. Compared with PS, D-PVCH possesses better thermal stability and improved solubility. (authors)

  7. Cross-validated stable-isotope dilution GC-MS and LC-MS/MS assays for monoacylglycerol lipase (MAGL) activity by measuring arachidonic acid released from the endocannabinoid 2-arachidonoyl glycerol.

    Science.gov (United States)

    Kayacelebi, Arslan Arinc; Schauerte, Celina; Kling, Katharina; Herbers, Jan; Beckmann, Bibiana; Engeli, Stefan; Jordan, Jens; Zoerner, Alexander A; Tsikas, Dimitrios

    2017-03-15

    2-Arachidonoyl glycerol (2AG) is an endocannabinoid that activates cannabinoid (CB) receptors CB1 and CB2. Monoacylglycerol lipase (MAGL) inactivates 2AG through hydrolysis to arachidonic acid (AA) and glycerol, thus modulating the activity at CB receptors. In the brain, AA released from 2AG by the action of MAGL serves as a substrate for cyclooxygenases which produce pro-inflammatory prostaglandins. Here we report stable-isotope GC-MS and LC-MS/MS assays for the reliable measurement of MAGL activity. The assays utilize deuterium-labeled 2AG (d 8 -2AG; 10μM) as the MAGL substrate and measure deuterium-labeled AA (d 8 -AA; range 0-1μM) as the MAGL product. Unlabelled AA (d 0 -AA, 1μM) serves as the internal standard. d 8 -AA and d 0 -AA are extracted from the aqueous buffered incubation mixtures by ethyl acetate. Upon solvent evaporation the residue is reconstituted in the mobile phase prior to LC-MS/MS analysis or in anhydrous acetonitrile for GC-MS analysis. LC-MS/MS analysis is performed in the negative electrospray ionization mode by selected-reaction monitoring the mass transitions [M-H] - →[M-H - CO 2 ] - , i.e., m/z 311→m/z 267 for d 8 -AA and m/z 303→m/z 259 for d 0 -AA. Prior to GC-MS analysis d 8 -AA and d 0 -AA were converted to their pentafluorobenzyl (PFB) esters by means of PFB-Br. GC-MS analysis is performed in the electron-capture negative-ion chemical ionization mode by selected-ion monitoring the ions [M-PFB] - , i.e., m/z 311 for d 8 -AA and m/z 303 for d 0 -AA. The GC-MS and LC-MS/MS assays were cross-validated. Linear regression analysis between the concentration (range, 0-1μM) of d 8 -AA measured by LC-MS/MS (y) and that by GC-MS (x) revealed a straight line (r 2 =0.9848) with the regression equation y=0.003+0.898x, indicating a good agreement. In dog liver, we detected MAGL activity that was inhibitable by the MAGL inhibitor JZL-184. Exogenous eicosatetraynoic acid is suitable as internal standard for the quantitative determination

  8. Deuterated drugs; updates and obviousness analysis.

    Science.gov (United States)

    Timmins, Graham S

    2017-12-01

    The pharmacokinetics and/or toxicity of many known drugs can be modified by selective deuteration, an area of significant commercial interest and scientific and regulatory progress. Areas covered: This review firstly discusses recent developments in deuterated drugs including the FDA approval of deutetrabenazine. Secondly, it discusses 35 U.S.C. §103 'obviousness' as it relates to recent patent prosecution, and also to Inter Partes Review (IPR). IPR is a new post-award review of patentability under §102 or §103, two IPR petitions upon deuterated drugs have been instituted and included §103 arguments. Finally, an extended analysis of §103 obviousness based upon the practices of major pharmaceutical companies is provided, that supports rather late priority dates, while §102 is also discussed. Expert opinion: The total value of transactions involving deuterated drugs is close to $5 billion. While the importance of §103 'obviousness' rejections remains in patent applications under current prosecution, IPR of issued patents is developing and will affect likely affect §103 interpretations in this area. However, patents are still issuing with later priority dates, and further litigation will likely occur.

  9. Measurement of 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid and its metabolite 12-oxo-5Z,8E,10E-heptadecatrienoic acid in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry

    International Nuclear Information System (INIS)

    Hofmann, U.; Seefried, S.; Meese, C.O.; Mettang, T.; Huebel, E.K.; Kuhlmann, U.

    1990-01-01

    Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by HPLC, and then derivatized to the trimethylsilyloxime. The method allows quantification of Oxo-HT in concentrations down to 10 pg/ml plasma. The reported methods have been used to measure HHT and Oxo-HT in stimulated platelet rich plasma and to quantify HHT in nonstimulated plasma. Determination of endogenous levels of these two arachidonic acid metabolites may give new insights into the overall biosynthesis of thromboxane A2 in man

  10. Involvement of arachidonate metabolism in neurotensin-induced prolactin release in vitro

    International Nuclear Information System (INIS)

    Canonico, P.L.; Speciale, C.; Sortino, M.A.; Scapagnini, U.

    1985-01-01

    Neurotensin increased in a concentration-dependent manner the level of hypophyseal [ 3 H]arachidonic acid in vitro as well as prolactin release from hemipituitary glands. The effect of 1 microM neurotensin on arachidonate release was already present at 2.5 min, maximal at 5, and disappeared after a 10-min incubation. Neurotensin analogues produced an enhancement of hypophyseal arachidonate similar to their relative potencies in other cellular systems, whereas other peptides (somatostatin and vasoactive intestinal peptide) were devoid of any effect on the concentration of the fatty acid in the pituitary. Seventy micromoles RHC 80267, a rather selective inhibitor of diacylglycerol lipase, completely prevented the neurotensin-stimulated prolactin release and decreased arachidonate release both in basal or in neurotensin-induced conditions. Similar results were obtained with 50 microM quinacrine, a phospholipase A2 inhibitor. To clarify whether arachidonate released by neurotensin requires a further metabolism through specific pathways to stimulate prolactin release, the authors used indomethacin and BW 755c, two blockers of cyclooxygenase and lipoxygenase pathways. Thirty micromoles indomethacin, a dose active to inhibit cyclooxygenase, did not affect unesterified arachidonate levels either in basal or in neurotensin-induced conditions; moreover, the drug did not modify basal prolactin release but slightly potentiated the stimulatory effect of neurotensin on the release of the hormone. On the other hand, 250 microM BW 755c, an inhibitor of both cyclooxygenase and lipoxygenase pathways, significantly inhibited both basal and neurotensin-stimulated prolactin release and further potentiated the increase of the fatty acid concentrations produced by 1 microM neurotensin

  11. Oxidation of esterified arachidonate by rat liver microsomes

    International Nuclear Information System (INIS)

    Davis, H.W.; Suzuki, T.; Schenkman, J.B.

    1986-01-01

    The authors have previously demonstrated a relationship between phospholipid arachidonate in liver microsomes and malondialdehyde (MDA) formation during lipid peroxidation. In this study arachidonic acid (U- 14 C) was incorporated into rat liver microsomes and NADPH-supported peroxidation was carried out at 37 0 C for 15 minutes. The microsomes were pelleted by centrifugation and the labeled products in the supernatant were isolated by a solid phase method. Pellets were hydrolyzed with phospholipase A 2 and extracted with diethyl ether and the products from both fractions were separated by reverse phase HPLC. The results show that (1) oxidation occurs in all of the major phospholipids but that phosphatidylethanolamine is the most susceptible; (2) a linear correlation exists between MDA formation and supernatant radioactivity; (3) several different polar products are found in both the supernatant and the hydrolyzed pellet but that the ratios of product peaks in HPLC do not change during the peroxidation, indicating no secondary metabolism or propagation; and (4) cytochrome P-450 is not involved in the peroxidative reactions since no oxidation occurs in the absence of Fe 3+ and since product formation is unaffected in the presence of carbon monoxide

  12. 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

    NARCIS (Netherlands)

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

    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

  13. Milk in the island of Chole [Tanzania] is high in lauric, myristic, arachidonic and docosahexaenoic acids, and low in linoleic acid - Reconstructed diet of infants born to our ancestors living in tropical coastal regions

    NARCIS (Netherlands)

    Kuipers, Remko S.; Smit, Ella N.; van der Meulen, Jan; Dijck-Brouwer, D. A. Janneke; Boersma, E. Rudy; Muskiet, Frits A. J.

    Background: We need information on the diet on which our genes evolved. Objective: We studied the milk fatty acid [FA] composition of mothers living in the island of Chole [Tanzania, Indian Ocean]. These mothers have high intakes of boiled marine fish and coconut, and consume plenty amount of fruits

  14. Boronization on NSTX using Deuterated Trimethylboron

    International Nuclear Information System (INIS)

    Blanchard, W.R.; Gernhardt, R.C.; Kugel, H.W.; LaMarche, P.H.

    2002-01-01

    Boronization on the National Spherical Torus Experiment (NSTX) has proved to be quite beneficial with increases in confinement and density, and decreases in impurities observed in the plasma. The boron has been applied to the interior surfaces of NSTX, about every 2 to 3 weeks of plasma operation, by producing a glow discharge in the vacuum vessel using deuterated trimethylboron (TMB) in a 10% mixture with helium. Special NSTX requirements restricted the selection of the candidate boronization method to the use of deuterated boron compounds. Deuterated TMB met these requirements, but is a hazardous gas and special care in the execution of the boronization process is required. This paper describes the existing GDC, Gas Injection, and Torus Vacuum Pumping System hardware used for this process, the glow discharge process, and the automated control system that allows for remote operation to maximize both the safety and efficacy of applying the boron coating. The administrative requirements and the detailed procedure for the setup, operation and shutdown of the process are also described

  15. Studies of insulin secretory responses and of arachidonic acid incorporation into phospholipids of stably transfected insulinoma cells that overexpress group VIA phospholipase A2 (iPLA2beta ) indicate a signaling rather than a housekeeping role for iPLA2beta.

    Science.gov (United States)

    Ma, Z; Ramanadham, S; Wohltmann, M; Bohrer, A; Hsu, F F; Turk, J

    2001-04-20

    A cytosolic 84-kDa group VIA phospholipase A(2) (iPLA(2)beta) that does not require Ca(2+) for catalysis has been cloned from several sources, including rat and human pancreatic islet beta-cells and murine P388D1 cells. Many potential iPLA(2)beta functions have been proposed, including a signaling role in beta-cell insulin secretion and a role in generating lysophosphatidylcholine acceptors for arachidonic acid incorporation into P388D1 cell phosphatidylcholine (PC). Proposals for iPLA(2)beta function rest in part on effects of inhibiting iPLA(2)beta activity with a bromoenol lactone (BEL) suicide substrate, but BEL also inhibits phosphatidate phosphohydrolase-1 and a group VIB phospholipase A(2). Manipulation of iPLA(2)beta expression by molecular biologic means is an alternative approach to study iPLA(2)beta functions, and we have used a retroviral construct containing iPLA(2)beta cDNA to prepare two INS-1 insulinoma cell clonal lines that stably overexpress iPLA(2)beta. Compared with parental INS-1 cells or cells transfected with empty vector, both iPLA(2)beta-overexpressing lines exhibit amplified insulin secretory responses to glucose and cAMP-elevating agents, and BEL substantially attenuates stimulated secretion. Electrospray ionization mass spectrometric analyses of arachidonic acid incorporation into INS-1 cell PC indicate that neither overexpression nor inhibition of iPLA(2)beta affects the rate or extent of this process in INS-1 cells. Immunocytofluorescence studies with antibodies directed against iPLA(2)beta indicate that cAMP-elevating agents increase perinuclear fluorescence in INS-1 cells, suggesting that iPLA(2)beta associates with nuclei. These studies are more consistent with a signaling than with a housekeeping role for iPLA(2)beta in insulin-secreting beta-cells.

  16. High bandwidth second-harmonic generation in partially deuterated KDP

    International Nuclear Information System (INIS)

    Webb, M.S.; Eimerl, D.; Velsko, S.P.

    1992-01-01

    We have experimentally determined the spectrally noncritical phasematching behavior of Type I frequency doubling in KDP and its dependence on deuteration level in partially deuterated KDP. The first order wavelength sensitivity parameter∂Δk/∂γ for Type I doubling of 1.053 μm light vanishes for a KD*P crystal with a deuteration level between 10 and 14%. Very high bandwidth frequency doubling of Nd:glass lasers is possible with such a crystal

  17. Laboratory Measurements for H3+ Deuteration Reactions

    Science.gov (United States)

    Bowen, Kyle; Hillenbrand, Pierre-Michel; Urbain, Xavier; Savin, Daniel Wolf

    2018-06-01

    Deuterated molecules are important chemical tracers of protostellar cores. At the ~106 cm-3 particle densities and ~20 K temperatures typical for protostellar cores, most molecules freeze onto dust grains. A notable exception is H3+ and its isotopologues. These become important carriers of positive charge in the gas, can couple to any ambient magnetic field, and can thereby alter the cloud dynamics. Knowing the total abundance of H3+ and its isotopologues is important for studying the evolution of protostellar cores. However, H3+ and D3+ have no dipole moment. They lack a pure rotational spectrum and are not observable at protostellar core temperatures. Fortunately H2D+ and D2H+ have dipole moments and a pure rotational spectrum that can be excited in protostellar cores. Observations of these two molecules, combined with astrochemical models, provide information about the total abundance of H3+ and all its isotopologues. The inferred abundances, though, rely on accurate astrochemical data for the deuteration of H3+ and its isotopologues.Here we present laboratory measurements of the rate coefficients for three important deuterating reactions, namely D + H3+/H2D+/D2H+ → H + H2D+/ D2H+/D3+. Astrochemical models currently rely on rate coefficients from classical (Langevin) or semi-classical methods for these reactions, as fully quantum-mechanical calculations are beyond current computational capabilities. Laboratory studies are the most tractable means of providing the needed data. For our studies we used our novel dual-source, merged fast-beams apparatus, which enables us to study reactions of neutral atoms and molecular ions. Co-propagating beams allow us to measure experimental rate coefficients as a function of collision energy. We extract cross section data from these results, which we then convolve with a Maxwell-Boltzmann distribution to generate thermal rate coefficients. Here we present our results for these three reactions and discuss some implications.

  18. Vascular permeabilization by intravenous arachidonate in the rat peritoneal cavity: antagonism by ethamsylate.

    Science.gov (United States)

    Hannaert, Patrick; Alvarez-Guerra, Miriam; Hider, Hamida; Chiavaroli, Carlo; Garay, Ricardo P

    2003-04-11

    The hemostatic agent, ethamsylate, inhibits arachidonic acid metabolism by a mechanism independent of cyclooxygenase activity and blocks carrageenan-induced rat paw edema. Here, ethamsylate was investigated for (i) in vivo actions on the free radical-dependent, permeabilizing responses to arachidonic acid and (ii) its antioxidant potential in vitro. Vascular permeability was equated to the extravasation rate of Evans blue from plasma into the rat peritoneal cavity. Antioxidant potential was investigated by classical in vitro tests for superoxide radicals, hydroxyl radicals (OH(.)), and nitric oxide. Intravenous ethamsylate induced a very important and significant reduction of permeability responses to arachidonate, both when given preventively and cumulatively. Thus, (i) ethamsylate significantly reversed arachidonate-induced permeabilization, even at the lowest dose tested (44+/-5% at 10 mg/kg) and (ii) a maximal reversal (about 70%) was reached between 50 and 200 mg/kg ethamsylate. In contrast, ethamsylate (100 mg/kg) was unable to antagonize the vascular permeabilization induced by serotonin (5-HT). In antioxidant assays, ethamsylate showed scavenging properties against hydroxyl radicals generated by the Fenton reaction (H(2)O(2)/Fe(2+)) even at 0.1 microM (-20+/-3%). OH(.) scavenging by ethamsylate reached 42+/-8% at 10 microM and 57+/-7% at 1 mM and was comparable to that of reference compounds (vitamin E, troxerutin, and mannitol). Conversely, ethamsylate was a poor scavenger of superoxide and nitric oxide radicals. In conclusion, intravenous ethamsylate potently antagonized the peritoneal vascular permeabilization induced by arachidonate, an action likely due to its antioxidant properties, particularly against hydroxyl radical. Such a mechanism can explain previous observations that ethamsylate inhibits carrageenan-induced rat paw edema. Whether it also participates in the hemostatic action of ethamsylate deserves further investigation.

  19. Mild Conditions for Deuteration of Primary and Secondary Arylamines for the Synthesis of Deuterated Optoelectronic Organic Molecules

    Directory of Open Access Journals (Sweden)

    Anwen M. Krause-Heuer

    2014-11-01

    Full Text Available Deuterated arylamines demonstrate great potential for use in optoelectronic devices, but their widespread utility requires a method for large-scale synthesis. The incorporation of these deuterated materials into optoelectronic devices also provides the opportunity for studies of the functioning device using neutron reflectometry based on the difference in the scattering length density between protonated and deuterated compounds. Here we report mild deuteration conditions utilising standard laboratory glassware for the deuteration of: diphenylamine, N-phenylnaphthylamine, N-phenyl-o-phenylenediamine and 1-naphthylamine (via H/D exchange in D2O at 80 °C, catalysed by Pt/C and Pd/C. These conditions were not successful in the deuteration of triphenylamine or N,N-dimethylaniline, suggesting that these mild conditions are not suitable for the deuteration of tertiary arylamines, but are likely to be applicable for the deuteration of other primary and secondary arylamines. The deuterated arylamines can then be used for synthesis of larger organic molecules or polymers with optoelectronic applications.

  20. Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Wolterbeek, A.P.M.; Suwa, Y.; Fujikawa, S.; Ishikura, Y.; Tsuda, S.; Dohnalek, M.

    2006-01-01

    Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) are natural constituents found in human milk, fish oil or egg yolk. Until recently, infant formulas, though providing the essential fatty acid precursors for these PUFAs, did not contain preformed ARA

  1. State of mixing of deuterated and non-deuterated block polymer chains

    International Nuclear Information System (INIS)

    Hasegawa, Hirokazu; Hashimoto, Takeji

    1984-01-01

    Prior to the small-angle neutron scattering study on the conformation of block polymer chains in the domain space, the state of mixing of two block polymers, an ordinary polystyrene-polyisoprene diblock polymer and a poly(deuterated styrene)-polyisoprene diblock polymer with a different molecular weight and composition, was investigated by a small-angle X-ray scattering (SAXS) technique. Only one kind of domain structure was observed for each blend, and the domain spacings obtained by SAXS were proportional to the two-thirds power of the number-average molecular weight of the blends (reduced to non-deuterated block polymer). The volume fractions of polystyrene domain in the blends evaluated by computer simulation of SAXS profiles well agreed with the values estimated from blend composition. All these facts suggest the molecular mixing of the two block polymers in the domain space. (author)

  2. Neutron Compton scattering from selectively deuterated acetanilide

    Science.gov (United States)

    Wanderlingh, U. N.; Fielding, A. L.; Middendorf, H. D.

    With the aim of developing the application of neutron Compton scattering (NCS) to molecular systems of biophysical interest, we are using the Compton spectrometer EVS at ISIS to characterize the momentum distribution of protons in peptide groups. In this contribution we present NCS measurements of the recoil peak (Compton profile) due to the amide proton in otherwise fully deuterated acetanilide (ACN), a widely studied model system for H-bonding and energy transfer in biomolecules. We obtain values for the average width of the potential well of the amide proton and its mean kinetic energy. Deviations from the Gaussian form of the Compton profile, analyzed on the basis of an expansion due to Sears, provide data relating to the Laplacian of the proton potential.

  3. Influencia del α-tocoferol en la incorporación y peroxidación del ácido araquidónico en alevines parr de salmón del Atlántico (Salmo salar L. Influence of α-tocopherol on arachidonic acid deposition and peroxidation in Atlantic salmon (Salmo salar L. fingerlings

    Directory of Open Access Journals (Sweden)

    Patricio Dantagnan

    2012-09-01

    Full Text Available Se evaluó el efecto sinérgico del ácido araquidónico (ARA (20:4n-6 y el α-tocoferol en la acumulación de estos nutrientes y su peroxidación en el músculo e hígado en juveniles de salmón del Atlántico (Salmo salar. Grupos por triplicado se alimentaron por 12 semanas con ocho dietas experimentales que contenían diferentes niveles de ácido araquidónico y α-tocoferol. Los parámetros productivos no se vieron afectados (P > 0,05 por las dietas suministradas. La acumulación del ARA en el músculo e hígado mostró diferencias significativas (P The synergistic effect of arachidonic acid (ARA (20:4n-6 and α-tocopherol on the accumulation of fatty acids and the peroxidation of lipids in liver and muscle was evaluated in Atlantic salmon (Salmo salar juveniles. Triplicate groups were fed during 12 weeks with eight experimental diets with different levels of ARA and α-tocopherol. In all experimental diets the productive parameters were not affected (P > 0.05. ARA accumulation in muscle and liver showed significant differences (P < 0.05 between treatments. The synergic relationship between ARAAx4ocopherol was influenced (P < 0.05 only in the liver, showing that high levels of α-tocopherol and ARA favored the fatty acids accumulation in this organ. Results indicate that a dietary concentration up to 0.6% ARA, the increment of α-tocopherol is not necessary. The data obtained in this study demonstrated that the interaction between the ARA and α-tocopherol influenced the accumulation of fatty acids in the liver.

  4. Fully deuterated microorganisms: Tools in magnetic resonance and neutron scattering

    International Nuclear Information System (INIS)

    Crespi, H.L.

    1988-01-01

    Current work at Argonne emphasizes the use of fully deuterated algae and cyanobacteria as tools in the study of photosynthesis and as a source of complex substrates for the culture of engineered overproducing bacteria. 17 refs., 1 fig., 1 tab

  5. Deuteration effect on the rotary power of hydrogen bonded compounds

    International Nuclear Information System (INIS)

    Kolbe, A.; Kolbe, A.; Martin-Luther-Universitaet Halle-Wittenberg, Halle

    1982-01-01

    The variation of the rotatory power caused by deuteration in menthol, isopulegol, α-terpineol-(4), elemol, and diphenylacetyl-L-leucin has been investigated. The results and a brief discussion are given

  6. Deuteration effect on the rotary power of hydrogen bonded compounds

    Energy Technology Data Exchange (ETDEWEB)

    Kolbe, A.; Kolbe, A. (Akademie der Wissenschaften der DDR, Halle/Saale. Inst. fuer Biochemie der Pflanzen; Martin-Luther-Universitaet Halle-Wittenberg, Halle (German Democratic Republic). Sektion Chemie)

    1982-01-01

    The variation of the rotatory power caused by deuteration in menthol, isopulegol, ..cap alpha..-terpineol-(4), elemol, and diphenylacetyl-L-leucin has been investigated. The results and a brief discussion are given.

  7. Pulse height model for deuterated scintillation detectors

    International Nuclear Information System (INIS)

    Wang, Haitang; Enqvist, Andreas

    2015-01-01

    An analytical model of light pulse height distribution for finite deuterated scintillation detectors is created using the impulse approximation. Particularly, the energy distribution of a scattered neutron is calculated based on an existing collision probability scheme for general cylindrical shaped detectors considering double differential cross-sections. The light pulse height distribution is analytically and numerically calculated by convoluting collision sequences with the light output function for an EJ-315 detector from our measurements completed at Ohio University. The model provides a good description of collision histories capturing transferred neutron energy in deuterium-based scintillation materials. The resulting light pulse height distribution details pulse compositions and their corresponding contributions. It shows that probabilities of neutron collision with carbon and deuterium nuclei are comparable, however the light pulse amplitude due to collisions with carbon nuclei is small and mainly located at the lower region of the light pulse distribution axis. The model can explore those neutron interaction events that generate pulses near or below a threshold that would be imposed in measurements. A comparison is made between the light pulse height distributions given by the analytical model and measurements. It reveals a significant probability of a neutron generating a small light pulse due to collisions with carbon nuclei when compared to larger light pulse generated by collisions involving deuterium nuclei. This model is beneficial to understand responses of scintillation materials and pulse compositions, as well as nuclei information extraction from recorded pulses.

  8. Production of deuterated switchgrass by hydroponic cultivation.

    Science.gov (United States)

    Evans, Barbara R; Bali, Garima; Foston, Marcus; Ragauskas, Arthur J; O'Neill, Hugh M; Shah, Riddhi; McGaughey, Joseph; Reeves, David; Rempe, Caroline S; Davison, Brian H

    2015-07-01

    The bioenergy crop switchgrass was grown hydroponically from tiller cuttings in 50 % D 2 O to obtain biomass with 34 % deuterium substitution and physicochemical properties similar to those of H 2 O-grown switchgrass controls. Deuterium enrichment of biological materials can potentially enable expanded experimental use of small angle neutron scattering (SANS) to investigate molecular structural transitions of complex systems such as plant cell walls. Two key advances have been made that facilitate cultivation of switchgrass, an important forage and biofuel crop, for controlled isotopic enrichment: (1) perfusion system with individual chambers and (2) hydroponic growth from tiller cuttings. Plants were grown and maintained for several months with periodic harvest. Photosynthetic activity was monitored by measurement of CO2 in outflow from the growth chambers. Plant morphology and composition appeared normal compared to matched controls grown with H2O. Using this improved method, gram quantities of switchgrass leaves and stems were produced by continuous hydroponic cultivation using growth medium consisting of basal mineral salts in 50 % D2O. Deuterium incorporation was confirmed by detection of the O-D and C-D stretching peaks with FTIR and quantified by (1)H- and (2)H-NMR. This capability to produce deuterated lignocellulosic biomass under controlled conditions will enhance investigation of cell wall structure and its deconstruction by neutron scattering and NMR techniques.

  9. Effects of deuteration on hematopoiesis in the mouse

    International Nuclear Information System (INIS)

    Adams, W.H.; Adams, D.G.

    1988-01-01

    Mice ingesting 30 to 50% D 2 O (heavy water, deuterium oxide) developed a dose-dependent depression of formed peripheral blood elements in 4 to 9 days. The principal mechanism of anemia and thrombocytopenia is impaired hematopoiesis. Despite pancytopenia in the peripheral blood, bone marrow cellularity and morphology remained normal. Upon replacement of D 2 O with tap water, platelet and neutrophil concentrations returned to normal within 48 to 72 hr. In contrast, blood lymphocyte concentrations remained low for several weeks. B-lymphocytes may be more affected by deuteration than other lymphocyte subsets. In vivo reticuloendothelial cell function, as assessed by 51 Cr-labeled sheep erythrocyte clearance, was unaffected by D 2 O. Although a dose-dependent decrease in fluid intake occurred during deuteration, hematocytopenia was not a consequence of dehydration. In view of the known kinetics of D 2 O in biological systems, the rapid response of myeloid elements to deuteration must be due primarily to the solvent (nonmetabolic) isotope effect. Prolonged deuteration has proven toxic when included in regimens for treatment of neoplasia, including leukemia, in animal models. The present study shows that modulation of hematopoiesis by D 2 O is possible without invoking the toxicities associated with prolonged deuteration

  10. Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation; Efecto de los componentes del aceite de oliva virgen extra en la cascada del ácido araquidónico, el cáncer colorrectal y la proliferación de células de cáncer de colon.

    Energy Technology Data Exchange (ETDEWEB)

    Storniolo, C.E.; Moreno, J.J.

    2016-07-01

    The mediterranean diet (MD) reduced the risk of colorectal cancer (CRC), and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO) is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA) cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development. [Spanish] La dieta Mediterranea (DM) y el aceite de oliva reducen el riesgo de cáncer colorrectal (CCR). Sin embargo, animales alimentados con dietas ricas en ácido oleico presentan un elevado número de tumores intestinales, lo que sugiere que el consumo de ácido oleico y aceite de oliva pueden tener efectos diferentes sobre el desarrollo de CCR. Considerando que el aceite de oliva extra virgen (AOEV) es una compleja mezcla de ácidos grasos y compuestos minoritarios como polifenoles, lignanos, hidrocarburos, fitoesteroles y triterpenos; y que algunos de estos compuestos son antioxidantes y modulan la cascada del ácido araquidónico (AA) y la producción de eicosanoides. Analizamos la información existente sobre el efecto de los componentes del AOEV sobre la cascada del AA y los mecanismos implicados en el CCR como el crecimiento de las células epiteliales intestinales/apoptosis, lo que nos permitirá entender por qué el consumo de aceites de semillas altos en oleico o AOEV probablemente tendr

  11. Deuterated scintillators and their application to neutron spectroscopy

    International Nuclear Information System (INIS)

    Febbraro, M.; Lawrence, C.C.; Zhu, H.; Pierson, B.; Torres-Isea, R.O; Becchetti, F.D.; Kolata, J.J.; Riggins, J.

    2015-01-01

    Deuterated scintillators have been used as a tool for neutron spectroscopy without Neutron Time-of-Flight (n-ToF) for more than 30 years. This article will provide a brief historical overview of the technique and current uses of deuterated scintillators in the UM-DSA and DESCANT arrays. Pulse-shape discrimination and spectrum unfolding with the maximum-likelihood expectation maximization algorithm will be discussed. Experimental unfolding and cross section results from measurements of (d,n), ( 3 He,n) and (α,n) reactions are shown

  12. Deuteration of metals through electric discharges; Deuteracion de metales bajo descargas electricas

    Energy Technology Data Exchange (ETDEWEB)

    Balderas G, L M

    1996-12-31

    In this work deuteration of titanium and a stainless steel through electrical discharges in a vacuum chamber was performed at different thermodynamic conditions. The samples were plates of 0.03 x 4.5 x 54 cm. The titanium sample was first cleaning with chloroform. The oxide layer was removed by cleaning the sample with a 1:1:1 mixture of water, nitric acid and sulphuric acid. Later was rinsed in water and dried with acetone. Finally, was treated with HCl to form an hydride layer on the surface. The stainless steel sample was only cleaned with soap and cleaning with acetone. The samples were cleaning at low pressure for several days with high temperature short cycles. The deuterium was loaded to the chamber at room temperature having absorption on the titanium samples at 10{sup 3} at 10{sup 1} mbar. Afterwards that the samples were heated up at 330 C and was observed the deuterium absorption in the same pressure range. Forced deuteration through electrical discharges between the sample and the chamber was tried obtaining absorption in the range of 10{sup 3} at 10{sup 2} mbar, however the deuterium absorption only was observed in specific cases. In order to detect neutron emission or released particles in this experiment were used alanine detectors and series of plastic CR-39 and borate films. No neutron were detected in the passive systems used in the experiments. (Author).

  13. Deuterated fibre Z-pinch on the S-300 generator

    NARCIS (Netherlands)

    Klir, D.; Kravarik, J.; Kubes, P.; Bakshaev, Yu L.; Blinov, P. I.; Chernenko, A. S.; Danko, S. A.; Korolev, V. D.; Ustroev, G. I.; Ivanov, M. I.; Cai, Hongchun

    2006-01-01

    Dense Z-pinch experiments were carried out on the S-300 generator (3.5 MA, 100 ns, 0.15 Omega) at the Kurchatov Institute in Moscow. The experiments were performed at a peak current of 2 MA with a rise time of about 100 ns. The Z-pinch was formed from a deuterated polyethylene fibre of 100 mu m

  14. X-ray structure determination and deuteration of nattokinase

    International Nuclear Information System (INIS)

    Yanagisawa, Yasuhide; Chatake, Toshiyuki; Naito, Sawa; Ohsugi, Tadanori; Yatagai, Chieko; Sumi, Hiroyuki; Kawaguchi, Akio; Chiba-Kamosida, Kaori; Ogawa, Megumi; Adachi, Tatsumi; Morimoto, Yukio

    2013-01-01

    X-ray structure determination and deuteration of nattokinase were performed to facilitate neutron crystallographic analysis. Nattokinase (NK) is a strong fibrinolytic enzyme, which is produced in abundance by Bacillus subtilis natto. Although NK is a member of the subtilisin family, it displays different substrate specificity when compared with other subtilisins. The results of molecular simulations predict that hydrogen arrangements around Ser221 at the active site probably account for the substrate specificity of NK. Therefore, neutron crystallographic analysis should provide valuable information that reveals the enzymatic mechanism of NK. In this report, the X-ray structure of the non-hydrogen form of undeuterated NK was determined, and the preparation of deuterated NK was successfully achieved. The non-hydrogen NK structure was determined at 1.74 Å resolution. The three-dimensional structures of NK and subtilisin E from Bacillus subtilis DB104 are near identical. Deuteration of NK was carried out by cultivating Bacillus subtilis natto in deuterated medium. The D 2 O resistant strain of Bacillus subtilis natto was obtained by successive cultivation rounds, in which the concentration of D 2 O in the medium was gradually increased. NK was purified from the culture medium and its activity was confirmed by the fibrin plate method. The results lay the framework for neutron protein crystallography analysis

  15. X-ray structure determination and deuteration of nattokinase

    Energy Technology Data Exchange (ETDEWEB)

    Yanagisawa, Yasuhide [Chiba Institute of Science, 15-8 Shiomi-cho, Cho-shi, Chiba 288-025 (Japan); Chatake, Toshiyuki [Kyoto University, Asashironishi 2, Kumatori, Osaka 590-0494 (Japan); Naito, Sawa; Ohsugi, Tadanori; Yatagai, Chieko; Sumi, Hiroyuki [Kurashiki University of Science and the Arts, 2640 Nishinoura, Tsurajima-cho, Kurashiki, Okayama 712-8505 (Japan); Kawaguchi, Akio [Kyoto University, Asashironishi 2, Kumatori, Osaka 590-0494 (Japan); Chiba-Kamosida, Kaori [Nippon Advanced Technology Co. Ltd, J-PARC, 2-4 Shirane Shirakata, Tokai, Ibaraki 319-1195 (Japan); Ogawa, Megumi; Adachi, Tatsumi [Chiba Institute of Science, 15-8 Shiomi-cho, Cho-shi, Chiba 288-025 (Japan); Morimoto, Yukio [Kyoto University, Asashironishi 2, Kumatori, Osaka 590-0494 (Japan)

    2013-11-01

    X-ray structure determination and deuteration of nattokinase were performed to facilitate neutron crystallographic analysis. Nattokinase (NK) is a strong fibrinolytic enzyme, which is produced in abundance by Bacillus subtilis natto. Although NK is a member of the subtilisin family, it displays different substrate specificity when compared with other subtilisins. The results of molecular simulations predict that hydrogen arrangements around Ser221 at the active site probably account for the substrate specificity of NK. Therefore, neutron crystallographic analysis should provide valuable information that reveals the enzymatic mechanism of NK. In this report, the X-ray structure of the non-hydrogen form of undeuterated NK was determined, and the preparation of deuterated NK was successfully achieved. The non-hydrogen NK structure was determined at 1.74 Å resolution. The three-dimensional structures of NK and subtilisin E from Bacillus subtilis DB104 are near identical. Deuteration of NK was carried out by cultivating Bacillus subtilis natto in deuterated medium. The D{sub 2}O resistant strain of Bacillus subtilis natto was obtained by successive cultivation rounds, in which the concentration of D{sub 2}O in the medium was gradually increased. NK was purified from the culture medium and its activity was confirmed by the fibrin plate method. The results lay the framework for neutron protein crystallography analysis.

  16. Low Penetrance Alleles in Colorectal Cancer: the arachidonic acid pathway

    NARCIS (Netherlands)

    C.L.E. Siezen

    2006-01-01

    textabstractIn summary, we can conclude that we have successfully identified low penetrance alleles in the PPAR., PLA2G2A and ALOX15 genes, conferring differential colorectal adenoma risk, and two such alleles in the PTGS2 gene, one of which is also involved in colorectal cancer risk. These

  17. Arachidonic acid is a chemoattractant for Dictyostelium discoideum ...

    Indian Academy of Sciences (India)

    SEARCHU

    binding proteins and calmodulin-dependent phosphorylation linked to calmodulin-dependent chemotaxis to folic and cAMP in Dictyostelium; Cell Signal 13 575–584. Gerisch G and Hess B 1974 Cyclic-AMP-controlled oscillations in suspended Dictyostelium cells: Their relation to morphogenetic cell interactions; Proc. Natl.

  18. Effect of arachidonic acid supplementation and cyclooxygenase/lipoxygenase inhibition on the development of early bovine embryos Influência do ácido araquidónico e da inibição da ciclo-oxigenase ou lipo-oxigenase no desenvolvimento inicial de embriões bovinos

    Directory of Open Access Journals (Sweden)

    Rosa Maria Pereira

    2006-04-01

    Full Text Available The effect of arachidonic acid (AA cascade on bovine embryo development in a granulosa cell co-culture system was studied. Arachidonic acid (100 µM was supplemented from 1-cell to 8-16 cell block stage (first three days of co-culture and from 1-cell to hatching. Specific cyclooxygenase (indomethacin, 28 µM and lipoxygenase (nordihydroguaiaretic acid - NDGA, 28 µM inhibitors were used from 1-cell to 8-16 cell block stage with AA. Embryo development was assessed by cleavage, day 7-day 8 and hatched embryo rates and by measuring growth rates through development stages found in days 7-10 of culture (day 0 = insemination day. Embryo quality was scored at day 8. A 6.5-10.4% increase on cleavage rate after AA supplementation was found. This AA supplementation from 1-cell to hatching delayed embryo growth rate beyond day 7 and a reduction on hatching rate was detected. When AA supplementation was restricted to the first three days of co-culture those negative effects were overcome. Also, indomethacin and NDGA prevented the positive effect of AA and induced a significant reduction on cleavage, respectively. NDGA further decreased day 7 embryo rate and quality. Results suggest that AA has a two-phase action on bovine embryos, promoting early development and impairing embryo growth from day 7 onwards and hatching rates. Both cyclooxygenase and lipoxygenase were found to be important pathways to promote cleavage.Estudou-se a influência da cascata do ácido araquidónico (AA no desenvolvimento de embriões bovinos produzidos in vitro em co-cultura com células da granulosa. Os embriões foram suplementados com AA (100 µM desde o estádio de 1 célula até 8-16 células (primeiros três dias de co-cultura ou até a eclosão. Introduziram-se inibidores específicos da ciclo-oxigenase (indometacina, 28 µM e da lipo-oxigenase (ácido nordihidroguaiarético - NDGA, 28 µM, juntamente com o ácido araquidónico, desde o estádio de 1 célula até 8-16 c

  19. D-2 dopamine receptor activation reduces free [3H]arachidonate release induced by hypophysiotropic peptides in anterior pituitary cells

    International Nuclear Information System (INIS)

    Canonico, P.L.

    1989-01-01

    Dopamine reduces the stimulation of intracellular [ 3 H]arachidonate release produced by the two PRL-stimulating peptides angiotensin-II and TRH. This effect is concentration dependent and is mediated by stimulation of D-2 dopamine receptors. D-2 receptor agonists (bromocriptine, dihydroergocryptine, and dihydroergocristine) inhibit the release of fatty acid induced by angiotensin-II with a potency that parallels their ability to inhibit PRL release in vitro. Conversely, the selective D-2 receptor antagonist L-sulpiride completely prevents dopamine's effect, whereas SCH 23390 (a D-1 receptor antagonist) is ineffective. The inhibitory action of dopamine does not seem to be consequent to an action on the adenylate cyclase-cAMP system, as 8-bromo-cAMP (1 mM) does not affect either basal or dopamine-inhibited [ 3 H]arachidonate release. However, a 24-h pertussis toxin pretreatment significantly reduces the action of dopamine on fatty acid release. Collectively, these results suggest that D-2 dopamine receptor-mediated inhibition of intracellular [ 3 H]arachidonate release requires the action of a GTP-binding protein, but is not a consequence of an inhibitory action on cAMP levels

  20. Multilayer Formation and Evaporation of Deuterated Ices in Prestellar and Protostellar Cores

    Science.gov (United States)

    Taquet, Vianney; Charnley, Steven B.; Sipilä, Olli

    2014-08-01

    Extremely large deuteration of several molecules has been observed toward prestellar cores and low-mass protostars for a decade. New observations performed toward low-mass protostars suggest that water presents a lower deuteration in the warm inner gas than in the cold external envelope. We coupled a gas-grain astrochemical model with a one-dimensional model of a collapsing core to properly follow the formation and the deuteration of interstellar ices as well as their subsequent evaporation in the low-mass protostellar envelopes with the aim of interpreting the spatial and temporal evolutions of their deuteration. The astrochemical model follows the formation and the evaporation of ices with a multilayer approach and also includes a state-of-the-art deuterated chemical network by taking the spin states of H2 and light ions into account. Because of their slow formation, interstellar ices are chemically heterogeneous and show an increase of their deuterium fractionation toward the surface. The differentiation of the deuteration in ices induces an evolution of the deuteration within protostellar envelopes. The warm inner region is poorly deuterated because it includes the whole molecular content of ices, while the deuteration predicted in the cold external envelope scales with the highly deuterated surface of ices. We are able to reproduce the observed evolution of water deuteration within protostellar envelopes, but we are still unable to predict the super-high deuteration observed for formaldehyde and methanol. Finally, the extension of this study to the deuteration of complex organics, important for the prebiotic chemistry, shows good agreement with the observations, suggesting that we can use the deuteration to retrace their mechanisms and their moments of formation.

  1. Multilayer formation and evaporation of deuterated ices in prestellar and protostellar cores

    International Nuclear Information System (INIS)

    Taquet, Vianney; Charnley, Steven B.; Sipilä, Olli

    2014-01-01

    Extremely large deuteration of several molecules has been observed toward prestellar cores and low-mass protostars for a decade. New observations performed toward low-mass protostars suggest that water presents a lower deuteration in the warm inner gas than in the cold external envelope. We coupled a gas-grain astrochemical model with a one-dimensional model of a collapsing core to properly follow the formation and the deuteration of interstellar ices as well as their subsequent evaporation in the low-mass protostellar envelopes with the aim of interpreting the spatial and temporal evolutions of their deuteration. The astrochemical model follows the formation and the evaporation of ices with a multilayer approach and also includes a state-of-the-art deuterated chemical network by taking the spin states of H 2 and light ions into account. Because of their slow formation, interstellar ices are chemically heterogeneous and show an increase of their deuterium fractionation toward the surface. The differentiation of the deuteration in ices induces an evolution of the deuteration within protostellar envelopes. The warm inner region is poorly deuterated because it includes the whole molecular content of ices, while the deuteration predicted in the cold external envelope scales with the highly deuterated surface of ices. We are able to reproduce the observed evolution of water deuteration within protostellar envelopes, but we are still unable to predict the super-high deuteration observed for formaldehyde and methanol. Finally, the extension of this study to the deuteration of complex organics, important for the prebiotic chemistry, shows good agreement with the observations, suggesting that we can use the deuteration to retrace their mechanisms and their moments of formation.

  2. Multilayer formation and evaporation of deuterated ices in prestellar and protostellar cores

    Energy Technology Data Exchange (ETDEWEB)

    Taquet, Vianney; Charnley, Steven B. [Astrochemistry Laboratory and The Goddard Center for Astrobiology, Mailstop 691, NASA Goddard Space Flight Center, 8800 Greenbelt Road, Greenbelt, MD 20770 (United States); Sipilä, Olli [Department of Physics, University of Helsinki, P.O. Box 64, FI-00014 Helsinki (Finland)

    2014-08-10

    Extremely large deuteration of several molecules has been observed toward prestellar cores and low-mass protostars for a decade. New observations performed toward low-mass protostars suggest that water presents a lower deuteration in the warm inner gas than in the cold external envelope. We coupled a gas-grain astrochemical model with a one-dimensional model of a collapsing core to properly follow the formation and the deuteration of interstellar ices as well as their subsequent evaporation in the low-mass protostellar envelopes with the aim of interpreting the spatial and temporal evolutions of their deuteration. The astrochemical model follows the formation and the evaporation of ices with a multilayer approach and also includes a state-of-the-art deuterated chemical network by taking the spin states of H{sub 2} and light ions into account. Because of their slow formation, interstellar ices are chemically heterogeneous and show an increase of their deuterium fractionation toward the surface. The differentiation of the deuteration in ices induces an evolution of the deuteration within protostellar envelopes. The warm inner region is poorly deuterated because it includes the whole molecular content of ices, while the deuteration predicted in the cold external envelope scales with the highly deuterated surface of ices. We are able to reproduce the observed evolution of water deuteration within protostellar envelopes, but we are still unable to predict the super-high deuteration observed for formaldehyde and methanol. Finally, the extension of this study to the deuteration of complex organics, important for the prebiotic chemistry, shows good agreement with the observations, suggesting that we can use the deuteration to retrace their mechanisms and their moments of formation.

  3. Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro

    International Nuclear Information System (INIS)

    Lipchik, R.J.; Chauncey, J.B.; Paine, R.; Simon, R.H.; Peters-Golden, M.

    1990-01-01

    Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung

  4. Deuteration of Dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate (BDD)

    International Nuclear Information System (INIS)

    Tong Qiang

    1990-01-01

    A new antihepatitic drug, BDD(I), which is very active and powerful especially in lowering elevated SGPT levels, has been previously discovered during the systematic study of Schisandra chinensis. In order to study the metabolism of this new antihepatitic drug, deuterated BDD was prepared according to the following method. BDD 1g, sodium chloroplatinate 193 mg, deuterium oxide 16 ml, acetic anhydride 30 ml, and acetyl chloride 0.4 ml were well mixed in a sealed ampoule and heated to 120-130 deg C for 12h. The mixture was then poured into water. The precipitate (0.86g) contained the deuterated acid (IIa, IIb) of BDD. After esterification with methanol, a mixture (m.p. 150 ∼ 153 deg C) of mono-and di-deuterated BDD was obtained. Molecular clustering, as determined by GC/MS, showed that the product consisted of mono-deutero-BDD(IIIa) (m/e419) and dideutero-BDD(IIIb) (m/e420) in the ratio of 1:1.3

  5. Catalytic hydrogenation of carbonyl group for deuterated compound production

    International Nuclear Information System (INIS)

    Gluhoi, C. Andreea; Marginean, P.; Lazar, Diana; Almasan, V.

    1999-01-01

    The total deuterated isopropyl alcohol can be produced starting from acetone. The developed technology comprises two steps: Deuteration of acetone by H/D isotopic exchange between acetone and heavy water in homogeneous catalysis. Reduction of the deuterated acetone with deuterium in presence of a metal/support catalyst. H/D isotopic exchange reaction of the H atoms from CH 3 groups is easy to occur because carbonyl group weakens C-H bond (ceto-enolyc tautomery). The big difference between boiling points of acetone and water permits an easy separation of acetone by distillation method. The reduction of acetone with deuterium was performed in a dynamic reactor by passing a deuterium flow saturated with acetone vapour through a supported nickel catalyst bed. The reaction products were analysed on-line using a flame ionisation detector. The supported nickel catalysts were checked for this reaction. By using nickel over different supports the selectivity for isopropyl alcohol was about 100%. The propane was detected only as traces. The catalytic activity depends strongly on the support nature: the Ni/SiO 2 is less active, while the Ni/TiO 2 presents the larger value for the intrinsic activity. (authors)

  6. X-ray structure determination and deuteration of nattokinase.

    Science.gov (United States)

    Yanagisawa, Yasuhide; Chatake, Toshiyuki; Naito, Sawa; Ohsugi, Tadanori; Yatagai, Chieko; Sumi, Hiroyuki; Kawaguchi, Akio; Chiba-Kamosida, Kaori; Ogawa, Megumi; Adachi, Tatsumi; Morimoto, Yukio

    2013-11-01

    Nattokinase (NK) is a strong fibrinolytic enzyme, which is produced in abundance by Bacillus subtilis natto. Although NK is a member of the subtilisin family, it displays different substrate specificity when compared with other subtilisins. The results of molecular simulations predict that hydrogen arrangements around Ser221 at the active site probably account for the substrate specificity of NK. Therefore, neutron crystallographic analysis should provide valuable information that reveals the enzymatic mechanism of NK. In this report, the X-ray structure of the non-hydrogen form of undeuterated NK was determined, and the preparation of deuterated NK was successfully achieved. The non-hydrogen NK structure was determined at 1.74 Å resolution. The three-dimensional structures of NK and subtilisin E from Bacillus subtilis DB104 are near identical. Deuteration of NK was carried out by cultivating Bacillus subtilis natto in deuterated medium. The D2O resistant strain of Bacillus subtilis natto was obtained by successive cultivation rounds, in which the concentration of D2O in the medium was gradually increased. NK was purified from the culture medium and its activity was confirmed by the fibrin plate method. The results lay the framework for neutron protein crystallography analysis.

  7. Electrical conductivity measurement on DKDP Crystals with different deuterated degrees

    International Nuclear Information System (INIS)

    Liu, Baoan; Yin, Xin; Xu, Mingxia; Ji, Shaohua; Zhu, Lili; Zhang, Lisong; Sun, Xun; Xu, Xinguang; Zhao, Minglei; Zhang, Qinghua

    2012-01-01

    Ten DKDP single crystals with deuterated degrees ranging from 0 to 90 % were grown by a rapid growth method. The electrical conductivities of these crystals were measured along a and c directions at room temperature. The electrical conductivity increases with the increase for deuterium content. Also, the electrical conductivities of certain crystals were measured at various temperatures ranging from 20 to 130 C. The values of activation energy decrease as the increase of deuterium content. The present study indicates that the deuterium tunneling frequency is smaller than that of hydrogen, which may be the reason why the variation of electrical conductivity happens after the substitution of hydrogen for deuterium in KDP crystal. (orig.)

  8. Acyl-CoA synthetase activity links wild-type but not mutant a-Synuclein to brain arachidonate metabolism

    DEFF Research Database (Denmark)

    Golovko, Mikhail; Rosenberger, Thad; Færgeman, Nils J.

    2006-01-01

    Because alpha-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that the loss of alpha-synuclein had on brain arachidonic acid (20:4n-6) metabolism in vivo using Snca-/- mice. We measured [1-(14)C]20:4n-6 incorporation and turnover kinetics in brain phospholipids using......, our data demonstrate that alpha-synuclein has a major role in brain 20:4n-6 metabolism through its modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity, although mutant forms of alpha-synuclein fail to restore this activity....

  9. A novel method for the biosynthesis of deuterated proteins with selective protonation at the aromatic rings of Phe, Tyr and Trp

    International Nuclear Information System (INIS)

    Rajesh, Sundaresan; Nietlispach, Daniel; Nakayama, Hiroshi; Takio, Koji; Laue, Ernest D.; Shibata, Takehiko; Ito, Yutaka

    2003-01-01

    A novel biosynthetic strategy is described for the preparation of deuterated proteins containing protons at the ring carbons of Phe, Tyr and Trp, using the aromatic amino acid precursor shikimic acid. Specific protonation at aromatic side chains, with complete deuteration at C α/β positions was achieved in proteins overexpressed in bacteria grown in shikimate-supplemented D 2 O medium. Co-expression of a shikimate transporter in prototrophic bacteria resulted in protonation levels of 62-79%, whereas complete labeling was accomplished using shikimate auxotrophic bacteria. Our labeling protocol permits the measurement of important aromatic side chain derived distance restraints in perdeuterated proteins that could be utilized to enhance the accuracy of NMR structures calculated using low densities of NOEs from methyl selectively protonated samples

  10. Deuterated-decaborane using boronization on JT-60U

    Energy Technology Data Exchange (ETDEWEB)

    Yagyu, Jun-ichi; Arai, Takashi; Kaminaga, Atsushi; Miyata, Katsuyuki [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment; Arai, Masaru [Kaihatsu Denki Co., Ltd., Tokyo (Japan)

    2001-03-01

    In JT-60U, boronization using hydride-decaborane (B{sub 10}H{sub 14}) vaporization has been conducted for the first wall conditioning. Compared to other discharge cleaning (DC), boronization is claimed to be efficient in reduction of oxygen impurities and hydrogen recycling in plasma. However, there are some problems in reduction of hydrogen included in boron film and stabilization of DC glow discharge during the boronization. To solve these problems, a new boronization method using deuterated-decaborane (B{sub 10}D{sub 14}) was adopted instead of the conventional hydride-decaborane. As a result, hydrogen content in the boron film decreased clearly and discharge conditioning shots, for decreasing hydrogen content in plasmas, after the boronization were reduced to 1/10 in comparison to the conventional process. Furthermore, DC glow discharge became stable, with only helium carrier gas, and it was possible to save 30 hours in maximum of the time necessary to boronization. It is shown that the boronization using deuterated-decaborane is very efficient and effective method for the first wall conditioning. (author)

  11. Selective deuteration for molecular insights into the digestion of medium chain triglycerides.

    Science.gov (United States)

    Salentinig, Stefan; Yepuri, Nageshwar Rao; Hawley, Adrian; Boyd, Ben J; Gilbert, Elliot; Darwish, Tamim A

    2015-09-01

    Medium chain triglycerides (MCTs) are a unique form of dietary fat that have a wide range of health benefits. They are molecules with a glycerol backbone esterified with medium chain (6-12 carbon atoms) fatty acids on the two outer (sn-1 and sn-3) and the middle (sn-2) positions. During lipid digestion in the gastrointestinal tract, pancreatic lipase stereoselectively hydrolyses the ester bonds of these triglycerides on the sn-1 and sn-3 positions resulting in sn-2 monoglyceride and fatty acids as major products. However, the sn-2 monoglycerides are thermodynamically less stable than their sn-1/3 counterparts. Isomerization or fatty acid migration from the sn-2 monoglyceride to sn-1/3 monoglyceride may occur spontaneously and would lead to glycerol and fatty acid as final products. Here, tricaprin (C10) with selectively deuterated fatty acid chains was used for the first time to monitor chain migration and the stereoselectivity of the pancreatic lipase-catalyzed hydrolysis of ester bonds. The intermediate and final digestion products were studied using NMR and mass spectrometry under biologically relevant conditions. The hydrolysis of the sn-2 monocaprin to glycerol and capric acid did not occur within biologically relevant timescales and fatty acid migration occurs only in limited amounts as a result of the presence of undigested diglyceride species over long periods of time in the digestion medium. The slow kinetics for the exchange of the sn-2 fatty acid chain and the stereoselectivity of pancreatic lipase on MCTs is relevant for industrial processes that involve enzymatic interesterification and the production of high-value products such as specific structured triacylglycerols, confectionery fats and nutritional products. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Characterization of arachidonate 5-lipoxygenase and leukotriene A4 synthetase from RBL-1 cells

    International Nuclear Information System (INIS)

    Cook, M.; Hogaboom, G.K.; Sarau, H.M.; Foley, J.J.; Crooke, S.T.

    1986-01-01

    5-lipoxygenase (LO) and leukotriene (LT) A4 synthetase from RBL-1 high speed (105,000 x g for 60 min) supernatants were partially purified by protein-high performance liquid chromatography (HPLC) and characterized in detail. The partially purified preparation contained only 5-LO and LTA4 synthetase and was isolated from 12-LO, peroxidase and LTA4 hydrolase activities. Reaction products were separated by reversed phase HPLC and quantitated by absorption spectrophotometry and radiochemical detection. The enzyme preparation rapidly converted [ 14 C]arachidonate to [ 14 C]5-hydroperoxyeicosatetraenoic acid (HPETE) and [ 14 C]5,12-dihydroperoxyeicosatetraenoic acids (diHETEs). The 5,12-diHETEs were primarily non-enzymatic breakdown products of LTA4 (e.g., 6-trans-LTB4 and 6-trans-12-epi-LTB4). Both the 5-LO and LTA4 synthetase activities were Ca 2+- and ATP-dependent. For both enzyme activities, the CA 2+ stimulation required the presence of ATP. The fatty acid hydroperoxides, 5-,12-, and 15-HPETE, both stimulated ([ 3 μM]) 5-LO and LTA4 synthetase activities. The rapid isolation and subsequent characterization of 5-LO and LTA4 synthetase provide the bases for the further understanding of the role of the LO pathway in biological processes

  13. Incoherent neutron scattering in acetanilide and three deuterated derivatives

    Science.gov (United States)

    Barthes, Mariette; Almairac, Robert; Sauvajol, Jean-Louis; Moret, Jacques; Currat, Roland; Dianoux, José

    1991-03-01

    Incoherent-neutron-scattering measurements of the vibrational density of states of acetanilide and three deuterated derivatives are presented. These data allow one to identify an intense maximum, assigned to the N-H out-of-plane bending mode. The data display the specific behavior of the methyl torsional modes: large isotopic shift and strong low-temperature intensity; confirm our previous inelastic-neutron-scattering studies, indicating no obvious anomalies in the range of frequency of the acoustic phonons. In addition, the data show the existence of thermally activated quasielastic scattering above 100 K, assigned to the random diffusive motion of the methyl protons. These results are discussed in the light of recent theoretical models proposed to explain the anomalous optical properties of this crystal.

  14. Infrared and Raman spectra of uric acid and its 15N and D labelled compounds

    International Nuclear Information System (INIS)

    Majoube, Michel

    Infrared and Raman spectra of polycrystalline uric acid (2, 6, 8-trioxypurine) 1.3, 7 and 9- 15 N and deuterated analogues have been determined. Band shifts with 15 N substitution and with deuteration are discussed. An assignment of fundamental vibrations of uric acid is proposed from the comparison of the eight isotopically substituted analogues [fr

  15. Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression

    Directory of Open Access Journals (Sweden)

    Mutch David M

    2002-10-01

    Full Text Available Abstract Background The functions, actions, and regulation of tissue metabolism affected by the consumption of long chain polyunsaturated fatty acids (LC-PUFA from fish oil and other sources remain poorly understood; particularly how LC-PUFAs affect transcription of genes involved in regulating metabolism. In the present work, mice were fed diets containing fish oil rich in eicosapentaenoic acid and docosahexaenoic acid, fungal oil rich in arachidonic acid, or the combination of both. Liver and hippocampus tissue were then analyzed through a combined gene expression- and lipid- profiling strategy in order to annotate the molecular functions and targets of dietary LC-PUFA. Results Using microarray technology, 329 and 356 dietary regulated transcripts were identified in the liver and hippocampus, respectively. All genes selected as differentially expressed were grouped by expression patterns through a combined k-means/hierarchical clustering approach, and annotated using gene ontology classifications. In the liver, groups of genes were linked to the transcription factors PPARα, HNFα, and SREBP-1; transcription factors known to control lipid metabolism. The pattern of differentially regulated genes, further supported with quantitative lipid profiling, suggested that the experimental diets increased hepatic β-oxidation and gluconeogenesis while decreasing fatty acid synthesis. Lastly, novel hippocampal gene changes were identified. Conclusions Examining the broad transcriptional effects of LC-PUFAs confirmed previously identified PUFA-mediated gene expression changes and identified novel gene targets. Gene expression profiling displayed a complex and diverse gene pattern underlying the biological response to dietary LC-PUFAs. The results of the studied dietary changes highlighted broad-spectrum effects on the major eukaryotic lipid metabolism transcription factors. Further focused studies, stemming from such transcriptomic data, will need to

  16. Uniform and selective deuteration in two-dimensional NMR of proteins

    International Nuclear Information System (INIS)

    LeMaster, D.M.

    1990-01-01

    This paper reports on the practicality of isotopic labeling, particularly deuteration, that has received considerable impetus from advances in molecular biology, which have allowed ready production of NMR quantities of labeled proteins. Protein expression in Escherichia coli allows use of the considerable metabolic genetics known for the organism in shaping the biosynthetic process to meet the labeling demands of the NMR experiments. In addition to deuteration's common use in spectral assignment problems, it also offers considerable potential for enhancing the quality of the nuclear Overhauser effect (NOE) distance and dihedral angle constraints used for solution structural analysis of proteins. Recent reviews emphasize the sample preparation and spectral benefits of protein deuteration

  17. Highly selective deuteration of pharmaceutically relevant nitrogen-containing heterocycles: a flow chemistry approach.

    Science.gov (United States)

    Ötvös, Sándor B; Mándity, István M; Fülöp, Ferenc

    2011-08-01

    A simple and efficient flow-based technique is reported for the catalytic deuteration of several model nitrogen-containing heterocyclic compounds which are important building blocks of pharmacologically active materials. A continuous flow reactor was used in combination with on-demand pressure-controlled electrolytic D(2) production. The D(2) source was D(2)O, the consumption of which was very low. The experimental set-up allows the fine-tuning of pressure, temperature, and flow rate so as to determine the optimal conditions for the deuteration reactions. The described procedure lacks most of the drawbacks of the conventional batch deuteration techniques, and additionally is highly selective and reproducible.

  18. [2H26]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

    Directory of Open Access Journals (Sweden)

    Christian A. Citron

    2013-12-01

    Full Text Available During growth on fully deuterated medium the volatile terpene [2H26]-1-epi-cubenol was released by the actinomycete Streptomyces griseus. This compound represents the first completely deuterated terpene obtained by fermentation. Despite a few previous reports in the literature the operability of this approach to fully deuterated compounds is still surprising, because the strong kinetic isotope effect of deuterium is known to slow down all metabolic processes in living organisms. Potential applications of completely labelled compounds from natural sources in structure elucidation, biosynthetic or pharmacokinetic investigations are discussed.

  19. Magnetic properties of nickel halide hydrates including deuteration effects

    Energy Technology Data Exchange (ETDEWEB)

    DeFotis, G.C., E-mail: gxdefo@wm.edu [Chemistry Department, College of William & Mary, Williamsburg, VA, 23187 United States (United States); Van Dongen, M.J.; Hampton, A.S.; Komatsu, C.H.; Trowell, K.T.; Havas, K.C.; Davis, C.M.; DeSanto, C.L. [Chemistry Department, College of William & Mary, Williamsburg, VA, 23187 United States (United States); Hays, K.; Wagner, M.J. [Chemistry Department, George Washington University, Washington, DC, 20052 United States (United States)

    2017-01-01

    Magnetic measurements on variously hydrated nickel chlorides and bromides, including deuterated forms, are reported. Results include locations and sizes of susceptibility maxima, T{sub max} and χ{sub max}, ordering temperatures T{sub c}, Curie constants and Weiss theta in the paramagnetic regime, and primary and secondary exchange interactions from analysis of low temperature data. For the latter a 2D Heisenberg model augmented by interlayer exchange in a mean-field approximation is applied. Magnetization data to 16 kG as a function of temperature show curvature and hysteresis characteristics quite system dependent. For four materials high field magnetization data to 70 kG at 2.00 K are also obtained. Comparison is made with theoretical relations for spin-1 models. Trends are apparent, primarily that T{sub max} of each bromide hydrate is less than for the corresponding chloride, and that for a given halide nD{sub 2}O (n=1 or 2) deuterates exhibit lesser T{sub max} than do nH{sub 2}O hydrates. A monoclinic unit cell determined from powder X-ray diffraction data on NiBr{sub 2}·2D{sub 2}O is different from and slightly larger than that of NiBr{sub 2}·2H{sub 2}O. This provides some rationale for the difference in magnetic properties between these. - Highlights: • The magnetism of Ni(II) chloride and bromide dihydrates and monohydrates is studied. • Effects of replacing H{sub 2}O by D{sub 2}O are examined for both hydration states and both halides. • Exchange interactions in bromides are weaker than in corresponding chlorides. • Exchange interactions are weaker in D{sub 2}O than in corresponding H{sub 2}O containing systems. • The unit cell of NiBr{sub 2}·2D{sub 2}O is different from and slightly larger than that of NiBr{sub 2}·2H{sub 2}O.

  20. Effect of deuteration on the vibrational spectra of organic molecules

    International Nuclear Information System (INIS)

    Billes, Ferenc; Endredi, Henrietta; Varady, Balazs

    2001-01-01

    The stable isotope substitution of organic compounds deforms their vibrational spectra. The modifications of the spectra appear as band shifts and changes in intensities and shapes of the bands. The magnitude of the effect depends on the ratio of the masses of the new and old isotopes and on the atom active position. According to these mentioned reasons large effects can be observed only if hydrogen atoms are substituted. With the effect of the substitution we dealt already in a former lecture. In this lecture we concentrate on the effect of the change of hydrogen to deuterium. We investigate the changes both experimentally and theoretically. There are two possibilities: - the hydrogen atom is in an active position, its interaction with the environment is strong, either it can dissociate or move on the skeleton of the molecule (tautomerism, resonance) and it can build hydrogen bond, (e.g. it is connected to nitrogen and oxygen atoms); - the hydrogen atom is in an indifferent position in the molecule, its interaction with the environment is weak (e.g. it joins carbon atom). When building the hydrogen bond besides the hydrogen donors also acceptors exist, namely, oxygen and nitrogen atoms having non-bonded electron pairs. When comparing the experimental and theoretical (calculated) effects of this type of isotope changes one must take into account that the calculations refer to the isolated molecule while the experimental spectra characterize the compound. The hydrogen bond is a very strong intermolecular interaction and produces tremendous changes in the infrared spectrum of the molecule in comparison to the imagined theoretical spectrum of the molecule. Some bands disappear, appear, or shift and deform drastically. The H/D change diminishes these effects. Of course, these changes entail the shift of several bands. The Raman spectrum is less sensitive to the large dipole moment changes therefore the deuteration effect is there less dramatic. Deuteration of hydrogen

  1. Studies on /sup 13/C-NMR spectroscopy of carbohydrates. Application of selective deuteration

    Energy Technology Data Exchange (ETDEWEB)

    Mizutani, Kenji; Kajita, Hitomi; Tashima, Takako; Tanaka, Osamu (Hiroshima Univ. (Japan). School of Medicine)

    1982-10-01

    Recently, Stuart et al. have reported that on heating with deuterated Raney nickel in D/sub 2/O, hexopyranosides and oligosaccharides were deuterated selectively at carbon atoms bound to a free hydroxyl group. For the application of this procedure to chemistry and biochemistry of more complex carbohydrates, further study on this reaction was conducted. On prolonged treatment with Raney nickel (24h), methyl ..cap alpha..-L-arabinopyranoside (4) and ..beta..-D-xylopyranoside (5) were partially epimerized to give (5) and methyl ..cap alpha..-L-lyxopyranoside (6) from (4), and methyl ..beta..-D-ribopyranoside (7) and (4) from (5), respectively. Methyl ..cap alpha..-L-rhamnopyranoside (8) was epimerized more slowly to yield methyl 6-deoxy-..cap alpha..-L-glucopyranoside (9). The best conditions for the deuteration under minimizing the epimerization was refluxing with W-7 type deuterated Raney nickel in D/sub 2/O-dioxane (1 : 1) or methanol-d/sub 4/-D/sub 2/O (1 : 1) for about 9h. Methyl ..beta..-sophoroside (13), methyl ..beta..-cellobioside (23) and ..beta..-sophorosyl and ..beta..-gentiobiosyl units of ginsenoside-Rb/sub 1/ (24), a Ginseng-saponin, were deuterated as expected under these conditions, while C-2 and 4 of the inner ..beta..-glucopyranosyl moiety of methyl ..beta..-laminaribioside (18) and C-4 of the inner ..beta..-glucopyranosyl moiety of methyl 2,3-di-O-..beta..-D-glucopyranosyl-..beta..-D-glucopyranoside (22) remained almost undeuterated. Deuteration of ..cap alpha..-1,6-glucan (25) proceeded rather slowly than those of mono- and oligosaccharide to obtain the expected deuteration after treatment for 24h. In the case of the deuteration of cis- and dl-trans-1, 2-cyclohexanediols (11) and ( (12), both deuteration and epimerization proceeded very fast to give an equilibrated mixture of (11-d/sub 2/) and (12-d/sub 2/) within 9h, while the isolated carbinyl carbon (C-12) of (24) was not deuterated. Further, by means of the above selective deuteration, /sup 13

  2. Solid deuterated water in space: detection constraints from laboratory experiments

    Science.gov (United States)

    Urso, R. G.; Palumbo, M. E.; Baratta, G. A.; Scirè, C.; Strazzulla, G.

    2018-06-01

    The comparison between astronomical spectra and laboratory experiments is fundamental to spread light on the structure and composition of ices found in interstellar dense molecular clouds and in Solar System bodies. Water is among the most abundant solid-phase species observed in these environments, and several attempts have been made to investigate the presence of its solid-phase isotopologues. In particular, the detection of the O-D stretching mode band at 4.1 μm due to both D2O and HDO within icy grain mantles is still under debate, and no detection have been reported about the presence of these species within icy bodies in the Solar System yet. In the near future, an important contribution could derive from the data acquired in the O-D stretching mode spectral range by the sensitive instruments on board the James Webb Space Telescope. With this in mind, we performed several laboratory experiments to study the O-D stretching mode band in solid mixtures containing water and deuterated water deposited in the temperature range between 17 and 155 K, in order to simulate astrophysical relevant conditions. Furthermore, samples have been studied at various temperature and irradiated with energetic ions (200 keV H+) in order to study the effects induced by both thermal and energetic processing. Our results provide some constraints on the detection of the 4.1 μm band in astronomical environments.

  3. Dispersion Relation for Skeletal Vibrations in Deuterated Polyethylene

    Energy Technology Data Exchange (ETDEWEB)

    Feldkamp, L. A.; Venkataraman, G.; King, J. S. [Department of Nuclear Engineering, University of Michigan, Ann Arbor, MI (United States)

    1968-09-15

    The low frequency vibrations in polyethylene have been studied previously, utilizing the incoherent scattering technique which yields an amplitude-weighted density of states. In the present work the dispersion relations have been obtained directly by observing the coherent scattering from a deuterated sample. This represents the first such measurement on a crystalline polymer. A target in which the molecular chain axes were approximately parallel was prepared by stretching polycrystalline material. The FWHM of the rocking curve for the (002) reflection was measured to be 9 Degree-Sign . Constant-Q and constant-E scans were made on the University of Michigan triple-axis spectrometer at room temperature to observe phonons propagating along the chain direction. The resulting dispersion curve for the v{sub 5} mode follows generally the calculated curve of Tasumi and Krimm with systematically lower frequencies. The maximum frequency of 1.36 x 10{sup 13} Hz agrees with the cut-off frequency determined previously from the incoherent scattering spectrum. (author)

  4. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics

    Directory of Open Access Journals (Sweden)

    Francesco Gatto

    2016-07-01

    Full Text Available Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.

  5. Deuterated-xylene (xylene-d{sub 10}; EJ301D): A new, improved deuterated liquid scintillator for neutron energy measurements without time-of-flight

    Energy Technology Data Exchange (ETDEWEB)

    Becchetti, F.D.; Raymond, R.S.; Torres-Isea, R.O. [Department of Physics, University of Michigan, Ann Arbor, MI 48109 (United States); Di Fulvio, A.; Clarke, S.D.; Pozzi, S.A. [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI 48109 (United States); Febbraro, M. [Oak Ridge National Laboratory, Oak Ridge, TN 37830 (United States)

    2016-06-01

    In conjunction with Eljen Technology, Inc. (Sweetwater,TX) we have designed, constructed, and evaluated a 3 in. ×3 in. deuterated-xylene organic liquid scintillator (C{sub 8}D{sub 10}; EJ301D) as a fast neutron detector. Similar to deuterated benzene (C{sub 6}D{sub 6}; NE230, BC537, and EJ315) this scintillator can provide good pulse-shape discrimination between neutrons and gamma rays, has good timing characteristics, and can provide a light spectrum with peaks corresponding to discrete neutron energy groups up to ca. 20 MeV. Unlike benzene-based detectors, deuterated xylene is less volatile, less toxic, is not known to be carcinogenic, has a higher flashpoint, and hence is much safer for many applications. In addition EJ301D can provide slightly more light output and better PSD than deuterated-benzene scintillators. We show that, as with deuterated-benzene scintillators, the light-response spectra can be unfolded to provide useable neutron energy spectra without need for time-of-flight (ToF). An array of these detectors arranged at many angles close to a reaction target can be much more effective (×10 to ×100 or more) than an array of long-path ToF detectors which must utilize a narrowly-bunched and pulse-selected beam. As we demonstrate using a small Van de Graaff accelerator, measurements can thus be performed when a bunched and pulse-selected beam (as needed for time-of-flight) is not available.

  6. THE L1157-B1 ASTROCHEMICAL LABORATORY: MEASURING THE TRUE FORMALDEHYDE DEUTERATION ON GRAIN MANTLES

    International Nuclear Information System (INIS)

    Fontani, F.; Codella, C.; Ceccarelli, C.; Lefloch, B.; Viti, S.; Benedettini, M.

    2014-01-01

    L1157 is a prototypical chemically active outflow driven by a low-mass class-0 protostar, and B1 is its brightest bow shock. Toward L1157-B1, several emission lines of deuterated molecules have been detected for the first time by Codella et al. The authors suggested that these were formed on grain mantles, and then released into the gas phase by the passage of the shock. In this Letter we report observations obtained at high angular resolution with the Plateau de Bure Interferometer of HDCO and CH 2 DOH. The emission of HDCO perfectly delineates the region of the interface between the fast jet and the slower ambient material, confirming the predictions of the previous work that deuterated species were formed on grain mantles and then released into the gas phase by the passage of the shock. CH 2 DOH emission is fainter and thus its emitting region is not well determined. The deuterated fraction HDCO/H 2 CO is ∼0.1 in the HDCO emitting region, an order of magnitude larger than the upper limit found in the surrounding material, probably dominated by warm-gas chemistry and less affected by grain evaporation. Our study represents the first clear evidence ever found of a deuterated molecule as shock tracer, and yields an indirect but ''clean'' measurement of the deuteration of the ices covering the dust grains during the cold pre-protostellar phase

  7. Helium (24He, 23He) within deuterated Pd-black

    International Nuclear Information System (INIS)

    Arata, Yoshiaki; Zhang, Yue-Chang

    1997-01-01

    Authors have clearly proven for the first time that deuterium nuclear reaction was continuously generated inside a highly deuterated solid by showing both of the excess energy and corresponding amount of helium as the reaction product generated simultaneously. Whenever there is a nuclear fusion reaction inside a metal, helium generated is unable to escape to the surroundings and is trapped in a frozen state inside that metal. The concentration of the helium within the metal will rise with increasing rate of reactions. Pd-black is under such state as the sample used and sealed within the 'closed QMS' developed by the authors (closed vessel including the Getter pump and the QMS). It is completely separated from the surroundings and the internal gases are removed to create super-vacuum. The reaction product released by the 'Sample-Heating' process (room temp. ↔ 1500(degC)) is thus the only matter which occupies the interior of the closed vessel and its detection by the QMS is assured. When the 'closed QMS' works under the above mentioned-state, it was clarified that the 'ash' or the reaction product of this fusion reaction within a solid is 2 4 He and 2 3 He and their ratio is 2 4 He/ 2 3 He ≅ 4. It can be concluded from the result that the main reaction product is 2 4 He and it is created directly as an inherent feature of the solid-state nuclear fusion. Authors think that the reaction process responsible for the creation of 2 3 He may be a different one from that created 2 4 He. One of which is the Rutherford reaction process and the other occurs based on the specific properties of solid, similar to the case of 2 4 He. The existence of 1 3 T will be required that the process is responsible for the generation of 2 3 He as the Rutherford reaction. The proof for the existence of 1 3 T within the 'closed QMS', however, was not obtained in this experiments. (author)

  8. The rate of lactate production from glucose in hearts is not altered by per-deuteration of glucose

    Science.gov (United States)

    Funk, Alexander M.; Anderson, Brian L.; Wen, Xiaodong; Hever, Thomas; Khemtong, Chalermchai; Kovacs, Zoltan; Sherry, A. Dean; Malloy, Craig R.

    2017-11-01

    This study was designed to determine whether perdeuterated glucose experiences a kinetic isotope effect (KIE) as glucose passes through glycolysis and is further oxidized in the tricarboxylic acid (TCA) cycle. Metabolism of deuterated glucose was investigated in two groups of perfused rat hearts. The control group was supplied with a 1:1 mixture of [U-13C6]glucose and [1,6-13C2]glucose, while the experimental group received [U-13C6,U-2H7]glucose and [1,6-13C2]glucose. Tissue extracts were analyzed by 1H, 2H and proton-decoupled 13C NMR spectroscopy. Extensive 2H-13C scalar coupling plus chemical shift isotope effects were observed in the proton-decoupled 13C NMR spectra of lactate, alanine and glutamate. A small but measureable (∼8%) difference in the rate of conversion of [U-13C6]glucose vs. [1,6-13C2]glucose to lactate, likely reflecting rates of Csbnd C bond breakage in the aldolase reaction, but conversion of [U-13C6]glucose versus [U-13C6,U-2H7]glucose to lactate did not differ. This shows that the presence of deuterium in glucose does not alter glycolytic flux. However, there were two distinct effects of deuteration on metabolism of glucose to alanine and oxidation of glucose in the TCA. First, alanine undergoes extensive exchange of methyl deuterons with solvent protons in the alanine amino transferase reaction. Second, there is a substantial kinetic isotope effect in metabolism of [U-13C6,U-2H7]glucose to alanine and glutamate. In the presence of [U-13C6,U-2H7]glucose, alanine and lactate are not in rapid exchange with the same pool of pyruvate. These studies indicate that the appearance of hyperpolarized 13C-lactate from hyperpolarized [U-13C6,U-2H7]glucose is not substantially influenced by a deuterium kinetic isotope effect.

  9. Low-temperature structural phase transition in deuterated and protonated lithium acetate dihydrate

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, F., E-mail: schroeder@kristall.uni-frankfurt.d [Goethe-Universitaet Frankfurt am Main, Institut fuer Geowissenschaften, Abt. Kristallographie, Altenhoeferallee 1, 60438 Frankfurt am Main (Germany); Winkler, B.; Haussuehl, E. [Goethe-Universitaet Frankfurt am Main, Institut fuer Geowissenschaften, Abt. Kristallographie, Altenhoeferallee 1, 60438 Frankfurt am Main (Germany); Cong, P.T.; Wolf, B. [Goethe-Universitaet Frankfurt am Main, Physikalisches Institut, Max-von-Laue-Strasse 1, 60438 Frankfurt am Main (Germany); Avalos-Borja, M. [Instituto Potosino de Investigacion Cientifica y Tecnologica, A.C. Camino a la Presa San Jose 2055, Col. Lomas 4 seccion CP 78216, San Luis Potosi (Mexico); Quilichini, M.; Hennion, B. [Laboratoire Leon Brillouin, CEN Saclay, 91191 Gif-sur-Yvette (France)

    2010-08-15

    Heat capacity measurements of protonated lithium acetate dihydrate show a structural phase transition at T = 12 K. This finding is in contrast to earlier work, where it was thought that only the deuterated compound undergoes a low temperature structural phase transition. This finding is confirmed by low temperature ultrasound spectroscopy, where the structural phase transition is associated with a velocity decrease of the ultrasonic waves, i.e. with an elastic softening. We compare the thermodynamic properties of the protonated and deuterated compounds and discuss two alternatives for the mechanism of the phase transition based on the thermal expansion measurements.

  10. A role for AMPK in the inhibition of glucose-6-phosphate dehydrogenase by polyunsaturated fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Kohan, Alison B.; Talukdar, Indrani; Walsh, Callee M. [Department of Biochemistry, West Virginia University, Morgantown, WV (United States); Salati, Lisa M., E-mail: lsalati@hsc.wvu.edu [Department of Biochemistry, West Virginia University, Morgantown, WV (United States)

    2009-10-09

    Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as {beta}-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK mimics the inhibition by arachidonic acid of the insulin-mediated induction of G6PD. Similar to intracellular signaling by arachidonic acid, AMPK decreases insulin signal transduction, increasing Ser{sup 307} phosphorylation of IRS-1 and a subsequent decrease in AKT phosphorylation. Overexpression of dominant-negative AMPK abolishes the effect of arachidonic acid on G6PD expression. These data suggest a role for AMPK in the inhibition of G6PD by polyunsaturated fatty acids.

  11. Pharmacological inhibition of arachidonate 15-lipoxygenase (ALOX15) protects human spermatozoa against oxidative stress.

    Science.gov (United States)

    Walters, Jessica L H; De Iuliis, Geoffry N; Dun, Matthew D; Aitken, Robert John; McLaughlin, Eileen A; Nixon, Brett; Bromfield, Elizabeth G

    2018-03-13

    One of the leading causes of male infertility is defective sperm function, a pathology that commonly arises from oxidative stress in the germline. Lipid peroxidation events in the sperm plasma membrane result in the generation of cytotoxic aldehydes such as 4-hydroxynonenal (4HNE), which accentuate the production of reactive oxygen species (ROS) and cause cellular damage. One of the key enzymes involved in the metabolism of polyunsaturated fatty acids to 4HNE in somatic cells is arachidonate 15-lipoxygenase (ALOX15). Although ALOX15 has yet to be characterized in human spermatozoa, our previous studies have revealed a strong link between ALOX15 activity and the levels of oxidative stress and 4HNE in mouse germ cell models. In view of these data, we sought to assess the function of ALOX15 in mature human spermatozoa and determine whether the pharmacological inhibition of this enzyme could influence the level of oxidative stress experienced by these cells. By driving oxidative stress in vitro with exogenous H2O2, our data reveal that 6,11-dihydro[1]benzothiopyrano[4,3-b]indole (PD146176; a selective ALOX15 inhibitor), was able to significantly reduce several deleterious, oxidative insults in spermatozoa. Indeed, PD146176 attenuated the production of ROS, as well as membrane lipid peroxidation and 4HNE production in human spermatozoa. Accordingly, ALOX15 inhibition also protected the functional competence of these cells to acrosome react and bind homologous human zonae pellucidae. Together, these results implicate ALOX15 in the propagation of an oxidative stress cascade within human spermatozoa and offer insight into potential therapeutic avenues to address male fertility that arises from oxidative stress.

  12. Quantitation of deuterated and non-deuterated phenylalanine and tyrosine in human plasma using the selective ion monitoring method with combined gas chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    Zagalak, M.-J.; Curtius, H.-Ch.; Leimbacher, W.; Redweik, U.

    1977-01-01

    A specific method is described for the quantitative analysis of deutarated and non-deuterated phenylalanine and tyrosine in human plasma by gas chromatography-mass spectrometry using selective ion monitoring. From the several derivatives investigated, the N- or N,O-trifluoroacetyl methyl esters were found to be the most suitable for our purposes. DL-Phenylalanine-4-d 1 and L-tyrosine-d 7 were used as internal standards. The sensitivity of this method permits the measurement of amounts as small as ca. 2.5 ng/ml in plasma for both phenylalanine and tyrosine. The coefficients of variation were found to be ca. 1.6% (n=12) for phenylalanine and 3.0% (n=12) for tyrosine. Using this method, an in vivo determination of phenylalanine-4-monooxygenase activity in humans is possible by loading the subjects with deuterated L-phenylalanine-d 5 (accepted as substrate by phenylalanine-4-monooxygenase E.C. 1.14.16.1) and the subsequent measuring of deuterated L-tyrosine-d 4 formed and residual L-phenylalanine-d 5

  13. A Neutron Scattering Study of Phonons in Per-Deuterated S-Triazine

    DEFF Research Database (Denmark)

    Doue, M. T.; Heilmann, I. U.; Kjems, Jørgen

    1983-01-01

    The lattice dynamics of a fully-deuterated single crystal of s-triazine is investigated using the technique of coherent inelastic neutron scattering. Detailed measurements of the temperature dependence of the dispersion of the soft acoustic mode associated with the ferroelastic phase transition...

  14. Habit control of deuterated potassium dihydrogen phosphate crystal for laser applications

    Science.gov (United States)

    Guzman, L. A.; Suzuki, M.; Fujimoto, Y.; Fujioka, K.

    2016-03-01

    In this study we investigate the habit of partially deuterated potassium dihydrogen phosphate (DKDP) crystals in the presence of Al3+ ions. We have grown single DKDP crystals in (50wt% and 80wt%) partially deuterated solutions and in solutions doped with Al3+ ions (2 ppm) by the point-seed rapid growth technique at controlled supercooling (ΔT=10°C). The growth length of each crystal face was measured and the aspect ratio was calculated. We found that crystals grown in partially deuterated solutions are similar in aspect ratio, while, crystals grown in deuterated solutions doped with Al3+ ions showed a relative change in aspect ratio, the crystal increased in size in the pyramidal direction (vertical axis direction). Crystal characteristics were also analyzed by X-ray diffraction, FTIR and Raman spectroscopy. We have speculated that the relative habit modification is due to a probably adsorption and inclusions of Al3+ ions in the prismatic section of the crystal.

  15. Habit control of deuterated potassium dihydrogen phosphate crystal for laser applications

    International Nuclear Information System (INIS)

    Guzman, L A; Suzuki, M; Fujimoto, Y; Fujioka, K

    2016-01-01

    In this study we investigate the habit of partially deuterated potassium dihydrogen phosphate (DKDP) crystals in the presence of Al 3+ ions. We have grown single DKDP crystals in (50wt% and 80wt%) partially deuterated solutions and in solutions doped with Al 3+ ions (2 ppm) by the point-seed rapid growth technique at controlled supercooling (ΔT=10°C). The growth length of each crystal face was measured and the aspect ratio was calculated. We found that crystals grown in partially deuterated solutions are similar in aspect ratio, while, crystals grown in deuterated solutions doped with Al 3+ ions showed a relative change in aspect ratio, the crystal increased in size in the pyramidal direction (vertical axis direction). Crystal characteristics were also analyzed by X-ray diffraction, FTIR and Raman spectroscopy. We have speculated that the relative habit modification is due to a probably adsorption and inclusions of Al 3+ ions in the prismatic section of the crystal. (paper)

  16. Biosynthetic preparation of selectively deuterated phosphatidylcholine in genetically modified Escherichia coli

    DEFF Research Database (Denmark)

    Maric, Selma; Thygesen, Mikkel Boas; Schiller, Jürgen

    2015-01-01

    Phosphatidylcholine (PC) is a major component of eukaryotic cell membranes and one of the most commonly used phospholipids for reconstitution of membrane proteins into carrier systems such as lipid vesicles, micelles and nanodiscs. Selectively deuterated versions of this lipid have many applicati...

  17. Experimental Observations of Nuclear Activity in Deuterated Materials Subjected to a Low-Energy Photon Beam

    Science.gov (United States)

    Steinetz, Bruce M.; Benyo, Theresa L.; Pines, Vladimir; Pines, Marianna; Forsley, Lawrence P.; Westmeyer, Paul A.; Chait, Arnon; Becks, Michael D.; Martin, Richard E.; Hendricks, Robert C.; hide

    2017-01-01

    Exposure of highly deuterated materials to a low-energy (nom. 2 MeV) photon beam resulted in nuclear activity of both the parent metals of hafnium and erbium and a witness material (molybdenum) mixed with the reactants. Gamma spectral analysis of all deuterated materials, ErD2.8+C36D74+Mo and HfD2+C36D74+Mo, showed that nuclear processes had occurred as shown by unique gamma signatures. For the deuterated erbium specimens, posttest gamma spectra showed evidence of radioisotopes of erbium ((163)Er and (171)Er) and of molybdenum ((99)Mo and (101)Mo) and by beta decay, technetium (99mTc and 101Tc). For the deuterated hafnium specimens, posttest gamma spectra showed evidence of radioisotopes of hafnium (180mHf and 181Hf) and molybdenum ((99)Mo and (101)Mo), and by beta decay, technetium ((99m)Tc and (101)Tc). In contrast, when either the hydrogenated or non-gas-loaded erbium or hafnium materials were exposed to the gamma flux, the gamma spectra revealed no new isotopes. Neutron activation materials showed evidence of thermal and epithermal neutrons. CR-39 solid-state nuclear track detectors showed evidence of fast neutrons with energies between 1.4 and 2.5 MeV and several instances of triple tracks, indicating (is) greater than 10 MeV neutrons. Further study is required to determine the mechanism causing the nuclear activity.

  18. Development of a new neutron mirror made of deuterated Diamond-like carbon

    International Nuclear Information System (INIS)

    Sakurai, Dai; Chiba, Junsei; Shimizu, Hirohiko M; Nishimura, Daiki; Ino, Takashi; Kaneko, Naokatsu; Muto, Suguru; Kakusho, Nobunori; Seki, Yoshichika; Katayama, Ryo; Kitaguchi, Masaaki; Mishima, Kenji; Yamashita, Satoru; Ozeki, Kazuhide; Yoshioka, Tamaki

    2014-01-01

    We developed a new neutron mirror made of Diamond-like carbon (DLC). DLC is a film of amorphous carbon that has characteristics of both diamond and graphite. We produced DLC mirrors by ionization deposition method which is one of the chemical vapor deposition (CVD). Generally, DLC made by CVD contents a few tens of percentages of hydrogen. It decreases the Fermi potential of the DLC coating because hydrogen has negative Fermi potential. In order to increase the Fermi potential of the coating, we deuterated the DLC by using deuterated benzene for the source gas. The characteristics of the deuterated DLC(DDLC) coating was evaluated by RBS, ERDA, x-ray reflectivity, AFM. As a result, DDLC coating has 243 neV due to deuteration, which is the same level as Ni. The RMS of height of the DDLC was 0.6nm so that the DDLC coating can be applied for a focusing mirror or specular transportation of pulsed neutron. Besides, we also develop Hydrogen/Deuterium DLC multiple layer mirror. So far, 4 layers mirror has been succeeded.

  19. Synthesis of multiple deuterated N-n-propyl-norapomorphine N-(d/sub 7/) and derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yigong; Trainor, T.M.; Vouros, Paul; Neumeyer, J.L.

    1988-03-01

    Novapomorphine has been labelled using n-propyl iodide through alkylation of norcodeine followed by a multistep route which also affords the related deuterated analogs N-n-propylnorapocodeine, the prodrug 10,11-methylenedioxy-NPA and 10,11-dimethoxy-NPA.

  20. Chemical synthesis of deuterated folate monoglutamate and in vivo assessment of urinary excretion of deuterated folates in man

    International Nuclear Information System (INIS)

    Gregory, J.F. III; Toth, J.P.

    1988-01-01

    The synthesis and in vivo application of stable-isotopically labeled folic acid was investigated to devise methods suitable for studies of folate metabolism in human subjects. Glutamate-labeled tetradeutero-pteroylglutamic acid (d4-folic acid) was prepared by mixed anhydride coupling of N10-trifluoroacetylpteroic acid and dimethyl L-[3,3,4,4-2H4]glutamic acid, saponification in sodium deuteroxide, and chromatographic purification. Retention of the isotopic label was verified by proton NMR and mass spectrometry of the para-aminobenzoylglutamic acid product of C9-N10 bond cleavage. A method was devised for determination of of isotopic enrichment of urinary d4-folates derived from orally administered d4-folic acid using affinity chromatographic purification, chemical cleavage of the C9-N10 bond, HPLC isolation of the p-[2H4]aminobenzoylglutamate product, followed by negative-ion chemical-ionization gas chromatography/mass spectrometry. Data concerning the urinary excretion of d4-folates derived from an oral dose of d4-folic acid in an adult human are presented

  1. Exploring molecular complexity with ALMA (EMoCA): Deuterated complex organic molecules in Sagittarius B2(N2)

    Science.gov (United States)

    Belloche, A.; Müller, H. S. P.; Garrod, R. T.; Menten, K. M.

    2016-03-01

    Context. Deuteration is a powerful tracer of the history of the cold prestellar phase in star-forming regions. Apart from methanol, little is known about deuterium fractionation of complex organic molecules in the interstellar medium, especially in regions forming high-mass stars. Aims: Our goal is to detect deuterated complex organic molecules toward the high mass star-forming region Sagittarius B2 (Sgr B2) and derive the level of deuteration for these molecules. Methods: We use a complete 3-mm spectral line survey performed with the Atacama Large Millimeter/submillimeter Array (ALMA) to search for deuterated complex organic molecules toward the hot molecular core Sgr B2(N2). We constructed population diagrams and integrated intensity maps to fit rotational temperatures and emission sizes for each molecule. Column densities are derived by modeling the full spectrum under the assumption of local thermodynamic equilibrium. We compare the results to predictions of two astrochemical models that treat the deuteration process. Results: We report the detection of CH2DCN toward Sgr B2(N2) with a deuteration level of 0.4%, and tentative detections of CH2DOH, CH2DCH2CN, the chiral molecule CH3CHDCN, and DC3N with levels in the range 0.05%-0.12%. A stringent deuteration upper limit is obtained for CH3OD (cyanide, the four deuterated species of ethanol, and CH2DOCHO. Ethyl cyanide is less deuterated than methyl cyanide by at least a factor five. The [CH2DOH]/[CH3OD] abundance ratio is higher than 1.8. It may still be consistent with the value obtained in Orion KL. Except for methyl cyanide, the measured deuteration levels lie at least a factor four below the predictions of current astrochemical models. The deuteration levels in Sgr B2(N2) are also lower than in Orion KL by a factor of a few up to a factor ten. Conclusions: The discrepancy between the deuteration levels of Sgr B2(N2) and the predictions of chemical models, and the difference between Sgr B2(N2) and Orion KL may

  2. Molecular differences between deuterated and protonated polystyrenes using reversed-phase high-performance liquid chromatography.

    Science.gov (United States)

    Kayillo, Sindy; Gray, Michael J; Shalliker, R Andrew; Dennis, Gary R

    2005-05-06

    Isotopic substitution is a technique used to highlight particular bonds within a molecule for kinetic, spectroscopic and structure analysis. It is presumed that although some properties such as stretching frequencies will not be the same for substituted analogues, the chemical interactions will not vary appreciably as a function of labelling. Reversed-phase liquid chromatography has been used to demonstrate that there are significant differences between the chromatographic behaviour of a sequence of deuterated and protonated oligomeric polystyrenes. Two-dimensional reversed-phase liquid chromatography was used to show that even the diasteromers of the oligomers (n = 5) have retention mechanisms that are dependent on the subtle changes to the molecular conformation and electronic structure, which are a consequence of deuteration.

  3. TEM and EELS study of deuterated carbon: application to the fuel retention in tokamaks

    International Nuclear Information System (INIS)

    Bernier, N.

    2007-12-01

    We developed a methodology, based on the combination of TEM and EELS techniques, for a structural and chemical characterization, at a high spatial resolution, of a wide range of carbon materials. We i) optimized, in the framework of theoretical models, the sp2 fraction quantification from pure carbons by EELS ii) transferred this quantification to deuterated amorphous carbon layers iii) showed, from graphitized carbons, how the TEM-EELS combination allows to detect low concentrations of implanted D. Due to the accomplishment of these developments, we applied our approach to the study of D retention in composites C/C, which are the plasma-facing materials in TS. We showed that specific localized retention sites correspond to relatively large (∼ 3 mm.) cracks between fibres and matrix; such cracks offer a simple and direct path for deuterated amorphous carbon. The particle balance performed in TS is discussed in the light of this trapping mechanism. (author)

  4. Electron spin resonance and its implication on the maximum nuclear polarization of deuterated solid target materials

    International Nuclear Information System (INIS)

    Heckmann, J.; Meyer, W.; Radtke, E.; Reicherz, G.; Goertz, S.

    2006-01-01

    ESR spectroscopy is an important tool in polarized solid target material research, since it allows us to study the paramagnetic centers, which are used for the dynamic nuclear polarization (DNP). The polarization behavior of the different target materials is strongly affected by the properties of these centers, which are added to the diamagnetic materials by chemical doping or irradiation. In particular, the ESR linewidth of the paramagnetic centers is a very important parameter, especially concerning the deuterated target materials. In this paper, the results of the first precise ESR measurements of the deuterated target materials at a DNP-relevant magnetic field of 2.5 T are presented. Moreover, these results allowed us to experimentally study the correlation between ESR linewidth and maximum deuteron polarization, as given by the spin-temperature theory

  5. Solid polystyrene and deuterated polystyrene light output response to fast neutrons

    International Nuclear Information System (INIS)

    Simpson, R.; Danly, C.; Merrill, F. E.; Volegov, P. L.; Wilde, C.; Glebov, V. Yu.; Hurlbut, C.

    2016-01-01

    The Neutron Imaging System has proven to be an important diagnostic in studying DT implosion characteristics at the National Ignition Facility. The current system depends on a polystyrene scintillating fiber array, which detects fusion neutrons born in the DT hotspot as well as neutrons that have scattered to lower energies in the surrounding cold fuel. Increasing neutron yields at NIF, as well as a desire to resolve three-dimensional information about the fuel assembly, have provided the impetus to build and install two additional next-generation neutron imaging systems. We are currently investigating a novel neutron imaging system that will utilize a deuterated polystyrene (CD) fiber array instead of standard hydrogen-based polystyrene (CH). Studies of deuterated xylene or deuterated benzene liquid scintillator show an improvement in imaging resolution by a factor of two [L. Disdier et al., Rev. Sci. Instrum. 75, 2134 (2004)], but also a reduction in light output [V. Bildstein et al., Nucl. Instrum. Methods Phys. Res., Sect. A 729, 188 (2013); M. I. Ojaruega, Ph.D. thesis, University of Michigan, 2009; M. T. Febbraro, Ph.D. thesis, University of Michigan, 2014] as compared to standard plastic. Tests of the relative light output of deuterated polystyrene and standard polystyrene were completed using 14 MeV fusion neutrons generated through implosions of deuterium-tritium filled capsules at the OMEGA laser facility. In addition, we collected data of the relative response of these two scintillators to a wide energy range of neutrons (1-800 MeV) at the Weapons Neutrons Research Facility. Results of these measurements are presented.

  6. Solid polystyrene and deuterated polystyrene light output response to fast neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, R., E-mail: raspberry@lanl.gov; Danly, C.; Merrill, F. E.; Volegov, P. L.; Wilde, C. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Glebov, V. Yu. [Laboratory for Laser Energetics, Rochester, New York 14623 (United States); Hurlbut, C. [Eljen Technology, Sweetwater, Texas 79556 (United States)

    2016-04-15

    The Neutron Imaging System has proven to be an important diagnostic in studying DT implosion characteristics at the National Ignition Facility. The current system depends on a polystyrene scintillating fiber array, which detects fusion neutrons born in the DT hotspot as well as neutrons that have scattered to lower energies in the surrounding cold fuel. Increasing neutron yields at NIF, as well as a desire to resolve three-dimensional information about the fuel assembly, have provided the impetus to build and install two additional next-generation neutron imaging systems. We are currently investigating a novel neutron imaging system that will utilize a deuterated polystyrene (CD) fiber array instead of standard hydrogen-based polystyrene (CH). Studies of deuterated xylene or deuterated benzene liquid scintillator show an improvement in imaging resolution by a factor of two [L. Disdier et al., Rev. Sci. Instrum. 75, 2134 (2004)], but also a reduction in light output [V. Bildstein et al., Nucl. Instrum. Methods Phys. Res., Sect. A 729, 188 (2013); M. I. Ojaruega, Ph.D. thesis, University of Michigan, 2009; M. T. Febbraro, Ph.D. thesis, University of Michigan, 2014] as compared to standard plastic. Tests of the relative light output of deuterated polystyrene and standard polystyrene were completed using 14 MeV fusion neutrons generated through implosions of deuterium-tritium filled capsules at the OMEGA laser facility. In addition, we collected data of the relative response of these two scintillators to a wide energy range of neutrons (1-800 MeV) at the Weapons Neutrons Research Facility. Results of these measurements are presented.

  7. Upper Bound for Neutron Emission from Sonoluminescing Bubbles in Deuterated Acetone

    International Nuclear Information System (INIS)

    Camara, C. G.; Putterman, S. J.; Hopkins, S. D.; Suslick, K. S.

    2007-01-01

    An experimental search for nuclear fusion inside imploding bubbles of degassed deuterated acetone at 0 degree sign C driven by a 15 atm sound field and seeded with a neutron generator reveals an upper bound that is a factor of 10 000 less than the signal reported by Taleyarkhan et al. The strength of our upper bound is limited by the weakness of sonoluminescence, which we ascribe to the relatively high vapor pressure of acetone

  8. Some Routes in Forming C3Hn+ Ions and Deuterated Variants under Interstellar Conditions

    International Nuclear Information System (INIS)

    Savic, Igor; Gerlich, Dieter

    2006-01-01

    Laboratory experiments on hydrogenation and deuteration of C 3 + , C3H+ and C 3 H 2 + in collisions with H2 and HD have been performed from room temperature down to 15 K using a 22-pole ion-trap. At room temperature C 3 + reacts slowly with H2 but the reactivity increases with decreasing temperature. It has been shown that the association reaction C 3 + + H 2 → C 3 H 2 + + hν can compete with the exothermic reaction C 3 + + H 2 → C 3 H + + H. In collisions of C 3 + with HD, formation of C3D+ is slightly favored over C3H+ formation. A pronounced competition between various channels has been detected for deuterated variants of the C3H+ + H2 system. Most surprising is that formation of C3HD+ is over one hundred times faster then formation of C 3 H 2 + in collisions of C3H+ and HD. An tentative explanation is that the H-HD exchange takes place via an open-chain H2CCCH+ intermediate. Reactions of C 3 H 2 + and C 3 H 3 + with H2 are very slow. The formation of C3H2D+ or C 3 HD 2 + and finally C3HD via dissociative recombination has been discussed. The reaction C 3 H 3 + + HD → C 3 H 2 D + + H 2 can be ignored in astrochemical models since the reaction rate at 15 K is very small; however, quite efficient routes have been found starting from C 3 + and proceeding via deuterated C3H+ to C 3 H 2 + and C 3 H 3 + . The new reaction rate coefficients are recommended to be included in astrophysical databases. Nonetheless it is still unclear how to explain the large abundance of C3H2 and larger hydrocarbons and their deuterated variants observed in cold interstellar clouds

  9. A Deuteration Survey of Starless Clumps in GemOB1 and the First Quadrant

    Science.gov (United States)

    Henrici, Andrew; Shirley, Yancy L.; Svoboda, Brian

    2018-01-01

    One very strong chemical process in star-forming regions is the fractionation of deuterium in molecules, which results in an increase in the deuterium ratio many orders of magnitude over the ISM [D]/[H] ratio and provides a chemical probe of cold, dense regions. Recent maps of dust continuum emission at (sub)millimeter wavelengths have identified tens of thousands of dense clumps of gas and dust. By comparing these regions to infrared and radio surveys, we have identified starless clump candidates which have no evidence for embedded star formation. These objects represent the earliest phase of star formation throughout the Milky Way. One benefit of the Milky Way surveys is that it is also possible to study the chemistry of entire core and clump populations within a single cloud. We used the 10m Heinrich Hertz Submillimeter Telescope to survey starless clump candidates in the First Quadrant identified from the Bolocam Galactic Plane Survey 1.1 mm continuum in the deuterated molecular transitions of DCO+ 3-2 and N2D+ 3-2. We also survey the entire clump population of the Gemini OB1 molecular cloud. In both surveys, we compared detection statistics and compare deuteration fraction to physical properties of the clumps and their evolutionary stage. High resolution ALMA observations of 9 starless clump candidates of the same lines are used to analyze how the cold deuterated gas is spatially distributed in these clumps.

  10. Labelling by deuteration and nitroxide radicals of mono-, oligo- and polysaccharides (cellulose and amylose)

    Energy Technology Data Exchange (ETDEWEB)

    Odier, L

    1975-01-01

    The application of NMR and deuteration labelling to the investigation of polysaccharides has led to considerable progress in recent years in the knowledge of these compounds. Although far more recent, the introduction of spin labelling techniques in the investigation of polymers, has given rise to interesting EPR studies of synthetic and natural macromolecules, but nothing appears to have been accomplished in the area of spin labelling of polysaccharides. This work was aimed at applying these two techniques to the study of glucose derivatives and of some of its oligomers (low molecular weight polymers): cellobiose, maltose and cyclodextrins; and its polymers: cellulose and amylose. Irrespective of the technique employed, the complexity of the polymers and problems connected with handling them always require the same procedure: an initial study of a model compound generally prepared from the monomer or an oligomer (dimer), followed by the oligomers, and finally the polymer. Part 1 is devoted to the deuteration labelling of mono- and oligosaccharides. Part 2 concerns spin labelling of cellulose acetate. In part 3, an attempt is made to apply the spin labelling technique to the determination of conformations of two disaccharides of different glycosidic configurations: cellobiose and maltose. Part 4 is devoted to spin and deuteration labelling of ..cap alpha.. and ..beta.. cyclodextrins.

  11. Stereospecific assignments of glycine in proteins by stereospecific deuteration and {sup 15}N labeling

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A.P.; Curley, R.W. Jr.; Panigot, M.J.; Fesik, S.W. [Ohio State Univ., Columbus, OH (United States)

    1994-12-01

    Stereospecific assignments are important for accurately determining the three-dimensional structures of proteins through the use of multidimensional NMR techniques. It is especially important to stereospecifically assign the glycine {alpha}-protons in proteins because of the potential for different backbone conformations of this residue. These stereospecific assignments are critical for interpreting the {sup 3}J{sub NH,{alpha}H} coupling constants and NOEs involving the glycine {alpha}-protons that determine the conformation of this part of the protein. However, it is often difficult to unambiguously obtain the stereospecific assignments for glycine residues by using only NOE data. In this poster, we present a method for unambiguous, stereospecific assignment of the {alpha}-protons of glycine residues. This method involves synthesis of stereo-specifically deuterated and {sup 15}N-labeled Gly using a slightly modified procedure originally described by Woodard and coworkers for the stereoselective deuteration of glycine. The stereospecifically deuterated and {sup 15}N-labeled Gy has been incorporated into recombinant proteins expressed in both bacterial systems (FKBP) and mammalian cells (u-PA). Two- and three-dimensional isotope-filtered and isotope-edited NMR experiments were used to obtain the stereospecific assignments of the glycine {alpha}-protons for these proteins.

  12. Analysis of Mammalian Cell Proliferation and Macromolecule Synthesis Using Deuterated Water and Gas Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Victoria C. Foletta

    2016-10-01

    Full Text Available Deuterated water (2H2O, a stable isotopic tracer, provides a convenient and reliable way to label multiple cellular biomass components (macromolecules, thus permitting the calculation of their synthesis rates. Here, we have combined 2H2O labelling, GC-MS analysis and a novel cell fractionation method to extract multiple biomass components (DNA, protein and lipids from the one biological sample, thus permitting the simultaneous measurement of DNA (cell proliferation, protein and lipid synthesis rates. We have used this approach to characterize the turnover rates and metabolism of a panel of mammalian cells in vitro (muscle C2C12 and colon cancer cell lines. Our data show that in actively-proliferating cells, biomass synthesis rates are strongly linked to the rate of cell division. Furthermore, in both proliferating and non-proliferating cells, it is the lipid pool that undergoes the most rapid turnover when compared to DNA and protein. Finally, our data in human colon cancer cell lines reveal a marked heterogeneity in the reliance on the de novo lipogenic pathway, with the cells being dependent on both ‘self-made’ and exogenously-derived fatty acid.

  13. Discriminative stimulus properties of beta-phenylethylamine, deuterated beta-phenylethylamine, phenylethanolamine and some metabolites of phenylethylamine in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Reid, D.; Goudie, A.J.

    1986-06-01

    The discriminative stimulus (cue) properties of phenylethylamine (PEA) were analysed in rodents in a conventional two lever FR10 operant drug discrimination task. Rats trained to discriminate phenylethylamine at 30 mg/kg showed complete dose-related generalization to PEA and to two potential PEA metabolites: phenylethanolamine (PEOH) and N-Methyl PEA (NMPEA). Only partial (50%) generalization was seen with N-Methylphenylethanolamine (NMPEOH), another potential PEA metabolite. The specificity of PEA's action as a discriminative stimulus was demonstrated by the finding that fenfluramine, a substituted phenylethylamine, failed to generalize to PEA even at high doses with marked behavioural effects which are known to have discriminative stimulus properties themselves. These data suggest that NMPEA and PEOH may be functionally important active metabolites of PEA, particularly if the major pathway of PEA metabolism to phenylacetic acid under the influence of MAO Type B is for any reason impaired. A long acting deuterium substituted form of PEA (alpha, alpha, d2 PEA), which is resistant to metabolism by MAO, produced complete dose-related generalization to the PEA cue but was more potent than PEA, due presumably to its resistance to metabolism by MAO. Deuterated PEA may therefore be a useful agent to use in future studies of the PEA cue, because the discriminability of PEA itself appears to be low due to its very rapid metabolism in vivo.

  14. Demonstration of In situ Anaerobic Transformation of Toluene and Xylene Using Single-Well Push-Pull Tests and Deuterated BTEX Surrogates

    Science.gov (United States)

    Field, J. A.; Reusser, D. E.; Beller, H. R.; Istok, J. D.

    2001-12-01

    Obtaining unambiguous evidence of in-situ transformation of benzene, toluene, ethylbenzene and xylene (BTEX) in the subsurface is a difficult task. Recently, benzylsuccinic acid and its methyl analogues were shown to be unequivocal degradation products of anaerobic toluene and xylene biodegradation. Conducting tracer tests at BTEX-contaminated field sites is problematic because background contaminant concentrations potentially interfere with the interpretation of field test data. To avoid the time and cost associated with removing background contaminants, alternative approaches are needed. Deuterated analogs of toluene and xylene are well-suited for use in field tracer tests because they are inexpensive and can be distinguished analytically from background toluene and xylene. In this study, single-well push-pull tests, in which deuterated toluene and xylene were injected, were performed to assess the in-situ anaerobic biotransformation of toluene and xylene in BTEX-contaminated wells. A total of 4 single-well push-pull tests were conducted at BTEX-contaminated field sites near Portland, OR and Kansas City, KS. Test solutions consisting of 100 mg/L bromide, 250 mg/L nitrate, 0.4 to 2.5 mg/L toluene-d8, and 0.4 to 1.0 mg/L o-xylene-d10.were injected at a rate of 0.5 - 2 L/min. During the extraction phase, samples were taken daily to biweekly for up to 30 days. Samples for volatile organic analytes were collected in 40-mL volatile organic analysis (VOA) vials without headspace. Samples for BSA and methyl-BSA were collected in 1 L glass bottles and preserved with 5% (w/w) formalin. Samples were shipped on ice and stored at 4 C until analysis. Unambiguous evidence of toluene and xylene biotransformation was obtained with the in-situ formation of BSA and methyl-BSA. The concentrations of BSA ranged from below the detection limit (0.2 ug/L) to 1.5 ug/L. The concentrations of methyl-BSA ranged from below detection to the quantitation limit (0.7 ug/L). The highest BSA

  15. Omega-6 fatty acid biomarkers and incident type 2 diabetes

    NARCIS (Netherlands)

    Wu, Jason H.Y.; Marklund, Matti; Imamura, Fumiaki; Tintle, Nathan; Ardisson Korat, Andres V.; Goede, de Janette; Zhou, Xia; Yang, Wei Sin; Oliveira Otto, de Marcia C.; Kröger, Janine; Qureshi, Waqas; Virtanen, Jyrki K.; Bassett, Julie K.; Frazier-Wood, Alexis C.; Lankinen, Maria; Murphy, Rachel A.; Rajaobelina, Kalina; Gobbo, Del Liana C.; Forouhi, Nita G.; Luben, Robert; Khaw, Kay Tee; Wareham, Nick; Kalsbeek, Anya; Veenstra, Jenna; Luo, Juhua; Hu, Frank B.; Lin, Hung Ju; Siscovick, David S.; Boeing, Heiner; Chen, Tzu An; Steffen, Brian; Steffen, Lyn M.; Hodge, Allison; Eriksdottir, Gudny; Smith, Albert V.; Gudnason, Vilmunder; Harris, Tamara B.; Brouwer, Ingeborg A.; Berr, Claudine; Helmer, Catherine; Samieri, Cecilia; Laakso, Markku; Tsai, Michael Y.; Giles, Graham G.; Nurmi, Tarja; Wagenknecht, Lynne; Schulze, Matthias B.; Lemaitre, Rozenn N.; Chien, Kuo Liong; Soedamah-Muthu, Sabita S.; Geleijnse, Johanna M.; Sun, Qi; Harris, William S.; Lind, Lars; Ärnlöv, Johan; Riserus, Ulf; Micha, Renata; Mozaffarian, Dariush

    2017-01-01

    Background: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with

  16. Multiple biological effects of inhibitors of arachidonic acid metabolism on human keratinocytes

    Czech Academy of Sciences Publication Activity Database

    Pacherník, Jiří; Hampl, Aleš; Souček, Karel; Kovaříková, Martina; Andrysík, Zdeněk; Hofmanová, Jiřina; Kozubík, Alois

    2002-01-01

    Roč. 293, č. 12 (2002), s. 626-633 ISSN 0340-3696 R&D Projects: GA ČR GA524/99/0694; GA AV ČR IBS5004009; GA ČR GA524/98/0190 Institutional research plan: CEZ:AV0Z5004920 Keywords : lipoxygenase * keratinocytes * cell cycle Subject RIV: BO - Biophysics Impact factor: 1.452, year: 2002

  17. The Arachidonic Acid Pathway: a potential application in the diagnosis and prognosis of prostate cancer

    NARCIS (Netherlands)

    G.A. Rodríguez-Blanco (Giovanny)

    2017-01-01

    markdownabstractProstate cancer (PCa) is the most common cancer in men, and in 2012 more than 400,000 cases were diagnosed in Europe. Although the introduction of the PSA test improved the management of the disease, its low specificity has led to overdiagnosis and unnecessary treatments for men

  18. Relationships between Arachidonic Acid, Uterine Activity and Metabolic Regulation of Placental Lactogen Secretion.

    Science.gov (United States)

    1982-08-01

    and R.E. Fellows. 1976. Circulating placental lactogen levels in dairy and beef cattle . Endocrinology 99:1273. Brinsmead, M.W., B.J. Bancroft, G.D... castrate sows. Am. J. Physiol. 217:1431. Felber, J.P., N. Zaragza, M. Benu7zi-Badoni and A.R. Genazzani. 1972. The double effect of HCS and pregnancy

  19. LysoPC and PAF Trigger Arachidonic Acid Release by Divergent Signaling Mechanisms in Monocytes

    Directory of Open Access Journals (Sweden)

    Janne Oestvang

    2011-01-01

    Full Text Available Oxidized low-density lipoproteins (LDLs play an important role during the development of atherosclerosis characterized by intimal inflammation and macrophage accumulation. A key component of LDL is lysophosphatidylcholine (lysoPC. LysoPC is a strong proinflammatory mediator, and its mechanism is uncertain, but it has been suggested to be mediated via the platelet activating factor (PAF receptor. Here, we report that PAF triggers a pertussis toxin- (PTX- sensitive intracellular signaling pathway leading to sequential activation of sPLA2, PLD, cPLA2, and AA release in human-derived monocytes. In contrast, lysoPC initiates two signaling pathways, one sequentially activating PLD and cPLA2, and a second parallel PTX-sensitive pathway activating cPLA2 with concomitant activation of sPLA2, all leading to AA release. In conclusion, lysoPC and PAF stimulate AA release by divergent pathways suggesting involvement of independent receptors. Elucidation of monocyte lysoPC-specific signaling mechanisms will aid in the development of novel strategies for atherosclerosis prevention, diagnosis, and therapy.

  20. Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation

    Czech Academy of Sciences Publication Activity Database

    Kubala, Lukáš; Schmelzer, K.R.; Klinke, A.; Kolářová, Hana; Baldus, S.; Hammock, B.D.; Eiserich, J.P.

    2010-01-01

    Roč. 48, č. 10 (2010), s. 1311-1320 ISSN 0891-5849 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : myeloperoxidase * sepsis * free radicals Subject RIV: BO - Biophysics Impact factor: 5.707, year: 2010

  1. Effects of chronic ethanol ingestion on arachidonic acid (AA) metabolism in rat macrophages

    International Nuclear Information System (INIS)

    Chanmugam, P.; Boudreau, M.; Hymel, G.; Jeffers, G.; Hwang, D.H.

    1986-01-01

    In a previous report, preincubation of rat platelets with ethanol resulted in dose dependent inhibition of AA metabolites whereas chronic ingestion of ethanol enhanced the synthesis of AA metabolites. Thus, the authors studied whether chronic ethanol ingestion also affects AA metabolism in MACS. Two groups of rats (10 each) were fed DeCarli/Lieber liquid diet containing 36 caloric % ethanol for 3 weeks. The control group was pair fed the same diet made isocaloric with dextrin-maltose. Resident MACS were collected by peritoneal lavage. The monolayers of MACS were incubated for 20 min with calcium ionophore (5μg/ml), and the incubation stopped with 4 vol. of ethanol. PGE 2 , LTB 4 and 5-HETE were assayed by radioimmunoassay. The results indicated that chronic ethanol ingestion did not affect the capacity of MACS to synthesize AA metabolites. There was also no difference in the levels of AA metabolites in heart and lung homogenates between the two groups

  2. Arachidonic Acid Derivatives in the Exhaled Breath Condensate in Pneumoconioses and their Correlation with Individual Factors

    Czech Academy of Sciences Publication Activity Database

    Pelclová, D.; Fenclová, Z.; Kačer, J.; Navrátil, Tomáš; Kuzma, Marek; Lebedová, J.; Klusáčková, P.

    2007-01-01

    Roč. 101, s (2007), s144-s146 E-ISSN 1213-7103. [Mezioborová česko-slovenská toxikologická konference /12./. Praha, 11.06.2007-13.06.2007] R&D Projects: GA MZd NR9338 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z50200510 Keywords : silica * asbestos * leukotrienes Subject RIV: CF - Physical ; Theoretical Chemistry

  3. Deuteration of ammonia in the starless core Ophiuchus/H-MM1

    Science.gov (United States)

    Harju, J.; Daniel, F.; Sipilä, O.; Caselli, P.; Pineda, J. E.; Friesen, R. K.; Punanova, A.; Güsten, R.; Wiesenfeld, L.; Myers, P. C.; Faure, A.; Hily-Blant, P.; Rist, C.; Rosolowsky, E.; Schlemmer, S.; Shirley, Y. L.

    2017-04-01

    Context. Ammonia and its deuterated isotopologues probe physical conditions in dense molecular cloud cores. The time-dependence of deuterium fractionation and the relative abundances of different nuclear spin modifications are supposed to provide a means of determining the evolutionary stages of these objects. Aims: We aim to test the current understanding of spin-state chemistry of deuterated species by determining the abundances and spin ratios of NH2D, NHD2 and ND3 in a quiescent, dense cloud. Methods: Spectral lines of NH3, NH2D, NHD2, ND3 and N2D+ were observed towards a dense, starless core in Ophiuchus with the APEX, GBT and IRAM 30-m telescopes. The observations were interpreted using a gas-grain chemistry model combined with radiative transfer calculations. The chemistry model distinguishes between the different nuclear spin states of light hydrogen molecules, ammonia and their deuterated forms. Different desorption schemes can be considered. Results: High deuterium fractionation ratios with NH2D/NH3 0.4, NHD2/ NH2D 0.2 and ND3/ NHD2 0.06 are found in the core. The observed ortho/para ratios of NH2D and NHD2 are close to the corresponding nuclear spin statistical weights. The chemistry model can approximately reproduce the observed abundances, but consistently predicts too low ortho/para-NH2D, and too large ortho/para-NHD2 ratios. The longevity of N2H+ and NH3 in dense gas, which is prerequisite to their strong deuteration, can be attributed to the chemical inertia of N2 on grain surfaces. Conclusions: The discrepancies between the chemistry model and the observations are likely to be caused by the fact that the model assumes complete scrambling in principal gas-phase deuteration reactions of ammonia, which means that all the nuclei are mixed in reactive collisions. If, instead, these reactions occur through proton hop/hydrogen abstraction processes, statistical spin ratios are to be expected. The present results suggest that while the deuteration of

  4. Neutron diffraction study of crystal structures of deuterated glycinium phosphite in paraelectric and ferroelectric phases

    International Nuclear Information System (INIS)

    Machida, Mitsuo; Uchida, Hiroyuki; Ishibashi, Toku; Taniguchi, Hiroki; Komukae, Masaru; Osaka, Toshio; Koyano, Nobumitsu

    2004-01-01

    Crystal structure of deuterated glycinium phosphite was studied in the paraelectric (P) phase at 348 K and in the ferroelectric (F) phase at 223 K by means of the single crystal neutron diffraction. Deuteration rate is estimated to be 0.939 by the least-squares refinement. In the P phase, quasi-one-dimensional hydrogen bond chains are built by mutually linking the DPO 3 2- anions through two different types of hydrogen bonds with the bond angles of 179.2 and 171.6deg. Two independent deuterons within the hydrogen bonds forming the chains are disordered over two sites separated by 0.545 and 0.539A. In the F phase, they order at a position nearly equal to one of two sites related by the disorder in the P phase. With the ordering of the deuterons, the P-O bonds with covalently bonded deuteron elongate, and those without covalently bonded deuteron reduce their lengths to some extend from the values determined in the P phase. Two oxygens involved in the hydrogen bond with the bond angle 179.2deg exhibits especially large displacements in the F phase. This suggests strongly an importance of this hydrogen bond in the polarization appearance and in the ferroelectric transition. Comparison with results of non-deuterated salt indicates that only the hydrogen bonds forming the chains show significant isotope shift. In particular, the hydrogen bond with the bond angle 179.2deg exhibits the most pronounced shift on the angle parameter defined by the angle between the line connecting two sites of disordered proton or deuteron and the line connecting two oxygens involved in the hydrogen bond. (author)

  5. Widespread deuteration across the IRDC G035.39-00.33

    Science.gov (United States)

    Barnes, A. T.; Kong, S.; Tan, J. C.; Henshaw, J. D.; Caselli, P.; Jiménez-Serra, I.; Fontani, F.

    2016-05-01

    Infrared Dark Clouds (IRDCs) are cold, dense regions that are usually found within Giant Molecular Clouds. Ongoing star formation within IRDCs is typically still deeply embedded within the surrounding molecular gas. Characterizing the properties of relatively quiescent IRDCs may therefore help us to understand the earliest phases of the star formation process. Studies of local molecular clouds have revealed that deuterated species are enhanced in the earliest phases of star formation. In this paper, we test this towards IRDC G035.39-00.33. We present an 80 arcsec by 140 arcsec map of the J = 2 → 1 transition of N2D+, obtained with the Institut de Radioastronomie Millimétrique 30 m telescope telescope. We find that N2D+ is widespread throughout G035.39-00.33. Complementary observations of N2H+ (1 - 0) are used to estimate the deuterium fraction, D_frac^N_2H^+ ≡ N(N2D+)/N(N2H+). We report a mean D_frac^N_2H^+ = 0.04 ± 0.01, with a maximum of D_frac^N_2H^+ = 0.09 ± 0.02. The mean deuterium fraction is ˜3 orders of magnitude greater than the interstellar [D]/[H] ratio. High angular resolution observations are required to exclude beam dilution effects of compact deuterated cores. Using chemical modelling, we find that the average observed values of D_frac^N_2H^+are in agreement with an equilibrium deuterium fraction, given the general properties of the cloud. This implies that the IRDC is at least ˜3 Myr old, which is ˜8 times longer than the mean free-fall time of the observed deuterated region.

  6. Fibronectin distribution in the extracellular matrix in the cells grown in deuterated media

    International Nuclear Information System (INIS)

    Buzgariu, Wanda; Caloianu, Maria; Moldovan, Lucia; Stefanescu, I.; Titescu, Gh.

    2003-01-01

    The aim of this work is the study of the influence of deuterated water upon the synthesis and organization of fibronectin (FN) in extracellular matrices. Changes were evidenced at the level of extracellular matrix in case of embryo fibroblast cultivation in media with different concentrations of heavy water (20%, 40% and 65%). FN was identified in the extracellular matrix by means of indirect immunocytochemical technique, using a secondary antibody coupled with peroxydase. In the presence of heavy water in culture medium, the arrangement and localization of cellular FN showed changes depending on the exposure time, D 2 O concentration in the medium and the FN polymerization step in the extra cellular matrix in correlation with the culture stage of the monolayer. The heavy water determined a strong reduction of the FN amount released by the cells. This reduction was most evident in the 65% D 2 O medium following a 5 day exposure. The FN distribution after 2 day exposure in an early stage with regards to the FN network formation in a the deuterated medium presented a FN pericellular distribution arranged in aggregates. The heavy water can act upon formation of FN fibrils immediately due to solvent role in the FN polymerization process but also indirectly through metabolic processes and so upon the protein synthesis and FN cellular secretion.The FN network arrangement in the cells cultivated in deuterated media as aggregates might be the effect of solvent role played by D 2 O while the quantitative reduction of FN results from perturbation of protein synthesis as well from biochemical synthesis reactions

  7. D/H isotope effects in π-complexes of deuterated hexamethylbenzenes with the nitrosonium cation

    International Nuclear Information System (INIS)

    Borodkin, G.I.; Elanov, I.R.; Shakirov, M.M.; Shubin, V.G.

    1993-01-01

    The isotope effects of deuterium, manifested in the 13 C NMR spectra of complexes of deuterated hexamethylbenzenes C 6 (CD 3 ) n ·(CH 3 ) 6-n with the nitrosonium cation, have been studied. The small values observed for the isotopic perturbation are evidence of π-bonding of the NO + group to the hexamethylbenzene molecule. The applicability of an additive scheme of calculation of isotope effects for the ring carbon atoms of the complexes, based on the increment of replacement of the CH 3 group by CD 3 in hexamethylbenzene, has been demonstrated

  8. A convenient synthesis of deuterated leukotriene A sub 4 methyl ester

    Energy Technology Data Exchange (ETDEWEB)

    Bestmann, H.J.; Roeder, T. (Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. fuer Organische Chemie); Meese, C.O. (Fischer-Bosch-Inst. fuer Klinische Pharmakologie, Stuttgart (Germany, F.R.))

    1989-11-01

    2,2,3,3-({sup 2}H{sub 4})-1-Iodopentane was prepared in four steps from propargyl alcohol and used in the C-alkylation of the THP-protected 3-butyne-1-ol. Subsequent protective group removal, semi-deuteration of the acetylenic alcohol and further transformation by known methods afforded the labelled key reagent 3,4,6,6,7,7-({sup 2}H{sub 6})-(Z)-(3-nonen-1-yl)triphenylphosphonium iodide. Wittig olefination of epoxy dienal with the ylide generated from the latter completed the convenient synthesis of hexadeuterated leukotriene A{sub 4} methyl ester. (author).

  9. Effects of deuterated water upon specific activity of some marker enzymes for cytosol and plasmatic membrane

    International Nuclear Information System (INIS)

    Buzgariu, Wanda; Coroiu, Viorica; Moldovan, Lucia; Titescu, G.; Stefanescu, I.

    2004-01-01

    Recently, numerous studies were devoted to the effects of an increased environmental deuterium concentration on physiological characteristics of various biological systems, from monocellular organisms up to mammals. Within these preoccupations the experiments on enzyme activity and parameters are of special interest since they throw light upon the mechanisms in metabolic biochemical reactions (glycolysis, photosynthesis, transport across membranes, etc). The present work concerns the effects of heavy water upon the activity of some enzymes (dehydrogenase-LDH lactate and 5' nucleotidase) implied in different metabolic pathways, serving as functional indicators for some cellular compartments such as the cytosols and cellular membranes. Enzyme activity was determined by growing for 6 days the cells (Hep 2, CHO, fibroblasts) in deuterated culture media at different concentration levels (20%, 40%, 65% si 90%), as well as in a reaction medium deuterated at 99.96%. In case of the first experimental run the LDH activity was monitored for the three cellular lines (Hep 2, CHO, fibroblasts) for different time intervals (1 d, 3 d and 6 d). After the first 24 h of cells' exposure the activity values were similar regardless of the heavy water concentration in the medium. Exposing the cells for longer time (6 days) led to modifications of LDH activity. In contrast to the case of media with relatively moderate D 2 O content, cell growing in conditions of intense deuteration 65% and 90 % D 2 O) led to an increase of cytosolic enzyme activity of about 50%. In case of 5' nucleotidase after 6 days of cell cultivation in deuteration conditions the activity decreased to 50% and 70% from the value corresponding to normal conditions for cell growth. This diminution of the activity was characteristic for the media with 65% and 90% D 2 O. In the second experimental run the activities of dehydrogenase lactate and 5' nucleotidase from the cellular homogenate obtained from cells grown in

  10. Partially-deuterated samples of HET-s(218–289) fibrils: assignment and deuterium isotope effect

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Albert A.; Ravotti, Francesco; Testori, Emilie; Cadalbert, Riccardo; Ernst, Matthias, E-mail: maer@ethz.ch [ETH Zürich, Physical Chemistry (Switzerland); Böckmann, Anja, E-mail: a.bockmann@ibcp.fr [Institut de Biologie et Chimie des Protéines, Bases Moléculaires et Structurales des Systèmes Infectieux, Labex Ecofect, UMR 5086 CNRS, Université de Lyon (France); Meier, Beat H., E-mail: beme@ethz.ch [ETH Zürich, Physical Chemistry (Switzerland)

    2017-02-15

    Fast magic-angle spinning and partial sample deuteration allows direct detection of {sup 1}H in solid-state NMR, yielding significant gains in mass sensitivity. In order to further analyze the spectra, {sup 1}H detection requires assignment of the {sup 1}H resonances. In this work, resonance assignments of backbone H{sup N} and Hα are presented for HET-s(218–289) fibrils, based on the existing assignment of Cα, Cβ, C’, and N resonances. The samples used are partially deuterated for higher spectral resolution, and the shifts in resonance frequencies of Cα and Cβ due to the deuterium isotope effect are investigated. It is shown that the deuterium isotope effect can be estimated and used for assigning resonances of deuterated samples in solid-state NMR, based on known resonances of the protonated protein.

  11. Isotopic fractionation of fentanyl and its deuterated analogues by capillary gas chromatography

    International Nuclear Information System (INIS)

    Sera, Shoji; Goromaru, Tsuyoshi

    1997-01-01

    Isotopic fractionation of fentanyl (FT) and its deuterated analogues by gas chromatography using capillary columns (CBP1 and CBP5) has been investigated. Seven kinds of analogues were labeled with 5 to 19 deuterium atoms at the anilino, propionyl and/or phenylethyl group of FT. The retention times of deuterated FT in CBP1 and CBP5 columns are inversely proportional to the number of labeled deuterium atoms in the molecule. The difference in free enegy changes (ΔΔG) had a linear relationship with the number of labeled deuterium atoms, except for labeling at anilino and phenylethyl group. The contribution of a deuterium atom to the ΔΔG value was estimated to be 1.13 cal/mol in CBP1 and 1.40 cal/mol in CBP5, respectively. While, its contribution in the propiony group was 2.84 cal/mol in CBP1 and 2.48 cal/mol in CBP5, respectively. An important factor in separation by GC may differences in interactions between the stationary phase of the column with the three dimensional protrusive moiety in the molecule. (author)

  12. Isotopic fractionation of fentanyl and its deuterated analogues by capillary gas chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Sera, Shoji; Goromaru, Tsuyoshi [Fukuyama Univ., Hiroshima (Japan)

    1997-12-01

    Isotopic fractionation of fentanyl (FT) and its deuterated analogues by gas chromatography using capillary columns (CBP1 and CBP5) has been investigated. Seven kinds of analogues were labeled with 5 to 19 deuterium atoms at the anilino, propionyl and/or phenylethyl group of FT. The retention times of deuterated FT in CBP1 and CBP5 columns are inversely proportional to the number of labeled deuterium atoms in the molecule. The difference in free enegy changes ({Delta}{Delta}G) had a linear relationship with the number of labeled deuterium atoms, except for labeling at anilino and phenylethyl group. The contribution of a deuterium atom to the {Delta}{Delta}G value was estimated to be 1.13 cal/mol in CBP1 and 1.40 cal/mol in CBP5, respectively. While, its contribution in the propiony group was 2.84 cal/mol in CBP1 and 2.48 cal/mol in CBP5, respectively. An important factor in separation by GC may differences in interactions between the stationary phase of the column with the three dimensional protrusive moiety in the molecule. (author)

  13. Study of deuterated water in the low-mass protostar IRAS16293-2422

    Science.gov (United States)

    Coutens, A.; Vastel, C.; Caux, E.; Ceccarelli, C.; Herschel Chess Team

    2011-05-01

    Observations of deuterated water are an important complement for studies of H2O, since they give strong constraints on the formation processes: grain surfaces versus gas-phase chemistry through energetic process as shocks. The CHESS (Chemical HErschel Surveys of Star forming regions) Key Program has allowed to detect a lot of transitions of HDO (8) and H2O (16) as well as its isotopes H_218O and H_217O towards the low-mass protostar IRAS16293-2422 thanks to the unbiaised spectral survey carried out with the HIFI instrument on board the Herschel Space Observatory. Complementary data of HDO from the ground-based telescopes IRAM and JCMT are also available, allowing a precise determination of the abundance of deuterated water through the protostar envelope. In order to reproduce the observed line profiles, we have performed a modeling of HDO from the hot corino through the envelope using the physical structure of the protostar (Crimier et al. 2010) and the spherical Monte Carlo radiative transfer code RATRAN, which takes also into account radiative pumping by continuum emission from dust. We have used new HDO collision rates with H_2, recently computed by Wiesenfeld, Scribano and Faure (2011, PCCP). The same method has been applied to model H_2O and its isotopes H_218O and H_217O. We will present the results of this analysis and discuss the determined abundances.

  14. Static structure factor of polymerlike micelles: Overall dimension, flexibility, and local properties of lecithin reverse micelles in deuterated isooctane

    DEFF Research Database (Denmark)

    Jerke, G.; Pedersen, J.S.; Egelhaaf, S.U.

    1997-01-01

    We report a systematic investigation of the static structure factor S(q,c) of polymerlike reverse micelles formed by soybean lecithin and trace amounts of water in deuterated isooctane using small-angle neutron scattering and static light scattering. The experimental data for different concentrat......We report a systematic investigation of the static structure factor S(q,c) of polymerlike reverse micelles formed by soybean lecithin and trace amounts of water in deuterated isooctane using small-angle neutron scattering and static light scattering. The experimental data for different...

  15. Synthesis and spectroscopic stereospecificity assay of the deuterated quinolizidine alkaloids (2S)-[2H]- and (2R)-[2H]-sparteine

    International Nuclear Information System (INIS)

    Ebner, T.; Meese, C.O.; Rebell, J.

    1989-01-01

    Borohydride reduction of the (+)-1,2-dehydrosparteinium salts proceeds almost exclusively from the Si side, yielding, respectively, the stereoselectively (2S)(β)-deuterated (-)-sparteine and the (2R)(α)-deuterated (-)-sparteine. Stereo-chemistry and isotopic purity of the deuterium label (≥98%) are established unequivocally by 1 H, 2 H and 13 C NMR spectroscopy. (author)

  16. Synthesis and spectroscopic stereospecificity assay of the deuterated quinolizidine alkaloids (2S)-( sup 2 H)- and (2R)-( sup 2 H)-sparteine

    Energy Technology Data Exchange (ETDEWEB)

    Ebner, T.; Meese, C.O. (Fischer-Bosch Inst. fuer Klinische Pharmakologie, Stuttgart (Germany, F.R.)); Rebell, J. (Stuttgart Univ. (Germany, F.R.). Inst. fuer Organische Chemie); Fischer, P. (Stuttgart Univ. (Germany, F.R.). Inst. fuer Organische Chemie Fischer-Bosch Inst. fuer Klinische Pharmakologie, Stuttgart (Germany, F.R.))

    1989-04-01

    Borohydride reduction of the (+)-1,2-dehydrosparteinium salts proceeds almost exclusively from the Si side, yielding, respectively, the stereoselectively (2S)({beta})-deuterated (-)-sparteine and the (2R)({alpha})-deuterated (-)-sparteine. Stereo-chemistry and isotopic purity of the deuterium label ({>=}98%) are established unequivocally by {sup 1}H, {sup 2}H and {sup 13}C NMR spectroscopy. (author).

  17. Effect of extracellular fatty acids on lipid metabolism in cultured rabbit articular chondrocytes

    International Nuclear Information System (INIS)

    Nagao, M.; Ishii, S.; Murata, Y.; Akino, T.

    1991-01-01

    Rabbit articular chondrocytes were cultured for 8 h in the presence of various concentrations (5-500 microM) of 14 C oleic, 14 C linoleic, and 3H arachidonic acids. The radioactive unsaturated fatty acids were incorporated into triacylglycerol (TG) and phosphatidylcholine (PC) in a concentration-dependent manner; more fatty acids were incorporated into TG than into PC, at higher concentrations of extracellular fatty acids. Among these fatty acids, arachidonic acid was incorporated into TG much more than into PC, in spite of a very low concentration of arachidonic acid in TG. After transfer of the labeled cells to maintenance medium, the radioactivity in TG declined rapidly and 3 H arachidonic acid radioactivity in PC increased continuously during the chase time periods. Palmitoyl-unsaturated species were mainly formed in PC when cultured at a concentration of 5 microM of each fatty acid. However, when cultured at 500 microM, unsaturated-unsaturated species, specific for each unsaturated fatty acid were actively formed. These findings indicate that (1) fatty acid composition of TG and PC in articular chondrocytes is influenced by the degree of fatty acid supply, (2) formation and turnover of TG plays a role in fatty acid metabolism of cells, and (3) fatty acid pairing in PC is modulated by extracellular fatty acid concentrations

  18. Deuterated water in the solar-type protostars NGC 1333 IRAS 4A and IRAS 4B

    NARCIS (Netherlands)

    Coutens, A.; Vastel, C.; Cabrit, S.; Codella, C.; Kristensen, L. E.; Ceccarelli, C.; van Dishoeck, E. F.; Boogert, A. C. A.; Bottinelli, S.; Castets, A.; Caux, E.; Comito, C.; Demyk, K.; Herpin, F.; Lefloch, B.; McCoey, C.; Mottram, J. C.; Parise, B.; Taquet, V.; van der Tak, F. F. S.; Visser, R.; Yıldız, U. A.

    2013-01-01

    Context. The measure of the water deuterium fractionation is a relevant tool for understanding mechanisms of water formation and evolution from the prestellar phase to the formation of planets and comets. Aims: The aim of this paper is to study deuterated water in the solar-type protostars NGC 1333

  19. Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products.

    Science.gov (United States)

    Green, Amy M; Barber, Victoria P; Fang, Yi; Klippenstein, Stephen J; Lester, Marsha I

    2017-11-21

    Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH 3 CHOO. IR excitation of selectively deuterated syn -CD 3 CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn -CD 3 CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, which is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ∼10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. At 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn -CH 3 CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ∼50.

  20. Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.

    Science.gov (United States)

    Barrett, Eoin; Fitzgerald, Patrick; Dinan, Timothy G; Cryan, John F; Ross, R Paul; Quigley, Eamonn M; Shanahan, Fergus; Kiely, Barry; Fitzgerald, Gerald F; O'Toole, Paul W; Stanton, Catherine

    2012-01-01

    The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (10(9) microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (pbreve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (pbreve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (pbreve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (pbreve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (pbreve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.

  1. Neutronic measurements on electrolytic cells with deuterated palladium in a submarine environment

    International Nuclear Information System (INIS)

    Granada, J.R.; Mayer, R.E.; Florido, P.C.; Gillette, V.H.; Gomez, S.E.

    1990-01-01

    Using a high efficiency system for the neutron thermal detection and a pulsed electrolytic current procedure, measurements were made on cells containing Pd cathodes and electrolytes at a D 2 O and H 2 O base. The peculiarity of these experiments is that they were carried out on board of the A.R.A. Santa Cruz submarine, at a depth of 50m under sea level, attaining ultra deep-down conditions in the measurements, corresponding to a reduction in a factor = 50 in relation to lab conditions. The mean level of the signal -obtained from counting combination of deuterated cathodes- results to be separated from the deep-down level by four standard deviations. (Author) [es

  2. Gas Chromatographic Mass Spectrometric Determination of Myo-inositol in Humans Utilizing a Deuterated Internal Standard

    DEFF Research Database (Denmark)

    Andersen, Jan Rud; Larsen, Elfinn; Harbo, Helge

    1982-01-01

    The isotopic dilution technique was used for determining the content of myo-inositol in human urine, plasma and haemolysed erythrocyte samples. A deuterated myo-inositol, synthesized from inosose-2 by base-catalysed exchange of hydrogens by deuterium, followed by reduction of the inosose with 2H2......, was added as internal standard to the samples at an early stage in the analytical procedure. After separation and derivatization to the hexa-acetate, the gas chromatographic mass spectrometric analysis was carried out. A 25 m fused silica capillary column coated with methyl silicone was used, and the ions...... selected for monitoring were m/z 210 and m/z 214, which are characteristic and abundant fragment ions from unlabelled and hexadeuterated myo-inositolhexa-acetate, respectively. Calibration curves from water, urine, plasma and haemolysed erythrocytes show parallel, linear responses in the ratio between...

  3. Spectroscopic study on deuterated benzenes. I. Microwave spectra and molecular structure in the ground state

    Energy Technology Data Exchange (ETDEWEB)

    Kunishige, Sachi; Katori, Toshiharu; Baba, Masaaki, E-mail: baba@kuchem.kyoto-u.ac.jp [Division of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Nakajima, Masakazu; Endo, Yasuki [Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8902 (Japan)

    2015-12-28

    We observed microwave absorption spectra of some deuterated benzenes and accurately determined the rotational constants of all H/D isotopomers in the ground vibrational state. Using synthetic analysis assuming that all bond angles are 120°, the mean bond lengths were obtained to be r{sub 0}(C–C) = 1.3971 Å and r{sub 0}(C–H) = r{sub 0}(C–D) = 1.0805 Å. It has been concluded that the effect of deuterium substitution on the molecular structure is negligibly small and that the mean bond lengths of C–H and C–D are identical unlike small aliphatic hydrocarbons, in which r{sub 0}(C–D) is about 5 mÅ shorter than r{sub 0}(C–H). It is considered that anharmonicity is very small in the C–H stretching vibration of aromatic hydrocarbons.

  4. OD bands in the IR spectra of a deuterated soda-lime-silica glass

    Energy Technology Data Exchange (ETDEWEB)

    Peuker, C.; Brzezinka, K.W.; Gaber, M.; Kohl, A.; Geissler, H. [Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin (Germany)

    2001-07-01

    IR spectra of a deuterated glass of the composition (in mol%) 16 Na{sub 2}O . 10 CaO . 74 SiO{sub 2} complete earlier spectroscopic studies on water-poor soda-lime-silica glasses. The approved IR spectroscopic method of the deuterium exchange allows a reliable assignment of the hydroxyl bands also in the case of glasses. By spectra comparison the assignment of the IR bands at 3500 and 2800 cm{sup -1} to hydroxyl groups with different hydrogen bonding is verified. The IR band at about 4500 cm{sup -1} is interpreted as both a combination of the stretching vibrations {nu}O-H and {nu}Si-OH and a combination of the stretching vibration {nu}O-H and the deformation vibration {delta}SiOH. The bands at 1763 and 1602 cm{sup -1} are attributed to combination vibrations of the glass network. (orig.)

  5. Crystal structures and phase transformation of deuterated lithium imide, Li2ND

    International Nuclear Information System (INIS)

    Balogh, Michael P.; Jones, Camille Y.; Herbst, J.F.; Hector, Louis G.; Kundrat, Matthew

    2006-01-01

    We have investigated the crystal structure of deuterated lithium imide, Li 2 ND, by means of neutron and X-ray diffraction. An order-disorder transition occurs near 360K. Below that temperature Li 2 ND can be described to the same level of accuracy as a disordered cubic (Fd3-bar m) structure with partially occupied Li 32e sites or as a fully occupied orthorhombic (Ima2 or Imm2) structure. The high temperature phase is best characterized as disordered cubic (Fm3-bar m) with D atoms randomized over the 192l sites. Density functional theory calculations complement and support the diffraction analyses. We compare our findings in detail with previous studies

  6. Water deuteration in star-forming regions: Contribution of Herschel/HIFI spectroscopic data

    International Nuclear Information System (INIS)

    Coutens, Audrey

    2012-01-01

    Water (H_2O) is one of the most abundant molecules in the interstellar medium. In addition to being a primordial ingredient in the emergence of life, this species plays an essential role in the process of star formation through the cooling of warm gas. It also controls the chemistry for many species, either in the gas phase or on the grain surfaces. Studying its deuterated form HDO is a unique opportunity, through the estimation of the HDO/H_2O ratio, to constrain the mechanisms of water formation and to better understand the origin of water contained in terrestrial oceans. Indeed, recent results obtained with the Herschel satellite show that the HDO/H_2O ratio observed in comets is similar to the value measured in oceans (∼1.5 10"-"4), which suggests that comets could have brought a large fraction to Earth to form the oceans during heavy bombardments (Hartogh et al. 2011). In this thesis, I was interested in the study of deuterated water in the first stages of star formation, the Class 0 stage, which precede the formation of the protoplanetary disk leading to the birth of comets and planets. Through a 1D non-Local Thermodynamic Equilibrium radiative transfer modeling of the line profiles of the numerous HDO and H_2"1"8O transitions detected with the HIFI (Heterodyne Instrument for Far-Infrared) instrument onboard the Herschel Space Observatory and ground-based telescopes (IRAM, JCMT), I determined that the HDO/H_2O ratios of the solar-type protostar IRAS 16293-2422 was about 2% in the hot corino, the inner part of the protostellar envelope sufficiently warm (T ≥ 100 K) to desorb in gas phase the water molecules trapped in the icy grain mantles, and about 0.5% in the colder part of the envelope. This study (Coutens et al. 2012) also allowed me to show that an absorbing layer rich in water surrounds the protostar. This layer could be produced by the photo-desorption through the UV field of the water molecules frozen on the grains, on the edges of the molecular

  7. Effect of N-methyl deuteration on metabolism and pharmacokinetics of enzalutamide

    Directory of Open Access Journals (Sweden)

    Jiang J

    2016-07-01

    Full Text Available Jinfang Jiang,1,2,* Xuehai Pang,2,3,* Liang Li,1,2 Xiaojian Dai,1,2 Xingxing Diao,1 Xiaoyan Chen,1,2 Dafang Zhong,1,2 Yingwei Wang,2,3 Yuanwei Chen2–4 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2University of Chinese Academy of Sciences, Beijing, 3Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, 4Hinova Pharmaceuticals Inc, Chengdu, People’s Republic of China *These authors contributed equally to this work Background: The replacement of hydrogen with deuterium invokes a kinetic isotope effect. Thus, this method is an attractive way to slow down the metabolic rate and modulate pharmacokinetics.Purpose: Enzalutamide (ENT acts as a competitive inhibitor of the androgen receptor and has been approved for the treatment of metastatic castration-resistant prostate cancer by the US Food and Drug Administration in 2012. To attenuate the N-demethylation pathway, hydrogen atoms of the N–CH3 moiety were replaced by the relatively stable isotope deuterium, which showed similar pharmacological activities but exhibited favorable pharmacokinetic properties.Methods: We estimated in vitro and in vivo pharmacokinetic parameters for ENT and its deuterated analog (d3-ENT. For in vitro studies, intrinsic primary isotope effects (KH/KD were determined by the ratio of intrinsic clearance (CLint obtained for ENT and d3-ENT. The CLint values were obtained by the substrate depletion method. For in vivo studies, ENT and d3-ENT were orally given to male Sprague Dawley rats separately and simultaneously to assess the disposition and metabolism of them. We also investigated the main metabolic pathway of ENT by comparing the rate of oxidation and hydrolysis in vitro. Results: The in vitro CLint (maximum velocity/Michaelis constant [Vmax/Km] of d3-ENT in rat and human liver microsomes were 49.7% and 72.9% lower than those of the non-deuterated compound, corresponding to the KH

  8. Deuterated silicon nitride photonic devices for broadband optical frequency comb generation

    Science.gov (United States)

    Chiles, Jeff; Nader, Nima; Hickstein, Daniel D.; Yu, Su Peng; Briles, Travis Crain; Carlson, David; Jung, Hojoong; Shainline, Jeffrey M.; Diddams, Scott; Papp, Scott B.; Nam, Sae Woo; Mirin, Richard P.

    2018-04-01

    We report and characterize low-temperature, plasma-deposited deuterated silicon nitride thin films for nonlinear integrated photonics. With a peak processing temperature less than 300$^\\circ$C, it is back-end compatible with pre-processed CMOS substrates. We achieve microresonators with a quality factor of up to $1.6\\times 10^6 $ at 1552 nm, and $>1.2\\times 10^6$ throughout $\\lambda$ = 1510 -- 1600 nm, without annealing or stress management. We then demonstrate the immediate utility of this platform in nonlinear photonics by generating a 1 THz free spectral range, 900-nm-bandwidth modulation-instability microresonator Kerr comb and octave-spanning, supercontinuum-broadened spectra.

  9. Intense deuterium nuclear fusion of pycnodeuterium-lumps coagulated locally within highly deuterated atom clusters

    CERN Document Server

    Yoshiaki, A; Zhang, Y C

    2002-01-01

    Embedded nano-Pd particles of 5 nm in size instantly abundant D-atoms more than 250% in the atomic ratio against Pd-atoms at room temperature when they are kept in D sub 2 gas pressurized to less than 10 atm. In such ultrahigh densities, 2-4 D-atoms can be coagulated inside each octahedral space of Pd lattice (pycnodeuterium-lump). When a stimulation energy such as latticequake causing by ultrasonic wave was supplied to those highly deuterated Pd particles, intense deuterium nuclear fusion (''solid fusion'') was generated there and both excess heat and sup 4 He gas were abundantly produced. Naturally, these facts can not be realized at all in bulk Pd. The results show that the nuclear fusion occurs without any hazardous rays in pycnodeuterium-lumps coagulated locally inside the each cell of the host metal lattice. These unit cells correspond to minimum unit of the solid fusion reactor as a ''Lattice Reactor''. (author)

  10. Chemical shift assignments of the partially deuterated Fyn SH2-SH3 domain.

    Science.gov (United States)

    Kieken, Fabien; Loth, Karine; van Nuland, Nico; Tompa, Peter; Lenaerts, Tom

    2018-04-01

    Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules involved in regulating the activity of many proteins such as tyrosine kinases and phosphatases by respective recognition of phosphotyrosine and proline-rich regions. In the Src family kinases, the inactive state of the protein is the direct result of the interaction of the SH2 and the SH3 domain with intra-molecular regions, leading to a closed structure incompetent with substrate modification. Here, we report the 1 H, 15 N and 13 C backbone- and side-chain chemical shift assignments of the partially deuterated Fyn SH3-SH2 domain and structural differences between tandem and single domains. The BMRB accession number is 27165.

  11. A neutron diffraction study on deuterated Rochelle salt structure at - 195degC paraelectric phase

    International Nuclear Information System (INIS)

    Iwata, Yutaka; Mitani, Shigeshi; Fukui, Susumu; Shibuya, Iwao

    1989-01-01

    Neutron diffraction study on the low temperature paraelectric phase of Rochelle salt was performed using deuterated single crystal specimen. Large anisotropic thermal motions of atoms are found to be prevailing in the lower paraelectric phase. This indicates the disordering of atoms and the analysis by two-site split-atom method showed that a split atom model holds equally well with an ordinary non-split model. By connecting split positions selectively, a disordered paraelectric structure, which is composed of half-occupied units, was obtained. These units can be regarded as ones in the ferroelectric phase according to a deduction from an order-disorder phase transition scheme. A possibility of existence of the 'local disorder' of O(5)-H group in the tartrate molecule was examined by Fourier method and a result proved to be negative. Present disordered model gives better understanding to the phase transition scheme of Rochelle salt than the local disorder model case. (author)

  12. Dietary Linoleic and a-Linolenic Acid Affect Anxiety-Related Responses and Exploratory Activity in Growing Pigs

    NARCIS (Netherlands)

    Clouard, C.M.; Gerrits, W.J.J.; Kerkhof, van I.; Smink, W.; Bolhuis, J.E.

    2015-01-01

    Background: Growing evidence suggests that the dietary ratio of linoleic acid (LA) to a-linolenic acid (ALA), the precursors of arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively, may affect behavior in mammals. Objective: This study aimed at evaluating the impact of dietary LA and

  13. THE HERSCHEL AND IRAM CHESS SPECTRAL SURVEYS OF THE PROTOSTELLAR SHOCK L1157-B1: FOSSIL DEUTERATION

    International Nuclear Information System (INIS)

    Codella, C.; Fontani, F.; Vasta, M.; Ceccarelli, C.; Lefloch, B.; Kahane, C.; Taquet, V.; Wiesenfeld, L.; Busquet, G.; Caselli, P.; Lis, D.; Viti, S.

    2012-01-01

    We present the first study of deuteration toward the protostellar shock L1157-B1, based on spectral surveys performed with the Herschel-HIFI and IRAM 30 m telescopes. The L1157 outflow is driven by a low-mass Class 0 protostar and is considered the prototype of the so-called chemically active outflows. The young (2000 yr), bright blueshifted bow shock, B1, is an ideal laboratory for studying the gas chemically enriched by the release of dust mantles due to the passage of a shock. A total of 12 emission lines (up to E u = 63 K) of CH 2 DOH, HDCO, and DCN are detected. In addition, two lines of NH 2 D and HDO are tentatively reported. To estimate the deuteration, we also extracted from our spectral survey emission lines of non-deuterated isotopologues ( 13 CH 3 OH, H 2 13 CO, H 13 CN, H 2 13 CO, and NH 3 ). We infer higher deuteration fractions for CH 3 OH (D/H = 0.2-2 × 10 –2 ) and H 2 CO (5-8 × 10 –3 ) than for H 2 O (0.4-2 × 10 –3 ), HCN (∼10 –3 ), and ammonia (≤3 × 10 –2 ). The measurement of deuteration of water, formaldehyde, and methanol in L1157-B1 provides a fossil record of the gas before it was shocked by the jet driven by the protostar. A comparison with gas-grain models indicates that the gas passed through a low-density (≤10 3 cm –3 ) phase, during which the bulk of water ices formed, followed by a phase of increasing density, up to 3 × 10 4 cm –3 , during which formaldehyde and methanol ices formed.

  14. Changes in cholesterol content and fatty acid composition of serum lipid in irradiated rat

    International Nuclear Information System (INIS)

    Ohashi, Shigeru

    1979-01-01

    The effect of a single dose of whole body irradiation on the serum cholesterol content and fatty acid composition of serum lipids in rats was investigated. A change in the fatty acid composition of liver lipids was also observed. After 600 rad of irradiation, the cholesterol content increased, reached a maximum 3 days after irradiation, and then decreased. After irradiation, an increase in cholesterol content and a marked decrease in triglyceride content were observed, bringing about a change in the amount of total serum lipids. The fatty acid compositions of normal and irradiated rat sera were compared. The relative percentages of palmitic and oleic acids in total lipids decreased while those of stearic and arachidonic acids increased. Serum triglyceride had trace amounts of arachidonic acid and the unsaturated fatty acid component decreased after irradiation. On the other hand, unsaturated fatty acid in cholesterol ester increased after irradiation, while linoleic and arachidonic acids made up 29% and 22% in the controls and 17% and 61% after irradiation, respectively. The fatty acid composition of total liver lipids after irradiation showed a decrease in palmitic and oleic acids and an increase in stearic and arachidonic acids, the same trend as observed in serum lipid fatty acid. Liver cholesterol ester showed trace amounts of linoleic and arachidonic acids and an increase in short-chain fatty acid after irradiation. The major component of serum phospholipids was phosphatidylcholine while palmitostearyl lecithine and unsaturated fatty acid were minor components. Moreover, phosphatidylcholine and phosphatidylethanolamine were the major components of liver phospholipids, having highly unsaturated fatty acids. The changes in fatty acid composition were similar to the changes in total phospholipids. (J.P.N.)

  15. Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

  16. Correlation between the structure and infra-red absorption characteristics of mono-deuterated compounds: contribution to the study of organo-magnesium compounds

    International Nuclear Information System (INIS)

    Paillous, A.

    1965-10-01

    The high sensitivity of the ν (C-D) vibration to the variations brought about by the substitution of the carbon attached to the deuterium is shown in the case of organic or organo-metallic mono-deuterated molecules. In particular, syntheses of various mono-deuterated organo-magnesium compounds have been carried out; results are given concerning an infra-red spectrometric examination of these compounds in the range 2100 - 2250 cm -1 . The results show the existence of only one type of deuterated carbon, which suggests that the same carbanion is involved in various ionic associations for the different magnesium-containing compounds. (authors) [fr

  17. Preparation of folic acid specifically labeled with deuterium at the 3',5'-positions

    International Nuclear Information System (INIS)

    Gregory, J.F. III; Toth, J.P.

    1988-01-01

    A method was devised for the synthesis of 3', 5'-[ 2 H 2 ]folic acid (d 2 -folic acid) for use in studies of folate metabolism in human beings. Labeling was accomplished by catalytic dehalogenation of 3', 5'-dibromofolate with deuterium gas and palladium/carbon catalyst. d 2 -Folic acid was separated from reduced forms and residual 3'-monobromofolate by chromatography on DEAE-Sephadex. Analysis by proton NMR and mass spectrometry indicated 70-75% deuteration of the 3',5'-positions and lack of deuteration at other carbons. (author)

  18. Targeted metabolomics analysis reveals the association between maternal folic acid supplementation and fatty acids and amino acids profiles in rat pups.

    Science.gov (United States)

    Liu, Zhipeng; Liu, Rui; Chou, Jing; Yu, Jiaying; Liu, Xiaowei; Sun, Changhao; Li, Ying; Liu, Liyan

    2018-07-15

    Maternal diet during pregnancy can influence offspring's health by affecting development and metabolism. This study aimed to analyze the influence of maternal folic acid (FA) supplementation on the metabolism of rat pups using targeted metabolomics. Twenty female rats were randomly assigned to a FA supplementation (FAS group, n = 10) or control group (n = 10), which were fed AIN93G diet with 2 or 10 mg/kg FA, respectively. We then measured amino acids and their derivatives, biogenic amines, and fatty acids in the female rats and their pups by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC/MS-MS) and gas chromatography-mass spectrometry (GC/MS-MS). In maternal rats, the significant changes of three metabolites (proline, γ-aminobutyric acid and esterified octadecatetraenoic acid, P acids (leucine, isoleucine, serine, proline) were obtained in FAS pups. Furthermore, there were the decreased esterified fatty acids (arachidonic acid, eicosapentaenoic acid, and docosatetraenoic acid) and free fatty acids (oleic acid, linoleic acid, γ-linolenic acid, octadecatetraenoic acid, arachidonic acid, eicosapentaenoic acid and selacholeic acid) in FAS pups. Metabolic changes in the FAS pups were characterized by changes in fatty acids and amino acids. These results suggested that FA supplementation during pregnancy influenced amino acids and fatty acids metabolism in rat pups. This study provides new insights into the regulation of amino acids and fatty acids metabolism during early life. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. The feasibility study of using deuterated gadolinium nitrate for moderator-poisoned shutdown and excess reactivity control in CANDU reactors

    International Nuclear Information System (INIS)

    Li, J.; Everatt, A.

    2006-01-01

    Gadolinium nitrate is used in CANDU stations as moderator poison for reactor shutdowns and excess reactivity control. The use of the light-water hydrate introduces significant quantities of light water into the moderator system, which must be removed from the moderator by periodically upgrading the moderator (isotopic maintenance). The benefit of using a deuterated gadolinium nitrate would be a higher moderator isotopic and/or a lesser isotopic maintenance requirement. This study evaluated the economics of using deuterated gadolinium nitrate, as opposed to the light-water hydrate, for moderator-poisoned shutdowns and excess reactivity control in CANDU-6 reactors. Normal gadolinium nitrate (i.e., the light-water hydrate) is available from suppliers at ∼125 $/kg. Supplier quotes for deuterated gadolinium nitrate ranged from 1900 to 4000 $/kg. To examine the possibility of producing deuterated gadolinium nitrate in-house at a lower cost than commercially available, a three-stage dissolution/evaporation manufacturing process was conceived and costed. Depending on the assumed demand for the product (i.e., the number of reactors adopting the use of the product) and the capital recovery period, the estimated unit cost for the dissolution/evaporation process ranged from 730 to 2500 $/kg. The determination of economic benefit from using deuterated gadolinium nitrate in existing CANDU stations was based on the cost savings resulting from a higher fuel burn-up (i.e., the higher moderator isotopic would give a higher fuel burn-up). The net benefit of using deuterated gadolinium nitrate for most CANDU stations was determined to be marginal (i.e., <20 k$/a). Only for those CANDU stations where the moderator isotopic was relatively low (e.g., 99.85 wt%) was there a potential significant benefit (20-100 k$/a). However, if the reason for the low moderator isotopic is a relatively high moderator light-water ingress rate from sources other than the use of the light-water hydrate

  20. TEM and EELS study of deuterated carbon: application to the fuel retention in tokamaks; Etude couplee MET-EELS du carbone deutere: application a la retention du combustible dans les tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Bernier, N

    2007-12-15

    We developed a methodology, based on the combination of TEM and EELS techniques, for a structural and chemical characterization, at a high spatial resolution, of a wide range of carbon materials. We i) optimized, in the framework of theoretical models, the sp2 fraction quantification from pure carbons by EELS ii) transferred this quantification to deuterated amorphous carbon layers iii) showed, from graphitized carbons, how the TEM-EELS combination allows to detect low concentrations of implanted D. Due to the accomplishment of these developments, we applied our approach to the study of D retention in composites C/C, which are the plasma-facing materials in TS. We showed that specific localized retention sites correspond to relatively large ({approx} 3 mm.) cracks between fibres and matrix; such cracks offer a simple and direct path for deuterated amorphous carbon. The particle balance performed in TS is discussed in the light of this trapping mechanism. (author)

  1. Developmentally dependent and different roles of fatty acids OMEGA-6 and OMEGA-3

    DEFF Research Database (Denmark)

    Mourek, J; Mourek, J

    2011-01-01

    The developmentally-dependent differences in the biological significances and effects of PUFA-OMEGA-6 (namely of arachidonic acid) and PUFA-OMEGA-3 (namely of docosahexaenoic acid) are discussed. The clinical results as well as developmental experiences are indicating a hypothesis of the evolution...... that created mutual relationship between those two substances (with immunological basis and following recuperation). The anti-inflammatory actions of PUFA-OMEGA-3 are the most visible (and significant) contrasts as compared with the large affects of namely arachidonic acid and its metabolites....

  2. Tritium aging effect of LaNi4.9Al0.1Dx on de-deuterating kinetics

    International Nuclear Information System (INIS)

    Xiong Yifu; Luo Deli; Li Rong

    2002-01-01

    Kinetics parameters are measured at different aging times of LaNi 4.9 Al 0.1 alloy. The influence of tritium aging on kinetic feature of LaNi 4.9 Al 0.1 alloy is assessed. The results show that reaction rate decreases with aging time, but tritium aging does not change de-deuterating reaction order. De-deuterating reaction orders a (with respect to deuterium pressure) and b (with respect to deuterium content) are 0.5 and 1, respectively. Activation energy (E) increases with aging time. After 1120 d, the reaction rate constant is decreased by two orders of magnitude, activation energy is increased by a factor of 0.3

  3. Deuteration of acetanilides and other substituted aromatics using [Ir(COD)(Cy3P)(Py)]PF6 as catalyst

    International Nuclear Information System (INIS)

    Hesk, D.; Das, P.R.; Evans, B.

    1995-01-01

    Deuterium exchange labelling using [Ir(COD)(Cy 3 P)(Py)]PF 6 as catalyst and deuterium gas was studied on a number of substituted acetanilides. In most cases products containing deuterium ortho to the anilide group were obtained with a high degree of enrichment. With one exception no evidence for meta, para or anilide methyl labelling was seen. The catalyst was also effective in the ortho deuteration of acetophenone, benzophenone and the β-lactam containing compound Sch 48461. (Author)

  4. Hexicon 2: automated processing of hydrogen-deuterium exchange mass spectrometry data with improved deuteration distribution estimation.

    Science.gov (United States)

    Lindner, Robert; Lou, Xinghua; Reinstein, Jochen; Shoeman, Robert L; Hamprecht, Fred A; Winkler, Andreas

    2014-06-01

    Hydrogen-deuterium exchange (HDX) experiments analyzed by mass spectrometry (MS) provide information about the dynamics and the solvent accessibility of protein backbone amide hydrogen atoms. Continuous improvement of MS instrumentation has contributed to the increasing popularity of this method; however, comprehensive automated data analysis is only beginning to mature. We present Hexicon 2, an automated pipeline for data analysis and visualization based on the previously published program Hexicon (Lou et al. 2010). Hexicon 2 employs the sensitive NITPICK peak detection algorithm of its predecessor in a divide-and-conquer strategy and adds new features, such as chromatogram alignment and improved peptide sequence assignment. The unique feature of deuteration distribution estimation was retained in Hexicon 2 and improved using an iterative deconvolution algorithm that is robust even to noisy data. In addition, Hexicon 2 provides a data browser that facilitates quality control and provides convenient access to common data visualization tasks. Analysis of a benchmark dataset demonstrates superior performance of Hexicon 2 compared with its predecessor in terms of deuteration centroid recovery and deuteration distribution estimation. Hexicon 2 greatly reduces data analysis time compared with manual analysis, whereas the increased number of peptides provides redundant coverage of the entire protein sequence. Hexicon 2 is a standalone application available free of charge under http://hx2.mpimf-heidelberg.mpg.de.

  5. Hexicon 2: Automated Processing of Hydrogen-Deuterium Exchange Mass Spectrometry Data with Improved Deuteration Distribution Estimation

    Science.gov (United States)

    Lindner, Robert; Lou, Xinghua; Reinstein, Jochen; Shoeman, Robert L.; Hamprecht, Fred A.; Winkler, Andreas

    2014-06-01

    Hydrogen-deuterium exchange (HDX) experiments analyzed by mass spectrometry (MS) provide information about the dynamics and the solvent accessibility of protein backbone amide hydrogen atoms. Continuous improvement of MS instrumentation has contributed to the increasing popularity of this method; however, comprehensive automated data analysis is only beginning to mature. We present Hexicon 2, an automated pipeline for data analysis and visualization based on the previously published program Hexicon (Lou et al. 2010). Hexicon 2 employs the sensitive NITPICK peak detection algorithm of its predecessor in a divide-and-conquer strategy and adds new features, such as chromatogram alignment and improved peptide sequence assignment. The unique feature of deuteration distribution estimation was retained in Hexicon 2 and improved using an iterative deconvolution algorithm that is robust even to noisy data. In addition, Hexicon 2 provides a data browser that facilitates quality control and provides convenient access to common data visualization tasks. Analysis of a benchmark dataset demonstrates superior performance of Hexicon 2 compared with its predecessor in terms of deuteration centroid recovery and deuteration distribution estimation. Hexicon 2 greatly reduces data analysis time compared with manual analysis, whereas the increased number of peptides provides redundant coverage of the entire protein sequence. Hexicon 2 is a standalone application available free of charge under http://hx2.mpimf-heidelberg.mpg.de.

  6. Tissue levels of fish fatty acids and risk of colorectal adenomas: a case-control study (Netherlands).

    NARCIS (Netherlands)

    Busstra, M.C.; Siezen, C.L.; Grubben, M.J.A.L.; Kranen, H.J. van; Nagengast, F.M.; Veer, P. van 't

    2003-01-01

    Epidemiological and animal studies have suggested that a high ratio of n-3 fish fatty acids to arachidonic acid (AA), might protect against colorectal carcinogenesis. Competition of n-3 and n-6 fatty acids, especially AA, for the enzyme cyclooxygenase-2 may be responsible for this effect. To examine

  7. Tissue levels of fish fatty acids and risk of colorectal adenomas: a case-control study (Netherlands)

    NARCIS (Netherlands)

    Busstra, M.C.; Siezen, C.L.E.; Grubben, M.J.A.L.; Kranen, H.J.; Nagengast, F.M.; Veer, van 't P.

    2003-01-01

    Epidemiological and animal studies have suggested that a high ratio of n-3 fish fatty acids to arachidonic acid (AA), might protect against colorectal carcinogenesis. Competition of n-3 and n-6 fatty acids, especially AA, for the enzyme cyclooxygenase-2 may be responsible for this effect. To examine

  8. The use of deuterated ethyl acetate in highly concentrated electrolyte as a low-cost solvent for in situ neutron diffraction measurements of Li-ion battery electrodes

    International Nuclear Information System (INIS)

    Petibon, R.; Li, Jing; Sharma, Neeraj; Pang, Wei Kong; Peterson, Vanessa K.; Dahn, J.R.

    2015-01-01

    A low-cost deuterated electrolyte suitable for in situ neutron diffraction measurements of normal and high voltage Li-ion battery electrodes is reported here. Li[Ni 0.4 Mn 0.4 Co 0.2 ]O 2 /graphite (NMC(442)/graphite) pouch cells filled with 1:0.1:2 (molar ratio) of lithium bis(fluorosulfonyl) imide (LiFSi):LiPF 6 : ethyl acetate (EA) and LiFSi:LiPF 6 :deuterated EA (d8-EA) electrolytes were successfully cycled between 2.8 V and 4.7 V at 40°C for 250 h without significant capacity loss, polarization growth, or gas production. The signal-to-noise ratio of neutron powder diffraction patterns taken on NMC(442) powder with a conventional deuterated organic carbonate-based electrolyte and filled with LiFSi:LiPF 6 :d8-EA electrolyte were virtually identical. Out of all the solvents widely available in deuterated form tested in highly-concentrated systems, EA was the only one providing a good balance between cost and charge-discharge capacity retention to 4.7 V. The use of such an electrolyte blend would half the cost of deuterated solvents needed for in situ neutron diffraction measurements of Li-ion batteries compared to conventional deuterated carbonate-based electrolytes

  9. Using deuterated PAH amendments to validate chemical extraction methods to predict PAH bioavailability in soils

    International Nuclear Information System (INIS)

    Gomez-Eyles, Jose L.; Collins, Chris D.; Hodson, Mark E.

    2011-01-01

    Validating chemical methods to predict bioavailable fractions of polycyclic aromatic hydrocarbons (PAHs) by comparison with accumulation bioassays is problematic. Concentrations accumulated in soil organisms not only depend on the bioavailable fraction but also on contaminant properties. A historically contaminated soil was freshly spiked with deuterated PAHs (dPAHs). dPAHs have a similar fate to their respective undeuterated analogues, so chemical methods that give good indications of bioavailability should extract the fresh more readily available dPAHs and historic more recalcitrant PAHs in similar proportions to those in which they are accumulated in the tissues of test organisms. Cyclodextrin and butanol extractions predicted the bioavailable fraction for earthworms (Eisenia fetida) and plants (Lolium multiflorum) better than the exhaustive extraction. The PAHs accumulated by earthworms had a larger dPAH:PAH ratio than that predicted by chemical methods. The isotope ratio method described here provides an effective way of evaluating other chemical methods to predict bioavailability. - Research highlights: → Isotope ratios can be used to evaluate chemical methods to predict bioavailability. → Chemical methods predicted bioavailability better than exhaustive extractions. → Bioavailability to earthworms was still far from that predicted by chemical methods. - A novel method using isotope ratios to assess the ability of chemical methods to predict PAH bioavailability to soil biota.

  10. Pharmacokinetics of methadone during maintenance therapy: Pulse labeling with deuterated methadone in the steady state

    International Nuclear Information System (INIS)

    Aenggard, E.; Nilsson, M.I.; Holmstrand, J.; Gunne, L.M.; Uppsala Univ.; Karolinsky Institutet, Stockholm

    1979-01-01

    A technique is presented for study of steady state kinetics of methadone using pulse labeling with deuterated methadone (d 3 ) and mass fragmentography to measure both unlabeled and labeled methadone in blood. Seven subjects maintained on methadone for at least 10 months were admitted to a closed metabolic ward. The daily dose of unlabeled methadone (d 0 ) was substituted by one dose of methadone-d 3 and plasma levels of methadone-d 0 and methadone-d 3 were followed for 48 h using a precise (SD +- 5%) and sensitive (30 pmol/ml) mass fragmentographic technique. Plasma half-lives (tsub(1/2)) for both methadone-d 0 and methadone-d 3 were calculated from samples obtained 8-24 h following the dose of methadone-d 3 . The tsub(1/2) of oral methadone-d 3 was shorter (22 +- 2 h) than that of methadone-d 0 (52 +- 20 h). The same pattern was observed after intravenous administration. The results indicate multiple pools of methadone in the body. (orig.) 891 AJ/orig. 892 MKO [de

  11. High-excitation lines of deuterated formaldehyde (HDCO) in the Orion molecular cloud

    International Nuclear Information System (INIS)

    Loren, R.B.; Wootten, A.

    1985-01-01

    Five HDCO lines (up to 35 cm -1 ) have been detected in the narrow OMC-1 kinematic component. The best estimate of the [HDCO]/[H 2 CO] abundance ratio in OMC-1 is 0.01-0.03, at least an order of magnitude greater than the observed [DCO + ]/[HCO + ] abundance ratio. The [DCO + ]/[HCO + ] ratio greatly exceeds the [HDCO]/[H 2 CO] radio in cold clouds where the enhancement of both HDCO and DCO + abundances originates from H 2 D + . H 2 D + is abundant only at temperatures lower than found in OMC-1. The combination of a low [DCO + ]/[HCO + ] and high [HDCO]/[H 2 CO] abundance ratio in OMC-1 requires a different HDCO formation route at high temperature. This alternate HDCO formation path can occur because the exothermicity of the ion exchange reaction of HD and CH 3 + is greater than for the HD+H 3 + reaction. The CH 2 D + thus formed survives to higher temperatures than H 2 D + . Subsequent reactions with H 2 lead to CH 4 D + which by electronic recombination forms CH 2 D. The HDCO (H 2 CO) forms in the neutral-neutral reaction of CH 2 D (CH 3 ) and O. These reactions are not competitive in forming a variety of deuterated molecules at low temperatures since electronic recombination rapidly removes CH 2 D + and CH 4 D + ions while the abundant H 2 D + ion is slow to recombine, as reported by Smith and Adam in 1984

  12. Synthesis of specifically deuterated pregnanolone and pregnanediol sulphates for metabolic studies in pregant women

    International Nuclear Information System (INIS)

    Baillie, T.A.; Herz, J.E.; Anderson, R.A.; Sjovall, J.

    1975-01-01

    A series of specifically deuterated isomers of pregnanolone sulphate and pregnanediol mono- and disulphate have been synthesized for use in a study of the formation and metabolism of C 21 -steroid sulphates in the plasma of pregnant women. Hecogenin, the starting material for the synthesis, was equilibrated with NaO 2 H- 2 H 2 O and the resulting 11,11- 2 H 2 derivative converted directly to its tosylhydrazone. Reduction with sodium borohydride and degradation of the sapogenin side-chain gave 3β-hydroxy-5α-[11,11- 2 H 2 ] pregn-16-en-20-one (isotopic purity 91.6%). Further deuterium atoms were introduced in the 3α and 3α,20β positions by reductions with sodium borodeuteride and lithium aluminum deuteride, respectively. These reactions led to 3β-hydroxy-5α-[3α,11,11- 2 H 3 ] pregnan-20-one (isotopic purity 87.2%) and 5α-[3α,11,11,20β- 2 H 4 ] pregnane-3β,20α-diol (isotopic purity 83.9%). Steroids possessing the less readily accessible 3α-hydroxy-5α-[3β- 2 H] configuration were obtained, without loss of label, by epimerization of the 3β isomers. Pregnanolone sulphates and pregnanediol disulphates were prepared directly from the free alcohols, while the pregnanediol 3-monosulphates were synthesized from the appropriate pregnanediol 20-monoacetate derivatives

  13. Preparation and infrared spectra of differently deuterated tetramethyl-derivatives of the IV. main group

    International Nuclear Information System (INIS)

    Biedermann, S.

    1972-01-01

    19 different deuterated tetramethyl derivates of the type (CH 3 )sub(4-n)M(CH 3 )sub(n) of C, Si, Ge, Sn and Pb were prepared. Gas cuvettes with polyethylene, NaCl and KBr windows were used to absorb the infra-red spectra, the IR equipment Beckman IR 11 and IR 12 were used. The infra-red spectra of the above mentioned compounds were indicated from 33 to 4,000 cm -1 , the ground, upper and combination vibrations assigned, the PR separations of the partly well resolved rotation-vibration outlines determined and were compared with the calculated PR separations. The revision of the correlations performed by Graham for γsub(s)CH 3 and γsub(as)CH 3 in the race of vibration F 2 with Sn(CH 3 ) 4 and Pb(CH 3 ) 4 and the proposed one with C(CH 3 ) 4 , Si(CH 3 ) 4 and Ge(CH 3 ) 4 could be disproved by the new experimental results. (FW) [de

  14. Rotation and rotation-vibration spectroscopy of the 0+-0- inversion doublet in deuterated cyanamide.

    Science.gov (United States)

    Kisiel, Zbigniew; Kraśnicki, Adam; Jabs, Wolfgang; Herbst, Eric; Winnewisser, Brenda P; Winnewisser, Manfred

    2013-10-03

    The pure rotation spectrum of deuterated cyanamide was recorded at frequencies from 118 to 649 GHz, which was complemented by measurement of its high-resolution rotation-vibration spectrum at 8-350 cm(-1). For D2NCN the analysis revealed considerable perturbations between the lowest Ka rotational energy levels in the 0(+) and 0(-) substates of the lowest inversion doublet. The final data set for D2NCN exceeded 3000 measured transitions and was successfully fitted with a Hamiltonian accounting for the 0(+) ↔ 0(-) coupling. A smaller data set, consisting only of pure rotation and rotation-vibration lines observed with microwave techniques was obtained for HDNCN, and additional transitions of this type were also measured for H2NCN. The spectroscopic data for all three isotopic species were fitted with a unified, robust Hamiltonian allowing confident prediction of spectra well into the terahertz frequency region, which is of interest to contemporary radioastronomy. The isotopic dependence of the determined inversion splitting, ΔE = 16.4964789(8), 32.089173(3), and 49.567770(6) cm(-1), for D2NCN, HDNCN, and H2NCN, respectively, is found to be in good agreement with estimates from a simple reduced quartic-quadratic double minimum potential.

  15. Development of new synthetic routes to bile pigments and synthesis of deuterated porphyrins

    International Nuclear Information System (INIS)

    Shim, Y.K.

    1985-01-01

    New synthetic routes to pyrromethanones using hydrogen peroxide/pyridine upon alpha-free pyrromethanes and a synthesis of mesobiliverdin are described. The pyrromethanones were applied to the synthesis of mesobiliverdin using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) oxidation of mesourbilin, to give a high yield of the desired mesobiliverdin. New synthetic methodology to pyrrolinones using various oxidizing reagents were also described. Treatment of alpha-free pyrrole with thallium(III) trifluoroacetate (TTFA) gave a mixture of a pyrrolinone and a dimeric compound. The yield and the ratio of the two products were variable depending upon the solvents and the mole ratio of the TTFA used. Pyrrolinone syntheses using the other oxidizing reagents are also described. Syntheses of carbon-14 labelled biliverdins are also described. In addition, the preparation of biliverdin IX-BETA using b-bilene route is described. The second part of this study contains an introduction to porphyrins and syntheses of 6,7-bis(2-methoxycarbonyl-1,1-dideuteroethyl)-1,3,5,8-tetramethyl-2,4-divinylporphyrin. The latter is important in the study of heme protein reconstitution experiments. As a result of numerous synthetic approaches the desired product was obtained from the appropriately deuterated formylpyrrole using the a,c-biladiene route

  16. Using deuterated PAH amendments to validate chemical extraction methods to predict PAH bioavailability in soils

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Eyles, Jose L., E-mail: j.l.gomezeyles@reading.ac.uk [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom); Collins, Chris D.; Hodson, Mark E. [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom)

    2011-04-15

    Validating chemical methods to predict bioavailable fractions of polycyclic aromatic hydrocarbons (PAHs) by comparison with accumulation bioassays is problematic. Concentrations accumulated in soil organisms not only depend on the bioavailable fraction but also on contaminant properties. A historically contaminated soil was freshly spiked with deuterated PAHs (dPAHs). dPAHs have a similar fate to their respective undeuterated analogues, so chemical methods that give good indications of bioavailability should extract the fresh more readily available dPAHs and historic more recalcitrant PAHs in similar proportions to those in which they are accumulated in the tissues of test organisms. Cyclodextrin and butanol extractions predicted the bioavailable fraction for earthworms (Eisenia fetida) and plants (Lolium multiflorum) better than the exhaustive extraction. The PAHs accumulated by earthworms had a larger dPAH:PAH ratio than that predicted by chemical methods. The isotope ratio method described here provides an effective way of evaluating other chemical methods to predict bioavailability. - Research highlights: > Isotope ratios can be used to evaluate chemical methods to predict bioavailability. > Chemical methods predicted bioavailability better than exhaustive extractions. > Bioavailability to earthworms was still far from that predicted by chemical methods. - A novel method using isotope ratios to assess the ability of chemical methods to predict PAH bioavailability to soil biota.

  17. Retinal Biocompatibility of Brilliant Blue G with Deuterated Water for Chromovitrectomy

    Directory of Open Access Journals (Sweden)

    Emmerson Badaró

    2014-01-01

    Full Text Available Purpose: To investigate the retinal biocompatibility of Brilliant Blue G with deuterated water (BBG-D2O as a vital dye for chromovitrectomy. Methods: In this animal study, 0.05 mL of 0.25 g/L Brilliant Blue G (BBG associated with 0.13 mL/mL of deuterium oxide (D2O was injected intravitreally in the right eye and the same amount of balanced salt solution (BSS was injected similarly in the left eye of rabbits. Clinical examination and histology with light microscopy were performed after seven days. Retinal cell layers were evaluated for morphologic alterations. Electroretinographic (ERG changes were also assessed at baseline and 7 days after the injections. Results: A total of 6 rabbits were included in the study. The gross histopathologic appearance of the retina, choroid, sclera and optic nerve was within normal limits without any sign of severe retinal necrosis or cystic degeneration. Light microscopy showed that BBG-D2O caused no substantial alterations in retinal layers as compared to control eyes. The injection of BBG-D2O did not induce considerable functional ERG alterations. Conclusion: Intravitreal injection of BBG-D2O 0.25 g/L seems to induce no retinal toxicity as documented by lack of functional and histological changes.

  18. THE HERSCHEL AND IRAM CHESS SPECTRAL SURVEYS OF THE PROTOSTELLAR SHOCK L1157-B1: FOSSIL DEUTERATION

    Energy Technology Data Exchange (ETDEWEB)

    Codella, C.; Fontani, F.; Vasta, M. [INAF, Osservatorio Astrofisico di Arcetri, Largo Enrico Fermi 5, I-50125 Firenze (Italy); Ceccarelli, C.; Lefloch, B.; Kahane, C.; Taquet, V.; Wiesenfeld, L. [UJF-Grenoble 1/CNRS-INSU, Institut de Planetologie et d' Astrophysique de Grenoble (IPAG) UMR 5274, Grenoble, F-38041 (France); Busquet, G. [INAF - Istituto di Astrofisica e Planetologia Spaziali, via Fosso del Cavaliere 100, I-00133, Roma (Italy); Caselli, P. [School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT (United Kingdom); Lis, D. [California Institute of Technology, Cahill Center for Astronomy and Astrophysics 301-17, Pasadena, CA 91125 (United States); Viti, S., E-mail: codella@rcetri.astro.it [Department of Physics and Astronomy, University College London, London (United Kingdom)

    2012-09-20

    We present the first study of deuteration toward the protostellar shock L1157-B1, based on spectral surveys performed with the Herschel-HIFI and IRAM 30 m telescopes. The L1157 outflow is driven by a low-mass Class 0 protostar and is considered the prototype of the so-called chemically active outflows. The young (2000 yr), bright blueshifted bow shock, B1, is an ideal laboratory for studying the gas chemically enriched by the release of dust mantles due to the passage of a shock. A total of 12 emission lines (up to E{sub u} = 63 K) of CH{sub 2}DOH, HDCO, and DCN are detected. In addition, two lines of NH{sub 2}D and HDO are tentatively reported. To estimate the deuteration, we also extracted from our spectral survey emission lines of non-deuterated isotopologues ({sup 13}CH{sub 3}OH, H{sub 2} {sup 13}CO, H{sup 13}CN, H{sub 2} {sup 13}CO, and NH{sub 3}). We infer higher deuteration fractions for CH{sub 3}OH (D/H = 0.2-2 Multiplication-Sign 10{sup -2}) and H{sub 2}CO (5-8 Multiplication-Sign 10{sup -3}) than for H{sub 2}O (0.4-2 Multiplication-Sign 10{sup -3}), HCN ({approx}10{sup -3}), and ammonia ({<=}3 Multiplication-Sign 10{sup -2}). The measurement of deuteration of water, formaldehyde, and methanol in L1157-B1 provides a fossil record of the gas before it was shocked by the jet driven by the protostar. A comparison with gas-grain models indicates that the gas passed through a low-density ({<=}10{sup 3} cm{sup -3}) phase, during which the bulk of water ices formed, followed by a phase of increasing density, up to 3 Multiplication-Sign 10{sup 4} cm{sup -3}, during which formaldehyde and methanol ices formed.

  19. Low-frequency ESR studies on permeable and impermeable deuterated nitroxyl radicals in corn oil solution.

    Science.gov (United States)

    David Jebaraj, D; Utsumi, Hideo; Milton Franklin Benial, A

    2018-04-01

    Low-frequency electron spin resonance studies were performed for 2 mM concentration of deuterated permeable and impermeable nitroxyl spin probes, 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl and 3-carboxy-2,2,5,5,-tetramethyl-1-pyrrolidinyloxy in pure water and various concentrations of corn oil solution. The electron spin resonance parameters such as the line width, hyperfine coupling constant, g factor, rotational correlation time, permeability, and partition parameter were estimated. The broadening of line width was observed for nitroxyl radicals in corn oil mixture. The rotational correlation time increases with increasing concentration of corn oil, which indicates the less mobile nature of spin probe in corn oil mixture. The membrane permeability and partition parameter values were estimated as a function of corn oil concentration, which reveals that the nitroxyl radicals permeate equally into the aqueous phase and oil phase at the corn oil concentration of 50%. The electron spin resonance spectra demonstrate the permeable and impermeable nature of nitroxyl spin probes. From these results, the corn oil concentration was optimized as 50% for phantom studies. In this work, the corn oil and pure water mixture phantom models with various viscosities correspond to plasma membrane, and whole blood membrane with different hematocrit levels was studied for monitoring the biological characteristics and their interactions with permeable nitroxyl spin probe. These results will be useful for the development of electron spin resonance and Overhauser-enhanced magnetic resonance imaging modalities in biomedical applications. Copyright © 2017 John Wiley & Sons, Ltd.

  20. COSMOLOGICAL CONCORDANCE OR CHEMICAL COINCIDENCE? DEUTERATED MOLECULAR HYDROGEN ABUNDANCES AT HIGH REDSHIFT

    International Nuclear Information System (INIS)

    Tumlinson, J.; Malec, A. L.; Murphy, M. T.; Carswell, R. F.; Jorgenson, R. A.; Buning, R.; Ubachs, W.; Milutinovic, N.; Ellison, S. L.; Prochaska, J. X.; Wolfe, A. M.

    2010-01-01

    We report two detections of deuterated molecular hydrogen (HD) in QSO absorption-line systems at z>2. Toward J2123-0500, we find N(HD) =13.84 ± 0.2 for a sub-Damped Lyman Alpha system (DLA) with metallicity ≅0.5Z sun and N(H 2 ) = 17.64 ± 0.15 at z = 2.0594. Toward FJ0812+32, we find N(HD) =15.38 ± 0.3 for a solar-metallicity DLA with N(H 2 ) = 19.88 ± 0.2 at z = 2.6265. These systems have ratios of HD to H 2 above that observed in dense clouds within the Milky Way disk and apparently consistent with a simple conversion from the cosmological ratio of D/H. These ratios are not readily explained by any available model of HD chemistry, and there are no obvious trends with metallicity or molecular content. Taken together, these two systems and the two published z>2 HD-bearing DLAs indicate that HD is either less effectively dissociated or more efficiently produced in high-redshift interstellar gas, even at low molecular fraction and/or solar metallicity. It is puzzling that such diverse systems should show such consistent HD/H 2 ratios. Without clear knowledge of all the aspects of HD chemistry that may help determine the ratio HD/H 2 , we conclude that these systems are potentially more revealing of gas chemistry than of D/H itself and that it is premature to use such systems to constrain D/H at high redshift.

  1. Deuterated (d6)-dextromethorphan elicits antidepressant-like effects in mice.

    Science.gov (United States)

    Nguyen, Linda; Scandinaro, Anna L; Matsumoto, Rae R

    2017-10-01

    The over-the-counter antitussive dextromethorphan (DM) may have rapid antidepressant actions based on its overlapping pharmacology with ketamine, which has shown fast antidepressant effects but whose widespread use remains limited by problematic side effects. We have previously shown that DM produces antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST) that are mediated in part through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic (AMPA) and sigma-1 receptors, two protein targets associated with a faster onset of antidepressant efficacy. To utilize DM clinically, however, a major challenge that must be addressed is its rapid first-pass metabolism. Two strategies to inhibit metabolism of DM and maintain stable therapeutic blood levels are 1) chemically modifying DM and 2) adding quinidine, an inhibitor of the primary metabolizer of DM, the cytochrome P450 (CYP) 2D6 enzyme. The purpose of this study was to determine if modified DM (deuterated (d6)-DM) elicits antidepressant-like effects and if AMPA and sigma-1 receptors are involved. Furthermore, d6-DM was tested in conjunction with quinidine to determine if further slowing the metabolism of d6-DM affects its antidepressant-like actions. In the FST and TST, d6-DM produced antidepressant-like effects. Upon further investigation in the FST, the most validated animal model for predicting antidepressant efficacy, d6-DM produced antidepressant-like effects both in the absence and presence of quinidine. However, pretreatment with neither an AMPA receptor antagonist (NBQX) nor sigma-1 receptor antagonists (BD1063, BD1047) significantly attenuated the antidepressant-like effects. The data suggest d6-DM has antidepressant-like effects, though it may be recruiting different molecular targets and/or acting through a different mix or ratio of metabolites from regular DM. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    International Nuclear Information System (INIS)

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalén; Palmqvist, Lars; Jeppsson, Anders; Hultén, Lillemor Mattsson

    2012-01-01

    Highlights: ► We found a 17-fold upregulation of ALOX15 in the ischemic heart. ► Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. ► We observed increased levels of proinflammatory markers in ischemic heart tissue. ► Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1α (HIF-1α) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1α mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield important insights into the underlying association between hypoxia and inflammation in the human ischemic heart disease.

  3. Residue-specific membrane location of peptides and proteins using specifically and extensively deuterated lipids and {sup 13}C-{sup 2}H rotational-echo double-resonance solid-state NMR

    Energy Technology Data Exchange (ETDEWEB)

    Xie Li; Ghosh, Ujjayini; Schmick, Scott D.; Weliky, David P., E-mail: weliky@chemistry.msu.edu [Michigan State University, Department of Chemistry (United States)

    2013-01-15

    Residue-specific location of peptides in the hydrophobic core of membranes was examined using {sup 13}C-{sup 2}H REDOR and samples in which the lipids were selectively deuterated. The transmembrane topology of the KALP peptide was validated with this approach with substantial dephasing observed for deuteration in the bilayer center and reduced or no dephasing for deuteration closer to the headgroups. Insertion of {beta} sheet HIV and helical and {beta} sheet influenza virus fusion peptides into the hydrophobic core of the membrane was validated in samples with extensively deuterated lipids.

  4. Omega-6 fatty acid biomarkers and incident type 2 diabetes : pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

    NARCIS (Netherlands)

    Wu, Jason H.Y.; Marklund, Matti; Imamura, Fumiaki; Tintle, Nathan; Ardisson Korat, Andres V.; de Goede, Janette; Zhou, Xia; Yang, Wei Sin; de Oliveira Otto, Marcia C.; Kröger, Janine; Qureshi, Waqas; Virtanen, Jyrki K.; Bassett, Julie K.; Frazier-Wood, Alexis C.; Lankinen, Maria; Murphy, Rachel A.; Rajaobelina, Kalina; Del Gobbo, Liana C.; Forouhi, Nita G.; Luben, Robert; Khaw, Kay Tee; Wareham, Nick; Kalsbeek, Anya; Veenstra, Jenna; Luo, Juhua; Hu, Frank B.; Lin, Hung Ju; Siscovick, David S.; Boeing, Heiner; Chen, Tzu An; Steffen, Brian; Steffen, Lyn M.; Hodge, Allison; Eriksdottir, Gudny; Smith, Albert V.; Gudnason, Vilmunder; Harris, Tamara B.; Brouwer, Ingeborg A.; Berr, Claudine; Helmer, Catherine; Samieri, Cecilia; Laakso, Markku; Tsai, Michael Y.; Giles, Graham G.; Nurmi, Tarja; Wagenknecht, Lynne; Schulze, Matthias B.; Lemaitre, Rozenn N.; Chien, Kuo Liong; Soedamah-Muthu, Sabita S.; Geleijnse, Johanna M.; Sun, Qi; Harris, William S.; Lind, Lars; Ärnlöv, Johan; Riserus, Ulf; Micha, Renata; Mozaffarian, Dariush

    2017-01-01

    Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with

  5. Dietary supplementation of essential fatty acids in larval pikeperch (Sander lucioperca); short and long term effects on stress tolerance and metabolic physiology

    DEFF Research Database (Denmark)

    Lund, Ivar; Skov, Peter Vilhelm; Hansen, Benni Winding

    2012-01-01

    The present study examined the effects of feeding pike perch larvae Artemia, enriched with either docosahexanoic acid (DHA), arachidonic acid (ARA), oleic acid (OA), olive oil (OO) or a commercial enrichment DHA Selco (DS) on tissue lipid deposition, stress tolerance, growth and development...

  6. Omega-6 fatty acid biomarkers and incident type 2 diabetes: Pooled analysis of individual-level data for 39740 adults from 20 prospective cohort studies

    Science.gov (United States)

    The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2...

  7. Oxidizability of unsaturated fatty acids and of a non-phenolic lignin structure in the manganese peroxidase-dependent lipid peroxidation system

    Science.gov (United States)

    Alexander N. Kapich; Tatyana V. Korneichik; Annele Hatakka; Kenneth E. Hammel

    2010-01-01

    Unsaturated fatty acids have been proposed to mediate the oxidation of recalcitrant, non-phenolic lignin structures by fungal manganese peroxidases (MnP), but their precise role remains unknown. We investigated the oxidizability of three fatty acids with varying degrees of polyunsaturation (linoleic, linolenic, and arachidonic acids) by measuring conjugated dienes...

  8. Effects of dietary conjugated linoleic acid and linoleic:linolenic acid ratio on polyunsaturated fatty acid status in laying hens.

    Science.gov (United States)

    Du, M; Ahn, D U; Sell, J L

    2000-12-01

    A study was conducted to determine the effects of dietary conjugated linoleic acid (CLA) and the ratio of linoleic:linolenic acid on long-chain polyunsaturated fatty acid status. Thirty-two 31-wk-old White Leghorn hens were randomly assigned to four diets containing 8.2% soy oil, 4.1% soy oil + 2.5% CLA (4.1% CLA source), 4.1% flax oil + 2.5% CLA, or 4.1% soy oil + 4.1% flax oil. Hens were fed the diets for 3 wk before eggs and tissues were collected for the study. Lipids were extracted from egg yolk and tissues, classes of egg yolk lipids were separated, and fatty acid concentrations of total lipids, triglyceride, phosphatidylethanolamine, and phosphatidylcholine were analyzed by gas chromatography. The concentrations of monounsaturated fatty acids and non-CLA polyunsaturated fatty acids were reduced after CLA feeding. The amount of arachidonic acid was decreased after CLA feeding in linoleic acid- and linolenic acid-rich diets, but amounts of eicosapentaenoic acid and docosahexaenoic acid were increased in the linolenic-rich diet, indicating that the synthesis or deposition of long-chain n-3 fatty acids was accelerated after CLA feeding. The increased docosahexaenoic acid and eicosapentaenoic acid contents in lipid may be compensation for the decreased arachidonic acid content. Dietary supplementation of linoleic acid increased n-6 fatty acid levels in lipids, whereas linolenic acid increased n-3 fatty acid levels. Results also suggest that CLA might not be elongated to synthesize long-chain fatty acids in significant amounts. The effect of CLA in reducing the level of n-6 fatty acids and promoting the level of n-3 fatty acids could be related to the biological effects of CLA.

  9. Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

    Directory of Open Access Journals (Sweden)

    Wei Hsum Yap

    2015-01-01

    Full Text Available Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS. The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in various in vivo and in vitro experimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB/COX-2 expression, upstream protein kinase signaling, and phospholipase A2 enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli.

  10. Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core

    Directory of Open Access Journals (Sweden)

    Sándor B. Ötvös

    2016-03-01

    Full Text Available Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D2 gas generation were exploited to suppress undesired over-reactions and to maximize reaction rates simultaneously. The novel deuterium-containing chalcone derivatives may have interesting biological effects and improved metabolic properties as compared with the parent compounds.

  11. The Deuterator: software for the determination of backbone amide deuterium levels from H/D exchange MS data

    Directory of Open Access Journals (Sweden)

    Tsinoremas NF

    2007-05-01

    Full Text Available Abstract Background The combination of mass spectrometry and solution phase amide hydrogen/deuterium exchange (H/D exchange experiments is an effective method for characterizing protein dynamics, and protein-protein or protein-ligand interactions. Despite methodological advancements and improvements in instrumentation and automation, data analysis and display remains a tedious process. The factors that contribute to this bottleneck are the large number of data points produced in a typical experiment, each requiring manual curation and validation, and then calculation of the level of backbone amide exchange. Tools have become available that address some of these issues, but lack sufficient integration, functionality, and accessibility required to address the needs of the H/D exchange community. To date there is no software for the analysis of H/D exchange data that comprehensively addresses these issues. Results We have developed an integrated software system for the automated analysis and representation of H/D exchange data that has been titled "The Deuterator". Novel approaches have been implemented that enable high throughput analysis, automated determination of deuterium incorporation, and deconvolution of overlapping peptides. This has been achieved by using methods involving iterative theoretical envelope fitting, and consideration of peak data within expected m/z ranges. Existing common file formats have been leveraged to allow compatibility with the output from the myriad of MS instrument platforms and peptide sequence database search engines. A web-based interface is used to integrate the components of The Deuterator that are able to analyze and present mass spectral data from instruments with varying resolving powers. The results, if necessary, can then be confirmed, adjusted, re-calculated and saved. Additional tools synchronize the curated calculation parameters with replicate time points, increasing throughput. Saved results can then

  12. Neutron and soft X-ray emission from wire array Z-pinch imploding onto deuterated fiber

    International Nuclear Information System (INIS)

    Klir, D.; Kravarik, J.; Kubes, P.

    2005-01-01

    The implosion of a wire array Z-pinch onto a deuterated fiber was studied. The peak power of soft X-rays exceeded 200 GW and the total emitted energy was 2-8 kJ. The radiation was close to the radiation of the blackbody with the temperature of 40 eV. The neutron yield from the D-D reaction reached 2x10 8 per shot. The mean energy of neutrons determined in the axial direction was shifted from 2.45 MeV towards higher energies [ru

  13. Measurement of the response of the deuterated scintillators NE 232 and NE 230 to protons and deuterons

    International Nuclear Information System (INIS)

    Tornow, W.; Arnold, W.; Herdtweck, J.; Mertens, G.

    1986-01-01

    The response of the deuterated scintillators NE 232 and NE 230 to protons and deuterons has been measured via elastic neutron-proton and neutron-deuteron scattering using the two mixtures of C 6 H 12 /C 6 D 12 and C 6 H 6 /C 6 D 6 and ''pure'' scintillators. The energy range covered for protons and deuterons was about 1-16 MeV. The light output relation Lsub(p)(E)=(1/2)Lsub(d) (2E) has been observed. (orig.)

  14. Raman spectra of ordinary and deuterated liquid ammonias; Spectres Raman des ammoniacs ordinaire et deuteries liquides

    Energy Technology Data Exchange (ETDEWEB)

    Ceccaldi, M; Leicknam, J P [Commissariat a l' Energie Atomique, 91 - Saclay (France). Centre d' Etudes Nucleaires, direction des materiaux et des combustibles nucleaires, departement de physico-chimie, service des isotopes stables, service de spectrometrie de masse

    1968-12-01

    The three deuterated ammonia molecules, as well as ordinary ammonia, have been examined in the liquid state by Raman spectroscopy using a high-pressure cell described elsewhere. This work thus completes the infrared spectrometry studies. We have examined the NH and ND valency absorption regions. The polarization measurements and isotope effect considerations make it possible to confirm most of the attributions recently proposed for interpreting the infrared spectra of the four isotopic molecules: the apparent disagreement between the NH{sub 3} and ND{sub 3} spectra obtained in this region by infrared and Raman spectroscopy is discussed: by the first technique the number of bands in the spectra corresponds well to the theoretically expected number, and the relative intensities conform more or less to expectations; the Raman spectra however have a strong supplementary band in the same region, produced by a Fermi resonance; it is possible to explain, from theoretical considerations, why this resonance appears so easily in the Raman spectrum, whereas it is detected in the infrared only by a very detailed analysis of the effects of solvents on the ammonia. (authors) [French] Les trois ammoniacs deuteries, ainsi que l'ammoniac ordinaire, sont examines a l'etat liquide par spectrometrie Raman, a l'aide d'une cuve haute pression decrite par ailleurs. Ce travail complete donc les etudes effectuees par spectrometrie infra-rouge. Nous avons examine les regions d'absorption de valence NH et ND. Les mesures de polarisation et des considerations sur les effets isotopiques permettent de confirmer la plupart des attributions proposees recemment pour interpreter les spectres infra-rouges des quatre molecules isotopiques: on discute egalement l'apparent desaccord entre les spectres de NH{sub 3} et de ND{sub 3} obtenus dans cette region par infra-rouge et Raman: par la premiere technique le nombre de bandes relevees sur les spectres correspond bien au nombre theoriquement attendu et

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

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

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

  16. Direct Detection of Hardly Detectable Hidden Chirality of Hydrocarbons and Deuterated Isotopomers by a Helical Polyacetylene through Chiral Amplification and Memory.

    Science.gov (United States)

    Maeda, Katsuhiro; Hirose, Daisuke; Okoshi, Natsuki; Shimomura, Kouhei; Wada, Yuya; Ikai, Tomoyuki; Kanoh, Shigeyoshi; Yashima, Eiji

    2018-03-07

    We report the first direct chirality sensing of a series of chiral hydrocarbons and isotopically chiral compounds (deuterated isotopomers), which are almost impossible to detect by conventional optical spectroscopic methods, by a stereoregular polyacetylene bearing 2,2'-biphenol-derived pendants. The polyacetylene showed a circular dichroism due to a preferred-handed helix formation in response to the hardly detectable hidden chirality of saturated tertiary or chiroptical quaternary hydrocarbons, and deuterated isotopomers. In sharp contrast to the previously reported sensory systems, the chirality detection by the polyacetylene relies on an excess one-handed helix formation induced by the chiral hydrocarbons and deuterated isotopomers via significant amplification of the chirality followed by its static memory, through which chiral information on the minute and hidden chirality can be stored as an excess of a single-handed helix memory for a long time.

  17. Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

    OpenAIRE

    Liu, Guangming; Bibus, Douglas M.; Bode, Ann M.; Ma, Wei-Ya; Holman, Ralph T.; Dong, Zigang

    2001-01-01

    Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 3 (ω3) fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 6 (ω6) fatty acids such as arachidonic ac...

  18. Estimation of nitrogenase activity in the presence of ethylene biosynthesis by use of deuterated acetylene as a substrate

    International Nuclear Information System (INIS)

    Lin-Vien, D.; Fateley, W.G.; Davis, L.C.

    1989-01-01

    Nitrogenase reduces deuterated acetylene primarily to cis dideuterated ethylene. This can be distinguished from undeuterated ethylene by the use of Fourier transform infrared spectroscopy. Characteristic bands in the region from 800 to 3,500 cm-1 can be used to identify and quantitate levels of these products. This technique is applicable to field studies of nitrogen fixation where ethylene biosynthesis by plants or bacteria is occurring. We have verified the reaction stoichiometry by using Klebsiella pneumoniae and Bradyrhizobium japonicum in soybeans. The most useful bands for quantitation of substrate purity and product distribution are as follows: acetylene-d0, 3,374 cm-1; acetylene-d1, 2,584 cm-1; acetylene-d2, 2,439 cm-1; cis-ethylene-d2, 843 cm-1; trans-ethylene-d2, 988 cm-1; ethylene-d1, 943 cm-1; ethylene-d0, 949 cm-1. (The various deuterated ethylenes and acetylenes are designated by a lowercase d and subscript to indicate the number, but not the position, of deuterium atoms in the molecule.) Mass spectrometry coupled to a gas chromatograph system has been used to assist in quantitation of the substrate and product distributions. Significant amounts of trans-ethylene-d2 were produced by both wild-type and nifV mutant K. pneumoniae. Less of this product was observed with the soybean system

  19. Theoretical modeling of deuteration-induced shifts of the 0-0 bands in absorption spectra of selected aromatic amines: the role of the double-well potential.

    Science.gov (United States)

    Andrzejak, Marcin; Kolek, Przemysław

    2013-12-05

    The harmonic approximation fails for inversion of the NH2 group in the ground state of aromatic amines as this vibration is characterized by a symmetric double-well potential with relatively small energy barrier. In such cases, the standard harmonic vibrational analysis is inapplicable: the inversion frequency calculated for the bottom of the potential well is strongly overestimated, while it attains imaginary values for the planar conformation of the molecule. The model calculations are discussed taking explicitly into account the presence of the double-well potential. The study is initially focused on reproduction of the deuteration-induced shifts of the 0-0 absorption band for anthranilic acid. The (incorrect) harmonic frequency of the NH2 inversion is replaced by a better one, obtained from numerical calculations employing a simple, quartic-quadratic model for the double-well potential, which is parametrized using just the harmonic frequency of the inversion and the height of the energy barrier. This operation brings theoretical results to qualitative agreement with experiment. A still better match is achieved with a modified version of the model that accounts for mixing of the NH2 inversion mode with other normal modes while retaining the initial simplicity of one-dimensional approach. The corrected results show surprisingly good accuracy, with deviations of the calculated shifts from the experimental values reduced to less than 5 cm(-1). In order to test the performance of the model for systems with higher energy barrier for the NH2 inversion, we have measured the LIF excitation spectra of three different amminobenzonitriles. Partial assignment of the 0-0 bands has been achieved based on their relative intensities for samples with different isotopic exchange ratios. Calculated shifts are in excellent agreement with experimental values for the identified bands. Theoretical predictions are used to complete the assignment of the 0-0 bands in the spectra of the

  20. Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells

    OpenAIRE

    Aires, Virginie; Hichami, Aziz; Moutairou, Kabirou; Khan, Naim Akhtar

    2003-01-01

    Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery.Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells.To assess the role of calcium in t...

  1. Crystal Structure of the Sodium Cobaltate Deuterate Superconductor NaxCoO2o4xD2O (x=1/3)

    OpenAIRE

    Jorgensen, J. D.; Avdeev, M.; Hinks, D. G.; Burley, J. C.; Short, S.

    2003-01-01

    Neutron and x-ray powder diffraction have been used to investigate the crystal structures of a sample of the newly-discovered superconducting sodium cobaltate deuterate compound with composition Na0.31(3)CoO2o1.25(2)D2O and its anhydrous parent compound Na0.61(1)CoO2. The deuterate superconducting compound is formed by coordinating four D2O molecules (two above and two below) to each Na ion in a way that gives Na-O distances nearly equal to those in the parent compound. One deuteron of the D2...

  2. Neutron total cross-section of hydrogenous and deuterated 1- and 2-propanol and n-butanol measured using the VESUVIO spectrometer

    Science.gov (United States)

    Rodríguez Palomino, L. A.; Dawidowski, J.; Márquez Damián, J. I.; Cuello, G. J.; Romanelli, G.; Krzystyniak, M.

    2017-10-01

    This work presents the total cross sections of a set of normal and deuterated alcohols (hydrogenous 1- and 2-propanol and n-butanol, 1-propanol(OD) and fully deuterated 2-propanol and n-butanol), measured at spectrometer VESUVIO (ISIS spallation neutron source, United Kingdom). Granada's Synthetic Model was applied to describe those systems and a satisfactory agreement with the measured total cross section was achieved in the range of energies from 10-3 to 100 eV. The input parameters of the model were determined from the essential features of the vibrational spectra of the atoms that compose the systems, which were studied using Molecular Dynamics.

  3. Syntheses of deuterated leu-enkephalins and their use as internal standards for the quantification of leu-enkephalin by fast atom bombardment mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Benfenati, E. (Istituto di Ricerche Farmacologiche Mario Negri, Bergamo (Italy) Istituto di Ricerche Farmacologiche Mario Negri, Milan (Italy)); Icardi, G.; Chen, S. (Istituto di Ricerche Farmacologiche Mario Negri, Bergamo (Italy)); Fanelli, R. (Istituto di Ricerche Farmacologiche Mario Negri, Milan (Italy))

    1990-04-01

    We have developed a synthetic method for the preparation of di- and pentadeuterated leu-enkephalin (LE), Tyr-Gly-Gly-Phe-Leu, by proton-deuterium exchange using CF[sub 3]COOO[sup 2]H. Four to six deuterium atoms are introduced using a reaction temperature of 120[sup o]C and if 5% of [sup 2]H[sub 2]O is added the di-deuterated LE is obtained. These deuterated compounds are used as internal standards to plot calibration curves of LE using fast atom bombardment mass spectrometry. (author).

  4. Effect of hydrostatic pressure on the antiferroelectric phase transitions in ammonium dihydrogen arsenate NH4H2AsO4 and deuterated analogue

    International Nuclear Information System (INIS)

    Gesi, Kazuo; Ozawa, Kunio

    1984-01-01

    Effect of hydrostatic pressure on the antiferroelectric phase transitions in NH 4 H 2 AsO 4 and deuterated analogue (deuterium concentration --80%) was studied by dielectric constant measurements at high pressures up to about 0.8GPa. The transition temperature linearly decreases with increasing pressure with the ratios of -19.7K GPa -1 and -14.5K GPa -1 for NH 4 H 2 AsO 4 and the deuterated compound, respectively. The pressure effect is compared with previously reported results of other KH 2 PO 4 -type ferro- and antiferroelectric crystals. (author)

  5. Time-related fatty acid profiles of plasma and lymph after gastric administration of fats to rats fed high-fat diets

    DEFF Research Database (Denmark)

    Porsgaard, Trine; Straarup, E. M.; Brand, C. L.

    2000-01-01

    investigated. Although decreasing during the early absorptive phase a continuous contribution of endogenous trans-C18:I and arachidonic acid was observed in plasma. Small differences were observed between the 4 dietary fats. In lymph, the transport of trans-C18:1 rose markedly after butter administration...... partly caused by the content of this fatty acid in butter, while the transport of trans-C18:1 after R/C10 was unchanged although still transported at a reasonable high rate. The transport of arachidonic acid increased after administration of both butter and R/C10. Minor changes were observed in plasma...

  6. Metabolism of arachidonic acid derivatives (prostaglandins and related compounds). Radioimmunological methods to measure certain of these compounds

    International Nuclear Information System (INIS)

    Sors, Herve.

    1978-06-01

    The detection of prostaglandins, present in tissues at concentrations of about 10 -7 to 10 -11 g/g and able to induce physiological effects at concentrations of the picomole order, sets the analyst a particularly difficult problem. Owing to the complexity of their metabolism, the existence of many structurally similar compounds and the low concentrations present, it is necessary to develop highly specific and sensitive methods. Suitable techniques are: the biological activity test or biotest; gas-liquid chromatogaphy combined with mass spectrometry; the radioimmunological method. The radioimmunological analysis procedure is developed: preparation of immunogens and immunisation; preparation of tracers; treatment of biological samples. The different radioimmunological systems are presented: determination of antiserum affinity constants; dose-response curves and sensitivities; specificities; applications to biological measurements. Some remarks are called for concerning the RIA of prostaglandins: the difficulty of obtaining antisera seems to depend on the nature of the PG, a good anti-PGB or PGFα is easier to get than an anti-PGA or PGE. The analysis of each compound implies the use of a corresponding immunoserum and it is therefore essential to have a range of immunosera in order to study as large a number of biosynthesis derivatives as possible; too many physiological investigations are still viewed in relation to one PG only (often a primary PG) at the expense of other derivatives [fr

  7. Senegalese sole (solea senegalensis) broodstock nutrition: arachidonic acid (20:4n-6, ARA) and reproductive physiology

    OpenAIRE

    Norambuena Filcun, Fernando

    2012-01-01

    Considerando la total ausencia del desove natural y fertilización de huevos en reproductores de lenguado Senegalés (Solea senegalensis) nacidos en cautividad (G1) comparados con peces salvajes mantenidos en cautivo que son capaces de producir huevos fertilizados viables para su cultivo. Esta tesis se realizó con el objetivo de determinar la importancia dietética de los ácidos grasos, específicamente del ácido graso araquidónico (20:4n-6, ARA) y su interacción en la disfunción reproductiva pre...

  8. Anti-Inflammatory Effects of Benfotiamine are Mediated Through the Regulation of Arachidonic Acid Pathway in Macrophages

    OpenAIRE

    Shoeb, Mohammad; Ramana, Kota V

    2011-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of...

  9. Cell Signaling and Neurotoxicity: 3H-Arachidonic acid release (Phospholipase A2) in cerebellar granule neurons

    Science.gov (United States)

    Cell signaling is a complex process which controls basic cellular activities and coordinates actions to maintain normal cellular homeostasis. Alterations in signaling processes have been associated with neurological diseases such as Alzheimer's and cerebellar ataxia, as well as, ...

  10. Quantitative imaging of water flow in soil and roots using neutron radiography and deuterated water

    Energy Technology Data Exchange (ETDEWEB)

    Zarebanadkouki, Mohsen

    2013-05-08

    Where and how fast do roots take up water? Despite its importance in plant and soil sciences, there is limited experimental information on the location of water uptake along the roots of transpiring plants growing in soil. The answer to this question requires direct and in-situ measurement of the local flow of water into the roots. The aim of this study was to develop and apply a new method to quantify the local fluxes of water into different segments of the roots of intact plants. To this end, neutron radiography was used to trace the transport of deuterated water (D{sub 2}O) into the roots of lupines. Lupines were grown in aluminum containers filled with sandy soil. The soil was partitioned into different compartments using 1 cm-thick layers of coarse sand as capillary barriers. These barriers limited the diffusion of D{sub 2}O within the soil compartments. D{sub 2}O was locally injected into the selected soil compartments during the day (transpiring plants) and night (non-transpiring plants). Transport of D{sub 2}O into roots was then monitored by neutron radiography with spatial resolution of 100 μm and time intervals of 10 seconds. Neutron radiographs showed that: i) transport of D{sub 2}O into roots was faster during the day than during the night; 2) D{sub 2}O quickly moved along the roots towards the shoots during the day, while at night this axial transport was negligible. The differences between day and night measurements were explained by convective transport of D{sub 2}O into the roots. To quantify the net flow of water into roots, a simple convection-diffusion model was developed, where the increase rate of D{sub 2}O concentration in roots depended on the convective transport (net root water uptake) and the diffusion of D{sub 2}O into roots. The results showed that water uptake was not uniform along the roots. Water uptake was higher in the upper soil layers than in the deeper ones. Along an individual roots, the water uptake rate was higher in the

  11. Nano-scale bubble thermonuclear fusion in acoustically cavitated deuterated liquid

    International Nuclear Information System (INIS)

    Robert I Nigmatulin; Richard T Lahey Jr; Rusi Taleyarkhan

    2005-01-01

    Full text of publication follows: It has been experimentally shown (Taleyarkhan, West, Cho, Lahey, Nigmatulin, Block, 2002, 2004) that neutron emission and tritium formation may occur in deuterated acetone (D-acetone C 3 DO 6 ) under acoustic cavitation conditions. Intensity of the fast neutron (2.45 MeV) emission and tritium nucleus production is ∼ 4 x 10 5 s -1 . This suggests ultrahigh compression of matter produced inside bubbles during their collapse. In the paper a systematic theoretical analysis of the vapor bubble growth and subsequent implosion in intense acoustic fields in D-acetone is presented. The goal is to describe and explain the experimental observations of thermonuclear fusion for collapsing cavitation bubble in D-acetone. The dynamics of bubbles formed during maximum rarefaction in the liquid is numerically studied on the basis of the developed models of a single bubble and bubble clusters. It is supposed that during their growth the bubbles coagulate and form a few bigger bubbles, which then collapse under the action of additional pressure pulses produced in the liquid through the intensification of acoustic waves within the cluster. A shock wave is shown to be formed inside the bubble during the latter's rapid contraction. Focusing of this shock wave in the bubble center initiates dissociation and ionization, violent increases in density (10 4 kg m 3 ), pressure (10 10 -10 11 bar) and temperature (2 x 10 8 K), high enough to produce nuclear fusion reactions. The bubble looks like micro-hydrogen bomb. The diameter of the neutron emission zone is about 100 nm. The highest neutron emission is recorded at about 10-20 nm from the bubble center. It is found out that the intensity of bubble implosion and the number of neutron emitted increase with variations in nucleation phase, positive half-wave amplitude, liquid temperature and also with the involvement of coagulation mechanisms within the cluster during the bubble simultaneous growth. The number

  12. Quantitative imaging of water flow in soil and roots using neutron radiography and deuterated water

    International Nuclear Information System (INIS)

    Zarebanadkouki, Mohsen

    2013-01-01

    Where and how fast do roots take up water? Despite its importance in plant and soil sciences, there is limited experimental information on the location of water uptake along the roots of transpiring plants growing in soil. The answer to this question requires direct and in-situ measurement of the local flow of water into the roots. The aim of this study was to develop and apply a new method to quantify the local fluxes of water into different segments of the roots of intact plants. To this end, neutron radiography was used to trace the transport of deuterated water (D 2 O) into the roots of lupines. Lupines were grown in aluminum containers filled with sandy soil. The soil was partitioned into different compartments using 1 cm-thick layers of coarse sand as capillary barriers. These barriers limited the diffusion of D 2 O within the soil compartments. D 2 O was locally injected into the selected soil compartments during the day (transpiring plants) and night (non-transpiring plants). Transport of D 2 O into roots was then monitored by neutron radiography with spatial resolution of 100 μm and time intervals of 10 seconds. Neutron radiographs showed that: i) transport of D 2 O into roots was faster during the day than during the night; 2) D 2 O quickly moved along the roots towards the shoots during the day, while at night this axial transport was negligible. The differences between day and night measurements were explained by convective transport of D 2 O into the roots. To quantify the net flow of water into roots, a simple convection-diffusion model was developed, where the increase rate of D 2 O concentration in roots depended on the convective transport (net root water uptake) and the diffusion of D 2 O into roots. The results showed that water uptake was not uniform along the roots. Water uptake was higher in the upper soil layers than in the deeper ones. Along an individual roots, the water uptake rate was higher in the proximal segments than in the distal

  13. Polyunsaturated fatty acids and prostate cancer risk

    DEFF Research Database (Denmark)

    Khankari, Nikhil K; Murff, Harvey J; Zeng, Chenjie

    2016-01-01

    BACKGROUND: Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations...... and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (ORLA=0.95, 95%CI=0.92, 0.98) and α-linolenic acids (ORALA=0.96, 95%CI=0.93, 0.98), among men ...-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men

  14. Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Eoin Barrett

    Full Text Available The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15 were orally gavaged with either B. breve DPC6330 (10(9 microorganisms/day alone or in combination with 0.5% (w/w linoleic acid & 0.5% (w/w α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11 in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05. Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11 in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05, whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05 compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01 and α-linolenic acid in adipose tissue (p<0.001, whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05, and α-linolenic acid in adipose tissue (p<0.001. B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated

  15. Trans isomeric octadecenoic acids are related inversely to arachidonic acid and DHA and positively related to mead acid in umbilical vessel wall lipids

    NARCIS (Netherlands)

    Decsi, T; Boehm, G; Tjoonk, HMR; Molnar, S; Dijck-Brouwer, DAJ; Hadders-Algra, M; Martini, IA; Muskiet, FAJ; Boersma, ER

    2002-01-01

    Long-chain PUFA play an important role in early human neurodevelopment. Significant inverse correlations were reported between values of trans isomeric and long-chain PUFA in plasma lipids of preterm infants and children aged 1-15 yr as well as in venous cord blood lipids of full-term infants. Here

  16. Maslinic acid modulates secreted phospholipase A2-IIA (sPLA2-IIA ...

    Indian Academy of Sciences (India)

    Wei Hsum Yap

    2018-03-29

    Mar 29, 2018 ... Further analysis revealed that sPLA2-IIA only induced modest LDL oxidation and that inhibitory .... COX-2, was also reduced in primary human chondrocyte, primary rat .... oxidation (4.34 nmol MDA/mg protein) compared to native ..... rheumatoid fibroblast-like synoviocyte arachidonic acid meta- bolism.

  17. Three-dimensional cooling pattern of a granitic pluton 2. The study of deuteric sub-solidus reactions in the Toki granite, Central Japan

    International Nuclear Information System (INIS)

    Yuguchi, Takashi; Tsuruta, Tadahiko; Nishiyama, Tadao

    2011-01-01

    Petrographical studies examining the development and variations of sub-solidus reactions recorded in the Toki granite represent the three-dimensional cooling pattern of this zoned pluton in Central Japan. Samples collected from 19 boreholes in the Toki granite show characteristics indicative of spatial variations in the extent of the sub-solidus reactions. Exsolution coarsening has produced microperthite, including albite-rich lamellae, in this pluton, while deuteric coarsening has resulted in the formation of patchperthite, myrmekite, and the reaction rim. The extent of the deuteric coarsening reactions can be evaluated from the width and spacing of the albite-rich patch in patchperthite and from the thickness of myrmekite and the reaction rim. The width, spacing, and thickness of these textural features increase systematically with elevation; they also increase gradually in the horizontal inward direction in the western part of the pluton but not in the eastern part of the pluton. The systematic variations in textural development indicate that the Toki granite cooled effectively from the roof and from the western margin during the deuteric coarsening stage. The deuteric coarsening may have occurred at temperatures below 500°C, as indicated by ternary feldspar thermometry. (author)

  18. Straightforward synthesis of 2,2,4,4,5,7,7-d{sub 7}-cholestane: a new deuterated standard in petroleum analysis

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, Maicon Guerra de; Albert, Andre Luis Mazzei; Cardoso, Jari Nobrega; Lopes, Rosangela Sabbatini Capella; Lopes, Claudio Cerqueira, E-mail: maicon_iq@yahoo.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Quimica

    2013-10-01

    A short and efficient synthesis of heptadeuterated 2,2,4,4,5,7,7-d7-cholestane (1) from cholesterol (3) is described. The deuterated material will be useful for the analysis of different sources of petroleum in analytical geochemistry laboratories as internal standard for quantification of steranes via gas chromatography-mass spectrometry (GC-MS). (author)

  19. Preparation of deuterated heterocyclic five-membered ring compounds (furan, thiophene, pyrrole, and derivatives) by base-catalyzed hydrogen isotope exchange with deuterium oxide

    International Nuclear Information System (INIS)

    Heinrich, K.H.; Herrmann, M.; Moebius, G.; Sprinz, H.

    1984-01-01

    Several deuterated heterocyclic compounds of the type of furan,thiophene and pyrrole were prepared by base-catalyzed proton exchange with deuterium oxide at temperatures above 423 K in a closed system. The determination of deuterium and its distribution within the molecules was carried out by mass spectrometry and 1 H nmr spectrometry. (author)

  20. Synthesis of 3 alpha-deuterated 7 alpha-hydroxy-DHEA and 7-oxo-DHEA and application in LC-MS/MS plasma analysis

    Czech Academy of Sciences Publication Activity Database

    Sosvorova, L.K.; Sarek, J.; Vitku, J.; Kvasnica, Miroslav

    2016-01-01

    Roč. 112, AUG (2016), s. 88-94 ISSN 0039-128X Institutional support: RVO:61389030 Keywords : 7 alpha-Hydroxy-DHEA * 7-Oxo-DHEA * Deuterated standard Subject RIV: CE - Biochemistry Impact factor: 2.282, year: 2016

  1. A neutron powder diffraction study of deuterated α-resorcinol: a test of profile refinement using TLS constraints

    International Nuclear Information System (INIS)

    Bacon, G.E.; Lisher, E.J.

    1979-01-01

    Constrained TL, TLX and TLS refinements have been used, with the powder-profile method, in the analysis of accurate neutron powder data for deuterated α-resorcinol at room temperature. There is good agreement between the translational and librational parameters derived from the TL refinement and those obtained from an equivalent analysis of accurate single-crystal neutron measurements. The fine details of the benzene ring are lost in the powder analysis, but the molecular orientation and the OH bond angles are in good agreement with the single-crystal values. No significant improvement could be found in the powder fit by applying the full TLS theory and, therefore, the approximate TLX model appears to be adequate for powder data. (Auth.)

  2. Systematic study of (d,n) reactions at Ed = 16 MeV using a deuterated scintillator array

    International Nuclear Information System (INIS)

    Febbraro, M.; Becchetti, F.D.; Torres-Isea, R.O.; Riggins, A.; Lawrence, C.; Howard, A.M.; Kolata, J.J.

    2014-01-01

    We have developed a multi-element deuterated liquid scintillator array for the study of reactions involving neutrons utilizing high-speed digital signal processing. The liquid organic scintillators exhibit good digital pulse shape discrimination (DPSD). Typical configuration involves the detectors fixed to adjustable aluminium mounts, secured to an 80/20 aluminium frame. This allows for quick and adaptable configurations to be made for varying experimental conditions including measurements over a large angular range. A systematic study of (d,n) reactions at E d = 16 MeV on 9 Be, 11 B, 13 C, 14 N, 15 N, and 19 F has been conducted from 10 to 160 degrees (lab). In addition to previously unmeasured back-angle cross sections, this data can complement existing and future ( 3 He,d) measurements as an analog to (p,γ) for astrophysics applications

  3. Ion acceleration and D-D nuclear fusion in laser-generated plasma from advanced deuterated polyethylene.

    Science.gov (United States)

    Torrisi, Lorenzo

    2014-10-23

    Deuterated polyethylene targets have been irradiated by means of a 1016 W/cm2 laser using 600 J pulse energy, 1315 nm wavelength, 300 ps pulse duration and 70 micron spot diameter. The plasma parameters were measured using on-line diagnostics based on ion collectors, SiC detectors and plastic scintillators, all employed in time-of-flight configuration. In addition, a Thomson parabola spectrometer, an X-ray streak camera, and calibrated neutron dosimeter bubble detectors were employed. Characteristic protons and neutrons at maximum energies of 3.0 MeV and 2.45 MeV, respectively, were detected, confirming that energy spectra of reaction products coming from deuterium-deuterium nuclear fusion occur. In thick advanced targets a fusion rate of the order of 2 × 108 fusions per laser shot was calculated.

  4. Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients

    Directory of Open Access Journals (Sweden)

    Calder P.C.

    2003-01-01

    Full Text Available Lipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6. Linoleic acid is the precursor of arachidonic acid (20:4n-6. In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach.

  5. Synthesis of selectively deuterated and tritiated lupane derivatives with cytotoxic activity

    Czech Academy of Sciences Publication Activity Database

    Vlk, M.; Urban, M.; Elbert, Tomáš; Šarek, J.

    2013-01-01

    Roč. 298, č. 2 (2013), s. 1149-1157 ISSN 0236-5731 Grant - others:GA ČR(CZ) GA305/09/1216 Institutional support: RVO:61388963 Keywords : isotopic labelling * tritium * deuterium * betulin * betulinic acid * cytotoxicity Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 1.415, year: 2013

  6. Proximate composition, amino acid and fatty acid composition of fish maws.

    Science.gov (United States)

    Wen, Jing; Zeng, Ling; Xu, Youhou; Sun, Yulin; Chen, Ziming; Fan, Sigang

    2016-01-01

    Fish maws are commonly recommended and consumed in Asia over many centuries because it is believed to have some traditional medical properties. This study highlights and provides new information on the proximate composition, amino acid and fatty acid composition of fish maws of Cynoscion acoupa, Congresox talabonoides and Sciades proops. The results indicated that fish maws were excellent protein sources and low in fat content. The proteins in fish maws were rich in functional amino acids (FAAs) and the ratio of FAAs and total amino acids in fish maws ranged from 0.68 to 0.69. Among species, croaker C. acoupa contained the most polyunsaturated fatty acids, arachidonic acid, docosahexaenoic acid and eicosapntemacnioc acid, showing the lowest value of index of atherogenicity and index of thrombogenicity, showing the highest value of hypocholesterolemic/hypercholesterolemic ratio, which is the most desirable.

  7. Changes of fatty acid aerosol hygroscopicity induced by ozonolysis under humid conditions

    Directory of Open Access Journals (Sweden)

    O. Vesna

    2008-08-01

    Full Text Available Unsaturated fatty acids are important constituents of the organic fraction of atmospheric aerosols originating from biogenic or combustion sources. Oxidative processing of these may change their interaction with water and thus affect their effect on climate. The ozonolysis of oleic and arachidonic acid aerosol particles was studied under humid conditions in a flow reactor at ozone exposures close to atmospheric levels, at concentrations between 0.5 and 2 ppm. While oleic acid is a widely used proxy for such studies, arachidonic acid represents polyunsaturated fatty acids, which may decompose into hygroscopic products. The hygroscopic (diameter growth factor at 93% relative humidity (RH of the oxidized arachidonic particles increased up to 1.09 with increasing RH during the ozonolysis. In contrast, the growth factor of oleic acid was very low (1.03 at 93% RH and was almost invariant to the ozonolysis conditions, so that oleic acid is not a good model to observe oxidation induced changes of hygroscopicity under atmospheric conditions. We show for arachidonic acid particles that the hygroscopic changes induced by humidity during ozonolysis are accompanied by about a doubling of the ratio of carboxylic acid protons to aliphatic protons. We suggest that, under humid conditions, the reaction of water with the Criegee intermediates might open a pathway for the formation of smaller acids that lead to more significant changes in hygroscopicity. Thus the effect of water to provide a competing pathway during ozonolysis observed in this study should be motivation to include water, which is ubiquitously present in and around atmospheric particles, in future studies related to aerosol particle aging.

  8. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Manuela Oraldi

    2009-01-01

    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  9. Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes?

    Science.gov (United States)

    Block, Robert C; Harris, William S; Reid, Kimberly J; Spertus, John A

    2008-12-01

    Although fatty acid intake has been associated with risk of coronary disease events, the association between blood omega-6 and trans fatty acids (FAs) at the time of an acute coronary syndrome (ACS) is unknown. The relationship of blood FA composition to ACS was analyzed in 768 incident cases and 768 controls (matched on age, sex, and race). Compared to controls, ACS cases' blood cell membrane content of linoleic acid was 13% lower (P 3 times the odds for being a case (odds ratio [OR] 3.23, 95% confidence interval [CI] 2.63-4.17). The relationship of arachidonic acid to ACS was U shaped; compared to the first quartile of arachidonic acid, the ORs for case status in the second, third, and fourth quartiles were 0.73 (95% CI 0.47-1.13), 0.65 (95% CI 0.41-1.04), and 2.32 (95% CI 1.39-3.90), respectively. The OR for a 1-SD increase in trans oleic acid was 1.24 (95% CI 1.06-1.45), and for trans-trans linoleic acid, 1.1 (95% CI 0.93-1.30). All associations were independent of membrane omega-3 FA content. High blood levels of linoleic acid but low levels of trans oleic acid are inversely associated with ACS. The relationship of arachidonic acid to ACS appears more complex.

  10. The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions

    OpenAIRE

    Walker, Celia G.; West, Annette L.; Browning, Lucy M.; Madden, Jackie; Gambell, Joanna M.; Jebb, Susan A.; Calder, Philip C.

    2015-01-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0–4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify...

  11. Constant Fiber Number During Skeletal Muscle Atrophy and Modified Arachidonate Metabolism During Hypertrophy

    Science.gov (United States)

    Templeton, G.

    1985-01-01

    A previously documented shift from Type I to IIA predominance of the soleus muscle during rat suspension was further investigated to determine if this shift was by selective reduction of a single fiber type, simultaneous reduction and formation of fibers with different fiber types, or a transformation of fiber type by individual fibers. By partial acid digestion and dissection, average total soleus fiber number was found to be 3022 + or - 80 (SE) and 3008 + or - 64 before and after four-week suspension (n=12). Another area of current research was based on previous studies which indicate that prostaglandins are biosynthesized by skeletal muscle and evoke protein synthesis and degradation.

  12. Electron autoradiographic study of intracellular conversion of fatty acids into glycogen in rats with alloxan diabetes

    International Nuclear Information System (INIS)

    Lebkova, N.P.; Bobkov, Y.I.; Gorbonova, V.D.; Kolesova, O.E.

    1985-01-01

    An electron-autoradiographic study was undertaken of the intracellular distribution of hydrogen of fatty acids in alloxan diabetes. Alloxan diabetes was induced in rats; between 2 weeks and 2 months after development of the disease 0.1 ml of tritium-oleic or tritium-arachidonic acid was injected into the caudel vein of the rats. After decapitation, myocardial tissue from the subendocardial zone of the left ventricle, liver tissue, and glycogen isolated from the liver by a biochemical method, were taken for electron-autoradiographic investigation. Analysis of the data showed that a radioactive isotope, injected into the blood stream of the animals in the form of oleic or arachidonic acids, is incorporated into various structures of hepatocytes and cardiomyocytes. Direct proof is obtained to show that glycogen in hepatocytes and cardiomyoctyes of diabetic rats may be formed from fatty acids

  13. Selectively deuterated liquid crystalline cyanoazobenzene side-chain polyesters. 3. Investigations of laser induced segmental mobility by Fourier transform infrared spectroscopy

    DEFF Research Database (Denmark)

    Kulinna, Christian; Hvilsted, Søren; Hendann, Claudia

    1998-01-01

    The laser-induced anisotropy in thin films of an extensive number of cyanoazobenzene sidechain liquid crystalline polytetradecanedioates, -dodecanedioates, and -adipates selectively deuterated at different positions have been investigated with polarized FTIR spectroscopy. The analysis of the segm......The laser-induced anisotropy in thin films of an extensive number of cyanoazobenzene sidechain liquid crystalline polytetradecanedioates, -dodecanedioates, and -adipates selectively deuterated at different positions have been investigated with polarized FTIR spectroscopy. The analysis...... of the segmental orientation based on dichroic ratios of characteristic absorption bands shows that, in polyesters with long main-chain spacing (tetradecanedioates and dodecanedioates), not only the light sensitive azo chromophore but also the main-chain methylene segment and to a smaller extent the flexible...

  14. In situ-observation of the vertical motion of soil waters by means of deuterated water using the gamma/neutron method: Laboratory and field

    International Nuclear Information System (INIS)

    Moutonnet, P.; Couchat, P.; Brissaud, F.; Puard, M.; Pappalardo, A.

    1978-01-01

    In order to study water movements in the field, the gamma/neutron method for measuring deuterated water was investigated. A laboratory device is presented which supplies measurements on 5 ml soil solution samples. A probe for in situ experiments is studied in all its performances: Background, calibration (count rate versus volumetric deuterated water content) and resolution. A dispersive transport of D 2 O pulses on soil column is presented and checked with a numerical simulation model. Then simultaneous measurement of soil water content and D 2 O concentration by neutron moisture gauge and gamma/neutron probe enable us to interpret the evolution of D 2 O pulse with an experimental field irrigation. (orig.) [de

  15. Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes

    International Nuclear Information System (INIS)

    Hallaq, H.; Leaf, A.; Sellmayer, A.; Smith, T.W.

    1990-01-01

    Isolated neonatal cardiac myocytes have been utilized as a model for the study of cardiac arrhythmogenic factors. The myocytes respond to the toxic effects of a potent cardiac glycoside, ouabain at 0.1 mM, by an increase in their spontaneous beating rate and a reduction in amplitude of contractions resulting within minutes in a lethal state of contracture. Incubating the isolated myocytes for 3 endash 5 days in culture medium enriched with 5 μM arachidonic acid had no effect on the development of lethal contracture after subsequent exposure to 0.1 mM ouabain. By contrast, incubating the myocytes for 3 endash 5 days with 5 μM eicosapentaenoic acid completely prevented the toxic effects of ouabain at 0.1 mM. No differences in bumetanide-inhibitable 86 Rb flux were observed between the three preparations. However, measurements with fura-2 of cytosolic free calcium levels indicated that control and arachidonic acid-enriched myocytes developed toxic cytosolic calcium concentrations of 845 ± 29 and 757 ± 64 nM, respectively, on exposure to 0.1 mM ouabain, whereas in eicosapentaenoic acid-enriched myocytes, physiologic calcium levels were preserved. Incubating the myocytes with eicosapentaenoic acid for 3 endash 5 days resulted in a small reduction of arachidonic acid and a small but significant increase of eicosapentaenoic acid in membrane phospolipids of the myocytes

  16. Chronic sucrose intake decreases concentrations of n6 fatty acids, but not docosahexaenoic acid in the rat brain phospholipids.

    Science.gov (United States)

    Mašek, Tomislav; Starčević, Kristina

    2017-07-13

    We investigated the influence of high sucrose intake, administered in drinking water, on the lipid profile of the brain and on the expression of SREBP1c and Δ-desaturase genes. Adult male rats received 30% sucrose solution for 20 weeks (Sucrose group), or plain water (Control group). After the 20th week of sucrose treatment, the Sucrose group showed permanent hyperglycemia. Sucrose treatment also increased the amount of total lipids and fatty acids in the brain. The brain fatty acid profile of total lipids as well as phosphatidylethanolamine, phosphatidylcholine and cardiolipin of the Sucrose group was extensively changed. The most interesting change was a significant decrease in n6 fatty acids, including the important arachidonic acid, whereas the content of oleic and docosahexaenoic acid remained unchanged. RT-qPCR revealed an increase in Δ-5-desaturase and SREBP1c gene expression. In conclusion, high sucrose intake via drinking water extensively changes rat brain fatty acid profile by decreasing n6 fatty acids, including arachidonic acid. In contrast, the content of docosahexaenoic acid remains constant in the brain total lipids as well as in phospholipids. Changes in the brain fatty acid profile reflect changes in the lipid metabolism of the rat lipogenic tissues and concentrations in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Temperature effect on life-time of electron-excited uranyl ion. III. Effect of deuteration of solvent

    International Nuclear Information System (INIS)

    Lotnik, S.V.; Khamidullina, L.A.; Kazakov, V.P.

    2001-01-01

    Effect of deuteration of solvent was detected. The effect appeared in significant difference of shape of curves of uranyl ion (UO 2 2+ )* life-time temperature dependences in electron-excited state (τ). The curves were plotted during heating of frozen up to 77 K H 2 SO 4 solutions in H 2 O and D 2 SO 4 solutions in D 2 O. It was shown that in the case of D 2 SO 4 τ value in glass-like solution was lower then in polycrystalline sample, whereas in frozen H 2 SO 4 solutions there was opposite picture. Detected isotope effect was explained just as different proceeding of phase transition in H 2 SO 4 and D 2 SO 4 solutions so significant decrease of probability of nonradiating deactivation of (UO 2 2+ )* absorbed on D 2 SO 4 ·4D 2 O crystallohydrate surface in comparison with (UO 2 2+ )* absorbed on H 2 SO 4 ·4H 2 O and H 2 SO 4 ·6.5H 2 O crystallohydrate surfaces [ru

  18. Thermal unimolecular decomposition of bicyclopropyl and deuterated analogues: infrared photoactivation as a diagnostic tool in mechanistic organic chemistry

    International Nuclear Information System (INIS)

    Farneth, W.E.; Thomsen, M.W.

    1982-01-01

    The infrared photochemistry of bicyclopropyl yields product mixtures that are not easily rationalized on the basis of the mechanistic scheme suggested by previous pyrolysis work. As a result of this inconsistency the thermal chemistry of bicyclopropyl and analogues deuterated specifically on one ring has been reexamined. A significant new reaction channel involving the chemically activated decomposition of cyclohexene to ethylene and butadiene has been demonstrated. Evidence for the involvement of chemically activated cyclohexene is as follows: (1) isotopic labeling studies implying a symmetric intermediate, (2) a pressure-dependent ratio of cyclohexene to butadiene and ethylene, (3) good agreement between experimental and calculated values for the unimolecular rate constant for retro-Diels-Alder decay of ''hot'' cyclohexene. A comprehensive mechanism for the unimolecular decay of bicyclopropyl is proposed. The important elements of this mechanism are a single first-formed 1,3 biradical common to all products and the intervention of chemical activation in the generation of several of the secondary products

  19. Commensurately modulated 1/4 and 1/5 phases of deuterated betaine calcium chloride dihydrate: a neutron structural study

    International Nuclear Information System (INIS)

    Hernandez, O.; Cousson, A.; Kiat, J.M.; Ecole Centrale des Arts et Manufactures, 92 - Chatenay-Malabry; Paulus, W.; Technische Hochschule Aachen; Ezpeleta, J.M.; Zuniga, F.J.

    1999-01-01

    The structures of the commensurate 1/4 and 1/5 phases of the displacively modulated compound D-BCCD [deuterated betaine (trimethylammonioacetate) calcium chloride dihydrate, i.e. (CD 3 ) 3 NCD 2 COOCaCl 2 (D 2 O) 2 or CaCl 2 x C 5 D 11 NO 2 x 2D 2 O] have been determined by single-crystal neutron diffraction at 100 and 68 K, respectively. The structural model of the 1/4 phase is found to be quite different from that obtained previously from X-ray diffraction data of the hydrogenated compound. This discrepancy comes from the fact that X-ray irradiation induces in this compound an unusual time-dependent decrease of the intensity of high-order satellite diffraction peaks. As a consequence and due to the commensurate nature of the phases investigated, X-ray diffraction failed to detect the large anharmonicity of the structural modulation which is clearly present in the two structures determined by neutron diffraction. (orig.)

  20. Ground-based Detection of Deuterated Water in Comet C/2014 Q2 (Lovejoy) at IR Wavelengths

    Energy Technology Data Exchange (ETDEWEB)

    Paganini, L.; Mumma, M. J.; Villanueva, G. L. [Goddard Center for Astrobiology, NASA Goddard Space Flight Center, Greenbelt, MD (United States); Gibb, E. L. [Department of Physics and Astronomy, University of Missouri, St. Louis, MO (United States)

    2017-02-20

    We conducted a deep search for deuterated water (HDO) in the Oort Cloud comet C/2014 Q2 (Lovejoy), through infrared (IR) spectroscopy with NIRSPEC at the Keck Observatory. In this Letter, we present our detections of HDO and water (H{sub 2}O) in comet Lovejoy on 2015 February 4 (post-perihelion) after 1 hr integration on source. The IR observations allowed simultaneous detection of H{sub 2}O and HDO, yielding production rates of 5.9 ± 0.13 × 10{sup 29} and 3.6 ± 1.0 × 10{sup 26} molecules s{sup −1}, respectively. The simultaneous detection permitted accurate determination of the isotopic ratio (D/H) in water of 3.02 ± 0.87 × 10{sup −4}, i.e., larger than the value for water in terrestrial oceans (or Vienna Standard Mean Ocean Water, VSMOW) by a factor of 1.94 ± 0.56. This D/H ratio in water exceeds the value obtained independently at millimeter wavelengths (0.89 ± 0.25 VSMOW; pre-perihelion). We discuss these parameters in the context of origins and emphasize the need for contemporaneous measurements of HDO and H{sub 2}O.

  1. Ground-based Detection of Deuterated Water in Comet C/2014 Q2 (Lovejoy) at IR Wavelengths

    International Nuclear Information System (INIS)

    Paganini, L.; Mumma, M. J.; Villanueva, G. L.; Gibb, E. L.

    2017-01-01

    We conducted a deep search for deuterated water (HDO) in the Oort Cloud comet C/2014 Q2 (Lovejoy), through infrared (IR) spectroscopy with NIRSPEC at the Keck Observatory. In this Letter, we present our detections of HDO and water (H 2 O) in comet Lovejoy on 2015 February 4 (post-perihelion) after 1 hr integration on source. The IR observations allowed simultaneous detection of H 2 O and HDO, yielding production rates of 5.9 ± 0.13 × 10 29 and 3.6 ± 1.0 × 10 26 molecules s −1 , respectively. The simultaneous detection permitted accurate determination of the isotopic ratio (D/H) in water of 3.02 ± 0.87 × 10 −4 , i.e., larger than the value for water in terrestrial oceans (or Vienna Standard Mean Ocean Water, VSMOW) by a factor of 1.94 ± 0.56. This D/H ratio in water exceeds the value obtained independently at millimeter wavelengths (0.89 ± 0.25 VSMOW; pre-perihelion). We discuss these parameters in the context of origins and emphasize the need for contemporaneous measurements of HDO and H 2 O.

  2. Production and X-ray crystallographic analysis of fully deuterated human carbonic anhydrase II

    Energy Technology Data Exchange (ETDEWEB)

    Budayova-Spano, Monika [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Institut Laue-Langevin, 6 Rue Jules Horowitz, BP 156, 38042 Grenoble (France); Fisher, S. Zoë [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); Dauvergne, Marie-Thérèse [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Agbandje-McKenna, Mavis [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); Silverman, David N. [Department of Pharmacology and Therapeutics, PO Box 100267, University of Florida, Gainesville, FL 32610 (United States); Myles, Dean A. A. [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Oak Ridge National Laboratory, PO Box 2008, Oak Ridge, TN 37831 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France)

    2006-01-01

    This article reports the production, crystallization and X-ray structure determination of perdeuterated human carbonic anhydrase (HCA II). The refined structure is shown to be highly isomorphous with hydrogenated HCA II, especially with regard to the active site architecture and solvent network. Human carbonic anhydrase II (HCA II) is a zinc metalloenzyme that catalyzes the reversible hydration and dehydration of carbon dioxide and bicarbonate, respectively. The rate-limiting step in catalysis is the intramolecular transfer of a proton between the zinc-bound solvent (H{sub 2}O/OH{sup −}) and the proton-shuttling residue His64. This distance (∼7.5 Å) is spanned by a well defined active-site solvent network stabilized by amino-acid side chains (Tyr7, Asn62, Asn67, Thr199 and Thr200). Despite the availability of high-resolution (∼1.0 Å) X-ray crystal structures of HCA II, there is currently no definitive information available on the positions and orientations of the H atoms of the solvent network or active-site amino acids and their ionization states. In preparation for neutron diffraction studies to elucidate this hydrogen-bonding network, perdeuterated HCA II has been expressed, purified, crystallized and its X-ray structure determined to 1.5 Å resolution. The refined structure is highly isomorphous with hydrogenated HCA II, especially with regard to the active-site architecture and solvent network. This work demonstrates the suitability of these crystals for neutron macromolecular crystallography.

  3. Plasma cholesterol synthesis using deuterated water in humans: effect of short-term food restriction

    International Nuclear Information System (INIS)

    Jones, P.J.; Scanu, A.M.; Schoeller, D.A.

    1988-01-01

    Our purpose was to develop methods in humans to determine the fractional synthetic rate (FSR) of plasma pool free cholesterol using the rate of deuterium incorporation from body water. The sensitivity of this method was examined by measuring FSR after periods of fasting and feeding. Five healthy men with normal lipoprotein levels were given a prepared diet containing 40% of calories as fat and a polyunsaturated/saturated fatty acid ratio of 0.25 for 8 days, except for day 7 when they were given only drinking water. Beginning after the supper meal on day 6, they received no food until 8 AM on day 8 when they consumed meals as normal. Over days 7 and 8 the subjects were given prime and constant deuterium oxide orally to maintain body water deuterium enrichment at about 0.05 atom % excess. Plasma samples were obtained at 0 hours (day 7, 8 AM) and at 12, 24, 36, and 48 hours thereafter. Free cholesterol was extracted, purified by thin-layer chromatography, and combusted to water. The water was reduced to H 2 and analyzed for deuterium enrichment by isotope ratio mass spectrometry. Analytic precision of this system was determined as 3.5 0/00 (parts per mil) vs Standard Mean Ocean Water. Deuterium enrichment of plasma water for the group during the 48-hour deuterium oxide administration period was 3143 0/00 +/- 310 0/00 (mean +/- SEM). Cholesterol deuterium enrichment for the group during the 12-hour period of fasting (10.9 0/00 +/- 4.1 0/00) was not different from that during feeding (14.2 0/00 +/- 6.2 0/00)

  4. Fourier transform infrared difference spectroscopy of bacteriorhodopsin and its photoproducts regenerated with deuterated tyrosine

    International Nuclear Information System (INIS)

    Dollinger, G.; Eisenstein, L.; Lin, S.L.; Nakanishi, K.; Termini, J.

    1986-01-01

    Fourier transform infrared (FTIR) difference spectroscopy has been used to detect the vibrational modes due to tyrosine residues in the protein that change in position or intensity between light-adapted bacteriorhodopsin (LA) and other species, namely, the K and M intermediates and dark-adapted bacteriorhodopsin (DA). To aid in the identification of the bands that change in these various species, the FTIR spectra of the free amino acids Tyr-d0, Tyr-d2 ( 2 H at positions ortho to OH), and Tyr-d4 ( 2 H at positions ortho and meta to OH) were measured in H 2 O and D 2 O at low and high pH. The characteristic frequencies of the Tyr species obtained in this manner were then used to identify the changes in protonation state of the tyrosine residues in the various bacteriorhodopsin species. The two diagnostically most useful bands were the approximately 1480-cm-1 band of Tyr(OH)-d2 and the approximately 1277-cm-1 band of Tyr(O-)-d0. Mainly by observing the appearance or disappearance of these bands in the difference spectra of pigments incorporating the tyrosine isotopes, it was possible to identify the following: in LA, one tyrosine and one tyrosinate; in the K intermediate, two tyrosines; in the M intermediate, one tyrosine and one tyrosinate; and in DA, two tyrosines. Since these residues were observed in the difference spectra K/LA, M/LA, and DA/LA, they represent the tyrosine or tyrosinate groups that most likely undergo changes in protonation state due to the conversions. These changes are most likely linked to the proton translocation process of bacteriorhodopsin

  5. Metabolism in humans of cis-12,trans-15-octadecadienoic acid relative to palmitic, stearic, oleic and linoleic acids

    International Nuclear Information System (INIS)

    Emken, E.A.; Rohwedder, W.K.; Adlof, R.O.; Rakoff, H.; Gulley, R.M.

    1987-01-01

    Mixtures of triglycerides containing deuterium-labeled hexadecanoic acid (16:0), octadecanoic acid (18:0), cis-9-octadecenoic acid (9c-18:1), cis-9,cis-12-octadecadienoic acid (9c, 12c-18:2) and cis-12,trans-15-octadecadienoic acid (12c,15t-18:2) were fed to two young-adult males. Plasma lipid classes were isolated from samples collected periodically over 48 hr. Incorporation and turnover of the deuterium-labeled fats in plasma lipids were followed by gas chromatography-mass spectrometry (GC-MS) analysis of the methyl ester derivatives. Absorption of the deuterated fats was followed by GC-MS analysis of chylomicron triglycerides isolated by ultracentrifugation. Results were the following: (i) endogenous fat contributed about 40% of the total fat incorporated into chylomicron triglycerides; (ii) elongation, desaturation and chain-shortened products from the deuterated fats were not detected; (iii) the polyunsaturated isomer 12c,15t-18:2 was metabolically more similar to saturated and 9c-18:1 fatty acids than to 9c,12c-18:2; (iv) relative incorporation of 9c,12c-18:2 into phospholipids did not increase proportionally with an increase of 9c,12c-18:2 in the mixture of deuterated fats fed; (v) absorption of 16:0, 18:0, 9c-18:1, 9c,12c-18:2 and 12c,15t-18:2 were similar; and (vi) data for the 1- and 2-acyl positions of phosphatidylcholine and for cholesteryl ester fractions reflected the known high specificity of phosphatidylcholine acyltransferase and lecithin:cholesteryl acyltransferase for 9c,12c-18:2. These results illustrate that incorporation of dietary fatty acids into human plasma lipid classes is selectively controlled and that incorporation of dietary 9c,12c-18:2 is limited

  6. Insights into the role of oxidative stress in the pathology of Friedreich ataxia using peroxidation resistant polyunsaturated fatty acids

    Directory of Open Access Journals (Sweden)

    M. Grazia Cotticelli

    2013-01-01

    Full Text Available Friedreich ataxia is an autosomal recessive, inherited neuro- and cardio-degenerative disorder characterized by progressive ataxia of all four limbs, dysarthria, areflexia, sensory loss, skeletal deformities, and hypertrophic cardiomyopathy. Most disease alleles have a trinucleotide repeat expansion in the first intron of the FXN gene, which decreases expression of the encoded protein frataxin. Frataxin is involved in iron–sulfur-cluster (ISC assembly in the mitochondrial matrix, and decreased frataxin is associated with ISC-enzyme and mitochondrial dysfunction, mitochondrial iron accumulation, and increased oxidative stress. To assess the role of oxidative stress in lipid peroxidation in Friedreich ataxia we used the novel approach of treating Friedreich ataxia cell models with polyunsaturated fatty acids (PUFAs deuterated at bis-allylic sites. In ROS-driven oxidation of PUFAs, the rate-limiting step is hydrogen abstraction from a bis-allylic site; isotopic reinforcement (deuteration of bis-allylic sites slows down their peroxidation. We show that linoleic and α-linolenic acids deuterated at the peroxidation-prone bis-allylic positions actively rescue oxidative-stress-challenged Friedreich ataxia cells. The protective effect of the deuterated PUFAs is additive in our models with the protective effect of the CoQ10 analog idebenone, which is thought to decrease the production of free radicals. Moreover, the administration of deuterated PUFAs resulted in decreased lipid peroxidation as measured by the fluorescence of the fatty acid analog C11-BODIPY (581/591 probe. Our results are consistent with a role for lipid peroxidation in Friedreich ataxia pathology, and suggest that the novel approach of oral delivery of isotope-reinforced PUFAs may have therapeutic potential in Friedreich ataxia and other disorders involving oxidative stress and lipid peroxidation.

  7. Visualization of root water uptake: quantification of deuterated water transport in roots using neutron radiography and numerical modeling.

    Science.gov (United States)

    Zarebanadkouki, Mohsen; Kroener, Eva; Kaestner, Anders; Carminati, Andrea

    2014-10-01

    Our understanding of soil and plant water relations is limited by the lack of experimental methods to measure water fluxes in soil and plants. Here, we describe a new method to noninvasively quantify water fluxes in roots. To this end, neutron radiography was used to trace the transport of deuterated water (D2O) into roots. The results showed that (1) the radial transport of D2O from soil to the roots depended similarly on diffusive and convective transport and (2) the axial transport of D2O along the root xylem was largely dominated by convection. To quantify the convective fluxes from the radiographs, we introduced a convection-diffusion model to simulate the D2O transport in roots. The model takes into account different pathways of water across the root tissue, the endodermis as a layer with distinct transport properties, and the axial transport of D2O in the xylem. The diffusion coefficients of the root tissues were inversely estimated by simulating the experiments at night under the assumption that the convective fluxes were negligible. Inverse modeling of the experiment at day gave the profile of water fluxes into the roots. For a 24-d-old lupine (Lupinus albus) grown in a soil with uniform water content, root water uptake was higher in the proximal parts of lateral roots and decreased toward the distal parts. The method allows the quantification of the root properties and the regions of root water uptake along the root systems. © 2014 American Society of Plant Biologists. All Rights Reserved.

  8. Long chain poly-unsaturated fatty acids attenuate the IL-1?-induced pro-inflammatory response in human fetal intestinal epithelial cells

    OpenAIRE

    Wijendran, Vasuki; Brenna, JT; Wang, Dong Hao; Zhu, Weishu; Meng, Di; Ganguli, Kriston; Kothapalli, Kumar SD; Requena, Pilar; Innis, Sheila; Walker, WA

    2015-01-01

    Background Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture. Methods Human fetal IEC in culture were derived from a healthy fetal small intestine (H4) or resected small intestine of a neonate wit...

  9. Amino acid and fatty acid compositions of Rusip from fermented Anchovy fish (Stolephorussp)

    Science.gov (United States)

    Koesoemawardani, D.; Hidayati, S.; Subeki

    2018-04-01

    Rusip is a typical food of Bangka Belitung Indonesia made from fermented anchovy. This study aims to determine the properties of chemistry, microbiology, composition of amino acids and fatty acids from fermented fish spontaneously and non spontaneously. Spontaneous rusip treatment is done by anchovy fish (Stolephorussp) after cleaning and added salt 25% (w/w) and palm sugar 10% (w/w). While, non-spontaneous rusip is done by adding a culture mixture of Streptococcus, Leuconostoc, and Lactobacillus bacteria 2% (w/v). The materials are then incubated for 2 weeks. The data obtained were then performed t-test at the level of 5%. Spontaneous and non-spontaneous rusip fermentation process showed significant differences in total acid, reducing sugar, salt content, TVN, total lactic acid bacteria, total mold, and total microbial. The dominant amino acid content of spontaneous and non-spontaneous rusip are glutamic acid and aspartic acid, while the dominant fatty acids in spontaneous and non-spontaneous rusip are docosahexaenoic acid, palmitic acid, oleic acid, arachidonic acid, stearic acid, eicosapentaenoic acid, palmitoleic acid, and myristic acid.

  10. Omega-3 fatty acids for breast cancer prevention and survivorship.

    Science.gov (United States)

    Fabian, Carol J; Kimler, Bruce F; Hursting, Stephen D

    2015-05-04

    Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.

  11. Deuterium oxide as a tool for the study of amino acid metabolism

    International Nuclear Information System (INIS)

    Mitra, R.; Burton, J.; Varner, J.E.

    1976-01-01

    We have used deuterium oxide in nontoxic concentrations to study, in intact seedlings, the biosynthesis of amino acids. The extent and pattern of deuteration, as determined by a gas--liquid chromatograph--mass spectrometer system, permits conclusions about the biosynthesis of individual amino acids and also about their exposure to transaminases and other enzymes that might introduce deuterium into specific positions of the amino acid by exchange. This method could be used to study amino acid biogenesis in any organism that can tolerate 20 to 40 percent deuterium oxide for a period of a few hours to a few days

  12. High-level expression and deuteration of sperm whale myoglobin: A study of its solvent structure by X-ray and neutron diffraction methods

    Energy Technology Data Exchange (ETDEWEB)

    Shu, F. [State Univ. of New York, Stony Brook, NY (United States); Ramakrishnan, V. [Brookhaven National Laboratory, Upton, NY (United States); Schoenborn, B.P. [Los Alamos National Laboratory, NM (United States)

    1994-12-31

    Neutron diffraction has become one of the best ways to study light atoms, such as hydrogens. Hydrogen however has a negative coherent scattering factor, and a large incoherent scattering factor, while deuterium has virtually no incoherent scattering, but a large positive coherent scattering factor. Beside causing high background due to its incoherent scattering, the negative coherent scattering of hydrogen tends to cancel out the positive contribution from other atoms in a neutron density map. Therefore a fully deuterated sample will yield better diffraction data with stronger density in the hydrogen position. On this basis, a sperm whale myoglobin gene modified to include part of the A cII protein gene has been cloned into the T7 expression system. Milligram amounts of fully deuterated holo-myoglobin have been obtained and used for crystallization. The synthetic sperm whale myoglobin crystallized in P2{sub 1} space group isomorphous with the native protein crystal. A complete X-ray diffraction dataset at 1.5{Angstrom} has been collected. This X-ray dataset, and a neutron data set collected previously on a protonated carbon-monoxymyoglobin crystal have been used for solvent structure studies. Both X-ray and neutron data have shown that there are ordered hydration layers around the protein surface. Solvent shell analysis on the neutron data further has shown that the first hydration layer behaves differently around polar and apolar regions of the protein surface. Finally, the structure of per-deuterated myoglobin has been refined using all reflections to a R factor of 17%.

  13. High-level expression and deuteration of sperm whale myoglobin: A study of its solvent structure by X-ray and neutron diffraction methods

    International Nuclear Information System (INIS)

    Shu, F.; Ramakrishnan, V.; Schoenborn, B.P.

    1994-01-01

    Neutron diffraction has become one of the best ways to study light atoms, such as hydrogens. Hydrogen however has a negative coherent scattering factor, and a large incoherent scattering factor, while deuterium has virtually no incoherent scattering, but a large positive coherent scattering factor. Beside causing high background due to its incoherent scattering, the negative coherent scattering of hydrogen tends to cancel out the positive contribution from other atoms in a neutron density map. Therefore a fully deuterated sample will yield better diffraction data with stronger density in the hydrogen position. On this basis, a sperm whale myoglobin gene modified to include part of the A cII protein gene has been cloned into the T7 expression system. Milligram amounts of fully deuterated holo-myoglobin have been obtained and used for crystallization. The synthetic sperm whale myoglobin crystallized in P2 1 space group isomorphous with the native protein crystal. A complete X-ray diffraction dataset at 1.5 Angstrom has been collected. This X-ray dataset, and a neutron data set collected previously on a protonated carbon-monoxymyoglobin crystal have been used for solvent structure studies. Both X-ray and neutron data have shown that there are ordered hydration layers around the protein surface. Solvent shell analysis on the neutron data further has shown that the first hydration layer behaves differently around polar and apolar regions of the protein surface. Finally, the structure of per-deuterated myoglobin has been refined using all reflections to a R factor of 17%

  14. Small-angle neutron scattering from the reconstituted TF sub 1 of H sup + -ATPase from thermophilic bacterium PS3 with deuterated subunits

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Yuji [Univ. of Tokyo (Japan) Brookhaven National Lab., Upton, NY (United States); Harada, Mitsuo [Univ. of Tokyo (Japan); Ohta, Shigeo; Kagawa, Yasuo; Aono, Osamu [Jichi Medical School, Tochigi (Japan); Schefer, J; Schoenborn, B P [Brookhaven National Lab., Upton (United States)

    1990-01-01

    Subunits {alpha}, {beta} and {gamma} of adenosine triphosphatase (H{sup +}-ATPase) from the thermophilic bacterium PS3 (TF{sub 1}) have been over-expressed in Escherichia coli. {alpha} and {beta} subunits deuterated to the level of 90% were obtained by culturing E. coli in {sup 2}H{sub 2}O medium. Both the subunits and the reconstituted {alpha}{beta}{gamma} complex, TF{sub 1}, which contain the deuterated components in various combinations, were studied in solution by small-angle neutron scattering. The individual shapes of the subunits and their organization in the {alpha}{beta}{gamma}-TF{sub 1} complex were examined using the techniques of selective deuteration and contrast variation. The {alpha} and {beta} subunits are well approximated as ellipsoids of revolution having minor semi-axes of 20{center dot}4({plus minus}0{center dot}4) and 20{center dot}0({plus minus}0{center dot}2) {angstrom}, and major semi-axes of 53{center dot}0({plus minus}1{center dot}4) and 55{center dot}8({plus minus}0{center dot}9) {angstrom}, respectively. In the TF{sub 1} complex, three {beta} subunits are aligned to form an equilateral triangle, with their major axes tilted by 35{degree} with respect to the 3-fold axis of the complex. The {beta}-{beta} distance is about 53 {angstrom}. Three {alpha} subunits are similarly arranged, positioned between the {beta} subunits, and with their direction of tilt opposite to that of the {beta} subunits. The centers of the {alpha} and {beta} subunits lie in the same plane, forming a hexagon. Adjacent subunits overlap in this model, suggesting that they are not simple ellipsoids of revolution.

  15. The deuteration of acetanilides

    International Nuclear Information System (INIS)

    Chin, S.K.; Collier, R.; Hutchinson, D.W.

    1982-01-01

    The base-catalysed exchange of a proton of the methyl groups in acetanilides can be used to incorporate deuterium into these amides. 4'-Hydroxyl-2[ 2 H]acetanilide (acetaminophen, paracetamol) can be prepared by the demethylation with boron tribromide of 4'-methoxy-2[ 2 H] acetamide obtained by this base-catalysed exchange. (author)

  16. Deuteration of acetanilides

    Energy Technology Data Exchange (ETDEWEB)

    Chin, S.K.; Collier, R.; Hutchinson, D.W. (Warwick Univ., Coventry (UK). Dept. of Chemistry and Molecular Sciences)

    1982-09-01

    The base-catalysed exchange of a proton of the methyl groups in acetanilides can be used to incorporate deuterium into these amides. 4'-Hydroxyl-2(/sup 2/H)acetanilide (acetaminophen, paracetamol) can be prepared by the demethylation with boron tribromide of 4'-methoxy-2(/sup 2/H) acetamide obtained by this base-catalysed exchange.

  17. Cadmium Alters the Concentration of Fatty Acids in THP-1 Macrophages.

    Science.gov (United States)

    Olszowski, Tomasz; Gutowska, Izabela; Baranowska-Bosiacka, Irena; Łukomska, Agnieszka; Drozd, Arleta; Chlubek, Dariusz

    2018-03-01

    Fatty acid composition of human immune cells influences their function. The aim of this study was to evaluate the effects of known toxicant and immunomodulator, cadmium, at low concentrations on levels of selected fatty acids (FAs) in THP-1 macrophages. The differentiation of THP-1 monocytes into macrophages was achieved by administration of phorbol myristate acetate. Macrophages were incubated with various cadmium chloride (CdCl 2 ) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM, and 2 μM CdCl 2 . Fatty acids were extracted from samples according to the Folch method. The fatty acid levels were determined using gas chromatography. The following fatty acids were analyzed: long-chain saturated fatty acids (SFAs) palmitic acid and stearic acid, very long-chain saturated fatty acid (VLSFA) arachidic acid, monounsaturated fatty acids (MUFAs) palmitoleic acid, oleic acid and vaccenic acid, and n-6 polyunsaturated fatty acids (PUFAs) linoleic acid and arachidonic acid. Treatment of macrophages with very low concentrations of cadmium (5-200 nM) resulted in significant reduction in the levels of arachidic, palmitoleic, oleic, vaccenic, and linoleic acids and significant increase in arachidonic acid levels (following exposure to 5 nM Cd), without significant reduction of palmitic and stearic acid levels. Treatment of macrophages with the highest tested cadmium concentration (2 μM) produced significant reduction in the levels of all examined FAs: SFAs, VLSFA, MUFAs, and PUFAs. In conclusion, cadmium at tested concentrations caused significant alterations in THP-1 macrophage fatty acid levels, disrupting their composition, which might dysregulate fatty acid/lipid metabolism thus affecting macrophage behavior and inflammatory state.

  18. Free radicals in dicarboxylic acids: an e.s.r. study of radical conversions in γ-irradiated single crystals of glutaric acid and glutaric-2,2,4,4-d4 acid

    International Nuclear Information System (INIS)

    Bergene, R.; Minegishi, A.; Riesz, P.

    1980-01-01

    The γ-radiation-induced free radicals in single crystals of glutaric acid and glutaric-2,2,4,4-d 4 acid were studied in the temperature range 77-300 K by e.s.r. techniques. At 77 K the decarboxylation radical and the anion are stabilized. At higher temperatures the decarboxylation radical is found to be converted into a hydrogen abstraction radical with an activation energy of 6.3 +- 0.5 kcal/mole for the non-deuterated crystal. This radical is stable at room temperature. The anion seems to be converted to a unidentified intermediate radical which in turn is converted to the σ-acyl radical. An analysis of the g-value anisotropy and of the 13 C hyperfine splitting variation for this radical in the deuterated crystal is consistent with the assigned radical structure. By heat treatment the σ-acyl radical is converted to another form of the hydrogen abstraction radical with an activation energy of 9.6 +- 0.6 kcal/mole in the deuterated crystal. U.V.-light (lambda= 254 nm) transforms one of the room temperature radicals into the other. (author)

  19. Definitive difference among [DS-D2O], [DS-H2O] and [Bulk-D2O] cells in the deuterization and deuterium-reaction

    International Nuclear Information System (INIS)

    Arata, Yoshiaki; Zhang, Yue Chang

    2000-01-01

    We observed a new phenomena that the enormous amount of deuterium/hydrogen can be absorbed quickly as a 'solute-atom' into fine metal powders embedded inside a double-structure (DS) cathode in the electrolyses of D 2 O and H 2 O-electrolytes, respectively, but such highly deuterated powders can be produced only using DS-cathode immersed in D 2 O-electrolyte; [DS-D 2 O], and never generated in H 2 O-electrolyte even using the DS-cathode; [DS-H 2 O]. On the other hand, [Bulk-D 2 O] with bulk-cathode made by the bulk Pd metal never produces highly deuterated metal as mentioned above even though using D 2 O-electrolyte. In short, the deuterium-concentration generating in [Bulk-D 2 O] is found to be much lower than that in [DS-D 2 O]. As a result, because of reason mentioned above, in marked contrast to the case with the [DS-D 2 O], neither excess heat nor 4 He production are observed with both [DS-H 2 O] and [Bulk-D 2 O]. (author)

  20. Application of the deuterated retinol dilution technique to detect changes in hepatic retinol reserves in infants who receive high dose vitamin A supplements

    International Nuclear Information System (INIS)

    Penny, M.; Lanata, C.; Butron, B.; Haskell, M.; Brown, K.

    1997-01-01

    The purpose of this pilot study is to determine whether the deuterated retinol dilution technique can detect changes in hepatic vitamin A reserves in Peruvian infants in response to supplementation with vitamin A palmitate. Approximately 40 infants, 9 months of age, will be recruited for the study and randomly assigned to four treatment groups. Hepatic vitamin A reserves will be estimated using the deuterated retinol dilution technique before and after administration of a single supplement containing either 0, 7.5, 15, or 30 mg RE as retinyl palmitate in corn oil. Mean hepatic vitamin A reserves will be calculated based on the plasma isotopic ratio of d4-retinol:retinol as per Furr, et. al. Hepatic vitamin A reserves will be compared within groups before and after supplementation, and among the four groups. The mean change in hepatic vitamin A reserves across the four treatment groups will be examined in relation to the amount of vitamin A supplement administered, using regression analysis. The results of the pilot study will provide information on the size and variation of hepatic vitamin A reserves in 9-month old Peruvian infants. This information will be useful for calculating samples sizes to evaluate vitamin A intervention strategies by estimating changes in hepatic vitamin A stores in this age group, using the DRD technique. (author)

  1. Application of the deuterated retinol dilution technique to detect changes in hepatic retinol reserves in infants who receive high dose vitamin A supplements

    Energy Technology Data Exchange (ETDEWEB)

    Penny, M; Lanata, C; Butron, B [Instituto de Investigacion Nutricional, Lima (Peru); Haskell, M; Brown, K [Programme in International Nutrition, Univ. of California, Davis, CA (United States)

    1998-12-31

    The purpose of this pilot study is to determine whether the deuterated retinol dilution technique can detect changes in hepatic vitamin A reserves in Peruvian infants in response to supplementation with vitamin A palmitate. Approximately 40 infants, 9 months of age, will be recruited for the study and randomly assigned to four treatment groups. Hepatic vitamin A reserves will be estimated using the deuterated retinol dilution technique before and after administration of a single supplement containing either 0, 7.5, 15, or 30 mg RE as retinyl palmitate in corn oil. Mean hepatic vitamin A reserves will be calculated based on the plasma isotopic ratio of d4-retinol:retinol as per Furr, et. al. Hepatic vitamin A reserves will be compared within groups before and after supplementation, and among the four groups. The mean change in hepatic vitamin A reserves across the four treatment groups will be examined in relation to the amount of vitamin A supplement administered, using regression analysis. The results of the pilot study will provide information on the size and variation of hepatic vitamin A reserves in 9-month old Peruvian infants. This information will be useful for calculating samples sizes to evaluate vitamin A intervention strategies by estimating changes in hepatic vitamin A stores in this age group, using the DRD technique. (author). 12 refs, 3 figs.

  2. Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid-phase extraction with ultra-high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard.

    Science.gov (United States)

    Yang, Zizhao; Wang, Lu; Xu, Mingcheng; Gu, Jingkai; Yu, Lushan; Zeng, Su

    2016-06-01

    A rapid and sensitive bioassay was established and validated to simultaneously determine gemfibrozil, morphine, morphine-3β-glucuronide, and morphine-6β-glucuronide in mouse cerebrum, epencephalon, and hippocampus based on ultra-high performance liquid chromatography and tandem mass spectrometry. The deuterated internal standard, M6G-d3, was mixed with the prepared samples at 10 ng/mL as the final concentration. The samples were transferred into the C18 solid-phase extraction columns with gradient elution for solid-phase extraction. The mobile phase consisted of methanol and 0.05% formic acid (pH 3.2). Multiple reaction monitoring has been applied to analyze gemfibrozil (m/z 249.0 → 121.0) in anion mode, and M6G-d3 (m/z 465.1 → 289.1), morphine (m/z 286.0 → 200.9), and M3G and M6G (m/z 462.1 → 286.1) in the positive ion mode. The method has a linear calibration range from 0.05 to 10 ng for gemfibrozil, morphine, and M3G and M6G with correlation coefficients >0.993. The lower limit of quantitation for all four analytes was 0.05 ng/mL, relative standard deviation of intra- and interday precision was less than 10.5%, and the relative error of accuracy was from -8.2 to 8.3% at low, medium, and high concentrations for all the analytes. In conclusion, gemfibrozil can influence the morphine antinociception after coronary heart disease induced chronic angina by the change in one of morphine metabolites', M3G, distribution in mouse brain. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Feedlot lamb meat fatty acids profile characterization employing gas chromatography

    Directory of Open Access Journals (Sweden)

    M.I. Cruz-Gonzalez

    2014-06-01

    Full Text Available Fat is an important constituent in diet, not only as an energy source, but for its essential fatty acids associated to fats in foods, considering that some polyunsaturated fatty acids like linoleic, linolenic and arachidonic cannot be synthesized by superior animals like humans. Scientific evidence show that the fatty acids ingest can affect the thrombotic tendency, cardiac rhythm, endothelial function systematic inflammation, insulin sensibility and oxidative stress. Samples from 21 ovine crossbreds from Pelibuey, Blackbelly, Dorper and Katahadin (40 kg average weight feed with corn based balanced diets were taken from loin area 18 h after refrigeration. Saturated and polyunsaturated fatty acids levels were analyzed by gas chromatography. Results in this work showed that the healthy fatty acids levels are higher as compared to saturated fatty acids levels, indicating that this meat can influence consumer’s buying choice decision regarded to their health.

  4. n-3 fatty acids reduce plasma 20-hydroxyeicosatetraenoic acid and blood pressure in patients with chronic kidney disease.

    Science.gov (United States)

    Barden, Anne E; Burke, Valerie; Mas, Emilie; Beilin, Lawrence J; Puddey, Ian B; Watts, Gerald F; Irish, Ashley B; Mori, Trevor A

    2015-09-01

    Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied. We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks. This study examined the effect of n-3 fatty acids on plasma and urinary 20-HETE in the same study, as well as plasma and urinary F2-isoprostanes, and relate these to changes in BP. Seventy-four patients completed the 8-week intervention. n-3 fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and F2-isoprostanes (P fatty acids. This is the first report that n-3 fatty acid supplementation reduces plasma 20-HETE in humans and that this associates with reduced BP. These results provide a plausible mechanism for the reduction in BP observed in patients with CKD following n-3 fatty acid supplementation.

  5. Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

    Directory of Open Access Journals (Sweden)

    P.C. Calder

    1998-04-01

    Full Text Available 1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs, eicosapentaenoic (20:5n-3 and docosahexaenoic (22:6n-3 acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, a-linolenic acid (18:3n-3. Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6, the precursor of arachidonic acid (20:4n-6. 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.

  6. Characterisation of (R-2-(2-Fluorobiphenyl-4-yl-N-(3-Methylpyridin-2-ylPropanamide as a Dual Fatty Acid Amide Hydrolase: Cyclooxygenase Inhibitor.

    Directory of Open Access Journals (Sweden)

    Sandra Gouveia-Figueira

    Full Text Available Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH and substrate selective cyclooxygenase (COX-2 inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl-N-(3-methylpyridin-2-ylpropanamide (Flu-AM1. These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known.COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R-Flu-AM1, COX-1 (arachidonic acid 6 μM; COX-2 (arachidonic acid 20 μM; COX-2 (2-AG 1 μM; (S-Flu-AM1, COX-1 (arachidonic acid 3 μM; COX-2 (arachidonic acid 10 μM; COX-2 (2-AG 0.7 μM. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R-Flu-AM1 (10 μM greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R-Flu-AM1 or by 10 μM flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 μM.Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon γ- stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the large induction of COX-2 produced by this treatment.

  7. Effects of global change factors on fatty acids and mycosporine-like amino acid production in Chroothece richteriana (Rhodophyta).

    Science.gov (United States)

    Gonzalez-Silvera, Daniel; Pérez, Sandra; Korbee, Nathalie; Figueroa, Félix L; Asencio, Antonia D; Aboal, Marina; López-Jiménez, José Ángel

    2017-10-01

    Under natural conditions, Chroothece richteriana synthesizes a fairly high proportion of fatty acids. However, nothing is known about how environmental changes affect their production, or about the production of protective compounds, when colonies develop under full sunshine with high levels of UV radiation. In this study, wild colonies of C. richteriana were subjected to increasing temperature, conductivity, ammonium concentrations and photosynthetically active radiation (PAR), and UV radiations to assess the potential changes in lipid composition and mycosporine-like amino acids (MAAs) concentration. The PERMANOVA analysis detected no differences for the whole fatty acid profile among treatments, but the percentages of α-linolenic acid and total polyunsaturated fatty acids increased at the lowest assayed temperature. The percentages of linoleic and α-linolenic acids increased with lowering temperature. γ-linolenic and arachidonic acids decreased with increasing conductivity, and a high arachidonic acid concentration was related with increased conductivity. The samples exposed to UVB radiation showed higher percentages of eicosapentaenoic acid and total monounsaturated fatty acids, at the expense of saturated fatty acids. MAAs accumulation increased but not significantly at the lowest conductivity, and also with the highest PAR and UVR exposure, while ammonium and temperature had no effect. The observed changes are probably related with adaptations of both membrane fluidity to low temperature, and metabolism to protect cells against UV radiation damage. The results suggest the potential to change lipid composition and MAAs concentration in response to environmental stressful conditions due to climate change, and highlight the interest of the species in future research about the biotechnological production of both compound types. © 2017 Phycological Society of America.

  8. Nutritional quality evaluation of rabbit meat (Flemish Giant breed corelated with fatty acids content

    Directory of Open Access Journals (Sweden)

    Gabriela Frunză

    2016-10-01

    Full Text Available The aim of this study was to assess the nutritional quality of rabbit meat (Flemish Giant breed in terms of content of fatty acids. The biological material consisted of 42 rabbits (17 females and 15 males from which were collected Longissimus dorsi, Semimembranosus and Triceps Brachii muscles immediately after slaughter. The samples were vacuum packaged, frozen at -80 0C, and immediately after thawing have been minced and freeze-dried at -110 0C (using lyophilizer CoolSafe Scanvac. The content in fatty acids was followed through NIRS methodology, using FOSS 6500 spectrophotometer, by gender. Was determined: the saturated fatty acids: C14:0 (Myristic acid, C15: 0 (Pentadecanoic acid, C16: 0 (Palmitic acid, C17: 0 (Heptadecanoic acid and C18: 0 (Stearic acid; monounsaturated fatty acids: Palmitoleic acid (C16: 1n-7, Vaccenic acid, cis-isomer of oleic acid (C18: 1n-7 and oleic acid (C18: 1n-9 and the polyunsaturated fatty acids (ω3 and ω6: C18: 2n-6 (linoleic acid, C18: 3n-3 (Linolenic acid, C20: 2n-6 (Eicosadienoic acid, C20: 3n-6 (Eicosatrienoic acid, C20: 4n-6 (arachidonic acid, C20: 5n-3 (Eicosapentaenoic acid, C22: 4n-6 (Docosatetraenoic acid, C22: 5n-3 (Docosopentaenoic acid and C22: 6n- 3 (docosahexaenoic acid. The results were statistically analyzed, including analysis of variance (ANOVA and was observed significant differences between gender.

  9. Essential fatty acids and lipid mediators. Endocannabinoids

    Directory of Open Access Journals (Sweden)

    G. Caramia

    2012-03-01

    Full Text Available In 1929 Burr and Burr discovered the essential fatty acids omega-6 and omega-3. Since then, researchers have shown a growing interest in polyunsaturated fatty acids (PUFA as precursors of “lipid mediator” molecules, often with opposing effects, prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipossines, resolvines, protectines, maresins that regulate immunity, platelet aggregation, inflammation, etc. They showed that the balance between omega-3 and omega-6 acids has a profound influence on all the body’s inflammatory responses and a raised level of PUFA omega-3 in tissue correlate with a reduced incidence of degenerative cardiovascular disease, some mental illnesses such as depression, and neuro-degenerative diseases such as Alzheimer’s. The CYP-catalyzed epoxidation and hydroxylation of arachidonic acid (AA were established recently as the so-called third branch of AGE cascade. Cytochrome P450 (CYP epoxygenases convert AA to four epoxyeicosatrienoic acid (EET regioisomers, that produce vascular relaxation anti-inflammatory effects on blood vessels and in the kidney, promote angiogenesis, and protect ischemic myocardium and brain. Eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA are accessible to CYP enzymes in the same way as AA. Metabolites derived from EPA include epoxyeicosatetraenoic acids (EETR and hydroxyeicosapentaenoic acids (19- and 20-HEPE, whereas DHA include epoxydocosapentaenoic acids (EDPs hydroxydocosahexaenoic acids (21- and 22-HDoHE. For many of the CYP isoforms, the n-3 PUFAs are the preferred substrates and the available data suggest that some of the vasculo- and cardioprotective effects attributed to dietary n-3 PUFAs may be mediated by CYP-dependent metabolites of EPA and DHA. From AA derives also endocannabinoids like anandamide (N-arachidonoylethanolamine and 2-arachidonoylglycerol, capable of mimicking the pharmacological actions of the active principle of Cannabis sativa preparations such as

  10. Loss of ammonia during electron-transfer dissociation of deuterated peptides as an inherent gauge of gas-phase hydrogen scrambling

    DEFF Research Database (Denmark)

    Rand, Kasper D; Zehl, Martin; Jensen, Ole Nørregaard

    2010-01-01

    detected by a depletion of deuterium when deuterated ammonia is lost from peptides during ETD. This straightforward method requires no modifications to the experimental workflow and has the great advantage that the occurrence of hydrogen scrambling can be directly detected in the actual peptides analyzed......The application of electron-transfer dissociation (ETD) to obtain single-residue resolution in hydrogen exchange-mass spectrometry (HX-MS) experiments has recently been demonstrated. For such measurements, it is critical to ensure that the level of gas-phase hydrogen scrambling is negligible. Here...... we utilize the abundant loss of ammonia upon ETD of peptide ions as a universal reporter of positional randomization of the exchangeable hydrogens (hydrogen scrambling) during HX-ETD experiments. We show that the loss of ammonia from peptide ions proceeds without depletion of deuterium when employing...

  11. Infrared and Raman study of the fast internal motions of non-rigid molecules in condensed state: method of selective deuteration

    International Nuclear Information System (INIS)

    Lascombe, J.; Cavagnat, D.; Lassegues, J.C.; Rafilipomanana, C.

    1983-01-01

    The dynamical behaviour of non-rigid molecules in the gas state is now well known but very little information is available on these molecules in condensed state. The authors present a method of study based on the analysis of the infrared and Raman spectra of selectively deuterated molecules. It is applied to the nitromethane and cyclopentene molecules which provide respectively characteristic examples of methyl internal rotation and ring-puckering motion. In each case, an isolated -C0 or -CD oscillator is modulated by the internal motion and several γ(CH) or γ(CD) bands are observed as a result of the dependence of the vibrational frequency of the oscillator on its conformational situation. Moreover, in the case of crystalline nitromethane a detailed study of the temperature dependence of the band profiles allows the main mechanism of relaxation of the -CH oscillator to be deduced. (orig.)

  12. Poly(dA-dT).poly(dA-dT) two-pathway proton exchange mechanism. Effect of general and specific base catalysis on deuteration rates

    International Nuclear Information System (INIS)

    Hartmann, B.; Leng, M.; Ramstein, J.

    1986-01-01

    The deuteration rates of the poly(dA-dT).poly(dA-dT) amino and imino protons have been measured with stopped-flow spectrophotometry as a function of general and specific base catalyst concentration. Two proton exchange classes are found with time constants differing by a factor of 10 (4 and 0.4 s-1). The slower class represents the exchange of the adenine amino protons whereas the proton of the faster class has been assigned to the thymine imino proton. The exchange rates of these two classes of protons are independent of general and specific base catalyst concentration. This very characteristic behavior demonstrates that in our experimental conditions the exchange rates of the imino and amino protons in poly(dA-dT).poly(dA-dT) are limited by two different conformational fluctuations. We present a three-state exchange mechanism accounting for our experimental results

  13. Selective remodeling of cardiolipin fatty acids in the aged rat heart

    Directory of Open Access Journals (Sweden)

    Rapoport Stanley I

    2006-01-01

    Full Text Available Abstract Background The heart is rich in cardiolipin, a phospholipid acylated in four sites, predominately with linoleic acid. Whether or not aging alters the composition of cardiolipin acyl chains is controversial. We therefore measured the fatty acid concentration of cardiolipin in hearts of 4, 12 and 24 month old rats that consumed one diet, adequate in fatty acids for the duration of their life. Results The concentration (nmol/g of linoleic acid was decreased in 24 month old rats (3965 ± 617, mean ± SD vs 4 month old rats (5525 ± 656, while the concentrations of arachidonic and docosahexaenoic acid were increased in 24 month old rats (79 ± 9 vs 178 ± 27 and 104 ± 16 vs 307 ± 68 for arachidonic and docosahexaenoic acids, 4 months vs 24 months, respectively. Similar changes were not observed in ethanolamine glycerophospholipids or plasma unesterified fatty acids, suggesting specificity of these effects to cardiolipin. Conclusion These results demonstrate that cardiolipin remodeling occurs with aging, specifically an increase in highly unsaturated fatty acids.

  14. Modification of essential fatty acid composition in broodstock of cultured European eel Anguilla anguilla L

    DEFF Research Database (Denmark)

    Støttrup, Josianne; Jacobsen, Charlotte; Tomkiewicz, Jonna

    2013-01-01

    Farmed eels had lower levels of arachidonic acid (20:4 n-6) (ARA) and higher ratios of eicosapentaenoic acid (20:5 n-3) (EPA):ARA compared to wild European eels collected from the Baltic Sea and southern Norwegian coast. Eels fed a formulated feed (JD) with a distribution of essential fatty acids...... and docosahexaenoic acid (22:6 n-3) (DHA) had accumulated in ovarian polar lipids......Farmed eels had lower levels of arachidonic acid (20:4 n-6) (ARA) and higher ratios of eicosapentaenoic acid (20:5 n-3) (EPA):ARA compared to wild European eels collected from the Baltic Sea and southern Norwegian coast. Eels fed a formulated feed (JD) with a distribution of essential fatty acids...... (EFA) resembling wild European eel were sampled after 0, 5, 10, 14 and 44 weeks of feeding to examine changes in fatty acid composition (FAC) in ovaries, visceral fat and muscle. The results showed a slow but steady incorporation of EFA. Lipids are incorporated in the oocytes early in oogenesis...

  15. Eicosapentaenoic Acid Supplementation Changes Fatty Acid Composition and Corrects Endothelial Dysfunction in Hyperlipidemic Patients

    Directory of Open Access Journals (Sweden)

    Ken Yamakawa

    2012-01-01

    Full Text Available We investigated the effects of purified eicosapentaenoic acid (EPA on vascular endothelial function and free fatty acid composition in Japanese hyperlipidemic subjects. In subjects with hyperlipidemia (total cholesterol ≥220 mg/dL and/or triglycerides ≥150 mg/dL, lipid profile and forearm blood flow (FBF during reactive hyperemia were determined before and 3 months after supplementation with 1800 mg/day EPA. Peak FBF during reactive hyperemia was lower in the hyperlipidemic group than the normolipidemic group. EPA supplementation did not change serum levels of total, HDL, or LDL cholesterol, apolipoproteins, remnant-like particle (RLP cholesterol, RLP triglycerides, or malondialdehyde-modified LDL cholesterol. EPA supplementation did not change total free fatty acid levels in serum, but changed the fatty acid composition, with increased EPA and decreased linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid. EPA supplementation recovered peak FBF after 3 months. Peak FBF recovery was correlated positively with EPA and EPA/arachidonic acid levels and correlated inversely with dihomo-γ-linolenic acid. EPA supplementation restores endothelium-dependent vasodilatation in hyperlipidemic patients despite having no effect on serum cholesterol and triglyceride patterns. These results suggest that EPA supplementation may improve vascular function at least partly via changes in fatty acid composition.

  16. Accumulation of eicosapolyenoic acids enhances sensitivity to abscisic acid and mitigates the effects of drought in transgenic Arabidopsis thaliana.

    Science.gov (United States)

    Yuan, Xiaowei; Li, Yaxiao; Liu, Shiyang; Xia, Fei; Li, Xinzheng; Qi, Baoxiu

    2014-04-01

    IgASE1, a C₁₈ Δ(9)-specific polyunsaturated fatty acid elongase from the marine microalga Isochrysis galbana, is able to convert linoleic acid and α-linolenic acid to eicosadienoic acid and eicosatrienoic acid in Arabidopsis. Eicosadienoic acid and eicosatrienoic acid are precursors of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, which are synthesized via the Δ(8) desaturation biosynthetic pathways. This study shows that the IgASE1-expressing transgenic Arabidopsis exhibited altered morphology (decreased leaf area and biomass) and enhanced drought resistance compared to wild-type plants. The transgenic Arabidopsis were hypersensitive to abscisic acid (ABA) during seed germination, post-germination growth, and seedling development. They had elevated leaf ABA levels under well-watered and dehydrated conditions and their stomata were more sensitive to ABA. Exogenous application of eicosadienoic acid and eicosatrienoic acid can mimic ABA and drought responses in the wild type plants, similar to that found in the transgenic ones. The transcript levels of genes involved in the biosynthesis of ABA (NCED3, ABA1, AAO3) as well as other stress-related genes were upregulated in this transgenic line upon osmotic stress (300 mM mannitol). Taken together, these results indicate that these two eicosapolyenoic acids or their derived metabolites can mitigate the effects of drought in transgenic Arabidopsis, at least in part, through the action of ABA.

  17. Cigarette smoke exposure alters [14C]arachidonic acid metabolism in aortas and platelets of rats fed various levels of selenium and vitamin E

    International Nuclear Information System (INIS)

    Valentovic, M.A.; Gairola, C.; Lubawy, W.C.

    1985-01-01

    Rats were placed on a basal diet supplemented with 0, 0.03, or 3 ppm selenium and 0 or 20 ppm vitamin E for 41-43 wk. Selenium deficiency decreased hepatic glutathione peroxidase activity and lowered both aortic prostacyclin (PGI2) and platelet thromboxane (TXA2) production compared to selenium- and vitamin E-supplemented animals. Vitamin E deficiency increased hepatic lipid peroxidation and decreased aortic PGI2 synthesis. Rats exposed daily for 31-32 wk to fresh smoke from a UK 2R1 reference cigarette had carboxyhemoglobin levels of 0.75 +/- 0.12 and 4.73 +/- 0.12% in sham- and smoke-exposed groups, respectively. Animals chronically exposed to cigarette smoke displayed a nearly twofold increase in pulmonary arylhydrocarbon hydroxylase activity. Smoke exposure produced a 26-33% decrease in aortic PGI2 synthesis compared to shams in the Se3E20, Se0.03E20, and Se3E0 groups. Smoking also increased platelet thromboxane 91% and 98% in the Se3E20 and Se3E0 groups compared to shams. It is concluded that cigarette-smoke exposure and selenium or vitamin E deficiency alter aortic PGI2 and platelet TXA2 production

  18. The effects of TNF-alpha and inhibitors of arachidonic acid metabolism on human colon HT-29 cells depend on differentiation status

    Czech Academy of Sciences Publication Activity Database

    Kovaříková, Martina; Hofmanová, Jiřina; Souček, Karel; Kozubík, Alois

    2004-01-01

    Roč. 72, č. 1 (2004), s. 23-31 ISSN 0301-4681 R&D Projects: GA ČR GA525/01/0419; GA ČR GP524/02/P051; GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : colon cancer * cell differentiation * TNF-alpha Subject RIV: BO - Biophysics Impact factor: 4.481, year: 2004

  19. The influence of the quinone antioxidants tert-butylhydroquinone and 2,5-di-tert-butylhydroquinone on the arachidonic acid metabolism in vitro

    Czech Academy of Sciences Publication Activity Database

    Kutil, Zsófia; Kvasnicová, Marie; Temml, V.; Schuster, D.; Vaněk, Tomáš; Fernandez, E.; Malík, J.; Landa, Přemysl

    2015-01-01

    Roč. 26, č. 4 (2015), s. 504-511 ISSN 0954-0105 Institutional support: RVO:61389030 Keywords : food additives * tert-butylhydroquinone * cyclooxygenase Subject RIV: CE - Biochemistry Impact factor: 1.548, year: 2015

  20. Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer.

    Science.gov (United States)

    Zhao, Yawei; Cui, Lianzhi; Pan, Yue; Shao, Dan; Zheng, Xiao; Zhang, Fan; Zhang, Hansi; He, Kan; Chen, Li

    2017-12-01

    Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy-induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation. The transwell system was used to mimic the co-culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy-treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE 2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot. Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE 2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3-iPLA 2 -AA-COX-2-PGE 2 pathway by inhibiting the expression of iPLA 2 and COX-2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE 2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment. Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation. © 2017 John Wiley & Sons Ltd.

  1. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels

    DEFF Research Database (Denmark)

    Reddy, I A; Pino, J A; Weikop, P

    2016-01-01

    Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocain...

  2. Arachidonic Acid Metabolism in the Nervous System; Physiological and Pathological Significance. Annals of the New York Academy of Science. Volume 5

    Science.gov (United States)

    1989-01-01

    488 Primary Structure of Rat Brain Prostaglandin D Synthetase Deduced from the cDNA Sequence. By YOSHIHIRO URADE, AKIHISA NAGATA, YASUHIKO SUZUKI...Synthetase Deduced from the cDNA Sequence YOSHIHIRO URADE,a AKIHISA NAGATA,b YASUHIKO SUZUKI,b YUTAKA FUJII,c AND OSAMU HAYAISHI a aDepartment of Enzymes

  3. Influence of dietary arachidonic acid combined with light intensity and tank colour on pigmentation of common sole (Solea solea L.) larvae

    DEFF Research Database (Denmark)

    Lund, Ivar; Steenfeldt, Svend Jørgen; Hansen, B.W.

    2010-01-01

    to be related to a higher feed intake. Early pigment cell (chromatophor) development until 11 dph (i.e. start of metamorphosis) was not significantly related to dietary treatment, but during metamorphosis (from 16 dph) total chromatophore concentration (cells larvae (-1)) was significantly lower for larvae...... treated with ARA and a possible lack of pigment cell differentiation or degeneration/cytolysis continued for this group during post metamorphosis....

  4. A general procedure for isotopic (deuterium) labelling of non-steroidal antiinflammatory 2-arylpropionic acids

    International Nuclear Information System (INIS)

    Castell, J.V.; Martinez, L.A.; Universidad Politecnica de Valencia; Miranda, M.A.; Tarrega, Pilar

    1994-01-01

    Alkaline treatment of nonsteroidal antiinflammatory 2-arylpropionic acids in deuterium oxide led in all cases to isotopic exchange of the proton located at the α-position of the side chain. Monodeuteration was observed in the case of carprofen, ibuprofen, ketoprofen, fenoprofen, flurbiprofen and naproxen. Additional exchange of one or two protons of the heterocyclic ring occurred in indoprofen, suprofen and tiaprofenic acid. The isotopic labelling survived under the conditions required to perform in vitro photoallergic studies (photolysis in non-deuterated aqueous media). (Author)

  5. A general procedure for isotopic (deuterium) labelling of non-steroidal antiinflammatory 2-arylpropionic acids

    Energy Technology Data Exchange (ETDEWEB)

    Castell, J.V. (Valencia Univ. Hospital (Spain). Centro de Investigacion); Martinez, L.A. (Valencia Univ. Hospital (Spain). Centro de Investigacion Universidad Politecnica de Valencia (Spain). Dept. de Quimica); Miranda, M.A.; Tarrega, Pilar (Universidad Politecnica de Valencia (Spain). Dept. de Quimica)

    1994-01-01

    Alkaline treatment of nonsteroidal antiinflammatory 2-arylpropionic acids in deuterium oxide led in all cases to isotopic exchange of the proton located at the [alpha]-position of the side chain. Monodeuteration was observed in the case of carprofen, ibuprofen, ketoprofen, fenoprofen, flurbiprofen and naproxen. Additional exchange of one or two protons of the heterocyclic ring occurred in indoprofen, suprofen and tiaprofenic acid. The isotopic labelling survived under the conditions required to perform in vitro photoallergic studies (photolysis in non-deuterated aqueous media). (Author).

  6. Fatty Acid Modulation of the Endocannabinoid System and the Effect on Food Intake and Metabolism

    Directory of Open Access Journals (Sweden)

    Shaan S. Naughton

    2013-01-01

    Full Text Available Endocannabinoids and their G-protein coupled receptors (GPCR are a current research focus in the area of obesity due to the system’s role in food intake and glucose and lipid metabolism. Importantly, overweight and obese individuals often have higher circulating levels of the arachidonic acid-derived endocannabinoids anandamide (AEA and 2-arachidonoyl glycerol (2-AG and an altered pattern of receptor expression. Consequently, this leads to an increase in orexigenic stimuli, changes in fatty acid synthesis, insulin sensitivity, and glucose utilisation, with preferential energy storage in adipose tissue. As endocannabinoids are products of dietary fats, modification of dietary intake may modulate their levels, with eicosapentaenoic and docosahexaenoic acid based endocannabinoids being able to displace arachidonic acid from cell membranes, reducing AEA and 2-AG production. Similarly, oleoyl ethanolamide, a product of oleic acid, induces satiety, decreases circulating fatty acid concentrations, increases the capacity for β-oxidation, and is capable of inhibiting the action of AEA and 2-AG in adipose tissue. Thus, understanding how dietary fats alter endocannabinoid system activity is a pertinent area of research due to public health messages promoting a shift towards plant-derived fats, which are rich sources of AEA and 2-AG precursor fatty acids, possibly encouraging excessive energy intake and weight gain.

  7. FATTY ACID COMPOSITION AND PROSTAGLANDIN CONTENT OF THE RED SEAWEED Gracilaria sp. FROM INDONESIA

    Directory of Open Access Journals (Sweden)

    Muhammad Ikbal Illijas

    2012-06-01

    Full Text Available High content of polyunsaturated fatty acids (PUFAs such as arachidonic and eicosapentaenoic acids are typical for the red alga. Analysis of fatty acid composition and prostaglandin content was conducted in the red alga Gracilaria sp. from Indonesia. Total lipid of the alga was extracted with CHCl3-MeOH (2:1, v/v. Analysis of the fatty acids composition was performed on gas chromatography (GC equipped with omega wax column (30 m x 0,32 mm i.d., Supelco, PA, USA and analysis of prostaglandins were carried